İçeriğe geç

July 2019

July 2019


Original Article

Conversion rate of prediabetes to diabetes in long-term followed patients

Salih Eker

Family Medicine, Sakarya University Research and Training Hospital, Adapazari, Sakarya, Turkey

DOI:10.4328/ACAM.5830 Received: 19.03.2018 Accepted: 10.04.2018 Published Online: 18.03.2019 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 421-5

Corresponding Author: Salih Eker, Family Medicine, Sakarya University Research and Training Hospital, 54100, Adapazari, Sakarya, Turkey. GSM: +905557131383 E-Mail: salihekerdr@hotmail.com

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: We aimed to determine the transition rate of the prediabetic state to Type 2 diabetes mellitus (T2DM) in the subjects for whom pharmaceutical interven-tion therapy was used. Method and Material: In this context, we analyzed the records of 39 prediabetic subjects who we had followed-up at approximately 3-month intervals for a mean duration of 8.77 years. The primary pharmaceutical agent used was metformin; acarbose and rosiglitazone were the other agents used. One subject used no pharmaceutical agent. Results: In the study we found a 43.6% transition rate to overt T2DM. 56.4 % of the subjects did not convert to DM and sustained their status as prediabetes. Discussion: This small but long-term study indicates the possibility that prediabetes can be at least partly prevented or T2DM onset can be delayed for years thorough pharmaceutical intervention. Furthermore, even if the prediabetic state is converted to DM, it can be managed with little intervention and we can maintain nearly the same glucose levels comparable to prediabetes.

Keywords: Prediabetes; Prevention; Metformin

Full Text

Introduction

Type 2 diabetes mellitus (T2DM) has become a common and devastating disease worldwide. Preventing the disease from transitioning to its overt form is of utmost importance. Prediabetes has been explained by the presence of impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). IGT is characterised by elevated postprandial glucose between 140-200 mg/dl and is identified by an oral glucose tolerance test (OGTT) whereby 2-hour glucose levels are measured after a 75 gr glucose load given in the fasting state. Both World Health Organization (WHO) and the American Diabetes Association (ADA) recognize 2-hour post challenge glucose levels of greater than or equal to 7.8 mmol L (140 mg/dl) and less than 11.1 mmol L (200 mg/dl) as indicating IGT [1,2]. IFG is characterized by elevated fasting glucose levels between 100 mg dl and 126 mg/dl (5.5 mmol L-7.0 mmol L) for ADA and 110 mg/dl-126 mg/dl (6.0 mmol L-7.0 mmol L) for WHO [1,2]. In-between these two boundaries exists a region of abnormal glucose control which is already characterized by concomitant insulin resistance and β-cell dysfunction but does not yet reach the criteria for T2DM [3]. Patients eventually diagnosed as T2DM spend an extended period in this region of impaired glucose regulation, sometimes for more than a decade, before progressing to outright T2DM [3].

Although National Institute for Health and Care Excellence (NICE) have recommended that HbA1c (A1c) levels of 6.0-6.5% can be used as an alternative to fasting or 2-hour glucose in the identification of prediabetes, evidence from United Kingdom (UK) and elsewhere suggest there is significant discordance in which individuals are identified with prediabetes through A1c levels versus traditional criteria [4,5].

There are two kinds of interventions to manage the prediabetes state. The; first is lifestyle intervention including managing obesity, physical activity, and diet, each of which has efficacy itself. The second is pharmaceutical intervention including in particular metformin, thiazolidinediones, alpha-glucosidase inhibitors and other agents. In this study we evaluated the second option.

In this study, because there is still controversy over whether if the prediabetic state is a disease or not, we prefer the term ‘’subjects’’ to describe the prediabetics.

 

Material and Method

The study was designed in a retrospective and cross-sectional manner and conducted after 2016 in Sakarya Research and Training Hospital in Turkey. The study protocol was approved by the ethics committee of Sakarya University on June 28, 2016, number 71522473/050.01.04/130. A1c was analyzed with PremierHb9210TM HbA1c analyzer. The instrument consists of an integrated HPLC system, a compact sample handler and the workstation with our Affinity™ control software. Serial Number: 100232, Kansas City, Trinity Biotech, USA. The data was designed and evaluated using the SPSS 20 program.

All the subjects were outpatients who were drug-naïve at the time of their first visit and diagnosed with diabetes or prediabetes. 39 patients were included into the study (30 (76.9%) female and 9 (23.1%) male) and subjects were selected from approximately 2500 files of patients who had been followed in the clinic for their diabetes or prediabetes. To diagnose the prediabetes state we used the internationaly adopted and afore mentioned WHO criteria [1]. Four of the subjects were diagnosed by oral glucose tolerance test (OGTT) while the other 35 were diagnosed according to the fasting glucose level criteria. All of the subjects had their own files and we followed these subjects at approximately 3-month intervals for a mean duration of 8.77 years. In particular, we used the pharmaceutical intervention measures to control the prediabetes state. The primary agent used was metformin, which has proved its efficacy and safety worldwide [6]. For subjects who converted to T2DM we increased the dose or added another agent to control glucose levels in an acceptable range. To identify conversion to T2DM, we used the aforementioned WHO criteria [1], which is fasting glucose level ≥ 126 mg/dl or A1c level ≥ 6.5%. During each visit, an A1c value was taken and saved in their files along with other parameters including biochemical ones (glucose, urea, creatinine, SGOT, SGPT, etc.), Body Mass Index (BMI) and systolic and diastolic tension values that were required to be logged for diabetes. Meanwhile, we also intended to manage confounding diseases including hypertension and dislipidemia, which are the most likely coexisting diseases with impaired glycemic status.

Exercise level was evaluated according to criteria of WHO recommendations on physical activity for health at the time of diagnosis [7] through asking the patient directly. WHO suggests 150 minutes of moderate-intensity exercise per week over daily routine activities. Because no subject could meet the criteria, between 120-150 minutes per week was accepted as the median level, while under 120 minutes per week was accepted as low level of exercise.

BMI of the subjects was calculated at every visit and recorded in their personal files. We used a BMI chart which takes into account the weight and height to calculate the value. Values taken at the baseline and at the last visit were taken into account in the study.

Blood tension values were measured at every visit through a manual manometer by experienced nurses and the values were recorded in the files. We used the baseline and the last value for statistical calculation.

For the majority of subjects, we commenced metformin as the therapy of first choice. We gave metformin 850 mg 1×1 for 18 (46.2%) subjects, metformin 850 mg 2×1 for 9 (23.1%) subjects, metformin 500 mg 2×1 for 8 (17.9%) subjects and metformin 1000 mg 2×1 for 1 (2.6%) subject. Acarbose [8] and rosiglitasone were other therapy options, and for one subject we gave no drug therapy. We gave acarbose 100 mg 3×1 for 2 (5.1%) patients and rosiglitazon 4 mg 1×1 for 1 (2.6%) subject (this subject could not tolerate metformin during the first stage and that is why we preferred rosiglitazone) but after withdrawal of rosiglitazone we did continue with pioglitazone 15 mg 1×1.

Results

30 (76.9%) of the 39 subjects enrolled were female and 9 (23.1%) were male. The mean age of the subjects at baseline was 50.15 and 58.92 at the end of the study. Mean years of follow-up was 8.77 (minimum 4, maximum 11). Mean fasting glucoses of the subjects were 110.05 at baseline and 112.82 at the end of the study, while mean A1c at baseline was 6.05% and 6.03% at the end of the study.

Exercise levels of the subjects were evaluated at the first visit and continued to be monitored until the last visit. The evaluation criteria are described under the methods and material section above. At the first visit, 15 (38.5%) subjects declared that they did not meet any acceptable level of exercise, 23 (59.0%) subjects declared low level of exercise and only 1 (2.6%) subject declared median level of exercise. At the last visit, 12 (30.8%) subjects declared that they could not meet any acceptable level of exercise, 25 (64.1%) subjects declared low level of exercise and 2 (5.1%) subjects declared median level of exercise (p=0.394). Actually, exercise levels of the subjects throughout the follow-up period were smilar to those described above.

Mean BMI of the subjects calculated at baseline was 31.662, and it was 31.423 at last visit (p=0864). These results represent obesity at both times. Also, there were no significant difference between converted and unconverted subjects’s BMIs both at the first and the last visits (Table 3).

Mean systolic and diastolic blood pressure of subjects at baseline were 127.69 and 75.13 respectively whereas they were 120.64 and 78.46 at the last visit ( p=0.004 for systolic and p=0.026 for diastolic).

Smoking status of subjects stratified as 5 (12.8%) smokers, 24 (61.5%) nonsmokers, and 10 (25.6%) ex-smokers at the beginning of the study, and this status had not changed from first to last visit, maintaining the same profile (Table 1). No subjects were alcohol users, either at first or last visit.

Results of the of the study, which aimed to detect the conversion rate from prediabetes state to diabetes, were found as follows: 17 of 39 patients (43.6%) converted to DM, while 22 (56.4%) did not convert (Graphic 1) and managed to maintain their status as prediabetes (Table 1). In detail, 8 (44.4%) of 18 subjects started with metformin 850 mg 1×1 converted to DM while 10 (55.6%) did not, 5 (55.6%) of 9 subjects started with metformin 850 mg 2×1 converted to DM while 4 (44.4%) did not, 2 (28.6%) of 7 subjects started with metformin 500 mg 2×1 converted to DM while 5 (71.4%) did not, 1 subject started with metformin 1000 mg 2×1 maintained as prediabetes, 1 (50.0%) of the 2 subjects started with acarbose 100 mg 3×1 converted to DM while the other subject did not, 1 subject started with rosiglitazone 4 mg 1×1, but after withdrawal of the drug continued with pioglitazone 15 mg 1×1, did not convert to DM [9,17], and lastly 1 subject followed without administering any drug therapy converted to DM (continued with metformin 850 mg 2×1 to control glycemia). This female subject had a BMI of 28.3 at baseline and 27.9 at the end of the study and her exercise level was always low.

Discussion

Unhealthy lifestyles and T2DM are tightly linked, with the former being the primary cause of the latter. These lifestyle practices could be attributed to modern industrialized environments at a rate of 80-90% for all cases of T2DM [10] and there is voluminous evidence for the causal link between diet and physical activity and the prevention of T2DM [11,12]. An expanding range of pharmaceutical agents targeting β-cell function or insulin sensitivity have been tested in the prevention of T2DM over the last two decades; these can be broadly grouped as metformin, PPARγ agonists, and α glucosidase inhibitors. In this study there were no statistically significant changes for BMI and exercise levels in the follow-up period, so the rate of prevention achieved might be broadly attributed to drug therapy.

Metformin is a commonly used and well-understood agent all over the world for the prevention of T2DM. In DPP (The Diabetes Prevention Program), metformin was associated with a 31% reduction in the incidence of T2DM at 3 years [6] but a recent meta-analysis demonstrated an average reduction in the risk of T2DM of 40% with metformin [13], which is more comparable to the finding of this study which was 56.4%. Acarbose is another agent which has proved its efficacy and safety in DM therapy and also has been used for prevention. The major study for prevention was STOP-NIDDM (Study to prevent non-insulin dependent diabetes) [7] and the risk reduction rate was 25%. Although we had only two subjects using acarbose, we found a 50% risk reduction rate.

Thiazolidinedions (TZD) are one of the two agents that have proved their durability in treating DM. We have much data about its efficacy both as monotherapy and in combination with other agents [14,15,16]. Two types of TZDs, rosiglitazone and pioglitazone, have been thoroughly assessed and found to reduce the risk of T2DM by 60-70% over a 2.6- to 3- year period in those with prediabetes [ 9,17]. However, the impressive efficacy of TZDs in the prevention of T2DM is restricted by serious side effects, which makes their use clinically inappropriate for his group. Trials have shown significant weight gain (2.6-7 kg) compared to placebo. More seriously, TZDs are also associated with an increased risk of cardiovascular disease and other adverse health effects [18]. We had only one subject using TZD and she maintained her status as prediabetes.

Another group of agents that has proved its durability is GLP-1 analogues, which have been used succesfully in the treatment of T2DM. These agents are attractive in prevention of T2DM because they are glucose dependent, meaning their effect on insulin secrection is proportionate to the amount of circulating glucose, thus reducing the risk of hypoglycemia and resulting in significant and sustained weight loss. There is scarcity of studies on this group of agents, but given those unique properties they deserve further investigation as DM prevention therapies and they might be the first line of therapy in DM prevention in the future. For example, just 20 weeks of liraglutide therapy has been shown to be effective and reduced the prevalence of prediabetes by 84-96% depending on the dosage used [19].

Nevertheless, although national organizations and regulatory authorities are increasingly recommending the use of metformin, with the other agents likely to be recommended in the future, there remains some controversy around the use of pharmaceutical intervention, and lifestyle modification programs should be the focus of diabetes prevention initiatives. In our daily practice, if we encounter a subject with a prediabetic state with fasting blood glucose over 110 or A1c over 6%, we additionally request an insulin level and C-peptide level. Sometimes an OGTT is performed to obtain 2-hour glucose level. However, there are important practical limitations regarding the utility and clinical value of carrying out OGTTs to identify those with a high risk of T2DM in routine care.Therefore, instead of performing an OGTT, we perform, in addition to blood tests, a risk analysis using variables such as sex,age,ethnicity, BMI, family history of T2DM, cardiovascular diseases, and hypertension assessments for treatment decisions. After taking into considiration all these factors, we decide whether therapy will involve a lifestyle modification program, pharmaceutical intervention, or both. Because for most healthcare units, these tools might be overwhelming or impossible, risk assessment tools such as FINDRISC [20], which is developed for identification of those with a high risk of T2DM, might be preferred.

In conclusion, one of the most confusing questions for physicians serving their patients with DM, a complicated and multifaceted disease, is to decide whether to apply pharmaceutical intervention in the face of prediabetes. That decision means the patients will have to use the drug for their entire life, and we know that some prediabetics do not convert to overt DM untill near the end of their lives. On the other hand, we know the devastating effects of DM and DM-associated diseases. So, preventing or delaying DM in any way is a great benefit to the patients.

At the end of this study we found a 43.6% conversion rate to overt T2DM. Thus, this small-scale but long-term study indicates the possibility that DM can be at least partly prevented or delayed for years through pharmaceutical intervention. Even if the prediabetic state converts to DM, it can be managed with little intervention, achieving nearly the same glucose levels compared to prediabetes.

Nonetheless, as mentioned earlier it should be kept in mind that the lifestyle practices are the first-line alternatives and the mainstay of prevention intervention programs for diabetes.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Bansal N: Prediabetes diagnosis and treatment: A review. World J Dia. 2015;6(2):296-303.

2. Buysschaert M, Medina JL, Buysschaert B, Bergman M: Definitions (and current controversies) of diabetes and prediabetes. Curr Dia Rev. 2016;12(1):8-13.

3. Tabak G, Herder C, Rathmann W, Brunner E, Kwimaki M. Prediabetes : a high-risk state for diabetes development. Lancet 2012;379(9833):2279-90.

4. Mostafa SA, Khunti K, Srinivasan BT, Webb D, Grey LJ, Davies MJ: The potential impact and optimal cut-points of using glycated haemaglobin, HbA1c,to detect people with impaired glucose regulation in a UK multi-ethnic cohort. Diabetes Res Clin Pract. 2010;90(1):100-8

5. James C, Bullard KM, Rolka DB, Geiss LS, Williams DE, Covie CC, et al.: Implications of alternative definitions of prediabetes for prevalence in US, adults. Diabetes Care 2011;34(2):387-91.

6. Knowler WC, Barrett-Connor E, Fowler SE: the Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with life style intervention or metformin. N Engl J Med. 2002;346(6):393-403.

7. Oja P, Titze S: Physical activity recommendations for puplic health: development and policy context. EPMA J. 2011;2(3):253-9.

8. Chiasson JL: Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract. 2006;12:25-30.

9. DeFronzo RA, Devjit Tripathy, Dawn C, MaryAnn B, George B, Thomas B, et al.: Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance. N Engl J Med 2011; 364:1104-15.

10. Mozaffarian D, Kamineni A, Carnethon M, Djousse L, Mukamal KJ, Siscovick D: Lifestyle risk factors and new onset diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med 2009;169(8):798-807.

11. Hawley JA: Exercise as a therapeutic intervention for the prevention and treatment of insulin resistance. Diabetes Metab Res Rev. 2004;20(5):383-93.

12. Telford RD: Low physicial activity and obesity: causes of chronic disease or simply predictors? Med Sci Sports Exerc. 2007;39(8):1233-40

13. Salpeter SR, Buckley NS, Kahn JA, Salpeter EE: Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med. 2008;121(2):149-57.

14. Aranoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL: Pioglitazone hydrocholoride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Diabetes Care 2000 Nov;23(11):1605-11.

15. Rosenblatt S, Miskin B, Glazer NB, Prince MJ, Robertson KE: Pİogitazon 026 Study Group. The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus. Coron Artery Dis. 2001;12(5):413-23.

16. Einhorn D, Rendell M, Rosenzweig J, Egan JW, Mathisen AL, Schneider RL: Pioglitazone hydrocholoride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, plecebo-controlled study. The Pioglitazone 027 Study Group. Clinical Therapeutics. 2000;22(12):1395-409.

17. Gerstein HC, Yusuf S, Bosch J, Pouge J, Sheridan P, Dinccag N, at al.: DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) trial: Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368(9549):1096-1105.

18. Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl JMedicine. 2007;356:2457-71

19. Astrup A, Rosner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, et al.: Effects of Liraglutide in the treatment of obesity: a randomised double-blind, placebo controlled study. Lancet 2009;374(9701):1606-16.

20. Lindström J, Tuomilehto J: The diabetes risk score: a practical tool to predict type 2 diabetes risk. Diabetes Care. 2003;26(3):725-31.

PDF

Download attachments: JCAM_5830.pdf

How to Cite

Salih Eker. Conversion rate of prediabetes to diabetes in long-term followed patients. Ann Clin Anal Med 2019;10(4): 421-5

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

CHA2DS2-VASc score is a predictor of angiographic high thrombus burden in patients with ST-Segment elevation myocardial infarction

Adil Bayramoğlu, Osman Bektaş

Department of Cardiology, Faculty of Medicine, Ordu University, Ordu, Turkey

DOI:10.4328/ACAM.5927 Received: 08.06.2018 Accepted: 21.07.2018 Published Online: 29.07.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 426-30

Corresponding Author: Adil Bayramoğlu, Department of Cardiology, Faculty of Medicine, Ordu University, Ordu, Turkey.F.: +90 4525953303 E-Mail: adilbayramoglu@gmail.com

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: High thrombus burden is an important indicator of complications that may occur in STEMI patients undergoing percutaneous coronary intervention. The CHA2DS2-VASc score is known as the score which is closely related to thrombosis. In this study, we aimed to investigate the association between CHA2DS2-VASc score and angiographic thrombus burden in patients with STEMI who underwent pPCI. Material and Method: A total of 570 consecutive STEMI patients who underwent pPCI were included in the study. The patients were divided into 2 groups: a high thrombus burden group and low thrombus burden group. The CHA2DS2-VASc scores were calculated for all patients. Results: The CHA2DS2-VASc scores were significantly higher in the high thrombus burden group, com-pared to the low thrombus burden group. Multivariate regression analysis showed that, prior MI history (odds ratio [OR] = 0.501, 95% confidence interval [CI]: 0.256-0.982, P =0.044), history of heart failure ( [OR] = 0.460, [CI]: 0.248-0.854, P = 0.014), CHA2DS2-VASc score ( [OR] = 1.812, [CI]: 1.369-2.400, P < 0.001) are predictors of high thrombus burden. Receiver–operating characteristics analysis revealed the cutoff value of CHA2DS2-VASc score ≥ 3 as a predictor of high thrombus burden with a sensitivity of 60.9% and a specificity of 75.0%. Discussion: In our study, we showed that CHA2DS2-VASc score is associated with high thrombus burden in STEMI patients who underwent primary PCI.

Keywords: CHA2DS2-VASc Score; STEMI; Primary PCI; TIMI Thrombus Grade

Full Text

Introduction

Intracoronary thrombus plays an important role in the patho-physiology of ST-segment elevation myocardial infarction (STEMI) [1,2]. Despite the effectiveness of percutaneous coro-nary intervention (PCI), high thrombus burden is an important indicator of complications, that may occur in STEMI patients undergoing PCI [3]. Long-term adverse cardiovascular events of intracoronary thrombus burden remain a serious risk fac-tor for stent thrombosis, distal embolization, and no-reflow [4-7]. Therefore, determination of the predictors of intracoronary thrombus may be helpful in the management of clinical and angiographic conditions. CHA2DS2-VASc is a score known to be related with thrombo-embolism and is used in the estimation of the risk of develop-ment of thromboembolism in patients atrial fibrillation. The risk of thromboembolism increases with the CHA2DS2-VASc score [8]. However, previous studies have shown a associa-tion between CHA2DS2-VASc score, poor prognosis and acute coronary syndrome. CHA2DS2-VASc is associated with the inci-dence of stroke and thromboembolism, and this score is known to be closely correlated with thrombosis [9-11].We aimed to investigate the association between CHA2DS2-VASc score and angiographic thrombus burden in patients with STEMI who underwent pPCI.

Material and Method

A total of 570 consecutive STEMI patient who presented to our center and underwent pPCI between June 2015 and June 2016 were retrospectively examined. Patients with the presence of ST elevation of at least 1 mm (2 mm for V1-V3) in the two adjacent segments within the first 12 hours after the onset of symptoms or new onset of the left bundle branch block were included in the study. Patients with non-STEMI, unstable angina pectoris, those using oral anticoagulants, patients with hemato-logical diseases, chronic inflammatory or autoimmune diseases were excluded from the study. The CHA2DS2-VASc score was calculated for each patient prior to PCI, and the relationship between the score and thrombus burden was investigated. The patients were divided into two groups according to thromboly-sis in myocardial infarction (TIMI) grade: high thrombus burden (HTB) (TIMI 4 and 5) and low thrombus burden (LTB) (TIMI 0–3). All patients were given aspirin (300 mg) and clopidogrel (600 mg) as well as unfractionated heparin (70 IU / kg IV) at first medical contact. Glycoprotein IIb or IIIa inhibitor was applied in some patients according to the clinician’s preference, but all patients received double antiplatelet therapy. Age, sex, history of hypertension, history of diabetes mellitus, hyperlipidemia, smoking status, previous MI history, previous PCI or coronary artery bypass graft (CABG), history of heart failure, history of stroke and clinical risk factors were recorded for all included patients. Additionally, blood pressure, heart rate, Killip class, previous medications, the presence of preinfarction angina, pain to balloon time were recorded for all patients dur-ing hospital admission.

Definition

Diagnosis of diabetes was established in the case of antidia-betic drug use, or when postprandial blood glucose was higher than 200 mg / dL or fasting plasma glucose was at least 126 mg/dL at any time [12]. Patients using antihypertensive drugs or having a systolic tension of 140 mmHg or a diastolic tension of 90 mmHg or higher measured during resting at different pe-riods of time were defined as hypertensive [13]. Hyperlipidemia was defined as a total cholesterol level over 200 mg/dL, tri-glycerides level over 160 mg/dL, or low density lipoprotein level over 130 mg/dL [14]. Ejection fraction was calculated using the modified Simpson’s method. Stenosis of ≥ 50% in noncoronary arteries was defined as peripheral arterial disease.Based on the CHA2DS2-VASc score, patients were given 1 point for congestive heart failure, hypertension, being aged between 65 to 74 years, diabetes mellitus, vascular disease (prior MI, peripheral artery disease, aortic plaque) and female gender; and 2 points for being aged 75 years and over, and previous cerebrovascular events (Transient Ischemic Attack (TIA)/stroke) [8]. One point was added to the score in all patients considering that they were admitted with STEMI [15].

Angiography:

Angiographic thrombus burden was scored as five grades as previously described by Gibson et al [16]. Grade 0: No angio-graphic evidence of thrombus; Grade 1: possible thrombus (reduced contrast density, haziness of contrast, irregular lesion contour, suggestive, but not firmly diagnostic of thrombus); Grade 2: firmly thrombus with severe filling defect and marked irregular lesion contour on more than one angiographic imag-ings (greatest dimension of thrombus < 1/2 vessel diameter); Grade 3: firmly presence of thrombus on all angiographic im-ages (greatest dimension from > 1/2 to < 2 vessel diameters); Grade 4: firmly presence of great thrombus (greatest dimen-sion > 2 vessel diameters) ; Grade 5: total occlusion of a vessel. The content of the occlusive thrombus need to be further in-vestigated in order to detect Grade 5 TIMI thrombosis. A guide wire or a small balloon are advanced along the thrombotic total occlusion to provide restoration of the antegrade flow in the vessel. This enables restrafication of the underlying residual thrombosis during coronary angiography (final TIMI thrombo-grade) [17]. In our study, first TIMI thrombus grade was calcu-lated based on the first imaging. In patients who had a grade 5 TIMI thrombus, underlying residual thrombus was restrained as a result of the restoration of antegrade flow through a guide-wire or a small balloon (final TIMI thrombus-grade) [5,18].Then the final TIMI grades were divided into two groups as LTB (0 to 3) and HTB (4 to 5). All TIMI thrombus scores were then evalu-ated by two experienced cardiologists, and the decision was made by consensus.Written or verbal informed consent was received from all pa-tients, and the study protocol was approved by the hospital’s local ethics committee in accordance with the Helsinki Declara-tion and Good Clinical Practice Guidelines.

Statistical analysis:

The data analysis was conducted using SPSS (version 20.0, SPSS Inc., Chicago, IL, USA) and MedCalc statistical software (trial version 12.7.8, Mariakerke, Belgium). Continuous variables data are expressed as the mean ± standard deviation. Cate-gorical variables were compared using Chi-square or Fisher’s exact tests and summarised as percentages. The Kolmogorov–Smirnov test was used to evaluate the distribution of the con-tinuous variables. In order to predict a high TIMI thrombus grade, age, gender, diabetes mellitus (DM), hypertension (HT), hyperlipidaemia (HL), smoking, preinfarct angina, time interval from pain to PCI, systolic and diastolic blood pressure, history of stroke, history of heart failure, history of prior MI, and Kil-lip ≥ 3, stent length, stent diameter , pre-MI medication and CHA2DS2-VASc score were included in the univariate analysis. The parameters with p < 0.05 were included in the multiple lo-gistic analysis. Receiver operating characteristic (ROC) curves were used to predict the future incidence of high TIMI thrombus grade. 

Results

A total of 570 STEMI patients were included in the study (mean age 62.3 + 12.4 and 71.6% male). The calculated thrombus grades based on the first angiographic imaging, and the final TIMI thrombus grades obtained by restratification of the under-lying residual thrombus in patients with TIMI thrombus grade 5 are given in Table 1. In conclusion, the final TIMI thrombus grades of the study population were low thrombus burden in 296 (51.9%), and high thrombus burden in 274 (48.1%) patients.Age, gender, hypertension, history of stroke or TIA, history of heart failure, pre-infarction angina pain-balloon time, EF, stent diameter, history of prior MI , CHA2DS2-VASc score and no-re-flow, were statistically different in the group of a high-thrombus burden compared to the low-thrombus burden group. The clini-cal characteristics as well as the angiographic and PCI features of the findings are listed in Table 2.Among the significant parameters in the univariate analysis (age, gender, history of prior MI, hypertension, history of stroke/TIA, history of heart failure, pain to –PCI time, Killip class ≥ 3, setent diameter, CHA2DS2-VASc score), those which were also found to be significant in the multiple regression analysis in-cluded prior MI history (odds ratio [OR] = 0.501, 95% confidence interval [CI]: 0.256 – 0.982, P = 0.044), History of Heart Failure ( [OR] = 0.460, [CI]: 0.248-0.854, P = 0.014), CHA2DS2-VASc score ( [OR] = 1.812, [CI]: 1.369-2.400, P < 0.001) (Table 3).The optimal threshold CHA2DS2-VASc score for predicting high- thrombus bureden was ≥ 3, with a 60.9% sensitivity and 75.0% specificity (area under the curve [AUC]: 0.725, 95% CI: 0.683 – 0.767, P < 0.001) (Figure 1).

Discussion

In our study, history of heart failure, history of prior MI and CHA2DS2-VASc score was found to predict the development of high- thrombus burden in STEMI patients who underwent to PCI. In addition, the CHA2DS2-VASc score has been shown sen-sitive to the prediction of the development of high thrombotic burden. (AUC: 0.725).Coronary artery thrombus is the main pathophysiological event of acute myocardial infarction, which develops after a plaque rupture, causing partial or complete occlusion of the coronary artery [19]. The amount of intracoronary thrombus burden is among the determinants of prognosis in STEMI [4,5]. Intra-coronary thrombus decreases coronary blood flow depending on partial or complete occlusion. Accordingly, distal emboliza tions developing due to the pieces which are broken spontane-ously or during PCI lead to myocardial damage [19]. Supporting this, Tandoğa et al. showed lower TIMI flow and less myocardial blush due to distal embolization following PCI in patients with a high thrombus burden [17]. The CHA2DS2-VASc score includes risk factors with proven sensitivity in the prediction of the risk for thromboembolism and stroke in patients with atrial fibrillation [8,20]. Stroke and transient ischemic attack may occur due to nonatheroscle-rotic vascular pathologies as well as thromboembolism and atherosclerosis [21]. In addition to its use in atrial fibrillation, the CHA2DS2-VASc score has been defined as an appropriate and helpful predictor of the vascular events such as coronary stenosis followed by MI, stroke, and death before coronary an-giography in patients with acute coronary syndrome [22,23]. Again, the CHA2DS2-VASc score has been shown to be associ-ated with atrial and ventricular arrhythmias, newly developed heart failure, and sudden cardiac death after STEMI [24]. Ipek et al. showed an association between CHA2DS2-VASc score and no-reflow [25]. However, in that study thrombus burden which is known to play an important role in the development of nore-flow was not mentioned. In our study, we found an associa-tion between CHA2DS2-VASc score and high thrombus burden and in patients with higher thrombus burden developed higher noreflow. Supporting the previous studies, this result suggests that CHADS2 VASc score may be indirectly associated with the development of noreflow [25]. Ünal et al. demonstrated a rela-tionship between acute stent thrombosis and CHA2DS2-VASc score in patients without atrial fibrillation [15]. In our study, CHA2DS2-VASc score was demonstrated to be an independent predictor of high thrombus burden. CHA2DS2 -VASc score may lead to poor results such as high thrombus burden because it involves such factors as including DM, HT, advanced age, and heart failure. F. Scudiero et al demostrated a relationship be-tween CHA2DS2-VASc score and high platelet reactivity [26]. In addition, the association between CHA2DS2-VASc score and acute stent thrombosis, noreflow, and thromboembolism and thrombosis in atrial fibrillation, which has been demonstrated in the previous studies may be helpful to explain the reason of its association with high thrombus burden in STEMI patients [8,15,25]. Again for the same reasons, we think it is not surpris-ing to observe that CHADS VASc is a predictor of the develop-ment of high thrombus burden.Study LimitationOur study was designed as a single center and retrospective study. Again, stratification of thrombus burden based on visual assessment may have some limitations. Intravascular ultraso-nography (IVUS) and Optik Koherans Tomografi (OCT) confirm thrombus in relation with (ruptured) atherosclerotic plaque in a large proportion of STEMI. In our study OCT and IVUS is not used. MI and PAD were included in the definition of vascular dis-ease during the study. Patients with complicated aortic plaque could not be evaluated. Therefore, calculation of CHADS2-VASc score in STEMI patients may be considered as a limited situa-tion.

Conclusion:

In our study, we demonstrated that CHADSVASc, which can be easily calculated in STEMI patients predicts high thrombus burden before the procedure. We believe that CHA2DS2-VASc score may be helpful for clinicians in practice in order to esti-mate high thrombus burden pre-procedure and take the neces-sary measures. However, it would be appropriate to test the CHA2DS2-VASc score in a wider range and prospective studies with different populations.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accor-dance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

Acknowledgement

The authors thank www.metstata.com for its contributions to the statistical analysis and trial design.

References

1. Ellis SG, Roubin GS, King SB 3rd, Douglas JS Jr, Weintraub WS, Thomas RG et al. Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. Circulation 1988; 77(2): 372–9.

2. Singh M, Berger PB, Ting HH, Rihal CS, Wilson SH, Lennon RJ et al. Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the cur-rent era the Mayo Clinic experience. Am J Cardiol. 2001; 88(10): 1091–6.

3. Ahmed T, Sorgdrager BJ, Cannegieter SC, van der Laarse A, Schalij MJ, Jukema W. Pre-infarction angina predicts thrombus burden in patients admitted for ST-segment elevation myocardial infarction. EuroIntervention. 2012; 7(12): 1396–05.

4. Sianos G, Papafaklis MI, Daemen J, Vaina S, van Mieghem CA, van Domburg RT et al. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol. 2007;50(7): 573-83.

5. Sianos G, Papafaklis MI, Serruys PW. Angiographic thrombus burden classifica-tion in patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention. J Invasive Cardiol. 2010; 22(10): 6-14.

6. Fukuda D, Tanaka A, Shimada K, Nishida Y, Kawarabayashi T, Yoshikawa J. Pre-dicting angiographic distal embolization following percutaneous coronary inter-vention in patients with acute myocardial infarction. Am J Cardiol. 2003;91(4): 403-7.

7. Iijima R, Shinji H, Ikeda N, Itaya H, Makino K, Funatsu A et al. Comparison of coronary arterial finding by intravascular ultrasound in patients with ‘‘transient noreflow’’ versus ‘‘reflow’’ during percutaneous coronary intervention in acute coronary syndrome. Am J Cardiol. 2006; 97(1): 29-33.

8. Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk strati-fication for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The Euro Heart Survey on atrial fibrillation. Chest. 2010;137(2): 263-72.

9. Yadav M, Généreux P, Palmerini T, Caixeta A, Madhavan MV, Xu K et al. SYNTAX score and the risk of stent thrombosis after percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: an ACUITY trial substudy. Catheter Cardiovasc Interv. 2015; 85(1): 1–10.

10. Palmerini T, Dangas G, Mehran R, Caixeta A, Généreux P, Fahy MP et al. Pre-dictors and implications of stent thrombosis in non-ST-segment elevation acute coronary syndromes: the ACUITY Trial. Circ Cardiovasc Interv. 2011; 4(6): 577–84.

11. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G et al. In-cidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005; 293(17): 2126–30.

12. American Diabetes Association. Diagnosis and classification of diabetes mel-litus. Diabetes Care 2014; 37(1): 81–90.

13.Whitworth JA, Chalmers J. World Health Organisation-International Society of Hypertension (WHO/ISH) hypertension guidelines. Clin Exp Hypertens. 2004; 26(7-8): 747–52.

14. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB et al. Implicationsof recent clinical trials forthe national cholesteroleducation program adult treatment panel III guidelines. Circulation 2004; 110(2): 227–39.

15. Ünal S, Açar B, Yayla Ç, Balci MM, Ertem A, Kara M et al. Importance and usage of the CHA2DS2-VASc score in predicting acute stent thrombosis Coronary Artery Disease. 2016; 27(6): 478–82.

16. Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP et al. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction. Circulation. 2001; 103(21): 2550–4.

17. Tanboga IH, Topcu S, Aksakal E, Kalkan K, Sevimli S, Acikel M. Determinants of Angiographic Thrombus Burden in Patients With ST-Segment Elevation Myocar-dial Infarction Clinical and Applied Thrombosis/Hemostasis. 2014; 20(7): 716-22.

18.Topaz O, Topaz A, Owen K. Thrombus grading for coronary interventions: the role of contemporary classifications. Interv Cardiol. 2011;3(6): 705-12.

19. Tarsia G, De Michele M, Polosa D, Biondi-Zoccai G, Costantino F, Del Prete G et al. Manual versus nonmanual thrombectomy in primary and rescue percutaneous coronary angioplasty. Heart Vessels. 2010; 25(4): 275-81.

20. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012f ocused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation De-veloped with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012; 33 (21): 2719-47.

21. Cha M-J, Lee HS, Kim YD, Nam HS, Heo JH. The association between asymp-tomatic coronary artery disease and CHADS2 and CHA2 DS2 -VASc scores in pa-tients with stroke. Eur J Neurol. 2013;20: 1256-63. DOI:.org/10.1111/ene.12158.

22. Cetin M, Cakici M, Zencir C, Tasolar H, Baysal E, Balli Met al. Prediction of coronary artery disease severity using CHADS2 and CHA2DS2-VASc scores and a newly defined CHA2DS2-VASc-HS score. Am J Cardiol. 2014; 113(6): 950-6.

23.Chua S-K, Lo H-M, Chiu C-Z, Shyu K-G. Use of CHADS2 and CHA2DS2-VASc scores to predict subsequent myocardial infarction, stroke, and death in patients with acute coronary syndrome: data from taiwan acute coronary syndrome full spectrum registry. PLoS One. DOI:10.1371/journal.pone.0111167

24. Uehara M, Funabashi N, Takaoka H, Ozawa K, Kushida S, Kanda Jet al. CHA2DS2-VASc score is a useful-predictor of not prognosis but coronaryarterio-sclerosis in chronic atrial-fibrillation compared with CHADS2 score: a two-center study of 320-slice CT, part 2. Int J Cardiol. 2014; 177(2): 368–73.

25. Ipek G, Onuk T, Karatas MB, Gungor B, Osken A, Keskin M et al. CHA2DS2-VASc Score is a Predictor of No-Reflow in Patients With ST-Segment Elevation Myocardial Infarction Who Underwent Primary Percutaneous Intervention Angiol-ogy. 2016; 67(9): 840-5.

26. F. Scudiero C, Zocchi R, Marcucci E, De Vito E, Gabrielli R, Valenti R et al. Dis-criminatory ability of CHA2DS2-VASc score to predict residual platelet reactivity and outcomes in patients with acute coronary syndrome. The European Heart Journal. 2017; 38(1): 243.

PDF

Download attachments: JCAM_5927.pdf

How to Cite

Adil Bayramoğlu, Osman Bektaş. CHA2DS2-VASc score is a predictor of angiographic high thrombus burden in patients with ST-Segment elevation myocardial infarction. Ann Clin Anal Med 2019;10(4): 426-30

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Assessment of thyroid functions in patients with opioid use disorder

Gülçin Elboğa, Lütfiye Şimşek, Muhammet Sancaktar, Şengül Şahin, Abdurrahman Altındağ

Department of Psychiatry, Gaziantep University, School of Medicine, Gaziantep, Turkey

DOI: 10.4328/ACAM.6223 Received: 06.03.2019 Accepted: 16.03.2019 Published Online: 18.03.2019 Printed:01.07.2019 Ann Clin Anal Med 2019;10(4):449-52

Corresponding Author: Gulcin Elboga, Department of Psychiatry, Gaziantep University, Research Hospital, Gaziantep, Turkey. T.: +90 3423606060 E-Mail: gulcincinpolat@yahoo.com ORCID ID: https://orcid.org/0000-0003-3903-1835

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: In recent years, there has been an increase in substance use prevalence. Endocrine and metabolic changes are known in substance use disorders. There are limited studies evaluating opioid effects on thyroid hormones. Studies about effects of addictive substances on the body indicate that opioid use affects thyroid functions via the hypothalamic-hypophyseal axis. In this study, we aimed to compare the thyroid dysfunctions of patients with opioid substance use disorder and those with non-opioid substance use disorder. Material and Method: The study group consisted of 175 inpatients with substance use disorders defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria between 2015 and 2017. Serum TSH, fT4, fT3 levels of admitted patients were retrospectively screened. The patients were divided into three groups as opioid, non-opioid, and multiple substance users. Serum TSH, fT4, fT3 levels were compared between three groups. Results: Patients with only opioid use disorder had significantly lower serum TSH levels than those with non-opioid use disor-der (p=0.018). TSH levels were significantly lower in patients with multiple substance users (opioid and non-opioid) compared with the patients with non-opioid subjects (p=0.006). However, there were no statistically significant differences between the groups in terms of fT3 and fT4 levels (p=0.756, p=0.467). Discus-sion: Opioid substance causes many physiological changes in the body. Endocrine reflections have been different depending on the type of substance used. This study suggests that opioid substance may also affect thyroid functions. Therefore, thyroid functions must be evaluated in patients with opioid use disorders.

Keywords: TSH, Thyroid Hormones; Substance Use Disorder; Opioid; Tetrahydrocannabinol

Full Text

Introduction

The prevalence of substance use has increased in recent years.
Cannabis has been identified as the most widely used illicit drug in the general population in Turkey and in the World. Among the participants, 0.7% reported that they used cannabis at least once in their lifetime in Turkey [1]. In the study conducted by Çakmak and Evren in 2006, the number of patients admitted to the Center for Treatment and Research of Alcohol and Substance Abuse has been shown to increase since the past [2]. In a study conducted in university students in 2017, 3184 people were included in this study, and 1020 students reported using substance abuse at least once and 225 reported having a history of substance abuse at least five times [3].

Due to the large spectrum of addictive substances, their effects on organisms are still being investigated. In addition to behavioral and cognitive discrepancies, opiate dependence also reveals physiological symptoms [4]. It has been shown that opiate use decreases adinopectin levels and increases the risk of development of metabolic disorders[5].
Apart from psychiatric symptoms such as coronary artery disease, diabetes mellitus can cause metabolic diseases [5,6].

Most opioid are mu receptor agonists and effect receptors in the central nervous system. These effects disturb the hormonal balance of the hypothalamic-pituitary as in other neural tissues [7]. Different results have been obtained in this axle especially in terms of its effects on thyroid hormones. In a study on rats, there was a decrease in TSH levels after morphine injection and no difference in T3 and T4 levels [9]. In a controlled study, increase in total T3 levels and changes in TSH levels were observed [8].
The aim of this study was to compare the thyroid function tests of patients according to the type of substance used by the patients diagnosed with substance use disorder.

Material and Method

Patients diagnosed with substance use disorder according to theDSM–5 criteria and treated in the psychiatry clinic betweenJanuary 2015 and December 2017 were included in this retrospective study. Patients were detected in this review of inpatients records. Patients with hypothyroidism, hyperthyroidism, and history of thyroid surgery were excluded from the study. Firstly, 160 cases were included in this study; patients are divided into three groups: opiate, non-opiate, and multiple substances (opiate and non-opiate) use disorders.

The number of patients using non-opiate substance was determined as 15, and the first 15 persons with non-opiate substance use were included in the study by retrospective screening before January 2015 for statistical comparison.A total of 175 people were included in the study.
Thyroid hormone concentrations were measured using the electrochemiluminescence immunoassey method.
TSH, free T4, free T3 hormone levels, and categorical and numerical variables were compared between the groups. The approval for the study was obtained from the Ethics Committee before the collection of data.

Data analysis was performed on SPSS Windows 22.0 software. Percentage, arithmetic mean, and standard deviation values were used. The normal distribution of numerical variables was tested with the Shapiro- Wilk test. ANOVA and LSD tests were used for comparison of normally distributed numerical variables in three groups; the Kruskall-Wallis and All Pairwise tests were used to compare the numerical variables that do not distribute normally. The relationships between categorical variables were tested with the Chi-Square test.

Results

One hundred and seventy-five cases were included in the study with the diagnosis of substance use disorder.
Thirty-five (20%) of the cases were diagnosed as opiate use disorder, 30 (17%) were non-opiate substance use disorder and 110 (62%) were diagnosed as multiple substance use disorder. There were no significant differences between the groups in terms of age, sex, duration of hospitalization, psychiatric comorbidities, use of the intravenous substance, the presence of forensic events, and history of treatment due to substance use disorder. There were significant differences between the groups in terms of age of onset of substance use, duration of substance use, self-mutilating behaviors, the presence of psychotic features (p=0.048, p=0.016, p=0.013, p=0.004) (Table 1 and Table 2).
When hormone levels indicating thyroid function were examined, a significant difference was found in TSH levels between the groups; there was no statistically significant difference between the groups for free T3 and free T4 levels (Table 3).
In binary comparison, TSH levels were significantly higher in patients with non-opiate use than those in opiate patients (p = 0.002) and multiple substance use (p = 0.014).
There was a significant difference between the opiate use group and the multiple substance use group among TSH values (p=0.02).

Discussion

Among the 160 patients who were hospitalized due to substance use disorder between 2015 and 2017, 15 (9.4%) patients had diagnosed non-opiates use disorder, 35 (21.8%) opiates and 110 (68.8%) multiple substance use disorder. In the studies, substance preference data differ. The difference may be affected by factors such as city size, level of economic development and income and education levels of individuals [10].

There was no statistically significant difference between the groups classified according to the type of substance used according to intravenous use. Of the 145 patients with opiate use, 27 had intravenous use. It is thought that those who do not have intravenous use in patients with opiate dependency are more likely to seek treatment and this may be due to the fact that this way of use is not widespread in our country. It is known that there are various ways of opiate use in the world. In the studies performed in the United States, the most frequent way to use is intravenous. In our country, this type of use has increased in recent years [11]. Although there are studies showing the effects of opiate use on the hypothalamic-pituitary axis, the data are limited and do not show consistency among themselves. In the literature, it has been shown that morphine administration leads to a decrease in TSH level and thyroid weight in observation studies [12]. In another study, patients with opiate use disorder were compared with healthy controls and TSH levels were found to be lower [13]. In our study, it was observed that TSH levels were low in opiates and in multiple substance users.
In a study by Zang et al., heroin addicts and healthy control group were compared; TSH levels were repeated in the study group at the beginning of the treatment and at certain periods of time. Initially, TSH levels were low, but these values increased in remission. Free T3 and free T4 fluctuations were observed during the 3-month follow-up period [14]. In our study, TSH values were significantly lower in the opiate group than normal values (normal range between 0.5-4.5 uU/ml).
This result suggests that the effect of TSH on opiate users will not lead to clinically significant results.

In some studies, it is claimed that opiates cause changes in the thyroid gland due to their effects on free T3 and free T4 levels. In these studies, there was no statistically significant difference in the TSH levels in opiate users, whereas free T3 and free T4 levels were found to be variable [15-17]. In our study, when the free T3 and free T4 levels were compared, there was no significant difference in opiate users compared to the other groups (p=0.75, p=0.46).
This suggests that the effect of opiates on the thyroid gland is not limited to thyroid hormones.

A study indicates that opiates do not affect thyroid function through pituitary or peripheral hormones, suppressing the release of TRH from the hypothalamus, thus reducing TSH secretion [18]. TRH plays an important role in the release of TSH from the pituitary gland and the opiates used are likely to affect this axis. The findings in our study may support this situation, but different studies are needed to reinforce this hypothesis as the content of our study does not directly address TRH changes. When we look at non-opiate substances, there are limited data showing that psychoactive substances also affect thyroid function.
In a study on methamphetamine use, TSH and T3 levels decreased and T4 levels increased [19]. In a case report, sudden onset hyperthyroidism (thyroid storm) was observed after the first methamphetamine use, and TSH levels were significantly lower [20]. In our study, the direct psychostimulant effect was not investigated and it was determined that opiates were more affected the TSH level when compared with patients with psychostimulant use and thyroid dysfunction in patients with opiate use. The duration of substance use was significantly longer and the serum TSH level was significantly lower. Longer substance use is likely to affect serum TSH levels more.

Limitations

Our study has some limitations, mainly due to its retrospective and naturalistic design.

Changes in the thyroid function tests during the period in which the groups used the substance could not be evaluated. In addition, thyroid parenchyma and thyroid autoantibody levels are not known. Another limitation is that there are significant differences in the duration of substance use.

Conclusion

TSH levels were lower in the two groups with the use of opiates. These data indicate that opiate use has an effect on the thyroid gland and that opiate use may affect thyroid function, especially through TSH.

However, substances such as methamphetamine, which are psychostimulant, may also impair thyroid functions, but a direct result could not be reached in the study.
There is a need for studies in which larger samples, thyroid autoantibodies and other factors affecting thyroid functions such as TRH are examined and repeated tests are performed in follow-up. Such studies will contribute to more objective conclusions and a certain degree of consensus.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Kotan Z, Ilhan, SO, İlhan, MN, Arikan, Z. Fundamental characteristics, attitudes and behaviors regarding substance use focusing on cannabis: findings from the General Population Survey in Turkey, 2011. Community mental health journa., 2018; 1-5.

2. Çakmak D, Evren C. Alkol ve madde kullanım bozuklukları. İstanbul: Özgül Matbaacılık; 2006. p.33-62

3. Atlam DH, Aldemir E, Altintoprak AE. Prevalence of Risky Behaviors and Relationship of Risky Behaviors with Substance Use Among University Students. Journal of psychiatry and neurological sciences. 2017; 30(4): 287-98.

4. Akyesdar Y, Arıkan Z, Berkman K, Dilbaz N, Oral G, Uluğ B, et al. Madde Bağımlılığı Tanı ve Tedavi Kılavuzu. Türkiye: T.C. Sağlık Bakanlığı Sağlık Hizmetleri Genel Müdürlüğü. 2012; 63-104.

5. Shahouzehi B, Shokoohi M, Najafipour H. The effect of opium addiction on serum adiponectin and leptin levels in male subjects: a case control study from Kerman coronary artery disease risk factors study (KERCADRS). EXCLI journal. 2013; 12: 916.

6. Azod L, Rashidi M, Afkhami-Ardekani M, Kiani G, Khoshkam F. Effect of opium addiction on diabetes. Am J Drug Alcohol Abuse. 2008; 34(4): 383–8.

7. Sadock BJ, Sadock VA. Klinik Psikiyatri. In Aydın H, 2th ed. Ankara: Güneş Kitabevi Ltd. Sti. 2005; 1265-91.

8. GozashtiM, MohammadzadehE, DivsalarK, ShokoohiM. The effect of opium addiction on thyroid function tests. J Diabetes Metab Disord. 2014; 13(1): 5.

9. Iglesias L, Calzada B, Vega JA, Hernandez LC, Perez-Casas A. Effects of morphine on the pituitary-thyroid axis: morphological and analytical studies. Funct Dev Morphol. 1991; 1(4): 3-6.

10. Bulut M, Savaş HA, Cansel N, Selek S, Kap Ö, Yumru M, et al.Gaziantep Üniversitesi alkol ve madde kullanım bozuklukları birimine başvuran hastaların sosyodemografik özellikleri. Bağımlılık Dergisi. 2006; 7: 65-70.

11. Özden SY. Uyuşturucu Madde Bağımlılığı. İstanbul: Nobel Tıp Kitapevleri. 2004; 205-98.

12. Bakke JL, Lawrence NL, Robinson S. The effect of morphine on pituitary-thyroid function in the rat. Eur J Pharmacol. 1994; 25(3): 402–6.

13. Moshtaghi-Kashanian GR, Esmaeeli F, Dabiri S. Enhanced prolactin levels in opium smokers. Addict Biol 2005. 10(4): 345–9.

14. Zhang GF, Tang YL, Smith AK, Liu ZQ, Sheng LX, Chi Y, et al. Alterations in pituitary-thyroid axis function among opioid-dependent subjects after acute and protracted abstinence. Addict Biol. 2009; 14(3): 310-14.

15. Hochberg ZE, Pacak K, Chrousos GP. Endocrine withdrawal syndromes. Endocr Rev. 2003; 24(4): 523–38.

16. Rauhala P, Mannisto PT, Tuominen RK. Effects of chronic morphine treatment on thyrotropin and prolactin levels and acute hormone responses in the rat. J Pharmacol Exp Ther. 198; 246(2): 649–54.

17. Dogar IA, Ali MS, Rehman S. Addictive drugs; effect on haematological and hormonal profiles in men. Professional Med J. 2005; 12(3): 237–46.

18. Ruzsas C, Mess B. Opioidergic regulation of thyroid activity: possible interference with the serotonergic system. Psychoneuroendocrinology 1983; 8(1): 89–94.

19. Li SX, Yan SY, Bao YP,  Lian ZQu ZWu YP,et al. Depression and alterations in hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axis function in male abstinent methamphetamine abusers. Hum Psychopharmacol: Clinical and Experimental. 2013; 28(5): 477–83.

20. Viswanath O, Menapace D, Headley D. Methamphetamine Use with Subsequent Thyrotoxicosis/ Thyroid Storm, Agranulocytosis, and Modified Total Thyroidectomy: A Case Report. Clin Med Insights: Ear Nose Throat. 2017; 10: 1-4.

PDF

Download attachments: JCAM_6223.pdf

How to Cite

Elboğa G, Şimşek L, Sancaktar M, Şahin Ş, Altındağ A. Assessment of thyroid functions in patients with opioid use disorder. Ann Clin Anal Med 2019;10(4):449-52

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Determination of cut-off values and sensitivities of tests for the diagnosis of subclinical cushing’s syndrome in functional investigation of adrenal incidentalomas

Abdurrahim Yıldırım 1, Feyzi Gokosmanoglu 2, Attila Onmez 3

1 Department of Internal Medicine, Gazi State Hospital, Ankara, 2 Department of Endocrinology, Medical Park Hospital, Ordu, 3 Department of Internal Medicine, Duzce University Medical Faculty, Duzce, Turkey

DOI: 10.4328/ACAM.5988 Received: 06.08.2018 Accepted: 18.10.2018 Published Online: 01.11.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 417-20

Corresponding Author: Attila Onmez, Duzce Universitesi Tıp Fakultesi, İç Hastalıkları, Konuralp Yerleşkesi, Duzce, Türkiye.GSM: +90506845869 F.: +90 3805421302 E-Mail: attilaonmez@duzce.edu.tr ORCID ID: https://orcid.org/0000-0002-7188-7388

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: The aim of our study was to determine the sensitivities of tests used in the diagnosis of subclinical Cushing’s syndrome (SCS) in patients with adrenal incidentalomas using clinical findings and other biochemical parameters. Material and Method: One hundred and twenty-nine patients with adrenal inciden-talomas who were followed up by our endocrinology clinic were included in the study. Patients were divided into 4 groups according to the 1-mg DST results and these groups were compared in terms of age, gender, hormonal parameters, and comorbidities associated with Cushing’s syndrome. The cut-off value of sali-vary cortisol level for the diagnosis of SCS was calculated by ROC curve analysis. Result: If the cut-off values of plasma cortisol levels after the 1-mg DST were considered ≥1,8 μg/dL, ≥3 μg/dL, and ≥5μg/dL, the detection rates of SCS were respectively 22,4%, 1,4%, and 3,8%. When the cut-off value of plasma cortisol levels after the 1-mg DST was considered ≥1,8μg/dL, the sensitivity, specificity, and cut-off value of salivary cortisol levels were calculated as 68%, 57%, and 0.195 μg/dL by ROC curve analysis. Discussion: As the adrenal mass size and patient age increased, cortisol suppression decreased according to the 1-mg DST. As the cut-off value of plasma cortisol level used in the 1-mg DST decreased, the incidence of SCS increased significantly. This leads to overdiagnosis of SCS in asymptomatic patients with adrenal incidentalomas. New cut-off values should be determined for salivary cortisol level according to different populations.

Keywords: Cushing’s Syndrome; Adrenal Incidentalomas; Salivary Cortisol

Full Text

Introduction

Adrenal incidentalomas are mass lesions greater than 1 cm that are detected in the adrenal gland on images taken for another reason [1]. The incidence of adrenal incidentalomas has shown a significant increase all over the world with the widespread use of imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI). Although the incidence of adrenal incidentalomas increases with age, it is seen between 4-10% on average [2]. Ten to fifteen percent (%) of adrenal masses secrete hormones [3]; 7% of adrenal incidentalomas cause subclinical Cushing’s syndrome (SCS). Patients who have the autonomic cortisol secretion without typical clinical signs and symptoms of Cushing’s syndrome are diagnosed as SCS [4]. After the 1-mg DST performed for the diagnosis of SCS, a high false-positive rate has been obtained due to a low cut-off value of plasma cortisol level whereas a high false-negative rate has been obtained due to a high cut-off value of plasma cortisol level [5]. The aim of our study was to determine the sensitivities of tests used in the diagnosis of SCS in patients with adrenal incidentalomas by clinical findings and other biochemical parameters.

Material and Method

The data of 129 patients who were followed up for adrenal incidentaloma in the Endocrinology Clinic of Ondokuz Mayıs University Medical Faculty between the years 2012-2014 were retrospectively analyzed. The Ethics approval was obtained from the Institutional Review Board of the Hospital. This study was conducted in accordance with the Declaration of Helsinki. There is no international standardized cut-off value for plasma cortisol level after the 1-mg dexamethasone test (DST) in patients with SCS. At different medical centers, the cut-off values for dexamethasone-induced suppression of plasma cortisol levels are considered <1.8 µg/dL, <3 µg/dL, and <5 µg/dL. We examined our patients according to these three cut-off values of plasma cortisol levels.

The patients who had plasma cortisol levels <1.8 μg/dL after the 1-mg DST were considered to have a positive response to the 1-mg DST (non-SCS group). The patients who had plasma cortisol levels ≥1.8 µg/dL after the 1-mg DST were divided into 3 groups (SCS groups): Group A (=1.8-3 µg/dL), Group B (=3-5 µg/dL), and Group C (≥5 µg/dL).Patients with and without SCS were compared according to their hormonal, biochemical, and comorbidity characteristics. However, 6 patients who had plasma cortisol levels ≥5 µg/dL after the 1-mg DST were not included in the statistical evaluation. Therefore, the data were obtained by comparing the non-SCS group with Groups A and B.

Statistical analysis

The Kolmogorov-Smirnov test was performed to examine whether the data showed a normal distribution. The Student’s t-test, Mann-Whitney U test, Kruskal-Wallis test, and Pearson’s Chi-square test were used to compare the data of 3 groups. In multiple significance tests, calculations were performed with the Bonferroni correction. ROC curve analysis was used to determine the cut-off value of salivary cortisol level. The results were considered statistically significant if statistical tests were based on a p-value of ≤ 0.05 with a confidence interval of 95%. The SPSS 15.0 package program was used for all calculations.

Results

A total of 129 patients were included in the study. Of these patients, 65.9% were female and 34.1% were male. The mean age was 57 ± 10.5 years. Patients were first divided into 2 groups according to the 1-mg DST results: non-SCS (n=87) (plasma cortisol level <1.8µg/dL) and SCS (n=42) (plasma cortisol level≥1.8 µg/dL). 42 patients who had plasma cortisol levels ≥1.8 µg/dL after the 1-mg DST were then divided into 3 groups (SCS groups): Group A (n=23) (=1.8-3 µg/dL), Group B (n=19) (=3-5 µg/dL), and Group C (n=6) (≥5 µg/dL). Since there were 6 patients in Group C, these patients were evaluated in Group B.The demographic characteristics of the non-SCS and SCS groups are shown in Table 1.

All patients underwent the 1-mg DST. Twenty-three of 42 patients with non-suppressed plasma cortisol levels after the 1-mg DST underwent the 2-mg DST. After the 2-mg DST, 6 patients had plasma cortisol levels <5µg/dL and 17 patients had plasma cortisol levels >5 µg/dL. Plasma cortisol level was not suppressed in 4 of 9 patients in Group A and in 13 of 14 patients in Group B (p=0.013). Nighttime salivary cortisol level was measured in all patients. The mean nighttime salivary cortisol level was 0.189 ± 0.99 µg/dL in the non-SCS group, 0.268 ± 0.137 µg/dL in Group A, and 0.266 ± 0.157 µg/dL in Group B, respectively. It was significantly higher in Groups A and B than in the non-SCS group (p=0.001). There was no significant difference between Groups A and B in terms of mean nighttime salivary cortisol level (p=0.990).Comparison of statistically significant results between non-SCS group, Group A, and Group B is shown in Table 2. When the cut-off value of plasma cortisol levels after the 1-mg DST was considered ≥1.8µg/dL, the sensitivity, specificity, and cut-off value of salivary cortisol levels were calculated as 68%, 57%, and 0.195 µg/dL by ROC curve analysis.The reference range for salivary cortisol level at our center was determined as 0.04-0.56 μg/dL (Figure 1). A second confirmatory test (baseline ACTH level <10 pg/ml, DHEA-S level <35 μg/dL, plasma cortisol level after the 2-mg DST ≥1.8 μg/dL, nighttime salivary cortisol level ≥0.56 μg/dL) was added to reevaluate the diagnosis of SCS. If the cut-off values of plasma cortisol levels after the 1-mg DST were considered ≥1.8 µg/dL, ≥3 µg/dL, and ≥5µg/dL, the detection rates of SCS were respectively 22.4% (n=29), 12.4% (n=16), and 3.8% (n=5).The same criteria were re-examined only by changing the cut-off value of salivary cortisol level.The cut-off value of salivary cortisol levels was considered 0.195 μg/dL in our study. According to this, if the cut-off values of plasma cortisol levels after the 1-mg DST were considered ≥1.8 µg/dL, ≥3 µg/dL, and ≥5µg/dL, the detection rates of SCS were respectively 28.6% (n=37), 14.7% (n=19), and 4.6% (n=6).

Discussion

The vast majority of adrenal incidentalomas are non-functional benign cortical adenomas. Recent studies have shown that some benign tumors may also be functional at a subclinical level. Depending on the diagnostic criteria used, the prevalence of SCS ranges from 5% to 20% [7]. In our study, we found that it varied between 4.6% and 28.6% according to different cut-off values of plasma cortisol levels.

In previous studies, patients with adrenal incidentalomas were in the middle- and older-age groups. The mean age of the patients participating in our study was 57.2 years. The mean age was found to be statistically significantly higher in the patients with SCS than in the patients without SCS. Accordingly, we think that incidental adrenal masses in older patients may be more functional in terms of cortisol hypersecretion.When the metabolic and biochemical parameters were assessed, we could not detect any significant difference between the groups in terms of parameters such as obesity, diabetes, cholesterol, triglyceride, DHEA-S, plasma ACTH, osteopenia, and osteoporosis. When the literature was examined, conflicting results were found for these parameters. The prevalence of hypertension was %84 in the patients having plasma cortisol levels ≥3µg/dL after the 1-mg DST (Group B) and 54%in the patients having plasma cortisol levels <1.8µg/dL after the 1-mg DST (the non-SCS) (p=0.015). Studies have also found that hypertension was more frequent in patients with SCS [8]. In accordance with the literature, basal cortisol level was also found to be higher in the patients with SCS in our study (p=0.001).

In our study, we found that the mean tumor size was significantly greater in the patients having plasma cortisol levels ≥3 µg/dL after the 1-mg DST (Group B) than in the patients having plasma cortisol levels <1.8µg/dL after the 1-mg DST (the non-SCS) (p=0.001). Many studies have shown a significant association between tumor size and cortisol hypersecretion [9]. This suggests that intrinsic secretory activity in tumor cells, the amount of cortisol produced, and gaining autonomy are associated with tumor size.

In the literature, the prevalence of SCS has been reported to be between 5% and 20% depending on different diagnostic criteria [10]. In our study, we determined that the prevalence of SCS varied between 3.8% and 22.4% based on different diagnostic criteria. We also determined that it varied between 4.6% and 28.6% based on the same diagnostic criteria when the cut-off value of salivary cortisol levels was considered 0.195 μg/dL. In our study, we found that the patients having plasma cortisol levels ≥3 µg/dL after the 1-mg DST (Group B) were older and had a greater mass and a higher prevalence of hypertension. We think that plasma cortisol cut-off values greater than 1.8 μg/dL after the 1-mg DST should be used in patients with adrenal incidentalomas. Studies have shown that the 2-mg 2-day DST is more specific for cortisol hypersecretion than the 1 mg DST. However, the first test has been not preferred in many studies due to difficulty in its administration [11]. In our study, 23 patients underwent the 2-mg DST. After the 2-mg DST, 6 patients had plasma cortisol levels <5 µg/dL and 17 patients had plasma cortisol levels >5 µg/dL. Plasma cortisol level was not suppressed in 4 of 9 patients in Group A and in 13 of 14 in Group B (p=0.013). We revealed that the 2-mg 2-day DST is a more specific test for the diagnosis of SCS. Due to the limitations in midnight serum cortisol measurement, many researchers have suggested additional hormone tests for the diagnosis of SCS. One study found that the sensitivity, specificity, and cut-off value of midnight salivary cortisol levels were 22.7%, 87.7%, and 0.18µg/dL. Another study found that the sensitivity, specificity, and cut-off value of midnight salivary cortisol levels were 66%, 69.1%, and 0.17 µg/dL [12-13]. Similarly, we found that the sensitivity, specificity, and cut-off value of salivary cortisol levels were calculated as 68%, 57%, and 0.195 µg/dL. The normal reference range of the kit used in our study was 0.04-0.56 μg/dL. For this reason, we have demonstrated that it is necessary to determine cut-off values specific to different populations.

Conclusions

Greater tumor size, older age, and deteriorated metabolic parameters increase the risk of development of SCS in patients with adrenal incidentalomas. As the cut-off value of plasma cortisol level used in the 1-mg DST decreased, the incidence of SCS increased significantly. This leads to overdiagnosis of SCS in asymptomatic patients with adrenal incidentalomas. We think that plasma cortisol cut-off values greater than 1.8 μg/dL after the 1-mg DST should be used in patients with adrenal incidentalomas. New cut-off values should be determined for salivary cortisol level according to different populations.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Young WF. Management approaches to adrenal incidentalomas: A view from Rochester, Minnesota. Endocrinol Metab clin of North Am. 2000; 29: 159-85.

2. Nieman LK. Approach to the patient with an adrenal incidentaloma. J Clin Endocrinol Metab. 2010; 95: 4106-113.

3. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally Discovered Adrenal Masses. Endocr Rev. 1995; 16: 460-84.

4. Akehi Y, Kawate H, Murase K, Nagaishi R, Nomiyama T, Nomura M, et al. Proposed diagnostic criteria for subclinical Cushing’s syndrome associated with adrenal incidentaloma. Endocr J. 2013; 60: 903-12.

5. Wood P, Barth J, Freedman D, Perry L, Sheridan B. Evidence for the low dose dexamethasone suppression test to screen for Cushing’s syndrome recommendations for a protocol for biochemistry laboratories. Ann Clin Biochem. 1997; 34: 222-9

6. Barzon L, Boscaro M. Diagnosis and management of adrenal incidentalomas. J Urol. 2000; 163: 398-407.

7. Grumbach MM. Management of the clinically inapparent adrenal mass (“incidentaloma”). Ann Intern Med. 2003; 138: 424-9.

8. Rossi R. Subclinical Cushing’s syndrome in patients with adrenal incidentaloma: clinical and biochemical features. J Clin Endocrinol Metab. 2000; 85: 1440-8.

9. Barzon L. Risk Factors and Long-Term Follow-Up of Adrenal Incidentalomas. J Clin Endocrinol Metab. 1999; 84: 520-6.

10. Barzon L, Fallo F, Sonino N, Boscaro M. Development of overt Cushing’s syndrome in patients with adrenal incidentaloma. Eur J Endocrinol. 2002; 146: 61-6.

11. Findling JW, Raff H, Aron DC. The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing’s syndrome. J Clin Endocrinol Metab. 2004; 89: 1222-6.

12. Masserini B. The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma. Eur J Endocrinol. 2009; 160: 87-92.

13. Nunes ML. Late-night salivary cortisol for diagnosis of overt and subclinical Cushing’s syndrome in hospitalized and ambulatory patients. J Clin Endocrinol Metabol. 2009; 94: 456-62.

How to cite this article:

Yıldırım A, Gokosmanoglu F, Onmez A. Determination of cut-off values and sensitivities of tests for the diagnosis of subclinical cushing’s syndrome in functional investigation of adrenal incidentalomas. Ann Clin Anal Med 2019; DOI: 10.4328/ACAM.5988.

PDF

Download attachments: JCAM_5988.pdf

How to Cite

Yıldırım A, Gokosmanoglu F, Onmez A. Determination of cut-off values and sensitivities of tests for the diagnosis of subclinical cushing’s syndrome in functional investigation of adrenal incidentalomas. Ann Clin Anal Med 2019;10(4):417-20

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

A survey of current practice of difficult airway management and equipment in pediatric anesthesia

Derya Karasu, Canan Yilmaz, Seyda E. Ozgunay, Umran Karaca

Anesthesiology and Reanimation, Health Sciences University Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey

DOI: 10.4328/ACAM.6160 Received: 14.01.2019 Accepted: 04.02.2019 Published Online: 11.02.2019 Printed:01.07.2019 AnnClinAnalMed2019;10(4):445-8

Corresponding Author: Derya Karasu, Department of Anesthesiology and Reanimation, Health Sciences University Bursa Yuksek Ihtisas Training and Research Hospital, Mimar Sinan Street Yildirim Bursa, 16290, Turkey. GSM: +905057281175 E-Mail: drderyatopuz@gmail.com ORCID ID: https://orcid.org/0000-0003-1867-9018

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: Airway management is one of the key areas of pediatric anesthesia practice. In this study, we aimed to investigate the availability of equipment for dif-ficult airways in pediatric anesthesia and to increase the awareness on the subject among anesthesiologists. Material and Method: The survey was carried out using the forms.google.com. Our questionnaire was forwarded to the members on the internet by the Turkish Society of Anesthesiology and Reanimation. Anesthesiologists working in Turkey and willing to join the survey were included in the study. Results: The mean age of the 390 participants who completed our questionnaire was 39.40±7.26 years. The majority (34.6%) of the participants were working for training and research hospitals; 35.4% had been working for 1-5 years; 53.1% had attended a training course on airway management. The frequency of pediatric anesthesia every day was 32.8% and 46% of the participants had been administering pediatric anesthesia to few pediatric patients each week. A special kit of equipment for difficult airway management was available to 35.4%. The classical LMA was most frequently used equipment (95.6%). While 40.8% of the participants had encountered difficult airway in 1-5 pediatric patients, 7.9% also had the previous experience of an emergency surgical airway. Discussion: Our study has determined that the incidence of emergency surgical airway experience was low despite the high risk of encountering difficult airway management in pediatric anesthesiology. We believe that the success rates in difficult airway management would be increased by starting training courses with frequent periodicity on pediatric difficult airway management at different centers in our country, by widening the availability of required equipment and by increasing experience.

Keywords: Airway Devices; Devices; Difficult; General Anesthesia; Education

Full Text

Introduction

Airway management is one of the key areas of anesthesia practice, it is also important for pediatric anesthesia. Because of anatomical differences, children are more prone to upper airway obstruction under anesthesia than adults. Also, children have a much higher oxygen consumption than adults, and as a result when they have airway obstruction or when they become apnoeic, hypoxemia develops much faster [1,2]. It has long been known that respiratory adverse events are the most encountered problem of perioperative critical events in pediatric patients [1,2]. Current guidelines addressing the difficult airway management in adults provide anesthesiologists a framework for managing the airway. Whereas in children, it is more difficult to establish guidelines due to fewer management options, failed airway management is less common, and recommendations would vary based on growth and development [3,4]. Supraglottic airway devices (SAD) inspired a fundamental change in the management of the difficult airway and are a key part of adult and pediatric difficult airway algorithms [5]. Use of SAD may reduce morbidity and in some cases be life-saving when used correctly and timely.

There is a little proof to determine the safest or most effective device to use for airway management. In addition, in difficult pediatric airway management, many of the adverse events occur frequently with unskilled personnel and insufficient resources available to respond to an unexpected crisis, often resulting in a worse outcome [6].

An unexpected pediatric difficult airway can lead to significant morbidity and mortality. Standardized emergency airway equipment should be available to prevent the adverse events related to a difficult airway. The aim of this study was to investigate the availability of difficult airway equipment in pediatric anesthesia in Turkey and to raise awareness on this subject among anesthesiologists.

Material and Method

The local ethics committee (Uludag University Ethics Committee Number: 2018-3/15) approved this study. Anesthesiologists who were working in Turkey and willing to participate were enrolled in this study. A survey approved by the Turkish Society of Anesthesiology and Reanimation was distributed using forms.google.com, among all members from Turkey.

All statistical analyses were performed using the IBM SPSS ver. 21.0 software package. While numeric variables were expressed as mean ± standard deviation, categorical variables were expressed in numbers and percentages. The Pearson’s Chi-Square and Fisher’s exact test were used to detect differences between groups of categorical variables. To determine risk factors binary logistic regression analysis was performed. A p-value < 0.05 was considered as statistically significant.

Results

A total of 390 participants were involved in the statistical analysis. Table 1 shows the demographic data of the participants. The study revealed that overall incidence of attendance among the participants to courses on the subject of respiratory airways was 53.1% (n=207); these being 62.9% in state universities, 54.8% in training and research hospitals, 50% in private hospitals, 47.7% in state hospitals and 44.4% in private universities. Overall attendance to adult type courses was 40.3% (n=157), to pediatric type courses was 14.6% (n=57), and to courses in other countries was 1.3% (n=5).

The experience of access to the equipment for difficult airways and using it is shown in Table 2. In this study, the classical laryngeal mask airway (LMA) was found to be the predominantly used equipment (95.6%) on which most experiences were based. The specially prepared kit of difficult airways equipment was available to 35.4% of the participants.

When the presence of a specially prepared kit was investigated on the basis of the hospital type, significant differences were found (p=0.030). Availability of specially prepared kit was noticed in state universities (44.3%), in training and research hospitals (41.5%), in state hospitals (28.5%), in private hospitals (28.3%), and in private universities 11.1%. There was also a significant relationship between the specially prepared kit and the frequency of pediatric anesthesia (p=0.001). Ownership of specially prepared kit was found 46.9% of the frequency of pediatric anesthesia every day, 30.9% of few pediatric anesthesia per week and 31.4% of few pediatric anesthesia per month.

Having encountered 1-5 cases of difficult pediatric airways, 40.8% of the participants have reported about it, while 19.2% had never observed a case. The incidence of the encounter of the pediatric difficult airway management was 50% among state hospitals, 43.7% in training and research hospitals, 30% in state universities, 26.1% in private hospitals and 22.2% in private universities.

Previous experience of the emergency surgical airway was 7.9% (n=31) among the participants. When the regression analysis of these data was performed, the experience of specialists affected these results significantly (p=0.001), but hospital type, course participation or age group did not (p> 0.05).

The term CICO (can’t intubate, can’t oxygenate) had been previously heard by 22.8% of the participants. Results of regression analyses on familiarity with the term CICO indicated that attendance to courses, having the specialist experience and the age group of participants were significantly effective (p<0.001, p=0.002 and p=0.026, respectively), whereas the hospital type was not (p=0.309). Results of regression analyses on hearing of CICO term demonstrate that attendance to courses, the specialist experience and the age group of participants were significantly effective (p<0.001, p=0.002 and p=0.026, respectively), whereas the hospital type was not effective (p=0.309). The lowest incidence (13.8%) of hearing of the term CICO was found to be in state hospitals, while it was in the 22.2-28% range in the other types of hospitals.

In short-term pediatric surgeries, such as for an inguinal hernia, 86.7% of the participants applied general anesthesia with LMA, and 9% preferred the endotracheal tube. In 97.7% of the laparoscopic surgery cases, general anesthesia was given by the endotracheal tube and 0.8% by using the LMA, preference is for the classical LMA (62%) followed by the I-gel LMA (28.5%). Reported difficulties with the SAD which limited their use included the performance of aspiration (64.9%), intraoperative displacement (56.2%), difficulty in placement (40.5%), postoperative airway problems 16.2% and hemorrhage related trauma during removal (11.9%). Other reasons limiting SAD use comprised unavailability of the suitable number (51.7%), inability to use with ease in infants under 5 kg body weight (26.4%), and not being generally used in pediatric cases (25.6%).

Of the participants, 85.6% think that further prospective randomized studies are needed in these subjects.

Discussion

In this study, we investigated the availability of airway equipment in pediatric anesthetic practice in Turkey. Classical LMA was most commonly used among airway equipment (95.6%). A specially prepared kit for pediatric difficult airway management was found in 35.4% of our participants. When the presence of a specially prepared kit was investigated on the basis of the hospital type and the frequency of pediatric anesthesia, significant differences were found. The survey has determined that availability of a specially kit of difficult airway equipment was high in state universities and training and research hospitals, with the highest availability being in the frequency of pediatric anesthesia every day. Only 7.9% of participants had previous emergency surgical airway experience. The rate of attendance of a course about difficult airway management was 53.1%.

In our study, the Macintosh laryngoscope, miller laryngoscope, Pro-seal LMA, and I-gel LMA were available over 40%. The McCoy laryngoscope, video laringoscope, fiberoptic bronchoscope, cricothyroidotomy kit, tube changer catheter, and gum elastic bougie were available at 20-40%. Optical stile, combitube, laryngeal tube, FastTrack LMA, and nasal airway were available at 9-20%. Jet ventilator, retrograde intubation equipment, the newer devices (Easy laryngeal tube, and Aintree catheter) were available at less than 5%. The reasons behind this could be the high-cost and the late entry of pediatric sizes for new equipment in our country. Fiber-optic intubation remains the gold standard for intubation of the difficult airway. In the present study, 30.3% of respondents had available fiberoptic bronchoscope, and 27.9% had experience with children in this technique.

SAD are frequently used in pediatric anesthesia [7]. In our study, general anesthesia with LMA in pediatric cases was preferred by 86.7% of participants in the short-term surgeries. The classical LMA being the most preferred type (%62), followed by the I-gel LMA (28.5%). Personal choice, availability, and institutional protocols may have influenced the selection of the device. In a meta-analysis using LMA during pediatric anesthesia, it is alarming that intraoperative displacement was a common problem encountered to their anesthesiologists whereas aspiration was not [8]. In our study, the difficulties of using SDA were as reported in the literature, mostly experienced during aspiration and intraoperative displacement.

Kaniyil et al. [7] reported a questionnaire survey among the anesthesiologists who participated in the National Pediatric Anesthesia Conference in 2016. The questionnaire evaluated the practice preferences of SAD in pediatric anesthesia and difficult airway management, availability of devices, and any difficulties in their usage. First-generation SAD were frequently present (97%), and 64% of the participants preferred to use it for short-term pediatric surgeries. They found that intraoperative displacement (55%) was a common problem and 11% of the participants found aspiration as a problem [7]. In our survey, the frequency of using SAD in pediatric short cases was 86.7% and the causes limiting their use were headed by the inability to do aspiration.

Calder et al. [9] conducted a survey with members of the Association of Pediatric Anesthetists of Great Britain and Ireland, European Society for Pediatric Anesthesiology, Canadian Pediatric Anesthesia Society, Society for Pediatric Anesthesia in New Zealand and Australia. They searched pediatric anesthetists’ knowledge, experience, and confidence with the difficult airway trolley, 633 (92%) of participants defined that they had a difficult airway trolley in their theater room. They considered that training and recent use of the difficult airway trolley would increase self-assurance of the anesthetists [9]. A specially prepared kit for pediatric difficult airway management was available in 35.4% of our respondents. In the study by Calder et al. [9], a majority (35%) of the participants were treating 5 pediatric anesthesia cases per week. In the present survey, the majority of the participants (46.4%) had been administering pediatric anesthesia to few pediatric patients each week.

The Difficult Airway Society suggested a number of educational materials including a Consultant Airway Coordinator, an Airway Training Room, and special lists for airway training [5,10]. It is important that training programs realize the individual and professional significance of experiences for new physicians. Education should support the development of constructive skills through discussion and learning [11].

Among the participants of our survey 40.8% had met 1-5 difficult airway cases while 19.2% had never experienced difficult airway. Low incidences may be due to the preferred use of LMA instead of the endotracheal intubation technique in the majority of pediatric cases. In our study, 86.7% of the participants opted for LMA for short pediatric surgeries such as an inguinal hernia.

The CICO scenario is a rare but life-threatening situation in pediatric anesthesia [12]. In pediatric CICO, the Difficult Airway Society guideline suggests some airway rescue techniques [12,13]. However, pediatric CICO is very rare, and this suggestion is mostly based on animal experimental results and expert opinions [5]. Therefore, further reports are necessary to consider the best strategy for pediatric CICO [14]. The recently released the American Society of Anesthesiologists recommended cannula cricothyroidotomy for management of the CICO scenario in the increasingly hypoxic and/or bradycardic child [15]. In our survey, 23.4% of the participants had knowledge about the meaning of the CICO and it was found that the experience of airway management in pediatric surgery was 7.9%. Anesthesiologists have to identify their strategies for the CICO rescue events and should increase their experience.

Kaniyil et al. [7] reported that most of their respondents (84%) felt the need for further randomized controlled studies on the safety of SAD in children. Similarly, in our survey, 85.6% of the participants admitted the need for further studies in this subject.

Limitations of our survey include the inability to reach all anesthesiologists in our country. Thus our results on the difficult airway equipment may not reflect the entire practice. Had the survey queried the difficult mask ventilation and difficult tracheal intubation separately, more detailed data could have been obtained. Other limitations were lack of knowledge about the frequency of pediatric anesthesia annually in Turkey and the number of pediatric anesthesiologists.

As a result, an early intervention in the difficult airway is very important. Our study has emphasized the areas with the potential for international development in pediatric difficult airway management. In hospitals admitting pediatric patients, a specially prepared kit for pediatric difficult airway management must be made generally available, and the variety in equipment types should be increased. There are no magical pieces of equipment in difficult airway management. Training about difficult airway management is an ongoing process, the most important structure of patient safety is preoperative evaluation and planning. We believe that by starting training courses on pediatric difficult airway management with frequent periodicity at different centers of the country; and by widening the availability of the required equipment, experience should be advanced for increased success in difficult airway management. Repetition of training sessions at frequent intervals can improve the performance in DA management and the critical decision in CICO.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Goldmann K. Recent developments in airway management of the paediatric patient. Current Opinion in Anaesthesiology. 2006;19:278-4.

2. Cohen MM, Cameron CB, Duncan PG. Pediatric anesthesia morbidity and mortality in the perioperative period. Anesth Analg. 1990;70:160-7.

3. Sunder RA, Haile DT, Farrell PT, Sharma A. Pediatric airway management: current practices and future directions. Pediatr Anesth. 2012;22:1008-15.

4. Brambrink AM, Braun U. Airway management in infants and children. Best Pract Res Clin Anaesthesiol. 2005;19:675-97.

5. Frerk C, Mitchell VS, McNarry AF, Mendonca C, Bhagrath R, Patel A, et al. Difficult Airway Society intubation guidelines working group. Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults. British Journal of Anaesthesia. 2015;115:827-48.

6. Cook TM, Woodall N, Harper J,  Benger JFourth National Audit Project. Major complications of airway management in the UK: results of the Foruth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 2: intensive care and emergency departments. Br J Anaesth. 2011;106:632-42.

7. Kaniyil S, Smithamol PB, Joseph E, Krishnadas A, Ramadas KT. A survey of current practice of supraglottic airway devices in pediatric anesthesia from India. Anesth Essays Res. 2017;11:578-82.

8. Luce V, Harkouk H, Brasher C,  Michelet DHilly JMaesani M, et al. Supraglottic airway devices vs. tracheal intubation in children: A quantitative meta-analysis of respiratory complications. Pediatr Anesth. 2014;24:1088-98.

9. Calder A, Hegarty M, Davies K, Von Ungern-Sternberg BS. The difficult airway trolley in pediatric anesthesia: an international survey of experience and training. Pediatr Anesth. 2012;22:1150-4.

10. Henderson JJ, Popat MT, Latto IP,  Pearce ACDifficult Airway Society. Difficult Airway Society guidelines for management of the unanticipated difficult intubation. Anaesthesia. 2004;59:675-94.

11. Engel KG, Rosenthal M, Sutcliffe KM. Resident’s responses to medical error: coping, learning, and change. Acad Med. 2006;81:86-93.

12. Sabato SC, Long E. An institutional approach to the management of the ‘Can’t Intubate, Can’t Oxygenate’ emergency in children. Pediatr Anesth. 2016;26:784-93.

13. Black AE, Flynn PE, Smith HL,  Thomas MLWilkinson KA, Association of Pediatric Anaesthetists of Great Britain and Ireland. Development of a guideline for the management of the unanticipated difficult airway in pediatric practice. Pediatr Anesth. 2015;25:346-62.

14. Okada Y, Ishii W, Sato N, Kotani H, Iiduka R. Management of pediatric ‘cannot intubate, cannot oxygenate’. Acute Medicine & Surgery. 2017;4:462-6.

15. Caplan R, Benumof L, Berry F. Practice guidelines for management of the difficult airway: an updated report from the american society of anesthesiologists task force on management of the difficult airway. Anesthesiology. 2003;98:1269-77.

PDF

Download attachments: JCAM_6160.pdf

How to Cite

Karasu D, Yilmaz C, Ozgunay SE, Karaca U. A survey of current practice of difficult airway management and equipment in pediatric anesthesia. Ann Clin Anal Med 2019;10(4):445-8

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Posterior segment eye diseases: prevalence, pattern, and attribution to visual impairment among adult saudi population

Ekramy Elmorsy 1, Mujeeb Ur Rehman Parrey 2

1 Department of Pathology, Faculty of Medicine, 2 Department of Surgery, Faculty of Medicine,Northern Border University, Arar, Kingdom of Saudi Arabia

DOI:10.4328/ACAM.6089 Received: 17.11.2018 Accepted: 10.12.2018 Published Online: 14.12.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 505-9

Corresponding Author: Ekramy Elmorsy, P.O. Box: 1321, Department of Pathology, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia. GSM: 00966-542459391 E-Mail: ekramy_elmorsy@yahoo.com ORCID ID: https://orcid.org/0000-0002-7444-2499

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: In this study, we aimed to investigate the prevalence and pattern of posterior segment eye disease (PSEDs) and their attribution to visual impairment (VI) in Saudi adults of Arar city, Saudi Arabia. Material and Method: Prevalence and pattern of PSEDs were studied through ophthalmological evaluation including B-scan ultrasonography on 956 participants from Arar city. Results: The prevalence of PSEDs in the current study was 10.7%. Diabetic retinopathy (DR) was the commonest pathology found in 64 (6.7%) participants. Age-related macular degeneration (ARMD), optic atrophy (OA) and retinal detachment (RD) were found in 19 (2%), 16 (1.7%) and 10 (1%) cases respectively. Glaucoma was the commonest cause of OA found in 50% of cases. DR and high myopia were found to be the underlying cause in about 50% of RD cases. Vitreous hemorrhages in association with DR, ARMD, and RD were found in 39 (4%) cases. The current study revealed that DR was the commonest PSED diagnosed in cases of VI. Discussion: These data highlight the magnitude of the PSEDs as the causes of visual impairment and encourage proper healthcare planning to reduce the burden of the posterior segment eye diseases.

Keywords: Blindness; Diabetic Retinopathy; Low Vision; Macular Degeneration; Optic Atrophy; Posterior Segment Eye Diseases; Retinal Detachment; Visual Impairment; Vitreous Hemorrhage

Full Text

Introduction

Posterior segment eye diseases (PSEDs) are commonly defined as diseases of the retina, choroid and optic nerve. They primarily include glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR) [1]. PSEDs differ from the anterior segment eye diseases like cataract and refractive errors in terms of modalities for their prevention and treatment. Most of the posterior segment disorders are difficult to treat and established visual loss is difficult to reverse as for many PSEDS there is no ‘curative’ treatment [2]. Unfortunately, the infrastructure required to detect and treat PSED is very costly and often unavailable in most eye care centers [3]. In addition, highly skilled staff required for conducting posterior segment surgical interventions is not commonly available in most of the medical centers and hospitals.

Optic atrophy (OA) is the final common morphologic endpoint of any disease process that causes axon degeneration in the retinogeniculate pathway. Glaucoma is a common treatable cause of OA. Hence, medical and/or surgical intervention in cases of glaucoma can slow its progression and lower the risk of further sight loss caused by optic atrophy [4]. For diabetic retinopathy, proper control of diabetes mellitus, intravitreal anti-VEGF injections, retinal laser photocoagulation or even vitreoretinal surgery can improve the outcome and prevent vision loss [5]. However, PSEDs like age-related macular degeneration (AMD) have no definitive treatment, although intravitreal injections and laser therapy is available for wet type of AMD. Antioxidants have shown some evidence of risk reduction in progression of subtypes of AMD [6], but not prevention of AMD [7] and on the other hand, it may be prohibitively expensive.

In most countries, health programs are largely focused on the treatment of anterior segment diseases, such as cataract and refractive errors (RE), as it alone causes the majority of blindness and is highly curable through cataract surgery or RE corrections. The problem of PSED has not been focused to date in the national current health programs due to a lack of data on its pattern and prevalence. Prevalence of PSEDs was estimated in previous studies to range from 20% to 67% [8]. However, except for a study on diabetic retinopathy, the prevalence of PSEDs has not yet been broadly estimated in Saudi Arabia.

The proposed study aims to establish the magnitude of visual impairment and blindness attributed to PSEDs in Arar city through screening for ophthalmic disorders in the general population and identification of the PSEDs among the studied population. These data are necessary for better health service planning in Arar in the future, to improve the early diagnosis and management of cases of PSEDs.

Material and Method

Ethical issues: This study was conducted in Arar city, which is the capital of the Northern border region of the Kingdom of Saudi Arabia during the period from July 2017 to November 2017. The current research proposal and design were approved by the university local ethics committee. Only Saudi persons aged 12 years and above were included in the current study. Free informed consents were obtained from 956 participants or their legal guardian (if the age was below 16 years) who had agreed to participate in this study. Confidentiality and maleficence ethical principles were considered in all steps and cases which need further care were referred to the proper health facilities for medical or surgical treatment.

Study design:Free eye camps were organized for the purpose of general screening. After obtaining free informed consent from each participant, personal data and detailed history were collected. Then all participants were examined by ophthalmologists. Finger prick Random blood glucose (RBG) was estimated by calibrated glucometer by the accompanying well-trained nurses. Diabetes mellitus (DM) was considered if participants had a history of DM or RBG was >200 mg%. Diagnosed known diabetic patients under the treatment were considered as poorly controlled if RBG was >200 mg%. The examination protocol included visual acuity (VA) testing without correction, refraction, slit lamp examination, examination of the pupil, tonometry, and ophthalmoscopy on all subjects. Secondly, corrected VA retesting and dilated fundus examination was done on a subject who showed low vision or blindness. B-scan ultrasonography was performed on all cases where the fundus could not be visualized. Optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) was performed only when required. For DR, the study followed the Rapid Assessment for Avoidable Blindness and Diabetic Retinopathy (RAAB+DR) technique, which was developed by the International Centre for Eye Health, London School of Hygiene and Tropical Medicine (ICEH-LSHTM), London, United Kingdom. Among diabetic patients, DR was estimated following Scottish DR grading system. In the event of non-visualization of fundus, alternative re-evaluation examination at Arar Central Hospital was arranged for those participants. Cases of DR were followed up according to the recommendation of the Scottish DR grading system. In addition, cases of unilateral diminution of visual acuity (DOVA) were further examined to study the cause of their decreased vision. Data were collected for further statistical analysis.

Low vision and blindness in the current study were classified according to the World Health Organization (WHO) definition of visual impairment. Low vision was considered when the best corrected visual acuity (BCVA) in the better-seeing eye was less than 20/60 but not less than 20/400 and blindness when BCVA was less than 20/400. Unilateral diminution of vision (UDOVA) was considered when BCVA in one eye was < 20/30 with normal VA of the other eye. Visual acuity better than 20/30 in the best- corrected eye, was considered as normal VA. Statistical analysis: Prevalence of VI and different PSEDs in the studied population was calculated as the number of cases divided by the number of the studied population. Newcomb (1998) [9] formula was used to estimate the 95% confidence intervals. For nominal association, Chi-Square test was used. All statistical procedures were conducted by Prism7 (Graph Pad Software Inc., San Diego, CA). Significance was estimated with p-values <0.05.

Results

Demographic data of the studied subjects:Nine hundred and fifty-six Saudi persons were consented to participate in the current study. The ages of the studied subjects ranged from 12 to 65 years (43.6 ± 15.2). Regarding genders, 498 (52%) were males and 458 (48%) were females participated in the study. The participants were classified in 4 age groups as shown in Table 1. The studied groups were properly cross-matched without a significant difference between the age groups in relation to genders (p=0.7).

Regarding VA testing without correction, 744 subjects (77.8%) showed normal VA in both eyes while the remaining cases showed unilateral or bilateral diminution of their visual acuity (DOVA). On further examination with correction, only 81 (8.4%) cases were found to have VI and their level of VI was graded following WHO classification into a low vision and blind cases, while only 103 (10.8%) cases had shown unilateral DOVA. The prevalence of different degrees of VI and unilateral DOVA in relation to ages and genders of the studied population is shown in Table 1.

Regarding genders of the studied subjects, there was no significant difference between both genders in the prevalence of VI [p=0,534, X2(df)= 3.145,4]. While there was significant difference in VI distribution among the different age groups with more prevalence among elderly [p<0.0001, X2(df) = 96.58,12].

Regarding DM data, 234 (24.47%) participants were considered as diabetics (142 males and 92 were females) from whom only 156 (66.6%) were aware of having diabetes and were under therapeutic control.

Prevalence of the PSEDs: Posterior segment causes of VI and DOVA are shown in Table 2. Most of the causes of VI and DOVA were mainly attributed to the anterior segment problems with cataract and refractive errors representing the major part. In addition, PSEDs in relation to ages and genders in the studied population are shown in Table 3.

Regarding posterior segment causes of VI, diabetic retinopathy was the commonest and was found in 64 (6.7%) cases of the studied population. From these participants, retinal burns due to LASER therapy for DR were found in 2 cases. Prevalence and grading of DR among the screened diabetics are shown in Table 4.

The second commonest posterior segment cause of VI was AMD, which was found in 19 (2%) participants and optic atrophy was found to be the third commonest cause as it was found only in 16 (1.6%) subjects. Nine (56.25%) cases of optic atrophy (OA) gave a history of glaucoma, while 3 (18.75%) cases gave history suggesting hereditary OA. Other 3 (18.75%) cases gave a history of intracranial tumors, while the remaining one case (6.25%) of OA was firstly discovered and in need for further evaluation.

Retinal detachment was found in 10 (1%) cases of the studied population. Three cases had a prolonged history of uncontrolled diabetes mellitus, 2 cases showed high myopia and 1 case suffered RD following cataract surgery. In addition, 1 case had a history of RD after head trauma and in remaining 3 cases the cause for the RD could not be identified.

Interestingly, Vitreous hemorrhage was seen in 39 (19.3%) participants in association with DR (25 cases), ARMD (11 cases) and RD (3 cases).Vitreous hemorrhage alone was not seen in any of the participants.

Discussion

To the best of our knowledge, this is the first study focused on the prevalence of posterior segment eye diseases in cases of VI and DOVA in Saudi Arabia. The study was conducted in Arar city which is the capital of the Northern Border Region of Saudi Arabia. Nine hundred and fifty-six subjects were enrolled in the study. Prevalence of VI was estimated to be 8.4%. Low vision was found in 6.7% and blindness in 1.8% cases. While other studies in other regions in Saudi Arabia have reported prevalence of VI ranging from 7.8% to 13.9% and blindness from 0.7% to 1.5% [10-12]. Furthermore, the current study prevalence of blindness is higher than the prevalence reported in nearby countries which ranged from0.7% to 1.1% [13]. While the higher prevalence of blindness was estimated in other countries such as Pakistan (3.4%) [14] and Upper Egypt (9.3%) [15] among the studied populations.

Unilateral DOVA was estimated in 103 (10%) participants of the current study. The prevalence of unilateral DOVA was reported to be 7.3% in Australia [16] and only 2.57% in Pakistan [17]. From these previous numbers, it is clear that the prevalence of VI and blindness is a reflection to the planned health care system in the studied locations as well as the population awareness and attitude towards the available ophthalmic healthcare services and the importance of the periodic check-up. In addition, the used examination methods and definitions of VI are expected to affect the outcome results.

Interestingly, the gender difference did not affect the distribution of VI and PSEDs in the studied population. This is different from the previous studies as by al-Shaaln et al. (2011) [10], by Dimitrov et al. (2003) [16], and McCarthy et al. (2000) [18], which showed higher prevalence of VI among females than males due to a longer life expectancies with more susceptibility to age-related visual problems. However, we were keen in our study to choose well- matched groups of both genders in the studied different age groups. While ages of the studied population significantly affect the VA and PSEDs of the studied population with more VI in elderly as DR is more prevalent with longer years of diabetes. Also, ARMD is mainly seen in ages over 50 years.

The current study showed that diabetic retinopathy (13.2% cases) was the commonest PSED diagnosed in cases of VI and DOVA. The higher incidence of DR among studied cases is expected due to a very high prevalence of diabetes in Saudi Arabia. The prevalence of DM, which is an alarming public global health problem with its related complications as retinopathy, nephropathy, and neuropathy, was estimated to be 30% in Saudi Arabia [19]. The current data about DR is in accordance with other previously published data in Saudi Arabia as by Hajar et al. (2015) [20] who have estimated a prevalence of DR among the general population to be around 5-6%.

Vitreous hemorrhages were found in 39 subjects enrolled in the study. Most cases were found as a complication of the proliferative diabetic DR and wet forms of ARMD.

In the current study, the commonest cause of OA was glaucoma which is different from Mbekeanis et al. (2017) [21], who stated that tumors are the commonest causes of OA in 62.2% of their studied cases, while in the present study, history of tumors was found only in 16% of cases. The general prevalence of vitreous hemorrhage, OA and RD were not reported in the previous literature.

The present findings are important as they highlight, for the first time in Saudi Arabia, the prevalence of the PSEDs and their attribution to VI. Secondly, the study shows that we need the support of the culture of periodic ophthalmic screening of the population which is expected to improve detection of any visual aliment in the early stages with better-expected correction especially for cases of unilateral DOVA which are usually unnoticed by the patient. Most cases of UDOVA were first discovered during the screening phase of this study. Thirdly, the current data attract the attention to follow up of diabetics by the regular ophthalmic evaluation and timely proper intervention for cases of DR. Early diagnosis and proper management of glaucoma can reduce the prevalence of OA. Application of modern surgical techniques for cataracts should reduce the risk of posterior segment complications like RD and vitreous hemorrhages [22].

Conclusion

Visual impairment is a major global health problem with negative drawbacks in society. Posterior segment eye diseases are common among the cases with visual problems. Diabetic retinopathy was found to be the commonest PSED among the studied population in Arar city, followed by ARMD, OA, and RD. Proper follow up of diabetics by regular ophthalmic evaluation and proper intervention for cases of DR can reduce the burden of visual impairment. Early diagnosis and proper management of glaucoma can markedly reduce the prevalence of OA. In addition, modern techniques in cataract surgeries can reduce such the posterior segment complications as RD and vitreous hemorrhages.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Bastawrous A, Burgess PI, Mahdi AM, Kyari F, Burton MJ, Kuper H. Posterior segment eye disease in sub-Saharan Africa: review of recent population-based studies. TM & IH. 2014; 19(5): 600-9. DOI:10.1111/tmi.12276.

2. Nell B1, Walde I. Posterior segment diseases. Equine Vet J Suppl. 2010;(37): 69-79.

3. Bowler GS, Fayers T, Gouws P. 5.7 Times more expensive than liquid gold. Br J Ophthalmol. 2012; 96: 1046.

4. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002; 120: 1268–79.

5. Elman MJ, Ayala A, Bressler NM, Browning D, Flaxel CJ, Glassman AR, et al. Diabetic Retinopathy Clinical Research Network. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015; 122(2): 375-81.

6. Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. The Lancet. 2012;379(9827): 1728-38.

7. Kolber MR, Tennant M, Nickonchuk T. Vitamins for age-related macular degeneration demonstrate minimal differences. Can Fam Physician. 2013; 59(5): 503.

8. Polo MD, Lluís AT, Segura OP, Bosque AA, Appiani CE, Mitjana JM. Ocular ultrasonography focused on the posterior eye segment: what radiologists should know. Insights Imaging. 2016; 7(3): 351-64.

9. Robert G. Newcombe. Two-sided confidence intervals for the single proportion: comparison of seven methods.  Stat Med. 1998; 17: 857-72.

10. Al-Shaaln FF, Bakrman MA, Ibrahim AM, Aljoudi AS. Prevalence and causes of visual impairment among Saudi adults attending primary health care centers in northern Saudi Arabia.Ann Saudi Med.2011; 31(5): 473-80.

11. Budenz DL, Bandi JR, Barton K, Nolan W, Herndon L, Whiteside-de Vos J, et al. Blindness and visual impairment in an urban West African population: the Tema Eye Survey. Ophthalmology. 2012; 119(9): 1744-53.

12. Khandekar R1, Mohammed AJNegrel ADRiyami AA. The prevalence and causes of blindness in the Sultanate of Oman: the Oman Eye Study (OES). Br J Ophthalmol. 2002;86(9): 957-62.

13. Soori HAli JMNasrin R. Prevalence and causes of low vision and blindness in Tehran Province, Iran. J Pak Med Assoc. 2011; 61(6): 544-9.

14. Jadoon MZDineen BBourne RRShah SPKhan MAJohnson GJ, et al. Prevalence of blindness and visual impairment in Pakistan: the Pakistan National Blindness and Visual Impairment Survey. Invest Ophthalmol Vis Sci. 2006;47(11): 4749-55.

15. Mousa ACourtright PKazanjian ABassett K. Prevalence of visual impairment and blindness in Upper Egypt: a gender-based perspective. Ophthalmic Epidemiol. 2014; 21(3): 190-6. DOI: 10.3109/09286586.2014.906629.

16. Dimitrov PN1, Mukesh BNMcCarty CATaylor HR. Five-year incidence of bilateral cause-specific visual impairment in the Melbourne Visual Impairment Project. Invest Ophthalmol Vis Sci. 2003; 44(12): 5075-81.

17. Dineen B, Bourne RR, Jadoon Z, Shah SP, Khan MA, Foster A, et al.Causes of blindness and visual impairment in Pakistan. The Pakistan national blindness and visual impairment survey. Br J Ophthalmol. 2007; 91(8): 1005-10.

18. McCarty CANanjan MBTaylor HR. Attributable risk estimates for cataract to prioritize medical and public health action. Invest Ophthalmol Vis Sci. 2000; 41(12): 3720-5.

19. Alqurashi KA1, Aljabri KSBokhari SA. Prevalence of diabetes mellitus in a Saudi community. Ann Saudi Med. 2011; 31(1): 19-23. DOI: 10.4103/0256-4947.75773.

20. Hajar S, Al Hazmi A, Wasli M, Mousa A, Rabiu M. Prevalence and causes of blindness and diabetic retinopathy in Southern Saudi Arabia. Saudi Med J. 2015; 36(4): 449.

21. Mbekeani JN, Fattah MA, Poulsen DM, Al Hazzaa S, Dababo MA, Eldali A, et al. Etiology of optic atrophy: a prospective observational study from Saudi Arabia. Ann Saudi Med.2017; 37(3): 232-9.

22. Gogate P. Comparison of various techniques for cataract surgery, their efficacy, safety, and cost. Oman J Ophthalmol. 2010; 3(3): 105-6.

PDF

Download attachments: JCAM_6089.pdf

How to Cite

Elmorsy E, Rehman Parrey MU. Posterior segment eye diseases: prevalence, pattern, and attribution to visual impairment among adult saudi population. Ann Clin Anal Med 2019;10(4):505-9

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

A case-control study addressing the association between elevated body mass index and risk of multiple sclerosis

Azzam Khalid A Laskar

Pediatric Resident at MCH, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

DOI: 10.4328/ACAM.6060 Received: 22.10.2018 Accepted: 05.12.2018 Published Online: 10.12.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 501-4

Corresponding Author: Azzam Khalid A Laskar, Pediatric Resident at MCH, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. GSM: 00966557212698 Email: dr.research555@gmail.com, azzam.laskar@gmail.com ORCID ID: https://orcid.org/0000-0002-5322-6893

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: Obesity is an important risk factor of multiple sclerosis particularly in younger age. Many studies reported an association between elevated body mass index (BMI) and development of MS especially in teenagers and adolescents. As obesity is a major health problem in Saudi Arabia, an elevated risk of multiple sclerosis is expected. This study aimed to evaluate the association between elevated body mass index and multiple sclerosis. Material and Method: This case-control study included 231 participants aged ≥17 years old, of them 77 cases were multiple sclerosis and 154 controls. Patients previously diagnosed with MS or had no medical records were excluded. Controls had no MS or any related neurological symptoms and selected from outpatients’ clinics. Data were collected from hospital records regarding demographics and BMI. Results: The majority of the participants aged 21-40 years old. About 30% of them were 21-30 years old and 35% were 31-40 years old. Regarding BMI categorization of the respondents 51.5% had an elevated BMI, while 112 (48.5%) had a normal BMI. Find-ings of the binary logistic regression model showed an increased risk of multiple sclerosis by 2.3 times among participants with an elevated BMI than those with normal BMI (p value = 0.005, OR: 2.28, 95% CI=1.289 to 4.019). Discussion: As multiple sclerosis has been linked to genetic factors, an assessment of the presence of such association in different populations are meaningful. The cross-sectional approach is defective in the assessment of association, thus a retrospective analytical approach with the case-control study was the most appropriate design. Conclusions: There was a significant association between BMI and the occurrence of multiple sclerosis, the risk is doubled among overweight or obese people in Saudi Arabia in comparison to normal or underweight people.

Keywords: Obesity; Neurological Diseases; Adult; Overweight; Case-Control Study

Full Text

Introduction

Multiple sclerosis (MS) is defined as an autoimmune inflammatory disorder of the Central Nervous System (CNS). Pathologically MS characterized by myelin destruction (demyelination), mononuclear cells perivascular infiltration, axonal damage and multiple plaques formation in both of the spinal cord and the brain [1-3]. It has been considered as a progressive and chronic inflammatory disease that mostly attributed to environmental and genetic risk factors [1,4].

MS is considered the second prominent reason of neurological disability in both children and adolescent as stated by World Health Organization (multiple sclerosis resources in the world, 2008). Women most commonly affected than men with female/male ratio 4:3 in Saudi Arabia [5]. Several studies reported the prevalence of MS in different populations, in Kuwait (2000) a prevalence of 14.77/100,000 was reported, while in Turkey a high prevalence of 101.4/100,000 was found [6]. In the US, the prevalence of MS ranged from 47.2/100,000 in Texas to 109.5/100,000 population in Ohio. MS can affect any age, but it commonly affects young adults. The disease usually begins at an age of 20 years up to 50 years, with the mean age of 30 years. MS can occur in early childhood and can develop after 60 years of age with more severe clinical presentation in children and adolescent. The disease characterized by relapsing-remitting course in about 85% of affected patients. Furthermore, the remissions and exacerbations most commonly are unpredictable [7]. Disability may develop in about 60% of patients with MS and most of them may need ambulatory support [7-9]. MS can be progressive without relapsing phase in about 5 – 15 % of cases, in which the disease gradually worsens from the onset and become very progressive [10,11].

Obesity is considered an essential risk factor of MS especially in young age [12,13]. Many studies reported the association between elevated body mass index (BMI) and development of MS especially in teenagers and adolescents [12-15]. However, none of them was conducted in Saudi Arabia and those studies were found to show positive results supporting the association between elevated BMI and higher risks of developing MS. In Saudi Arabia, the prevalence of obesity is remarkably high, with 82% of the general population were overweight or obese in Riyadh city [16]. This case-control study aimed to assess the association between elevated body mass index and multiple sclerosis in Saudi Arabia.

Material and Method

This was a case-control study conducted in King Abdulaziz University Hospital (KAUH) with a total number of 77 patients with MS aged 17–64 years. For each case, two controls were randomly selected from the outpatient department at KAUH, matched by age (5-year age group) and gender. A total sample size of 231 study participants was calculated using StatCal in Epi-info (version 7) and included MS cases and non-MS controls. This study included cases aged ≥17 years old with newly confirmed diagnosis of MS. The exclusion criteria included patients previously diagnosed with MS or those who did not have documented BMI records. Controls were outpatient attendants who had no MS or any related neurological symptoms. Controls who were relatives of any studied case were excluded from the study to rule out the risk associated with the genetic effect. The authors explained information to the participants which included the objectives of the study, the right to refuse or withdrawal from participation, and the confidentiality of information provided. The Written consents were obtained from adult study participants, while parents provided consents for patients aged less than 18 years old. Data were collected from hospital records regarding age, gender, and BMI calculated in kg/m2. The statistical analysis was conducted using Statistical Package of Social Science (SPSS), version 23. The descriptive statistics were calculated and presented in tables and figures, while odds ratios were assessed for the association between MS and BMI with 95% confidence interval. Associations with p-value less than 0.05 were assessed as statistically significant.

Results

The total number of the study respondents was 231 with age ranged from 17 to 72 years old, of them 168 (72.7%) were females and 63 (27.3%) were males. The respondents were divided into six age groups; two thirds of them were in the age groups of 21-40 years old. About 30% were 21-30 years old and 35% were 31-40 years old. Regarding the BMI categorization of the respondents, 119 (51.5%) were categorized as having an elevated BMI, while 112 (48.5%) had a normal BMI (Table/Figure 1). The BMI of the respondents was also categorized into six groups according to the WHO classification. Approximately 9% of the respondents were underweight, while 28.1% were categorized in the pre-obesity phase (overweight) and 23% were obese as (Table/Figure 2).

Cross tabulation, using Chi-Square test, between demographic characteristics of the respondents and occurrence of MS revealed significant association between BMI and occurrence of MS. As the cases and controls were matched in age and gender, no significant associations were reported for these factors in relation to occurrence of multiple sclerosis (p-value = 0.996 and 0.559, respectively) as shown in Table/Figure 3.

Table/Figure 2. Body mass index grades of the respondents, (n =231)

The association between demographic characteristics and BMI of the respondents were significant with age (p-value = 0.004), while gender showed no significant association with BMI (Table/Figure 4). Results of the binary logistic regression model showed an increased risk of MS in participants with elevated BMI in comparison to those with normal BMI (Table/Figure 5). The elevated BMI compared to normal BMI have 2.3 times greater risk of developing multiple sclerosis (p-value = 0.005, OR: 2.276, 95% CI=1.289 to 4.019).

Discussion

Several reports highlighted the association between elevated body mass index (BMI) and development of MS [12-15], however, no study reported this association in Saudi Arabia. As MS has been linked to genetic factors [17], an assessment of the presence of such association in different populations is meaningful. The cross-sectional approach is defective in the assessment of association, thus a retrospective analytical approach with case-control study was the most appropriate design.

Results of our study showed a significant association between BMI and occurrence of MS. Findings of logistic regression modeling found 2.3 times greater risk of developing MS in people with the elevated BMI compared with those with normal BMI. Thus, elevated BMI can be considered as a risk factor of MS among adults in Saudi Arabia. Similarly, a population-based case-control study by Hedström et al. concluded that adults with BMI > 27 have two times greater risk of developing MS [14]. Another study by Mokry et al. reported that elevated BMI increases the risk of developing MS (OR: 1.41, 95% CI=1.20 to 1.66) [18]. Manouchehrinia et al. concluded in their study that; elevated BMI more than 30 can increase risk of MS in smokers by 1.5 times [19]. Our findings showed no significant association between each gender and age with the occurrence of MS. A systematic review and meta-analysis conducted by Heydarpour et al. found that MS is more common among females in Saudi Arabia (female: male ratio = 4:3) [6]. Gianfrancesco et al. reported twofold times increase in the risk of MS among people with elevated BMI. Additionally, they reported the increased risk of MS among females after controlling the environmental and genetic factors [20]. Regulations to decrease the obesity especially among females and to increase the awareness of multiple sclerosis among both patients and doctors might be needed. Hedström et al.concluded in their study that prevention of obesity in adolescent may reduce the risk of developing MS [21].

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Tur C, Tintoré M, Vidal-Jordana Á, Bichuetti D, González PN, Arévalo MJ, et al. Risk acceptance in multiple sclerosis patients on natalizumab treatment. PLoS One. 2013; 8(12): DOI: 10.1371/journal.pone.0082796.

2. Milo R, Miller A. Revised diagnostic criteria of multiple sclerosis. Autoimmunity Reviews. 2014; 13(4-5): 518-24.

3. Carton H, Vlietinck R, Debruyne J, De Keyser J, D’hooghe M-b, Loos R, et al. Risks of multiple sclerosis in relatives of patients in Flanders, Belgium. Journal of Neurology, Neurosurgery & Psychiatry. 1997; 62(4): 329-33.

4. Dean G. How many people in the world have multiple sclerosis? Neuroepidemiology. 1994; 13(1-2): 1-7.

5. Weinshenker BG. Epidemiology of multiple sclerosis. Neurologic Clinics. 1996; 14(2): 291-308.

6. Heydarpour P, Khoshkish S, Abtahi S, Moradi-Lakeh M, Sahraian MA. Multiple sclerosis epidemiology in Middle East and North Africa: a systematic review and meta-analysis. Neuroepidemiology. 2015; 44(4): 232-44.

7. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology. 1996; 46(4): 907-11.

8. Kremenchutzky M, Rice G, Baskerville J, Wingerchuk D, Ebers G. The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain. 2006; 129(3): 584-94.

9. Williamson DM, Noonan CW, Henry JP, Wagner L, Indian R, Lynch SG, et al. Peer Reviewed: The Prevalence of Multiple Sclerosis in 3 US Communities. Preventing Chronic Disease. 2010; 7(1)

10. Thompson A, Polman C, Miller D, McDonald W, Brochet B, Filippi M Montalban X, et al. Primary progressive multiple sclerosis. Brain: A Journal of Neurology. 1997; 120(6): 1085-96.

11. Christiansen CF, Christensen S, Farkas DK, Miret M, Sørensen HT, Pedersen L. Risk of arterial cardiovascular diseases in patients with multiple sclerosis: a population-based cohort study. Neuroepidemiology. 2010; 35(4): 267-74.

12. Munger KL, Bentzen J, Laursen B, Stenager E, Koch-Henriksen N, Sørensen TI, et al. Childhood body mass index and multiple sclerosis risk: a long-term cohort study. Multiple Sclerosis Journal. 2013; 19(10): 1323-9.

13. Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology. 2013; DOI: 10.1212/WNL.0b013e31828154f3.14.

14. Hedström AK, Olsson T, Alfredsson L. High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women. Multiple Sclerosis Journal. 2012; 18(9): 1334-6.

15. Munger KL, Chitnis T, Ascherio A. Body size and risk of MS in two cohorts of US women. Neurology. 2009; 73(19): 1543-50.

16. Al-Haqwi AI, Al-Nasir M, Ahmad N, Masaudi E, Alotaibi SS, Hamad B. Obesity and overweight in a major family practice center, central region, Saudi Arabia. Saudi Journal of Obesity. 2015; 3(1): 12.

17. Sadovnick A, Dyment D, Ebers G, Risch N, Group CCS. Evidence for genetic basis of multiple sclerosis. The Lancet. 1996; 347(9017): 1728-30.

18. Mokry LE, Ross S, Timpson NJ, Sawcer S, Smith GD, Richards JB. Obesity and multiple sclerosis: a Mendelian randomization study. PLoS medicine. 2016; 13(6): DOI:10.1371/journal.pmed.1002053.

19. Manouchehrinia A, Hedström AK, Alfredsson L, Olsson T, Hillert J, Ramanujam R. Association of pre-disease body mass index with multiple sclerosis prognosis. Frontiers in Neurology. 2018; 9. DOI:10.3389/fneur.2018.00232.

20. Gianfrancesco MA, Acuna B, Shen L, Briggs FB, Quach H, Bellesis KH, et al. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors. Obesity Research & Clinical Practice. 2014; 8(5): e435-e47.

21. Hedström AK, Bomfim IL, Barcellos L, Gianfrancesco M, Schaefer C, Kockum I, et al. Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis. Neurology. 2014; 82(10): 865-72.

PDF

Download attachments: JCAM_6060.pdf

How to Cite

Laskar AK. A case-control study addressing the association between elevated body mass index and risk of multiple sclerosis. Ann Clin Anal Med 2019;10(4): 501-4

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio acute rheu-matic fever in children with cardiac involvement

Hatice Buyukoflaz 1, Derya Arslan 2

1 Pediatrics, 2 Pediatric Cardiology, University of Health Sciences, Konya Educational Research Hospital, Konya, Turkey

DOI:10.4328/ACAM.5960 Received: 09.07.2018 Accepted: 11.12.2018 Published Online: 20.12.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 441-4

Corresponding Author: Hatice Büyükoflaz, Sağlık Bilimleri Üniversitesi Konya Eğitim ve Araştırma Hastanesi, Pediatri Kliniği, 42080, Konya, Türkiye. T.: +905302746575, E-Mail: haticebuyukoflaz@hotmail.com ORCID ID: https://orcid.org/0000-0001-8057-2815

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: In this study, we aimed to contribute to a better understanding of ARF pathophysiology by taking advantage of the NLR and PLR indices, which are consid-ered as SIR markers and to evaluate whether these parameters are related to the carditis degree. Material and Method: Patients who applied to the pediatric cardiology clinic between 2013 and 2016 and were provided with our service were included in the study. Patient’s laboratory and clinical data were obtained retrospectively from hospital records. Twenty-seven newly diagnosed patients were included in the study. Leukocyte, neutrophil, lymphocyte and thrombocyte counts, sedimentation, CRP, NLR, and PLR indices were compared before and after treatment. It was also evaluated whether these parameters were affected by the carditis degree. Results: There was no statistical significance in the change of NLR, PLR, and NLR, PLR after treatment with cardiac involvement at the time of diagnosis. In addition, there was no statistical significance in NLR, PLR index and CRP, sedimentation values before and after treatment between nor-mal and mild insufficiency, 1st-degree insufficiency, 2nd and 3rd-degree insufficiency in echocardiography findings. Positive correlation between NLR and PLR before treatment (p = 0,002, r = 0,567) was strong. After treatment, there was a moderate positive correlation between NLO and PLO (p = 0,088, r = 0,335). Discussion: In patients with ARF cardiac involvement was not associated with CRP, sedimentation increasing and NLR and PLR index. It should be considered that there may be other underlying causes that aggravate endothelial injury. Larger and prospective studies are needed to clarify this situation.

Keywords: Acute Rheumatic Fever; Neutrophil-Lymphocyte Ratio; Platelet-Lymphocyte Ratio; Child

Full Text

Introduction

Acute rheumatic fever (ARF) is a nonsuppurative sequela that occurs two to four weeks following group A Streptococcus pharyngitis and may consist of arthritis, carditis, chorea, erythema marginatum, and subcutaneous nodules. Damage to cardiac valves may be chronic and progressive, resulting in cardiac decompensation [1]. Acute rheumatic fever is the most common cause of acquired heart disease in children and young adults in many areas of the world and especially in developing countries. There are at least 15.6 million patients with rheumatic heart disease worldwide [2]. Each year 500 000 new ARF cases are seen. About 280 000 of these acquire rheumatic heart disease and 233 000 individuals are lost due to ARF or rheumatic heart disease yearly [3]. The pathogenic mechanisms that lead to the development of ARF remain incompletely understood. Streptococcal pharyngeal infection is clearly required, and genetic susceptibility may be present. On the other hand, the evidence that toxins produced by Streptococcus are important is sparse. Within this framework, molecular mimicry is thought to play an important role in the initiation of the tissue injury [4].

Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in peripheral blood are the markers of simple systemic inflammatory response (SIR). They are evaluated through blood parameters. NLR is highly important for the diagnosis of certain pathologies that are characterized by systemic or local inflammatory response such as diabetes mellitus, coronary artery disease, ulcerative colitis and inflammatory arthritis [5]. The proportion of these two cell types helps to detect inflammation [6].

In the current literature, there have not been any studies evaluating the relationship between ARF and NLR and PLR. Therefore, we aimed to investigate the correlations between ARF and NLR and PLR.

Material and Method

This study was carried out in the pediatric cardiology outpatient clinic and pediatric service of our hospital between January 2013 and December 2016.  The study population consisted of 30 patients newly diagnosed. We diagnosed ARF by using the modified Jones criteria [3]. The patients were compared before and after treatment. All patients were treated by the same pediatrician Echocardiography.

Patients with congenital heart disease or systemic diseases such as diabetes mellitus, hypertension, acute coronary artery disease, active connective tissue disorder, vasculitis, inflammatory bowel disease, chronic renal failure, and chronic liver failure were excluded. 

Hematological parameters were analyzed using a hematology analyzer within 30 minutes after the blood was collected. Leucocyte (103/μL), neutrophil (103/μL), lymphocyte (103/μL) and platelet (103/ μL) counts were recorded. The results were expressed in 103/μL. NLR and PLR were calculated using the results of these parameters. Hemoglobin values were expressed in g/dL. Sedimentation and CRP values of patients were recorded. Leukocyte, neutrophil, lymphocyte and platelet counts, NLR and PLR were compared between patients with ARF before and after the treatment. Also, it was determined whether these parameters were affected by the carditis degree.

Statistical Analysis

Version 15.0 of SPSS Windows program was used, for statistical analysis of the data. Number, percentage, mean, standard deviation and standard error were used in the evaluation of the data. The Mann-Whitney U test was used to compare the measurements of a particular variable in two separate groups, and the Kruskal Wallis test was used to compare the measurements of more than one group. The coefficient of correlation (r) between 0,000-0,249 regarded as weak; between 0.250-0.499 as medium; from 0,500 to 0,749 as strong. The relationship between 0,750-1,000 was evaluated as a very strong. The level of significance was p <0.05.

Results

The data of 30 patients were analyzed. The mean age of the analyzed group was 11.7 ± 3.1(SD), and 30% of the patients were male. There was no statistically significant difference in the ratio of diagnosis neutrophil/lymphocyte, platelet/lymphocyte, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio. In addition, there was no statistical significance between neutrophil/lymphocyte ratio, platelet/lymphocyte, neutrophil, lymphocyte, sediment, CRP and blood pressure between the patients with and without heart involvement. In addition, there was no statistically significant difference in neutrophil/lymphocyte ratio, platelet/lymphocyte ratio changes before and after treatment between normal and mild insufficiency, first-degree insufficiency, second and third-degree insufficiency in echo findings.

Spearman’s correlation analysis showed a strong positive correlation between systolic (p = 0,000, r = 0,706) and diastolic (p = 0,002, r = 0,578) and systolic (p = 0.004, r = 0.535) positive correlation was found between blood pressure and strength. Positive correlation was found between neutrophil/lymphocyte ratio and platelet / lymphocyte ratio (p = 0.002, r = 0.567) before treatment. After treatment, there was a moderate positive correlation between neutrophil/lymphocyte ratio and platelet/lymphocyte ratio (p = 0,088, r = 0,335). There was a moderate negative correlation between CRP and neutrophil (p = 0,050, r = -0,381), CRP and neutrophil/lymphocyte (p = 0,018, r = -0,452) after treatment. Moderate positive correlation between sediment CRP before treatment (p = 0,012, r = 0,477) and moderate positive correlation between sediment CRP (p = 0,059, r = 0,368) after treatment were found. There was a weak negative correlation between pre- and post-treatment CRP.

Discussion

In this study, we aimed at contributing to the better understanding of the pathophysiology of ARF by evaluating the NLR, PLR, sedimentation, CRP that are considered as SIRS markers and to evaluate whether these parameters are related to the carditis degree.

The potential complications of group A Streptococcus (GAS) pharyngeal infection include both suppurative and inflammatory, nonsuppurative conditions. The disease presents with various manifestations that may include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum [1]. The pathogenic mechanisms that lead to the development of ARF remain incompletely understood. Streptococcal pharyngeal infection is clearly required, and genetic susceptibility may be present. On the other hand, the evidence that toxins produced by Streptococcus are important is sparse. Within this framework, molecular mimicry is thought to play an important role in the initiation of the tissue injury. However, the factors responsible for the perpetuation of the process remain unclear [4]. The significance of rheumatic fever is almost solely due to its cardiac sequel. Cardiac involvement leads to Rheumatic Heart Disease (RHD) [7]. People who have had ARF previously are at higher risk of subsequent episodes associated with further cardiac valve damage. RHD is the most common form of pediatric heart disease in the world and is the leading cause of cardiac death in the first five decades of life [8].

There are noteworthy studies that have been conducted recently and have evaluated SIRS markers in peripheral blood such as NLR, PLR that can be easily measured through hemogram test. Neutrophils are related to the hypercoagulability and viscosity of blood and responsible for the microvascular damage on endothelial surface [9]. Lymphocytopenia induced by the systemic inflammatory response reveals depression of innate cellular immunity indicated by a marked decrease in T4 helper lymphocytes and an increase in T8 suppressor lymphocytes [10]. Platelets can increase in number in response to various stimuli such as systemic infection, inflammatory conditions, bleeding, and tumors as acute phase reactants, which can result in the overproduction of pro-inflammatory cytokines that stimulate megakaryocytic proliferation and produce a relative thrombocytosis [11]. Higher platelet counts may reflect underlying inflammation and lower lymphocyte counts may represent an uncontrolled inflammatory pathway. Thus, a higher PLR may be a useful inflammatory marker [12]. The studies conducted show that high NLR and PLR values indicate increased inflammation, and are reported to be associated with increased cardiovascular risk, related to poor prognosis [13].

Turak et al. [14] showed that admission NLR was an independent predictor of poor prognosis in patients with infective endocarditis. According to these data, we thought that there might be a relationship between NLR and cardiac involvement [14]. Unfortunately, in our study, there was no statistically significant difference in NLR, between those with heart involvement and those without heart involvement. In addition to parameters used for risk stratification in various cardiovascular diseases, a recent review has shown the NLR to be a simple, easily obtainable marker of inflammation [15].

Previous reports have shown convincing evidence that there is ongoing inflammation in RHD. Intralesional mononuclear cells that are secreting inflammatory cytokines have been identified in the chronic phase of RKD [16]. In our study, there was no statistically significant difference in NLR, PLR between those with heart involvement and those without heart involvement. In addition, there was no statistically significant difference in NLR, PLR changes before and after treatment between normal and mild insufficiency, first-degree insufficiency, second and third-degree insufficiency in echo findings. We showed that the NLR was severe positively correlated with the PLR before treatment, and also there was a moderate positive correlation between NRL and PLR. In a study by Polat et al. [17], the NLR was significantly higher in patients with rheumatic mitral valve stenosis (RMVS) compared to those with RHD without stenosis and control patients. In another study by Akboğa et al. [18], the NLR was significantly higher in patients with RHD.

In a study by Davutoglu et al. [19], patients with RMVD had increased levels of chronic inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL-2 receptor, tumor necrosis factor a, and hs-CRP) as indicators of ongoing inflammation compared with the control group. The CRP is a well-known inflammation marker. In a study by Golbasi et al., levels of high-sensitivity C-reactive protein (hsCRP) were higher in patients with chronic rheumatic valvular disease than in healthy participants and patients with valve replacement [20]. Similarly, in a study conducted on patients with RMS, hs-CRP levels were significantly higher in patients with RMS than in the control group, and hs-CRP values correlated with the Wilkins valve score and its components [21]. Unlike our study, there was no statistical significance between the cardiac involvement degree and CRP value. Kaya et al. [22], detected a significant positive correlation between the hs-CRP and the NLR in patients with RMS. In this study, only patients with RMS were included, and patients with and without spontaneous echo contrast were compared in terms of NLR [22]. In our study, there was a moderate negative correlation between after treatment CRP levels and neutrophil counts, and a moderate negative correlation between after treatment CRP level and NLR.

Our study had several limitations. First, this study is retrospective and includes a small number of patients. Second limitation of this study is that in the current literature, there is no study evaluating the relationship between ARF cardiac involvement and NLR and PLR indices in children. The third limitation is that there is no control group in the study.

Conclusion

In patient with ARF, cardiac involvement was not associated with CRP, sedimentation, and NLR and PLR indices. It should be considered that there may be other underlying causes that aggravate endothelial injury. Larger and prospective studies are needed to clarify this situation.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Parks T, Smeesters PR, Steer AC. Streptococcal skin infection and rheumatic heart disease. Curr Opin Infect Dis. 2012; 25: 145.

2. Lawrence JGCarapetis JRGriffiths KEdwards KCondon JR. Acute rheumatic fever and rheumatic heart disease: incidence and progression in the Northern Territory of Australia. 1997 to 2010. Circulation. 2013; 128: 492

3. Jaine R, Baker M, Venugopal K. Acute rheumatic fever associated with household crowding in a developed country. Pediatr Infect Dis J. 2011; DOI: 10.1097/INF.0b013e3181fbd85b.

4. Whitnack E, Bisno L. Rheumatic fever and other immunologically-mediated cardiac diseases. In: Clinical immunology, Parker C (Ed).Philadelphia: WB Saunders; 1980. 2: 894.

5. Imtiaz FShafique KMirza SSAyoob ZVart PRao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012; 5: 2

6. Zahorec R. Ratio of neutrophil to lymphocyte counts Rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001; 102: 5-14.

7. Zühlke LJ, Steer AC. Estimates of the global burden of rheumatic heart disease. Glob Heart. 2013; 8: 189.

8. Carapetis, JR. Rheumatic heart disease in developing countries. N Engl J Med. 2007; 357: 439.

9. Gibson PHCuthbertson BHCroal BLRae DEl-Shafei HGibson G, et al. Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery baypass grafting. Am J Cardiol. 2010; 105: 186-91.

10. Menges TEngel JWelters IWagner RMLittle SRuwoldt R, et al. Changes in blood lymphocyte populations after multiple trauma: association with posttraumatic complications. Crit Care Med. 1999; 27: 4: 733-40.

11. Waehre TDamås JKYndestad ATaskén KPedersen TMSmith C, et al. Effect of activated platelets on expression of cytokines in peripheral blood mononuclear cells—potential role of prostaglandin E2. Thromb Haemost. 2004; 92: 1358–67.

12. Damas JK, Waehre T, Yndestad A, Otterdal K, Hognestad A, Solum NO, et al. Interleukin-7-mediated inflammation in unstable angina: possible role of chemokines and platelets. Circulation. 2003; 107:2670–76.

13. Tamhane UUAneja SMontgomery DRogers EKEagle KAGurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008; 102: 653-7.

14. Turak O, Ozcan F, Isleyen A, Basar N, Gül M, Yılmaz S, et al. Usefulness of neutrophil-to-lymphocyte ratio to predict in-hospital outcomes in infective endocarditis. Can J Cardiol. 2013; 12: 1672-8.

15. Bhat TTeli SRijal JBhat HRaza MKhoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther. 2013; 11: 1: 55-9.

16. Guilherme LCury PDemarchi LMCoelho VAbel LLopez AP, et al. Rheumatic heart disease. Proinflammatory cytokines play a role in the progression and maintenance of valvular lesions. Am J Pathol. 2004; 165: 5: 1583-91.

17. Polat NYildiz AYuksel MBilik MZAydin MAcet H, et al. Association of neutrophil-lymphocyte ratio with the presence and severity of rheumatic mitral valve stenosis. Clin Appl Thromb Hemost. 2014; 20: 8: 793-8.

18. Akboğa MK, Akyel A, Sahinarslan A, Yayla C, Alsancak Y, Gökalp G, et al. Neutrophil-to-lymphocyte ratio is increased in patients with rheumatic mitral valve stenosis? Anadolu Kardiyol Derg. 2014; 380–4.

19. Davutoglu V, Celik A, Aksoy M. Contribution of selected serum inflammatory mediators to the progression of chronic rheumatic valve disease, subsequent valve calcification and NYHA functional class. J Heart Valve Dis. 2005; 14: 2: 251-6.

20. Gölbasi ZUçar OKeles TSahin ACagli KCamsari A , et al. Increased levels of high sensitive C-reactive protein in patientswith chronic rheumatic valve disease: evidence of ongoing inflammation. Eur J Heart Fail. 2002; 4: 593-5.

21. Alyan OMetin FKacmaz FOzdemir OMaden OTopaloglu S, et al. High levels of high sensitivity C-reactive protein predict the progression of chronic rheumaticmitral stenosis. J Thromb Thrombolysis. 2009; 28: 63-9.

22. Kaya MGAkpek MElcik DKalay NYarlioglues MKoc F, et al. Relation of left atrial spontaneousechocardiographic contrast in patients with mitral stenosis to inflammatory markers. Am J Cardiol. 2012; 109: 851-5

PDF

Download attachments: JCAM_5960.pdf

How to Cite

Buyukoflaz H, Arslan D. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio acute rheumatic fever in children with cardiac involvement. Ann Clin Anal Med 2019;10(4): 441-4

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Evaluation of perioperative results of total laparoscopic hysterectomy cases: a tertiary referral center experience

Hüseyin Kıyak, Pınar Kadiroğulları, Kerem Doğa Seckin

Department of Obstetrics and Gynecology, Istanbul Health Sciences University, Kanuni Sultan Süleyman Research and Training Hospital, İstanbul, Turkey

DOI:10.4328/ACAM.5987 Received: 03.08.2018 Accepted: 05.09.2018 Published Online: 17.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 475-8

Corresponding Author: Pınar Kadiroğulları, Department of Obstetrics and Gynecology, Kanuni Sultan Süleyman Research and Training Hospital, İstanbul, Turkey Gsm: +905054947235 E-Mail: pinarsezer33@hotmail.com ORCID ID: https://orcid.org/0000 0002 3268 4940

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: The aim of this study is to evaluate the patient characteristics, operative indications and postoperative results of total laparoscopic hysterectomy (TLH) cases performed due to benign conditions in our hospital which is a tertiary referral center and to analyze the complications. Material and Method: Our study was conducted retrospectively with 530 patients who had been hospitalized for TLH for benign conditions between 2013 and 2016. Demographic characteris-tics such as age, gravida, parity, body mass index, previous surgical operation, accompanying disease, preoperative and postoperative hemoglobin levels were examined. Operative indications of patients, duration of operation, duration of hospital stay and complications were evaluated. Results: A total of 530 TLH-cases were included in the study. The mean age of these patients was 48,8 years, gravida 4.4, parity 3.3, body mass index 29.7, mean change in hemoglobin 1.5 g / dl, and hematocrite was 4.2 g / dl. The most frequent indication for clinical operation was myoma uteri (n: 231). The average duration of operation was calculated as 151 minutes. The complication rate was 16% (n: 85). The mean hospital stay of patients was 2.16 days. Discussion: Following an increasing trend in less invasive surgeries and laparoscopic operation techniques, hysterectomy is performed laparoscopically in selected patients in our hospital. In TLH series, the operation time is shortened and hospitalization durations of the patients decrease. Complication rates are not different from laparotomy series. Careful selection of patients, adequately trained surgeons and close follow-up are critical to reduce morbidity. Complication rates are relatively low in correlation with increasing experience.

Keywords: Total Laparoscopic Hysterectomy; Complication; Adhesion; Leiomyoma

Full Text

Introduction

Total laparoscopic hysterectomy (TLH) is a well established surgical technique in gynecology which is performed frequently as an alternative to both abdominal hysterectomy (AH) and vaginal hysterectomy (VH). Laparoscopic surgeons have well-known advantages, such as shorter hospital stay, reduced post-operative pain, faster return of normal activities of the patient, fewer wound infections, and less blood loss [1,2].Although there are different specific designs, uterus sizes, and patient selection, it is generally accepted that complication rates are higher in abdominal surgery than in minimally invasive approaches [3]. Considering these obvious benefits, the use of laparoscopy has increased significantly and is the preferred approach when vaginal hysterectomy is not possible [2,4,5]. In our study, we aimed to evaluate the patient characteristics, operation indications and postoperative results of total laparoscopic hysterectomy cases performed with benign conditions within a period of three and a half years in our tertiary referral center and to analyze the complications.

Material and Method

This study was a retrospectively designed descriptive study in which the researchers reviewed the medical records of patients who underwent total laparoscopic hysterectomy with benign conditions in Istanbul Health Sciences University, Kanuni Sultan Süleyman Education and Research Hospital, Obstetrics and Gynecology Department between January 2013 and June 2016. Patient characteristics (age, body mass index, surgical indications, uterus weight), operative characteristics (duration of operation, additional procedures, prophylactic bilateral salpingectomy) and clinical outcomes (blood loss, complications, and length of stay in the hospital) were noted from the medical records of the patients. The duration of the operation was taken as the time from the beginning of the operation to the end of the procedure. The amount of blood loss in the operation was calculated by subtracting the amount of fluid used for irrigation from the aspirated amount in the aspirator. Intraoperative and postoperative complications were recorded. Analysis of the data was done by using the IBM SPSS Statistics 20.0 program. Continuous variables are expressed as mean ± standard deviation or median (minimum-maximum), nominal variables as number of cases and (%).

Results

The mean age of the patients was 48.8 ± 7.2 (31-80) years, gravida 4.4 ± 2.4 (0-15), parity 3.3 ± 2.0 (0-15), body mass index 29.7 (17.9-49.2 years), and totally 530 laparoscopic hysterectomies were performed, mean change in hemoglobin level was 1.5 (5-7) g / dl, and in hematocrit it was 4.2 ± 2.3 (2-22). Sixty-three (11.7%) patients were given erythrocyte suspension transfusion. Forty-six (73%) patients were transfused to increase hemoglobin levels preoperatively, and 17 (26.9%) were transfused due to the postoperative blood loss. A total of 179 (33.9%) patients had accompanying comorbid diseases and 122 (23.1%) patients had prior abdominal operations and associated adhesions at varying degrees (Table 1). The most frequent indications for clinical operation were myoma uteri (n: 231, %43.8), treatment-resistant abnormal uterine bleeding (n: 152, %28.8), and atypical endometrial hyperplasia (n: 73, %13.8) (Table 2). The average duration of operation was calculated as 15142.4(60-300) minutes. The complication rate was 16 % (n: 85). The number of conversions to laparotomy was 9. Postoperative complications were following: 30 patients had vaginal cuff hematoma, 6 patients had abscess on vaginal cuff, 20 patients had subcutaneous emphysema, 4 patients had ureter injury, 12 patients had bladder injury, and 4 patients had vaginal cuff cellulitis (Table 3). The mean hospital stay of the patients who underwent surgery was 2.161.2 (2-6) days. In the pathologic evaluation of hysterectomy specimens, diagnoses were as follows: leiomyoma 276 (52%), adenomyosis 162 (30,5%), endometrial hyperplasia 42 (7.9%), atrophic endometrium 32 (6%) and endometrial polyp 18 (3.3%) (Table 4).

Dıscussion

The second most common gynecologic operation after cesarean section is hysterectomy. Laparoscopic hysterectomy is a minimally invasive procedure with established morbidity and mortality rates that are considerably lower compared to laparotomy and mean duration of post operative hospitalization is shorter. In the United States, in 2009, 56% of hysterectomies performed for benign causes were performed abdominally, 20% laparoscopically, 19% vaginally and 5% by robotic surgery [6].In the study done by Loring, M et al., 8% of hysterectomies were performed by laparoscopy, and this ratio was more than 50 % in 2008 and increased to 72% in 2012 [7].The factors affecting the decision on what technique is the most appropriate for hysterectomy are the indication of the operation, whether there is any other intervention to accompany it, the comorbid diseases of the patient and the experience of the surgeon. The least invasive method should be chosen. The American College of Obstetrics and Gynecology (ACOG) recommends vaginal hysterectomy (VH) as the first choice [8]. Laparoscopy Assisted Vaginal Hysterectomy (LAVH) was more popular among gynecologists in the first years of hysterectomy by laparoscopic surgery, but TLH gained the upper hand in time because it was shown that the risk of bleeding from the uterine artery pedicle was greater with LAVH [9]. TLH has a wide spectrum of indications including dysfunctional uterine bleeding, myoma uteri, gynecologic cancers, uterovaginal prolapse, endometriosis, adenomyosis, pelvic inflammatory disease and obstetric complications [10]. The most common indications in TLH are abnormal uterine bleeding and uterine fibroids [11]. In our study, myoma uteri was the leading reason with a frequency of 43.8 %. The advantages such as less postoperative pain, shorter hospitalization time, and a shorter interval to return to daily activities are the reasons why laparoscopic operations are preferred more frequently by surgeons for gynecological procedures. Application of this procedure to routine practice has taken time because of the high cost for departments, lengthier learning curves for surgeons, longer working hours and higher complication risks during the learning period [12]. In many studies, TLH was associated with shorter hospital stays, less postoperative pain, less blood loss, shorter time interval to return to normal daily activity, fewer wound infections, longer operating times, and more urinary tract injuries compared with abdominal hysterectomy [13,14]. The mean duration of operation in our study was 151 ± 42.4 (60-300) mins. The duration of the operation was found to be longer in the first years. This is considered to be due to the incomplete learning curves of our specialists, and we think that this is the effect during the teaching period because we are a resident training clinic. We observed that operation times decrease as the experiences of the surgeons build up.

Although there are different outcomes in the literature regarding TLH complications, TLH has been shown to have higher complication rates compared to other operation techniques in a number of studies [15]. In a study performed by Johnson et al., [16] involving 3643 patients from multiple centers, although vaginal and laparoscopic hysterectomy techniques were reported to be significantly more advantageous in terms of rapid wound healing and return to daily routine, bladder and ureter injury complications were more common in patients who underwent laparoscopic hysterectomy [17]. In a study by Makinen et al., authors evaluated 10110 patients who underwent hysterectomy according to the operation technique and found that urinary tract complications occurred between 0.2% and 0.5% in abdominal hysterectomies, whereas the frequency of urinary tract complications was 1.1% to 1.3% with the laparoscopic approach. Some studies in the literature report these complications to be as frequent as 3 % [14,18]. In a study by Malik et al. involving 106 patients, they had 11 cases of urinary complications [19]. In our study, ureter damage was seen in 4 patients, bladder injury occurred in 12 patients. Eleven of these 12 patients had previous operations, endometriosis and adhesions developed associated with these factors. In some studies, it has been demonstrated that proper dissection of the ureter during laparoscopy significantly reduced the likelihood of iatrogenic ureter injuries [20]. In our practice, ureteral dissection is not routinely performed during operations, but it is done if the probability of any injury to ureter arise or in the presence of severe adhesions.

Bowel injuries are a more prominent threat when the patients have endometriosis and/or adhesions formed due to prior abdominal surgeries or more rarely during electrocoagulation [21,22]. Shen et al. evaluated 284 patients in their study and detected intestinal complications in 6 patients (2.1%). Bowel complications were not observed in our study group.

In TLH operations, prior abdominal surgery increases the rate of conversion to laparotomy between 2.7% to 3.9%. Prevailing reasons for conversion to laparotomy are intra-abdominal dense adhesions, uncontrolled bleeding, unsuccessful pneumoperitoneum, and intra-abdominal organ injuries [14]. In our series, laparotomy was performed in 9 cases due to dense adhesions. Colling et al. compared abdominal hysterectomy with laparoscopic or robotic minimally invasive surgery. In abdominal hysterectomy cases, duration of post-operative hospital stay and surgical site infections were significantly more frequent [23]. In another study, the duration of hospitalization in the TLH group was significantly shorter than the abdominal hysterectomy group but not shorter than the vaginal hysterectomy group [24]. In our study, mean hospital stay was 2.16 days and this length was in accordance with other reports in the literature.

Preoperative hemoglobin values of patients scheduled for operation due to abnormal uterine bleeding are low and may require postoperative transfusion [25]. In our study, the mean hemoglobin decrease in the post-operative period was 1.5 g / dl in patients scheduled for the hysterectomy. Blood transfusions were performed in 46 (8,6%) patients with low preoperative hemoglobin levels and in 17 (3,2%) patients owing to post-operative blood loss and thus in total 63 (11.8%) patients.

As a result, laparoscopic hysterectomy is a more preferable method than abdominal hysterectomy when vaginal hysterectomy is not a feasible option. In our study, we presented our clinical experience from a retrospective view. In the light of our own experience, we suggest that total laparoscopic hysterectomy is a minimally invasive procedure which is associated with less-complications in experienced hands with shorter durations of hospital stay, faster return to daily routine and better cosmetic results. Although total operation duration is longer in the average compared with other techniques, as the experience of the surgeon builds up, the procedure becomes shorter in duration, safer and more efficient.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Walsh CA, Walsh SR, Tang TY, Slack M. Total abdominal hysterectomy versus total laparoscopic hysterectomy for benign disease: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2009; 144 (1): 3–7.

2. Nieboer TE, Johnson N, Lethaby A, Tavender E, Garry R, Van Voorst S, et al. Surgical approach to hysterectomy for benign gynaecological disease. Cochrane Database Syst Rev. 2009; 3: DOI: 10.1002/14651858. CD003677.pub4.

3. Divya K. Shah, MME, Bradley J. Van Voorhis, Allison F. Vitonis, and Stacey A. Missmer. Association Between Body Mass Index, Uterine Size, and Operative Morbidity inWomen Undergoing Minimally Invasive Hysterectomy. Journal of Minimally Invasive Gynecology. 2016; 23(7): 1113-22. DOI: 10.1016/j.jmig.2016.08.003

4. Chopin N, Malaret JM, Lafay-Pillet MC, Fotso A, Foulot H, Chapron C. Total laparoscopic hysterectomy for benign uterine pathologies: obesity does not increase the risk of complications. Hum Reprod. 2009; 24: 3057–62.

5. Twijnstra AR, Blikkendaal MD, van Zwet EW, Jansen FW. Clinical relevance of conversion rate and its evaluation in laparoscopic hysterectomy. J Minim Invasive Gynecol. 2013; 20: 64–72.

6. Cohen SL, Vitonis AF, Einarsson JI. Updated hysterectomy surveillance: Factors associated with minimally invasive hysterectomy, a cross-sectional analysis. JSLS 2014; 18: DOI: 10.4293/JSLS.2014.00096.

7. Loring M, Morris SN, Isaacson KB. Minimally invasive specialists and rates of laparoscopic hysterectomy. JSLS: Journal of the Society of Laparoendoscopic Surgeons/Society of Laparoendoscopic Surgeons. JSLS. 2015; 19(1): DOI: 10.4293/JSLS.2014.00221.

8. ACOG Committee Opinion No. 444. Choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009; 114:1156-8.

9. Gol M, Kizilyar A, Eminoglu M. Laparoscopic hysterectomy with retroperitoneal uterine artery sealing using Ligasuretrade mark: Gazi hospital experience. Arch Gynecol Obstet. 2007; 276: 311-4.

10. Davies A, Magos AL. Indications and alternatives to hysterectomy. Baillieres Clin Obstet Gynaecol. 1997; 11: 61-75.

11. Terzi H, Kale A, Aydın AY. Kliniğimizde ger.ekleştirilen laparoskopik histerektomi olgularının klinik .zelliklerinin değerlendirilmesi. Kocaeli Tıp Dergisi. 2012; 2: 22-5.

12. Hunter EK. Evidence-based implementation and increase in the rate of laparoscopic hysterectomy. Aust N Z J Obstet Gynaecol. 2015; 55: 112-5.

13. Johnson N, Barlow D, Lethaby A, Tavender E, Curr E, Garry R. Surgical approach to hysterectomy for benign gynaecological disease. Cochrane Database Syst Rev. 2006; 19: DOI: 10.1002/14651858.

14. Garry R, Fountain J, Mason S, Hawe J, Napp V, Abbott J, et al. The evaluate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy. BMJ. 2004; 328: 129.

15. Donnez O, Jadoul P, Squifflet J, Donnez J. A series of 3190 laparoscopic hysterectomies for benign disease from 1990 to 2006: evaluation of complications compared with vaginal and abdominal procedures. BJOG. 2009; 116: 492-500.

16. Johnson N, Barlow D, Lethaby A, Tavender E, Curr L, Garry R. Methods of hysterectomy: systematic review and meta-analysis of randomized controlled trials. BMJ. 2005; 330: 1478.

17. Sendag F, Akman L, Öztekin K. Intraoperative Management And Urinary System Complications During Total Laparoscopic Hysterectomy. Turk J Obstet Gynecol. 2013; 10(1): 26-30.

18. Mäkinen J, Johansson J, Tomás C, Tomas E, Heinonen PK, Laatikainen T, et al. Morbidity of 10 110 hysterectomies by type of approach. Hum Reprod 2001; 16: 1473-8.

19. Malik E, Schmidt M, Scheidel P. Complications after 106 laparoscopic hysterectomies. Zentrabl Gynakol. 1997; 119: 611-5.

20. Ng CC, Chern BS. Total laparoscopic hysterectomy: a 5- year experience. Arch Gynecol Obstet. 2007; 276: 613-8.

21. Levy BS, Soderstrom RM, Dail DH. Bowel injuries during laparoscopy. Gross anatomy and histology. J Reprod Med. 1985; 30:168-72.

22. Phillips JM, Hulka JF, Peterson HB. American Association of Gynecologic Laparoscopists’ 1982 membership survey. J Reprod Med. 1984; 29: 592-4.

23. Colling KP, Glover JK, Statz CA, Geller MA, Beilman GJ. Abdominal Hysterectomy: Reduced Risk of Surgical Site Infection Associated with Robotic and Laparoscopic Technique. Surg infect (Larchmt). 2015; 16(5): 498-503. DOI: 10.1089/sur.2014.203.

24. Garry R, Fountain J, Mason S, Hawe J, Napp V, Abbott J, et al. The evaluate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy. BMJ. 2004; 328: 129.

25. Sordia-Hernandez LH, Rodriquez DS, Vidal-Gutierrez O, Morales-Mertinez A, Sordia-Pineyro MO, Guerrero-Gonzalez G. Factors associated with the need for blood transfusion during hysterectomy. Int J Gynaecol Obstet. 2012; 118(3): 239-41. DOI: 10.1016/J.Ijgo.2012.03.040.

PDF

Download attachments: JCAM_5987.pdf

How to Cite

Kıyak H, Kadiroğulları P, Seckin KD. Evaluation of perioperative results of total laparoscopic hysterectomy cases: a tertiary referral center experience. AnnClinAnalMed2019;10(4):475-8

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Physical therapy protocol for obese adolescent girls with polycystic ovarian syndrome: a within-subject design

Haidy N. Ashem 1, Gehan A. Abdelsamea 2, Doaa A. Osman 3 , Hamada A. Hamada 4, Hamada El-Sayed Ayoub 5, Gaber S. Soliman 6

1 Department of Physical Therapy for Surgery, Faculty of Physical Therapy, Cairo University, Cairo, Egypt, 2 Department of Physical Therapy for Woman’s Health, Faculty of Physical Therapy, Cairo University, Cairo, Egypt,Department of Women’s Health, Faculty of Physical Therapy, Delta University for science and technology, Egypt, 3 Department of Physical Therapy for Woman’s Health, Faculty of Physical Therapy, Cairo University, Cairo, Egypt, 4 Department of Biomechanics, Faculty of Physical Therapy, Cairo University, Cairo, Egypt, 5 Department of Physical Therapy for Pediatrics, Faculty of Physical Therapy, Cairo University, Cairo, Egypt, 6 Department of Physical Therapy for Cardiovascular/Respiratory Disorder and Geriatrics, Faculty of Physical Therapy, Cairo University, Giza, Egypt and Department of Physical Therapy and Health Rehabilitation, College of Applied Medical Sciences in Al Qurayyat, Jouf University, Kingdom of Saudi Arabia

DOI:10.4328/ACAM.6027 Received: 22.09.2018 Accepted: 15.11.2018 Published Online: 18.11.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 496-500

Corresponding Author: Hamada Ahmed, Lecturer of Biomechanics, Faculty of Physical Therapy, Cairo University, Cairo, Egypt. T.: 00201117893697 E-Mail: Hamada.Ahmed@pt.cu.edu.eg ORCID ID: https://orcid.org/0000-0002-6661-3948

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: In this study, we aimed to explore the effect of a suggested physical therapy protocol on the anthropometric parameters and hormonal profile of obese adolescent girls with polycystic ovarian syndrome (PCOS). Material and Method: Twenty obese adolescent girls with PCOS participated in this study. Their ages ranged from 14 to 18 years and their body mass index (BMI) ranged from 30 to 35 kg/m2. They received a specific diet therapy connected with a program of aerobic exercise for 6 months. Anthropometric parameters and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured before starting the study, after 3 months and after 6 months of the suggested physical therapy protocol. Results: There was a statistically highly significant reduction in the anthropometric parameters and LH/FSH ratio in the post 6 months of treatment compared with the pre-treatment and post 3 months of treatment (p<0.01). Also, there was a statistically highly significant reduction in the anthropometric parameters (p<0.01), while there was a statistically signifi-cant reduction in the LH/FSH ratio in the post 3 months of treatment compared with the pre-treatment (p<0.05). Discussion: The suggested physical therapy protocol for obese adolescent girls with PCOS is optimal for improving their anthropometric parameters and hormonal profile.

Keywords: PCOS; Physical Therapy; Diet; Aerobic Exercise; Obesity; Adolescent Girls; Anthropometric Parameters; LH/FSH Ratio

Full Text

Introduction

Polycystic ovarian syndrome is a complex, multifactor, heterogeneous disorder that affects 4% to 18% of reproductive-aged women [1], typically presents during adolescence [2] and is associated with reproductive, metabolic and psychological dysfunctions [1].

Polycystic ovarian syndrome is caused by a hormonal disturbance that has a role in ovulation. Its biochemical profile includes high levels of circulating free testosterone, LH/FSH ratio, estrogen and insulin with reduced levels of sex-hormone binding globulin (SHBG) [3, 4].

Adolescent obesity is prevalent worldwide [5]. There is a major association between PCOS and obesity, in a way that the mean of obesity among women with PCOS is higher than the mean of obese women without PCOS [6]. About 50% of women with PCOS suffer from obesity, especially abdominal obesity [7, 8]. Since the menstrual function is dependent on BMI, obese women with PCOS have greater ovulatory dysfunction and menstrual irregularity when compared to non-obese women [9, 10].

Weight reduction is the first recommendation in PCOS patients since it causes lowering of insulin and androgens, as well as the rise in SHBG [11]. The weight loss is usually able to correct the changed physiology of the body and resume regular ovulatory function. Ideally, a woman should reach a BMI of less than 27 kg/m2, which will induce ovulation and increase pregnancy rates [12].

Accordingly, lifestyle modification should be chosen as the first line of treatment for overweight or obese women with PCOS to promote weight loss and improve reproductive outcomes [13].

Although previous research had examined the effect of lifestyle interventions on the anthropometric parameters and hormonal profile of women with PCOS [1, 13-17], few studies have addressed this question in adolescent girls suffering from PCOS. Therefore, the aim of this study was to investigate the effect of a suggested physical therapy protocol (specific diet therapy connected with a program of aerobic exercise) on the anthropometric parameters and hormonal profile of obese girls with PCOS.

Material and Method

The study was designed as a within-subject design. The institutional review board at the Faculty of Physical Therapy, Cairo University approved this study before its commencement. The study has followed the Guidelines of the Declaration of Helsinki on the conduct of human research. The study was conducted between March 2017 and March 2018. The samples of twenty obese adolescent girls were recruited from a private center, Cairo, Egypt. They were enrolled and assessed for their eligibility to participate in the study. The participants included in the study were chosen among adolescent obese girls suffering from PCOS. They should have two of the 3 features of Rotterdam criteria for the diagnosis of PCOS which include oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism (i.e. hirsutism, acne, male pattern balding, elevated serum androgens), and polycystic ovaries on ultrasound; other etiologies should be excluded [18]. The girls’ age ranged from 14 to 18 years and their BMI ranged from 30 to 35 kg/m2. The participants with a constitutional delay of puberty, hyperprolactinemia, androgen-secreting neoplasia, thyroid dysfunction, Cushing’s syndrome, ovarian tumor, and malignancy were excluded. All adolescent girls did not receive any medical therapy for treating PCOS or for weight reduction.

All adolescent girls with PCOS received a suggested physical therapy protocol (specific diet therapy connected with a program of aerobic exercise) for 6 months.

Specific diet therapy

All adolescent girls were instructed to follow a specific diet therapy for 6 months. They received a low-calorie diet of 1200 Kcal/day for 3 days/week followed by a very low-calorie diet of 800 Kcal/day for the rest 4 days in the week and this diet therapy was repeated for 6 months. The calories were divided into small frequent meals with maintaining a well-balanced diet, including 55% carbohydrates, 30% fat and 15% proteins.

Aerobic exercise program

Each adolescent girl participated in an aerobic exercise program for 3 sessions a week for 6 months. Each exercise session consisted of 3 stages. The warm-up stage started with pedaling on an electronic bicycle ergometer (UNIVERSAL, made in New York, USA) at a speed of 60 revolutions per minute without load for 5 minutes. The active stage consisted of 30 minutes of pedaling at a speed of 60 revolutions/minute with load adjusted to achieve 60% of the predictive age maximal heart rate. The maximal heart rate was calculated by subtracting the age from 220. The program terminated with 5 minutes cool downstage on the electronic bicycle ergometer, during which each girl was instructed to pedal at a speed of 60 revolutions per minute without load [19].

Outcome Measures

Anthropometric parameters:

The weight-height scale was used to measure the weight and height of each adolescent girl before and after the protocol. Then, BMI was calculated by dividing weight by height squared (Kg/m2). In addition, the waist-hip ratio was calculated after measurement of both waist and hip circumferences. The waist circumference was measured when the tape measure was positioned horizontally just above the iliac crest and exactly under umbilicus, while the hip circumference was measured at the maximum circumference of the buttocks by a tape measure.

LH/FSH ratio:

Blood samples were collected from each adolescent girl to measure the levels of the circulating LH and FSH. They were collected, following overnight fasting, at 10.00 a.m. to avoid the hormonal diurnal variation. The levels of LH and FSH were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA). A microplate reader (MRX) made in USA with DYNEX technologies, with serial number ICXD3442 and par code number 052100119 was used to measure hormonal levels.

Statistical analysis

All statistical measures were performed using the Statistical Package for Social science (SPSS) program version 20 for Windows. The current test involved one independent variable the measuring periods; within-subject factor which had three levels (pre and post 6 months of treatment and post 6 months). In addition, this test involved three tested dependent variables (weight, waist/ hip ratio, and LH/FSH ratio). So, repeated measure MANOVA was used to compare the weight, waist/ hip ratio and LH/FSH ratio at different measuring periods. There were no outliers and the data were normally distributed, as assessed by boxplot and Shapiro-Wilk test (p > .05), respectively. The assumption of sphericity was violated, as assessed by Mauchly’s test of sphericity, χ2(2) = 7.244, p = .027 for weight, χ2(2) = 3.049, p = .218 and, χ2(2) = 10.913, p = .004 for LH/FSH ratio. Therefore, a Greenhouse-Geisser correction was applied (epsilon ε = 0.742) for weight and (epsilon ε = 679) for LH/FSH ratio to correct the one-way repeated measures MANOVA. P value ≤ 0.05 was considered significant and < 0.01 was considered highly significant.

Results

As indicated by the repeated measures MANOVA, there was a statistically highly significant difference in weight, waist/ hip ratio, and LH/FSH ratio among the three measuring periods (pre and post 3 months of the treatment, and post 6 months) ( F= 162.137, p < .0001, partial η2 = 0.0001*). A Bonferroni multiple comparison tests (Post-hoc tests) revealed that there was a statistically highly significant reduction in the weight, waist/ hip ratio, and LH/FSH ratio at6 months post-treatment compared with the pre-treatment and at 3 months post-treatment (p<0.01). Also, there was a statistically highly significant reduction in the anthropometric parameters (p<0.01), while there was a statistically significant reduction in the LH/FSH ratio at 3 months post-treatment compared with the pre-treatment (p<0.05) (table 1).

Discussion

Polycystic ovarian syndrome is a complex heterogeneous disorder that commonly manifests during adolescence. Early detection and management of this syndrome are crucial to prevent its long-term negative consequences on the reproductive and metabolic systems [20]. However, little is known about the effect of lifestyle interventions on obese adolescent girls with PCOS. Therefore, this study was conducted to examine the effect of a suggested physical therapy protocol (specific diet therapy connected with a program of aerobic exercise) on the anthropometric parameters and hormonal profile of obese adolescent girls with PCOS.

Regarding the anthropometric parameters, results showed a highly significant reduction in the weight and waist-hip ratio at 6 months post-treatment compared with the pre-treatment and at 3 months post-treatment. Also, there was a highly significant reduction at 3 months post-treatment compared with the pre-treatment. These results were consistent with Abd Elmenim and Emam [21] who reported a highly significant reduction in the anthropometric parameters of girls with PCOS after 1 year of lifestyle changes. They explained the highly significant reduction in the anthropometric parameters by the fact that most of the girls wish to maintain a good body image and to conceive in the future. Therefore, they have been motivated to adhere to the program.

Additionally, the results of this study agreed with a recent systematic review and meta-analysis, which studied the effect of lifestyle interventions (exercise and diet) on clinical measures of women with PCOS. It reported that a combined exercise and dietary program, lasting more than 20 weeks, may result in a significant improvement of body composition parameters (weight, BMI, waist circumference, waist-hip ratio and body fat percentage) [14]. Moreover, a Cochrane review by Moran et al. [1] supported the results of the present study as it concluded that following a healthy diet and a regular exercise decreases body weight and improves body composition in women with PCOS.

Furthermore, many studies had investigated the beneficial effects of the combination of exercise and diet together on promoting weight loss and improving body composition in overweight and obese women with PCOS [13, 17]. These beneficial effects could be attributed to the effect of exercise and dietary control on increasing the energy expenditure more than the energy intake [22]. The addition of exercise to dietary management induces the fat mass reduction while preserving lean mass [23].

On the other hand, Lass et al. [16] showed that after 1 year of lifestyle interventions, 26 obese adolescent girls with PCOS had a successful weight loss while the other 33 girls with PCOS didn’t achieve a successful weight loss.

Regarding the hormonal profile, results showed a highly significant reduction in the LH/FSH ratio at 6 months post-treatment compared with the pre-treatment and at 3 months post-treatment. Also, there was a significant reduction at 3 months post-treatment compared with the pre-treatment. These findings were consistent with Lass et al. [16] who demonstrated a highly significant reduction in the LH/FSH ratio in the obese adolescent girls with PCOS who achieved a successful weight loss in contrast to the girls who didn’t attain a successful weight loss. In addition, Haqq et al. [15] concluded that lifestyle interventions (exercise plus diet) have a favorable effect on improving FSH levels significantly in women with PCOS.

The highly significant reduction in the LH/FSH ratio could be explained by the highly significant reduction in the anthropometric parameters, including both weight and waist-hip ratio. Previous research suggests that lifestyle interventions with modest weight reduction goals of 5-10%, especially in the abdominal area, play an effective role in reversing reproductive system dysfunction and restoring ovulation and fertility in obese women with PCOS [6, 24-26].

In contrast, Vigorito et al. [27] reported no changes in hormonal profile of young women with PCOS after 3 months of combined exercise and nutritional counseling. Additionally, Bruner et al. [28] investigated the effect of exercise and nutritional counseling for 12 weeks on the hormonal profile of women suffering from PCOS. They found a slight improvement in the LH/FSH ratio, while it was statistically non-significant. The improvement in the LH/FSH ratio occurred in the absence of significant weight loss and in the presence of significant reduction of body fatness, suggesting that the improvement of body composition may be effective in lowering the metabolic dysfunction in obese women with PCOS.

The controversy among studies regarding the effect of combined exercise and dietary program on the anthropometric parameters and hormonal profile of patients with PCOS could be attributed to the variations in intensity, duration, frequency and type of exercise; the differences in dietary restriction protocols; the lack of standardization of timing of blood draws; the difference in subject’s mood changes and degrees of motivation for the program.

Although the present study provides objective data with statistically significant differences, it has some limitations. First, the adolescent girls’ mood changes and degrees of motivation for the suggested physical therapy program were not considered. In addition, the lack of untreated control group is te second limitation. However, it is not ethical to prevent adolescent girls with PCOS from having an actual treatment.

Conclusion

The suggested physical therapy protocol for obese adolescent girls with PCOS is an effective modality in decreasing their weight, waist-hip ratio and LH/FSH ratio.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle change in women with polycystic ovary syndrome. Cochrane Database Sys Rev. 2011; 16: doi: 10.1002/14651858.CD007506.pub2.

2. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005; 352: 1223-36.

3. Tena G, Moran C, Romero R, Moran S. Ovarian morphology and endocrine function in polycystic ovary syndrome. Arch Gynecol Obstet. 2011; 284: 1443-8.

4. Toscani MK, Mario FM, Radavelli-Bagatini S, Spritzer PM. Insulin resistance is not strictly associated with energy intake or dietary macronutrient composition in women with polycystic ovary syndrome. Nutr Res. 2011; 31: 97-103.

5. Vilmann LS, Thisted E, Baker JL, Holm JC. Development of obesity and polycystic ovary syndrome in adolescents. Horm Res Paediatr. 2012; 78: 269-78.

6. Faghfooria Z, Fazelianb S, Shadnoushc M, Goodarzid R. Nutritional management in women with polycystic ovary syndrome: A review study. Diabetes Metab Syndr. 2017; 11: S429-32.

7. Lecke SB, Mattei F, Morsch DM, Spritzer PM. Abdominal subcutaneous fat gene expression and circulating levels of leptin and adiponectin in polycystic ovary syndrome. Fertil Steril. 2011; 95: 2044-49.

8. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004; 89: 2745-49.

9. Hoeger K, Oberfield S. Do women with PCOS have unique predisposition to obesity? Fertility and Sterility. 2012; 97: 13-17.

10. Al-Azemi M, Omu FE, Omu AE. The effect of obesity on the outcome of infertility management in women with polycystic ovary syndrome. Arch Gynecol Obstet. 2004; 270: 205-10.

11. Berek J. Berek, Novak’s Gynecology. 15th ed. Philadelphia: Lippincott Williams and Williams; 2011.

12. Hollmann M, Runnebaum B, Gerhard I. Effects of weight loss on hormonal profile in obese infertile women. Hum Reprod. 1996, 11: 1884-89.

13. Nybacka Å, Carlström K, Ståhle A, Nyrén S, Hellström PM, Hirschberg AL. Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome. Fertil Steril. 2011; 96: 1508-13.

14. Haqq L, McFarlane J, Dieberg G, Smart N. The effect of lifestyle intervention on body composition, glycemic control, and cardiorespiratory fitness in polycystic ovarian syndrome: A systematic review and meta-Analysis. Int J Sport Nutr Exerc Metab. 2015; 25: 533-40.

15. Haqq L, McFarlane J, Dieberg G, Smart N. Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: A systematic review and meta-analysis. Endocr Connect. 2014; 3: 36-46.

16. Lass N, Kleber M, Winkel K, Wunsch R, Reinehr T. Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls. J Clin Endocrinol Metab. 2011; 96: 3533-40.

17. Thomson RL, Buckley JD, Noakes M, Clifton PM, Norman RJ, Brinkworth GD. The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008; 93: 3373-80.

18. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81: 19-25.

19. Barlow SE. Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: Summary report. Pediatrics. 2007; (Suppl.4): S164-S192.

20. Lanzo E, Monge M, Trent M. Diagnosis and management of polycystic ovary syndrome in adolescent girls. Pediatr Ann. 2015; 44: e223-30.

21. Abd Elmenim SO, Emam AM. Effect of lifestyle changes on symptoms of polycystic ovarian syndrome in obese girls. IOSR Journal of Nursing and Health Science. 2016; 5: 1-10.

22. Norman RJ, Noakes M, Wu R, Davies MJ, Moran L, Wang JX. Improving reproductive performance in overweight/obese women with effective weight management. Hum Reprod Update. 2004; 10: 267-80.

23. Ross R, Janssen I, Tremblay A. Obesity reduction through lifestyle modification. Can J Appl Physiol. 2000; 25: 1-18.

24. Hoeger KM. Role of lifestyle modification in the management of polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab 2006; 20: 293-310.

25. Hoeger KM, Kochman L, Wixom N, Craig K, Miller RK, Guzick DS. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: A pilot study. Fertil Steril. 2004; 82: 421-9.

26. Zain MM, Norman RJ. Impact of obesity on female fertility and fertility treatment. Womens Health (Lond). 2008; 4: 183-94.

27. Vigorito C, Giallauria F, Palomba S, Cascella T, Manguso F, Lucci R, et al. Beneficial effects of a three-month structured exercise training program on cardiopulmonary functional capacity in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007; 92: 1379-84.

28. Bruner B, Chad K, Chizen D. Effects of exercise and nutritional counseling in women with polycystic ovary syndrome. Appl Physiol Nutr Metab. 2006; 31: 384-91.

PDF

Download attachments: JCAM_6027.pdf

How to Cite

Ashem HN, Abdelsamea GA, Osman DA, Hamada HA, Ayoub HES, Soliman GS. Physical therapy protocol for obese adolescent girls with polycystic ovarian syndrome: a within-subject design. Ann Clin Anal Med 2019;10(4): 496-500

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Use of the TI-RADS scoring system in the evaluation of thyroid nodules

Feyzi Gökosmanoğlu 1, Erkan Aksoy 2, Yasemin Kaya 3

1 Endocrinology Department, Medical Park Hospital Group, 2 General Surgery Department, Medical Park Hospital Group, 3 Department of Internal Medicine, Ordu University Medical School, Ordu, Turkey

DOI:10.4328/ACAM.5981 Received: 24.07.2018 Accepted: 13.09.2018 Published Online: 17.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 466-9

Corresponding Author: Yasemin Kaya, Department of Internal Medicine, Ordu University Medical School, 52000, Ordu, Turkey. T.: +90 4522252342 F.: +90 4522250190 E-Mail: ysmnkcmz@gmail.comORCID ID: https://orcid.org/0000-0002-6432-8668

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: Thyroid ultrasonography-guided fine needle aspiration is known to be a cost-effective, safe diagnostic method for evaluating thyroid nodules but it is an invasive procedure. Various sonographic criteria have been proposed to estimate the risk of malignancy in thyroid nodules. TI-RADS (Thyroid Image Reporting and Data System) is one of these scoring systems. In this study, it was aimed to investigate the reliability and applicability of the TI-RADS system in our oper-ated patients with definite TI-RADS results. Material and Method: A total of 134 patients who underwent surgery for nodular or multinodular goiter diagnosis between September 2005 and June 2018 in the Medical Park Hospital and Fatsa State Hospital endocrinology clinic and general surgery clinic were included in the study. Demographic characteristics, preoperative thyroid ultrasonographic findings and postoperative pathology results were collected retrospectively.Results: In our study, we found the rate of thyroid cancer as 0% in cases with TI-RADS score 2-3, the rate of cancer as 61.5% (12 papillary thyroid cancer and 4 follicular thyroid cancer in total 16 thyroid cancer n: 16) in cases with TI-RADS score 4 and the rate of cancer 88.2% (papillary thyroid cancer n: 24, medullary thyroid cancer n: 2, follicular thyroid cancer n: 2, indeterminate thyroid cancer n: 2) in cases with TI-RADS score 5. Discussion: Many studies have shown that this thyroid ultrasonography function is not only a risk classification, but also an effective treatment for patients. In our study, we clearly demonstrated that the use of the TI-RADS scoring system in thyroid nodules assessed by experienced individuals prevented the need for unnecessary fine needle aspiration. These findings show that TI-RADS classification provides reliable results in well-categorized thyroid nodules.

Keywords: Thyroid; Nodular Goiter; Ultrasound; Thyroid Imaging Reporting; Data System

Full Text

Introduction

Thyroid nodules are very common in the general populationand can be found clinically in 4-7% of the general population. However, it seems that the true prevalence of thyroid nodules is higher (the prevalence is from 8 to 65% in autopsy and from 19 to 35% in ultrasound survey) [1,2]. Although most thyroid nodules are benign hyperplastic lesions, past research has determined that thyroid cancer occurs in 5 to 15% of thyroid nodules [3-5].

Thyroid ultrasonography (US) guided fine needle aspiration (FNA) is known to be a cost-effective, safe diagnostic method for evaluating thyroid nodules [6,7] but it is an invasive procedure [5]. However, nodules made by FNA are found to be 10-42% non-diagnostic and 3-18% unknown follicular lesions [8]. FNA has some limitations such as these. There have been many discussions on the maling characteristics of nodules in the last two decades but no definitive classification has been made yet [9,10].

A typical sonographic pattern of thyroid cancer is absent. During the last 5 years, sonographic studies have been conducted to establish a reliable guide for thyroid nodule [11,12]. Based on the previously established BI-RADS (Breast Imaging Reporting and Data System) for breast nodules, some researchers have developed TI-RADS. In 2009, a TI-RADS (Thyroid Imaging Reporting and Data System) scoring system based on nodule models with ultrasound imaging was published [5,13]. In this study, it was aimed to investigate the reliability and applicability of the TI-RADS system in our operated patients with definite TI-RADS results.

Material and Method

A total of 134 patients who underwent surgery for nodular or multinodular goiter diagnosis between September 2005 and June 2018 in the Medical Park Hospital and Fatsa State Hospital endocrinology clinic and general surgery clinic were included in the study. Demographic characteristics, preoperative thyroid ultrasonographic findings and postoperative pathology results were collected retrospectively.

In the preoperative US of the cases, pathology results were compared according to the nodule with the highest TI-RADS score. The malignancy risk ratio of all TI-RADS categories was analyzed according to the postoperative pathology results.Certain criteria (mild hypoechogenicity, marked hypoechogenicity, microlobulation or irregular margins, microcalcifications, taller than wide, irregular thin halo) were taken into account in the imaging of the thyroid nodule by an experienced endocrinologist. The cases were taken into the study according to these criteria. Thyroid ultrasonography was performed with a high-resolution apparatus (The Philips Affiniti 70 ultrasound; Philips North America Corporation 3000 Minuteman Road M / S 109 Andover, MA 01810, USA) equipped with a 5-12 MHz broad-band linear array probe. All the steps in the work were done by an experienced person. The TI-RADS classification is shown in Table 1 [4].

Statistics

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), Version 23. The numeric variables as mean ± SD, the categorical variables as percentage were expressed. The groups were compared using the chi square-test. Statistically, p <0.05 was accepted.

Results

A total of 134 patients (84 females, 50 males) were included in the study. The mean age of the patients was 45.67 ± 13.4 years. The demographic characteristics of the cases are shown in Table 2. The pathology results of 134 patients included in the study were reported as 65.6 % (n = 88) benign, 32.8 % (n = 44) malignant and 1.49 % (n = 2) malignancy potential in the post-operative period. The distribution of malignancies was 26,86 % (n = 36) papillary thyroid cancer, 4,47% (n = 6) follicular thyroid cancer and 1,49 % (n = 2) medullary thyroid cancer.

The pathology result of patients with TI-RADS score 2 and 3 were 100% bening and with TI-RADS score 4 was % 61,5 maling and with TI-RADS score 5 was % 82,3 maling, %5,8 malingnancy in indeterminate. The distribution of cases according to the TI-RADS classification and the analyses of pathological data are shown in Table 3.

Discussion

The pathology result of patients with TI-RADS score 2 and 3 were 100% bening and with TI-RADS score 4 was % 61,5 maling and with TI-RADS score 5 was % 82,3 maling, %5,8 malignancy in indeterminate in our study.

Recommendation on who should be submitted to FNA is still controversial. Despite the fact that various studies have been carried out in this regard, a consensus has not been established. [5]

In recent years, both the American Thyroid Association and the British Thyroid Association have published risk guidelines that can be identified with thyroid US for thyroid nodules [14]. In both guidelines, the main determinant factor for thyroid biopsy was the sonographic patterns of thyroid nodules in place of size. TI-RADS classification predicts malignancy risks according to US characteristics of nodules. Many studies have shown that this thyroid US function is not only a risk classification but also an effective treatment for patients [15]. The TI-RADS classification aims to correlate USG features to cytological classification according to the number of features present in the USG [5]. In our study, we clearly demonstrated that the use of the TI-RADS scoring system in thyroid nodules assessed by experienced individuals prevented the need for unnecessary FNA.

The TI-RADS scoring system is deficient in the diagnosis of cancer when cytologic examinations of nodules with a TI-RADS score between 1 and 3 are non-diagnostic, atypical or focal uncertainty. These patients are difficult to diagnose because they are not operated. The risk of cancer in TI-RADS 2 is reported to be 0%, and the risk of cancer in TI-RADS 3 is reported to be 2-4%. In other studies, the expected malignancy rate in TI-RADS 3 was 0.7% [16,17]. Horvath et al. found 14.1%, Russ et al. found % 4.3, Macedo et al.found %5.5 in TI-RADS 3 [9,13,18] In our study, malignancy was 0% in post-operative pathology reports in TI-RADS 2-3 cases.

The risk of cancer was reported to be 6-17% in patients with a TI-RADS score of 4 [8]. In one study, they found malignancy rate of 12.6-66.6% in TI-RADS 4 [19]. In our study, 19.4% (n = 26) of the cases were TI-RADS 4. Of these cases, 61.5% (n = 16) had thyroid cancer diagnosis and these patients (n = 12, papillary thyroid cancer, n = 4, thyroid follicular cancer) constitute 11.9% of the whole group. These findings indicate that TI-RADS classification provides reliable results in well-categorized thyroid nodules.

The risk of cancer in the TI-RADS score 5 group was 26-87%. Other studies have shown that this risk is 85.7%- 75.6% [9,20]. In our study, we found a 88.2% (n = 30) cancer rate in our TI-RADS 5 cases. The distribution of thyroid cancer cases in TI-RADS 5 group was 80% (n = 24) papillary, 6.6% (n = 2) medullary, 6.6% (n = 2) follicular and 6.6% (n = 2) malignancy in indeterminate. When the malignancy rate is analyzed according to TI-RADS categories, statistically significant difference between the groups was detected.

This study has some limitations, such as being retrospective, low number of cases, sonographic assessment performed by different operators.

Conclusion

When we examined the nodules with pathologic findings in our study, we found that the TI-RADS scoring system in our patients is sufficient to predict the malignancy rate. To avoid unnecessary FNA; we showed that the TI-RADS scoring system is safe.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Liao LJLo WCHsu WLCheng PWWang CP. Assessment of pain score and specimen adequacy for ultrasound-guided fine-needle aspiration biopsy of thyroid nodules. J Pain Res. 2017; 11: 61-6. 

2. Godazandeh GKashi ZZargarnataj SFazli MEbadi RKerdabadi EH. Evaluation the Relationship Between Thyroid Nodule Size with Malignancy and Accuracy of Fine Needle Aspiration Biopsy (FNAB). Acta Inform Med. 2016; 24(5): 347-50.

3. Alvarado-Santiago MAlvarez-Valentin DRuiz-Bermudez OGonzalez-Sepulveda LAllende-Vigo MSantiago-Rodriguez E, et al. Fine-Needle Thyroid Aspiration Biopsy: Clinical Experience at the Endocrinology Clinics of the University Hospital of Puerto Rico. P R Health Sci J. 2017; 36(1): 5-10.

4. Kwak JY, Han KH, Yoon JH, Moon HJ, Son EJ, Park SH, et al. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology. 2011; 260(3): 892-9.

5. Rahal A JuniorFalsarella PMRocha RDLima JPIani MJVieira FA, et al. Correlation of Thyroid Imaging Reporting and Data System [TI-RADS] and fine needle aspiration: experience in 1,000 nodules. Einstein (Sao Paulo). 2016; 14(2): 119-23.

6. Jeong EJ, Chung SR, Baek JH, Choi YJ, Kim JK, Lee JH. A Comparison of Ultrasound-Guided Fine Needle Aspiration versus Core Needle Biopsy for Thyroid Nodules: Pain, Tolerability, and Complications. Endocrinol Metab. (Seoul). 2018; 33(1): 114-20.

7. Ziemiańska KKopczyński JKowalska A. Repeated nondiagnostic result of thyroid fine-needle aspiration biopsy. Contemp Oncol (Pozn). 2016; 20(6): 491-5. 

8. Lee YH, Baek JH, Jung SL, Kwak JY, Kim JH, Shin JH. Ultrasound-guided fine needle aspiration of thyroid nodules: a consensus statement by the korean society of thyroid radiology. Korean J Radiol. 2015; 16(2): 391-401.

9. Russ G, Royer B, Bigorgne C, Rouxel A, Bienvenu-Perrard M, Leenhardt L. Prospective evaluation of thyroid imaging reporting and data system on 4550 nodules with and without elastography. Eur J Endocrinol. 2013; 168(5): 649-55.

10. Park JY, Lee HJ, Jang HW, Kim HK, Yi JH, Lee W, et al. A proposal for a thyroid imaging reporting and data system for ultrasound features of thyroid carcinoma. Thyroid. 2009; 19(11): 1257-64.

11. Kwak JY. Indications for fine needle aspiration in thyroid nodules. Endocrinol Metab (Seoul). 2013; 28(2): 81-5.

12. Lagalla R, Caruso G, Romano M, Midiri M, Novara V, Zappasodi F. Echo-color

Doppler in thyroid disease. Radiol Med. 1993; 85(5 Suppl 1): 109-13.

13. Horvath E, Majlis S, Rossi R, Franco C, Niedmann JP, Castro A, et al. An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management. J Clin Endocrinol Metab. 2009; 94(5): 1748-51.

14. Perros P, Boelaert K, Colley S,  Evans CEvans RMGerrard Ba G, et al. British Thyroid Association. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf). 2014; 81 (Suppl 1):1-122.

15. Moon HJ, Kim EK, Yoon JH, Kwak JY. Malignancy risk stratification in thyroid nodules with nondiagnostic results at cytologic examination: combination of thyroid imaging reporting and data system and the Bethesda System. Radiology. 2015; 274: 287-95.

16. Wei X, Li Y, Zhang S, Gao M. Meta-analysis of thyroid imaging reporting and data system in the ultrasonographic diagnosis of 10,437 thyroid nodules. Head Neck. 2016; 38(2): 309-15.

17. Moon HJ, Kim EK, Kwak JY. Malignancy risk stratification in thyroid nodules with benign results on cytology: combination of thyroid imaging reporting and data system and Bethesda system. Ann Surg Oncol. 2014; 21(6): 1898-903.

18. Macedo BMIzquierdo RFGolbert LMeyer ELS. Reliability  of  Thyroid  Imaging  Reporting  and Data System (TI-RADS), and  ultrasonographic classification of the  American  Thyroid  Association (ATA) in differentiating benign from malignant thyroid nodules. Arch Endocrinol Metab. 2018; 62 (2): 131-8.

19. Mendes GF, Garcia MR, Falsarella PM, Rahal A, Cavalcante Junior FA, Nery DR, et al. Fine needle aspiration biopsy of thyroid nodule smaller than 1.0 cm: accuracy of TIRADSclassification system in more than 1000 nodules. Br J Radiol. 2018; 91(1083): DOI: 10.1259/bjr.20170642.

20. Al Dawish MAAlwin Robert AThabet MABraham R. Thyroid  Nodule  Management:  Thyroid- Stimulating  Hormone, Ultrasound, and  Cytological Classification  System  for  Predicting  Malignancy. Cancer Inform. 2018; 17: 1-9.

PDF

Download attachments: JCAM_5981.pdf

How to Cite

Gökosmanoğlu F, Aksoy E, Kaya Y. Use of the TI-RADS scoring system in the evaluation of thyroid nodules. Ann Clin Anal Med 2019;10(4): 466-9

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Should there be an upper age limit for breast cancer screening?

Hamza Cinar, Cagri Akalin, Murat Karakahya

Department of General Surgery, Ordu University Medical Faculty, Ordu, Turkey

DOI:10.4328/ACAM.5965 Received: 07.07.2018 Accepted: 27.09.2018 Published Online: 02.10.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 458-61

Corresponding Author: Hamza Cinar, Ordu Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ordu, Türkiye. E-Mail: drhamzacinar@gmail.com ORCID ID: https://orcid.org/ 0000-0003-1748-1392

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: Breast cancer screening age is between 40-69 years in women of our country. The purpose of this study is to examine the effect of breast cancer screen-ing on tumor diameter and surgical technique for women at or above the screening age interval. Material and Method: The data of 133 female patients aged 40 and above who underwent surgery due to the breast cancer between years 2010 and 2018 in Ordu, Turkey, were collected retrospectively. Patients were divided into two groups as Group 1 (n = 102, between ages 40-69) and Group 2 (n = 31, aged 70 and above). Results: In Group 1, the average tumor diameter of 48 patients (47.1%) diagnosed with physical examination (PE) was 2.96 ± 1.2 cm and average tumor diameter of 54 patients (52.9%) diagnosed with mam-mography (MG) was 1.48 ± 0.58 cm (p < 0,001). In Group 1, 36 (66.7%) of 54 patients diagnosed with MG underwent breast conserving surgery (BCS), and 18 (33.3%) underwent modified radical mastectomy (MRM). Meanwhile, 25 (52.1%) of 48 patients diagnosed with PE underwent BCS and 23 (47.9%) underwent MRM (p = 0.13). In Group 2, the average tumor diameter of 24 (77.4%) patients diagnosed with PE was 3.18 ± 1.48 cm and the average tumor diameter of 7 (22.6%) patients diagnosed with MG was 2.74 ± 0.79 cm (p = 0,55). In Group 2, 3 (42.9%) of 7 patients diagnosed with MG underwent BCS, and 4 (57.1%) underwent MRM. Meanwhile, 9 (37.5%) of 24 patients diagnosed with PE underwent BCS, and 15 (62.5%) underwent MRM (p = 0.79). Discussion: Tumor di-ameter was determined to be smaller in breast cancer screening group among women at or above the age interval of the breast cancer screening program. Although, the effect of screening on surgery type was not statistically significant, it has increased breast-conserving surgery. The breast cancer screening program should not be planned according to the chronological age, and instead, life expectancy should be regarded.

Keywords: Breast Cancer; Screening Program; Surgical Technique

Full Text

Introduction

Breast cancer is the most common cancer type in women and it constitutes 23% of ~ 1.7 million cancers newly diagnosed in women every year [1,2]. The purpose of breast cancer screening is to detect tumor at a small size while it has not presented clinical symptoms yet, and thus provide a decrease in deaths associated with breast cancer. Five-year relative survival rates for breast cancers are as follows: 99 percent for localized cancers, 85 percent for regional cancers and 26 percent for metastatic cancers [3]. Breast cancer screening programs are performed until age 70 in many countries. Nevertheless, with the advancement of contemporary life standards, preventive medicine and the increases in treatment opportunities, lifespan has significantly increased. The incidence of breast cancer increases with age. More than 30% of breast cancer patients are older than 70 [4]. The purpose of our study was to compare tumor diameter between patients between ages 40-69 who were included in a breast cancer screening program, and patients aged above 70 years old, and to examine the relation between surgical techniques and mammography (MG) screening.

Material and Method

Patients aged 40 and above, who underwent surgery due to the breast cancer between years 2010 and 2018 in public hospitals connected to local health authority of Ordu, and whose data were available in the retrospective review, were included in the study. Patients were separated into two groups according to their age; Group 1 consisted of women aged between 40-69 years that is breast cancer screening age interval (and Group 2 consisted of women aged 70 and above. In our study, whether patients had undergone breast cancer screening, and data on tumor diameter and surgery techniques were reviewed retrospectively for screened and not screened patients. Ethical approval of the work has been approved by the Institutional Review Board of Ordu University.

Statistics

Descriptive statistics for continuous variables are presented as average, standard deviation, minimum and maximum values; and they are presented in numbers and percentage for categorical variables. Kolmogorov-Smirnov normality test has been performed in order to compare tumor diameters in numeric variables, and the Mann-Whitney U test was performed to compare the tumor diameter of groups. Chi-square test and Fisher’s test have been performed to determine the relationship between categorical variables (groups). In calculations, statistically significant level was assumed as 5% (p = 0,05), and SPSS (IBM SPSS for Windows, Ver.24) statistical package program has been used for calculations.

Results

All 133 patients who were included in the study were female, and the average age was 60.47 ± 12.77 (41-94) years. Group 1 included 76.7% (n=102) of patients, and 23.3% (n=31) of patients were assigned to Group 2.

Seventy-two (54.1%) patients were diagnosed based on their physical examination (PE) and 61 (45.9%) patients were diagnosed with MG. Forty-seven point one percent of Group 1 patients (n=48) were diagnosed with PE and 52.9% (n=54) were diagnosed with MG. Seventy-seven point four percent (n=24) of Group 2 patients were diagnosed with PE and 22.6% (n=7) were diagnosed with MG. There was a statistically significant difference between the two groups with regards to diagnosis method (p = 0003).

Average tumor diameters of patients operated for breast cancer were 2.35 ± 1.28 (min. 0.2 – max. 9) cm. Average tumor diameter was 2.17 ± 1.19 cm (min. 0.2- max. 6.5) in Group 1, and it was 2.92 ± 1.41 (min. 1.3 – max. 9) cm in Group 2. There was a statistically significant difference between groups with regards to tumor diameter (p = 0.001).

While the average tumor diameter of 48 patients diagnosed with PE in Group 1 was 2.96 ± 1.2 cm, average tumor diameter of 54 patients diagnosed with MG was 1.48 ± 0.58 cm. There was a statistically significant difference between diagnosis method and tumor diameter (p < 0,001).

While the average tumor diameter of 24 patients diagnosed with PE in Group 2 was 3.18 ± 1.48 cm, average tumor diameter of 7 patients diagnosed with MG was 2.74 ± 0.79 cm. Although not statistically significant, a quantitative difference was observed between the diagnosis method and tumor diameter (p=0,55).

Upon evaluating tumor diameter according to diagnosis method for all patients included in the study, average tumor diameter of 72 patients diagnosed with PE was 3.04 ± 1.3 (min. 1 – max. 9) cm, and average tumor diameter of 61 patients diagnosed with MG was 1.62 ± 0.73 (min. 0.2 – max. 3.7) cm. There was a statistically significant difference between diagnosis method and tumor diameter (p < 0,001).

With regards to the surgery type and diagnosis method in Group 1 patients, 66.7% of 54 patients diagnosed with MG underwent breast-conserving surgery (BCS) (n=36), and 33.3% underwent modified radical mastectomy (MRM) (n=18). Meanwhile, 52.1% of 48 patients diagnosed with PE underwent BCS (n=25), and 47.9% underwent MRM (n=23). Although diagnosis method affected the surgery type, there was no statistically significant difference (p=0.13).

Upon examining the surgery type and diagnosis method in Group 2 patients, 42.9% of 7 patients diagnosed with MG underwent BCS (n=3), and 57.1% underwent MRM (n=4). Meanwhile, 37.5% of 24 patients diagnosed with PE underwent BCS (n=9), and 62.5% underwent MRM (n=15). There was no statistically significant difference between those (p=0.79).

When all patients included in the study were examined for a difference between diagnosis method and surgery type, it was determined that 63.9% (n=39) of 61 patients diagnosed with MG underwent BCS and 36.1% (n=22) underwent MRM. Meanwhile, 47.2% of 72 patients diagnosed with PE underwent BCS (n=34), and 52.8% underwent MRM (n=38). There was no statistically significant difference between diagnosis method and surgery types (p=0.054). The data of the study are summarized in Table 1.

Discussion

Delays in diagnosis and treatment of breast cancer increase the morbidity and mortality in patients. Screening programs have great importance since breast cancer in the most common form of cancer observed in women and there is an increase in its prevalence. The most common method of early detection is MG, low dose X-ray imaging of the breasts used to identify abnormalities. Screening of breast cancer with MG was first performed starting from the 1960s in New York with the Health Insurance Plan [5]. Particularly after the 1980s, upon understanding the benefit of MG, MG screening became prevalent all around the world starting with the Western countries. The use of this method has shown a 25%-30% decrease in death due to the breast cancer as a result of 25-year follow-up [6]. The relationship between the combination of early stage and effective treatment and the good prognosis is obvious. According to the American Cancer Society’s 2014 data, 61% of breast cancer diagnoses can be determined at an early stage. Five-year survival expectancy of patients who were diagnosed at the early stage is 99%.

In 2014, the standards to follow in population-based breast cancer screening program studies have been re-established by Turkey Ministry of Health Public Health Institute and they were issued under the title ‘National Standards of Breast Cancer Screening Program’. Accordingly, in Turkey, it was adopted to perform screening MG once every two years in all women aged between 40-69 years old. In the breast cancer screening guidelines prepared by Turkish Society of Radiology, starting age for mammographic screening was adopted as 40 and yearly checks were recommended.

Nowadays, the number of patients aged over 70 years is increasing. The health status of a significant part of women aged 70 is good and their life expectancy may be longer than 10 years. According to 2016 data of Turkish Statistical Institute, overall lifespan in Turkey is 78 years; 75.3 years for men and 80.7 years for women. While life expectancy is 15.3 years for women aged 70, it is 8.7 years for women aged 80. According to 2010 data from the USA, approximately 50% of women aged 80 and 25% of women aged 85 will live for at least another 10 years [7,8]. The most important risk factor of breast cancer is advancing age [9]. According to 2013 data of American Cancer Society (ACS), breast cancer is predominantly a disease of older women with 43 % of incident cases, and 57.0 % of deaths due to breast cancer occurring in women aged 65 years and older. Breast cancer develops in the following 10 years in 3.8% of patients aged 70 and above [10]. In our study, a significant rate of (23.3%) breast cancer cases consisted of women aged 70 and above. So, can’t these women be included in the screening program for an earlier diagnosis?

When women aged 70 and above were included in the screening MG which were applied once every 2 years for 10 years, it was found that mortality due to the breast cancer decreased by 0.2% compared to patients who have attended those until age of 69 [8]. MG was confirmed to have high value for cancer detection rate and positive biopsy estimation rate in women aged 70 and above, and screening efficiency have been approved for elderly patients [11]. The American Cancer Society recommends that women continue participation in MG screening, regardless of age, as long as they have no serious chronic conditions or shortened life expectancy. MG screening should be performed in patients with life expectancy longer than 5 years without setting an upper age limit [12]. In our study, tumors were detected at an earlier stage (with smaller diameter) in women aged 70 and above who underwent breast cancer screening, as in young women.

The basic approach in the surgical treatment of breast cancer is choosing the method that is least likely to affect the quality of life of patients, after obtaining acceptable oncological results. Mastectomy is a more traumatic procedure than BCS for every woman with breast cancer. According to the clinical trials, there is no difference between total and disease-free survival between BCS and MRM [13]. Quality of life-determining problems such as anxiety, depression, psychosexual problems, being bothered by physical appearance and limitation in physical functions, which are experienced due to cancer, are observed less in patients who underwent BCS compared to patients who underwent MRM [14]. The tumor size of breast cancers detected with screening is smaller and they are more likely to be treated with BCS instead of MRM [11]. Independent from the age of breast cancer patients, tumor size of cases diagnosed with MG is smaller in our cases. Although many factors such as the life expectancy of the patient, experience of the surgeon, technical possibilities, the willingness of the patient, size of the breast and location of the tumor affect the surgery type, BCS rate is higher in quantity in screened patients, albeit not statistically different in our study.

Conclusion

Breast cancer is the most common malignancy observed in women and its prevalence increases with age. Since life-span of populations gets longer, the elderly population is ever-increasing. In parallel, the number of elderly women with breast cancer is also increasing. Independent from their age, tumors in women included in the screening program is determined at a smaller diameter. Consequently, life-span of people is getting longer, it would be more appropriate to plan a screening program according to the life expectancy instead of chronological age.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65: 87–108.

2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012; 62: 10–29.

3. Siegel RL, Miller KD, Jemal A. “Cancer statistics, 2016.” CA: a cancer journal for clinicians. 2016; 66(1): 7–30.

4. Kimmick GG, Balducci L. Breast cancer and aging. Clinical interactions. Hematol Oncol Clin North Am. 2000; 14: 213–34.

5. Shapiro S, Venet W, Strax P, Venet L. Periodic screening for breast cancer. The Health Insurance Plan Project and its sequelae, 1963-1986. Baltimore: Johns Hopkins University Press. 1988; 59–83.

6. Gotzsche PC, Nielsen M. Screening of breast cancer with mammography. Cochrane Database of Systemic Reviews. 2006; DOI:10.1002/14651858.

7. Walter LC, Covinsky KE. Cancer Screening in Elderly PatientsA Framework for Individualized Decision Making. JAMA. 2001; 285(21): 2750–6.

8. Walter LC, Schonberg MA. Screening Mammography in Older WomenA Review. JAMA. 2014; 311(13): 1336–47.

9. Crawford J, Cohen HJ. Relationship of cancer and aging. Clin Geriatr Med. 1987; 3(3): 419-32.

10. DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2014; 64: 52-62.

11. Monticciolo DL, Newell MS, Hendrick RE, Helvie MA, Moy L, Monsees B, et al. Breast Cancer Screening for Average-Risk Woman: Recommendations From the ACR Commission on Breast Imaging. J Am Coll Radiol. 2017; 14(9): 1137-43.

12. Smith RA, Brooks D, Cokkinides V, Saslow D, Brawley OW. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin. 2013; 63(2): 88–105.

13. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002; 347: 1233-41.

14. Zanapalıoğlu Y, Atahan K, Gür S, Çökmez S, Tarcan E. Effect of breast conserving surgery in quality of life in breast cancer patients. J Breast Health. 2009; 5: 152-6.

PDF

Download attachments: JCAM_5965.pdf

How to Cite

Cinar H, Akalin C, Karakahya M. Should there be an upper age limit for breast cancer screening? Ann Clin Anal Med 2019;10(4): 458-61

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Polyneuropathy disease forecast in the type 2 diabetes mellitus patients using data mining based approach

Nur Kuban Torun 1, Umman Tuğba Şimşek Gürsoy 2, Saadet Kader 3, M. Burak Oztop 4

1 Faculty of Economics and Administrative Sciences, Department of Business Administration/Quantitive Methods, Bilecik Seyh Edebali University, Bilecik, 2 Faculty of Business Administration, Department of Quantitative Methods, Istanbul University, İstanbul, 3 Department of Medical Biochemistry, Bilecik Public Health Laboratory, Bilecik, 4 Department of General Surgery Bilecik Public Hospital, Bilecik, Turkey

DOI:10.4328/ACAM.6000 Received: 08.08.2018 Accepted: 07.09.2018 Published Online: 17.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 485-90

Corresponding Author: Nur Kuban Torun, Faculty of Economics and Administrative Sciences, Department of Business Administration/Quantitive Methods, Bilecik Seyh Edebali University, Bilecik, Turkey. GSM: 905534811839 E-Mail: akdemir.kuban@gmail.com ORCID ID: https://orcid.org/ 0000-0002-9115-5838

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: The aim of this research was to predict the availability of polyneuropathy disease of the type 2 diabetes mellitus patient through data mining algorithms. Material and Method: The dataset was obtained from the Bilecik Public Hospital and the instance number is 2907. Models were created with two different classification data mining algorithms. The data set includes Gender, Glycated Haemoglobin (HbA1c), Creatinine, Total Cholesterol, Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL). Numerical data were transformed into interval forms and the percentiles were calculated for each interval. Results: Data analysis and performance evaluation were performed with R, RStudio. Random Forest Tree was found as the best algorithm for polyneuropathy disease prediction (the accuracy = 0,922547332185886). The accuracy of the C4.5 was found 0,920826161790017. The percentages of the normal levels HbA1c are 6%, the impaired fasting glucose levels are 22% and the diabetes mellitus type 2 levels are %72. The percentage of the low Creatinine is 2%, the normal Creatinine is %86 and the high Creatinine is 12%. The percentage of the desirable levels Total Cholesterol is 46%, the percentage of the borderline levels of Total Cholesterol is 31% and the the percentage of high levels of Total Cholesterol is 23%. The percentage of the optimal levels LDL is 30%, the percentage of the near optimal levels of LDL is 31%, the percentage of the borderline high levels of LDL is 23%, the percentage of the high levels of LDL is 12% and the percentage of the very high levels of LDL is 4%. The percentage of the bad levels of HDL is 43%, the percentage of the better levels of HDL is 42% and the percentage of the best levels HDL is 19%. This model indicated that Creatinine, LDL and HbA1c are the primary three determinative factors on polyneuropa-thy disease. Furthermore, the model created the following 5 rules. Rule 1: If Creatinine ≤0,6 mg/dL and HbA1c ≤5,7 mmol/L then polyneuropathy disease is available for male, if Creatinine ≤0,5 mg/dL and HbA1c ≤5,7 mmol/L then polyneuropathy disease is available for female. Rule 2: If Creatinine ≤0,5 mg/dL and HbA1c >5,7 mmol/L and 160 ≤ LDL ≤189 mg/dL and LDL ≤189 mg/dL then polyneuropathy disease is unavailable. Rule 3: If Creatinine ≤0,5 mg/dL and HbA1c >5,7 mmol/L and 160 ≤ LDL ≤ 189 mg/dL and LDL >189 mg/dL, then polyneuropathy disease is unavailable. Rule 4: If Creatinine ≤0,5 mg/dL and HbA1c >5,7 mmol/L and 160 ≤ LDL ≤ 189 mg/dL, then polyneuropathy disease is unavailable. Rule 5: If Creatinine >0,5 mg/dL then polyneuropathy disease is unavailable.Discussion: The results show that HDL, Gender and Total Cholesterol have no significant effect on the polyneuropathy disease in this model. To determine the availability of polyneuropathy disease through the given data mining algorithms, researchers may consider the Creatinine, LDL and HbA1c scores.

Keywords: Data Mining; C4.5; Random Forest Tree; Polyneuropathy Disease; Diabetes Mellitus

Full Text
Introduction

Nowadays, due to the increasingly growing IT technologies, every single data of a patient is recording and storing in databases. These bulk datum comprise utility knowledge for both profit and non-profit organizations. However, it’s a big issue that transforming datum into the reliable and significant knowledge to meet the practitioners’ expectation. Therefore, there is a concept named data mining [1]. The main manner of data mining is mining the datum to create the intelligible and utility knowledge by analyzing the hidden patterns and relationships between given attributes [2]. Through the growing usage of Internet technologies in almost all fields, data mining has increased attention and utilization in both profit and non-profit companies. In this manner, there has been a new era in healthcare and medical via data mining modeling [3]. The research about data mining shows that it will help healthcare and medicine field to redound the success in diagnosis, patient services, prevent of the prevalence of chronic diseases, the efficiency of the health budget, cut of corruptions and etc. [4]. Data mining in healthcare and medicine is called health information that is a mixture of bio-information, clinical information, public health information, and neuro-information. These fields contribute to health information to gain datum and health information analyzes these datum to create significant information and store to use in the future [5].

Healthcare data mining is based on the datum of clinical records and used to determine the risk factors and prevalence [6]. Accordingly, data mining needs both qualitative and quantitative datum to use in data mining algorithms. These algorithms are clustering and making classification to the given datum to predict or estimate a situation. The classification in data mining is being used for prevention of mortality risk related to the diseases of cancer, diabetes mellitus and cardiovascular [7]. On the other hand, patients’ printed documents and e-records are vitally important to gain information about the correlations between disease and its reasons. For this purpose, text mining and clustering algorithms are being used to put forward these relationships [8]. Herewith, the algorithms of data mining being used in healthcare can be divided into 2 subgroups which are classification algorithms and clustering algorithms. Classification algorithms include decision tree, k-nearest neighbor, neural networks, support machine, Naive Bayes and logistic regression. The most used clustering algorithm is K-means clusters. These algorithms are applied in specific software to obtain knowledge [9].

Post-modern era evokes the over-consumption of people. Consequently, the chronic disease such as diabetes mellitus is also increasing, and it is a major problem that will be ended by mortality all over the world [10]. There are too many people have diabetes mellitus all over the world [11]. Thence, it is important to estimate the prevalence of diabetes mellitus via data mining. In order to obtain the data on diabetes mellitus, data warehouse including e-records, clinical data, inspection values, personal information, heritability and interviews with patients is substantial [12].

Material and Method

There are 7 variables related to diabetes mellitus to predict the diabetic polyneuropathy. The variables are Diabetic Polyneuropathy, Gender, Glycated Haemoglobin (HbA1c), Creatinine, Total Cholesterol, High-Density Lipoprotein (HDL), and Low-Density Lipoprotein (LDL). Datum was obtained from local health institution and includes 2907 type 2 diabetes mellitus patients. The variables are following:

a- Diabetic Polyneuropathy:

Diabetic neuropathies are a heterogeneous group of pathological manifestations with the potential to affect every organ, with clinical implications such as organ dysfunction, which leads to low-quality life and increased morbidity. DPN is defined as peripheral nerve dysfunction with positive and negative symptoms. Risk factors include age, male gender, duration of diabetes, uncontrolled glycemia, height, overweight and obesity, and insulin treatment [13].

b- Gender:

There is increasing evidence that sex and gender differences are important in epidemiology, pathophysiology, treatment, and outcomes in many diseases, but they appear to be particularly relevant for noncommunicable diseases. Sex differences describe biology-linked differences between women and men, which are caused by differences in sex chromosomes, sex-specific gene expression of autosomes, sex hormones, and their effects on organ systems. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome [10].

c- Glycated Haemoglobin (HbA1c):

HbA1c is a blood test that measures the average blood glucose level over the previous 3–4 months [14].

d- Creatinine:

Creatinine is a waste product of muscle metabolism that is normally removed by the kidneys. The presence of excess creatinine is an indication of increased muscle breakdown or a disruption of kidney function [14].

e- Total Cholesterol:

Total cholesterol is measured in terms of milligrams (mg) per deciliter (dL) of blood. A milligram is equal to one-thousandth of a gram. A deciliter is equal to one-tenth of a liter. Desirable levels are below 200 mg/dL. Borderline high levels are 200–239 mg/dL.

High levels are 240 mg/dL and above [14].

f- Low-Density Lipoprotein (LDL):

LDL is referred to as bad cholesterol because excess quantities of LDL contribute to plaque buildup in the arteries. Optimal levels are below 100 mg/dL. Near optimal is between 100 and 129 mg/dL. Borderline high level is between 130 and 159 mg/dL. High level is between 160 and 189 mg/dL. Very high level is 190 mg/dL and above [14].

g- High-Density Lipoprotein (HDL):

HDL is referred to as a good cholesterol because it carries unneeded cholesterol back to the liver for processing and does not contribute to plaque buildup. Bad levels are below 40 mg/dL. Better levels are between 40 and 59 mg/dL. Best levels are 60 mg/dL and above [14].

Statistical Analysis

All variables were subjected to the data mining algorithms that are C4.5 decision tree and random forest algorithm to estimate the diabetic polyneuropathy. Accordingly, the software of R programming was also used to apply these algorithms and findings were noted.

a-C4.5. Decision Tree

A decision tree is a classifier expressed as recursive partition of the instance space. The decision tree consists of nodes that branch within a rooted tree. It starts with a root at the top that has no incoming edges. A node with outgoing edges is called an internal node, and all the other nodes are called leaves, also known as decision nodes. Each leaf is assigned to one class representing the majority target value at that node [15].

b- Random Forest Tree

The RF algorithm, which is widely used for classification in bioinformatics, builds nTree (a parameter) Random Trees (RT) during its training phase. This involves randomizing the training set in two ways for each RT: First, the training set is re-sampled with replacement, maintaining the original size of the dataset. As a second source of randomness for building an RT, the search for the best feature to split the set of instances at each RT node considers a randomly chosen feature subset of size mtry (a parameter), typically much smaller than the original feature set’s size. The instances at the current node are then split into two subsets according to a condition based on the values of the selected feature, creating two child nodes. This split aims to increase the similarity of classes within each instance subset and to decrease class similarity across the subsets. Next, the algorithm recurses in each instance subset until a stopping criterion is met  [16].

Results

Due to the processing of data mining, the following steps are applying [17]:

Pre-processing:

In the given dataset, there were numbers of noisy datum that affect the modelling process. These noisy data are occurred by incorrect non-numerical columns. Accordingly, handle with these missing values, the clearance step was applied and some of the data were removed from the dataset.

Transformation of the Datum:

Due to the nature of using algorithms of datamining, dataset numbers were transformed into percentage values shown in Table 1, Table 2, Table 3, Table 4 and Table 5. The HbA1c dataset is divided into 3 sub-groups. The first one is the normal group, the second one is the impaired fasting glucose and the third group is the diabetes mellitus type 2. The accepted values for the normal group is below 5,7 mmol/L, the impaired fasting glucose is 5,7-6,4 mmol/L, and the diabetes mellitus type 2 is 6,4 mmol/L and above. Accordingly, normal sub-group includes 166 patients was transformed into 6%, impaired fasting glucose sub-group includes 641 patients was transformed into 22%, and diabetes mellitus type 2 sub-group includes 2100 patients was transformed into 72%.

The Creatinine dataset was divided into 3 sub-groups. The first one is the low Creatinine, the second one is the normal Creatinine and the third one is the high Creatinine. The accepted values for the low Creatinine is below 0,6 mg/dL for male and below 0,5 mg/dL for female, the normal Creatinine is 0,6-1,2 mg/dL for male and 0,5-1,1 mg/dL for female and the high Creatinine is 1,2 mg/dL and above for male and 1,1 mg/dL and above for female. The percentage of the low Creatinine is 2%, the normal Creatinine is 86%, and the high Creatinine is 12%.

The Total Cholesterol dataset was divided into 3 sub-groups. The first one is the desirable levels, the second one is the borderline levels and the third one is the high levels. The accepted values for the desirable levels are below 200 mg/dL, the borderline levels are 200-240 mg/dL and the high levels are 240 mg/dL and above. The percentages of the desirable levels are 46%, of the borderline levels are 31%, and of the high levels are 23%.

The HDL data set was divided into 3 sub-groups. The first one is the bad levels, the second one is better levels and the third one is the best levels. The accepted values for the bad levels are below 40 mg/dL for male and below 50 mg/dL for female, the better levels are 40-60 mg/dL for male and 50-60 mg/dL for female and the best levels are 60 mg/dL and above for male and 60 mg/dL and above for female. The percentages of the bad levels are 43%, the better levels are 42% and the best levels are 19%.

The LDL dataset was divided into 5 sub-groups. The first one is the optimal levels, the second one is the near optimal levels, the third one is the borderline high levels, the fourth one is the high levels and the fifth one is the very high levels. The accepted values for the optimal levels are below 100 mg/dL, the near optimal levels are 100-129 mg/dL, the borderline high levels are 130-159 mg/dL, the high levels are 160-189 mg/dL, and the very high levels are 189 mg/dL and above. The percentages of the optimal levels are 30%, the near optimal levels are 31%, the borderline high levels are 23%, the high levels are 12%, and the very high levels are 4%.

Processing

Data were analyzed with R programming based on the classification algorithms and shown in Table 6. In the R programming, the random start point was obtained by “set.seed()” function code. Afterward, the dataset was divided into the training set and the test set. The training set is a learning process to ascertain the algorithms and the test set is for testing the accuracy of this algorithm. In addition to accuracy, for evaluating the performance of the algorithms, the correspondence matrix was used.

Data Mining Process for C4.5.

The results of data mining with C4.5 algorithm are shown in Figure 1 and the accuracy rate is shown in Table 7. Due to the results, the accuracy value is 92%. Accordingly, the codes are:

• J48 pruned tree

• Creatinine <= 2

• HbA1c <= 6: available (2.0)

• HbA1c> 6

• LDL <= 12

• LDL <= 4: unavailable (3.0)

• LDL > 4: available (6.0/1.0)

• LDL > 12: unavailable (24.0/1.0)

• Creatinine > 2: unavailable (2291.0/170.0)

• Number of Leaves : 5

• Size of the tree : 9

According to the codes, the rules of C4.5 algorithm data mining are following:

Rule 1: If Creatinine <=2 and if HbA1c <= 6 then diabetic polyneuropathy: available.

Rule 2: If Creatinine <=2 and if HbA1c > 6 and if LDL<=12 and if LDL<=4 then diabetic polyneuropathy: unavailable.

Rule 3: If Creatinine <=2 and if HbA1c>6 and if LDL<=12 and if LDL>4 then diabetic polyneuropathy is available.

Rule 4: If Creatinine <=2 and if HbA1c>6 and if LDL>12 then diabetic polyneuropathy: unavailable.

Rule 5: If Creatinine >2, then diabetic polyneuropathy: unavailable.

Data Mining Process for Random Forest Tree

In the Random Forrest Tree algorithm, 500 trees were found. The number of variables tired at each split is 2. The correspondence matrix and the accuracy are shown in Table 8. The accuracy value is %92.

Discussion

According to the results, there are 5 rules for the availability of polyneuropathy disease. Due to the rule 1, if Creatinine ≤ 2 and if HbA1c ≤ 6 then polyneuropathy disease is available. In this condition, we should look at the Creatinine table. In this expression, 2 is a percentage and in the real data set, it refers to the 0,6 mg/dL for male and 0,5 mg/dL for female. Likewise, the score of HbA1c refers to 5,7 mmol/L. Hereby, the rule 1 is:

If Creatinine ≤ 0,6 mg/dL and HbA1c≤5,7 mmol/L then polyneuropathy disease is available for male.

If Creatinine ≤ 0,5 mg/dL and HbA1c≤5,7 mmol/L then polyneuropathy disease is available for female.

Considering the rule 2, if we peruse the related tables, we acquire the following formula:

If Creatinine ≤ 0,5 mg/dL and HbA1c >5,7 mmol/L and 160 ≤ LDL ≤ 189 mg/dL and LDL ≤ 189 mg/dL then polyneuropathy disease is unavailable.

Considering the rule 3, the formula is:

If Creatinine ≤ 0,5 mg/dL and HbA1c > 5,7 mmol/L and 160 ≤ LDL ≤ 189 mg/dL and LDL>189 mg/dL, then polyneuropathy disease is unavailable.

Considering the rule 4, the formula is:

If Creatinine ≤ 0,5 mg/dL and HbA1c >5,7 mmol/L and 160 ≤ LDL ≤ 189 mg/dL, then polyneuropathy disease is unavailable.

Considering the rule 5, the formula is:

If Creatinine >0,5 mg/dL then polyneuropathy disease is unavailable.

The conclusion of these rules is Creatinine, LDL and HbA1c are the primary three determinative factors on polyneuropathy disease. However, through the given dataset, Gender, HDL and Total Cholesterol have no significant relationships with the prediction of polyneuropathy disease.

On the other hand, one of the foremost results of this research is the accuracy of C4.5 classification algorithm. Previous significant studies on diabetes mellitus put forth the accuracy value of their C4.5 classification algorithm. Lakshmi and Kumar (18) used C4.5 classification algorithm to predict the diabetes mellitus. In this research, the accuracy value of the C4.5 was found at 72%. Another research is Radha and Srinivasan’s study (19) used C4.5 algorithm to clinical data set to predict the diabetes mellitus. In this research, the accuracy value of C4.5 algorithm was found at 86%. Furthermore, Devi and Shyla (20) consulted to C4.5 algorithm in their research to predict the diabetes mellitus. In this study, C4.5 algorithm’s accuracy was found at 86%. In our study, the accuracy value was found 0,920826161790017. Comparing with these studies, C4.5 algorithm is running with a high accuracy value of 92%. The score elucidates that the model can estimate 2154 instances correctly in 2326 classified instances. Moreover, the random forest creates 500 trees and it has almost the same accuracy value with C4.5. The accuracy for the Random Forest Tree is 0,922547332185886 and it shows that the model is in high accuracy in the value of 92%.

Consequently, to determine the availability of polyneuropathy disease through the given data mining algorithms, researchers may consider the Creatinine, LDL and HbA1c scores. However, the data set variables are the main limitation of this study. The model estimates the polyneuropathy disease with 6 variables. In the future, the model would be tested with varied variables and the results would be compared with the current outcomes. Another limitation is the generalization problem. The results are only valid for the discussed instance, and outcomes could be changeable with other population.

This research consists of a part of the doctoral thesis research have being written by Nur Kuban Torun and conducted under the consultancy of Prof. Dr. U. Tugba Simsek Gursoy in the Department of Quantitive Methods, Istanbul University.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Jiawei H, Kamber M. Data mining: concepts and techniques. CA: Morgan Kaufmann; 2006. p.5.

2. Hand D, Mannila H, Smyth P. Principles of data mining. USA: The MIT Press; 2001. p.6.

3. Earley S. The promise of healthcare analytics. IT Professional. 2015; 17(2): 7–9.

4. Koyuncugil A.S, Özgülbaş N. Veri madenciliği: tıp ve sağlık hizmetlerinde kullanımı ve uygulamaları. Bilişim Teknolojileri Dergisi. 2009; 2(2): 21-32.

5. Herland M, Khoshgoftaar T. M, Wald R. A review of data mining using big data in health informatics. Journal of Big Data. 2014; 1(1): 1-35.

6. Ressing M, Blettner M, Klug S. Data analysis of epidemiological studies. Dtsch Arztebl Int. 2010: 107(11); 187–92.

7. Sharma R, Singh S. N, Khatri S. Medical data mining using different classification and clustering techniques: a critical survey. Computational Intelligence & Communication Technology (CICT). 2016: 687–91.

8. Raja U, Mitchell T, Day T, Hardin J. M. Text mining in healthcare: applications and opportunities. Journal of Healthcare Information Management. 2008: 22(3): 52–6.

9. Bramer, M. Principles of data mining. UK: Springer; 2007. p.5-8.

10. Kautzky-Willer A, Harreiter J, Pacini G. Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocr. Rev. 2016; 37(3): 278-316.

11. Shaw J.E, Sicree R.A, Zimmet P.Z. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice. 2010; 87: 4-14.

12. Kob H. C, Tan G. Data mining applications in healthcare. Journal of Healtcare Information Management. 2011; 19(2): 64-72.

13. Román-Pintos L. M, Villegas-Rivera G, Cardona-Munoz E.G, Rodríguez-Carrizalez A. D, Moreno-Ulloa A, Rubin N, et al. Diabetic polyneuropathy in type 2 diabetes mellitus: inflammation, oxidative stress, and mitochondrial function. J. Diabetes Res. 2016: 1-16.

14. Ehrlich A, Schroeder C.L. Medical terminology. NY: Delmar Cangage; 2009. p.144.

15. Maimon O, Rokach L. Datamining and knowledge discovery handbook. Berlin: Springer; 2010. p.151.

16. Fabis F, Doherty A, Palmer D, Magalhaes J.P.D, Freitas A.A. A new approach for interpreting random forest models and its application to the biology of ageing. Bioinformatics. 2018; 34(14): 2449-56.

17. Larose D. T. Discovering knowledge in data: an introduction to data mining. Canada: Wiley-Interscience; 2005. p.27.

18. Lakshmi K. R. Utilization of data mining techniques for prediction and diagnosis of tuberculosis disease survivability. International journal of modern education and computer science. 2013: 5(8): 8–17.

19. Radha P, Srinivasan B. Predicting diabetes by cosequencing the various data mining classification techniques. International journal of ınnovative science, engineering & technology. 2014: 1(6): 334–9.

20. Devi M. R, Shyla J. M. Analysis of various data mining techniques to predict diabetes mellitus. International journal of applied engineering research. 2016: 11(1): 727–30.

PDF

Download attachments: JCAM_6000.pdf

How to Cite

Torun NK, Şimşek Gürsoy UT, Kader S, Oztop MB. Polyneuropathy disease forecast in the type 2 diabetes mellitus patients using data mining based approach. Ann Clin Anal Med 2019;10(4): 485-90

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Prognostic importance of plasma heparin binding protein in the diagnosis of acute appendicitis

Ayetullah Temiz 1, Konca Altınkaynak 2, Yavuz Albayrak 3, Yılmaz Özdemir 4, Saime Özbek Şebin 5, Ceren Şen Tanrıkulu 6

1 Department of General Surgery, Erzurum Regional Training and Research Hospital, Erzurum, 2 Department of Biochemistry, Erzurum Regional Training and Research Hospital, Erzurum, 3 Department of General Surgery, Atatürk University School of Medicine, Erzurum, 4 Department of Gastroenterology Surgery, Erzurum Regional Training and Research Hospital, Erzurum, 5 Department of Physiology, Atatürk University School of Medicine, Erzurum, 6 Department of Emergency Medicine, Konya Education and Research Hospital, Konya, Turkey

DOI:10.4328/ACAM.6004 Received: 16.08.2018 Accepted: 25.09.2018 Published Online: 26.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 491-5

Corresponding Author: Ayetullah Temiz, Department of General Surgery, Erzurum Regional Training and Research Hospital, 25100 Erzurum, Turkey.T.: +90 4422325248 E-Mail: temiz-49@hotmail.com ORCID ID: https://orcid.org/ 0000-0003-2178-3369

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: In recent years, it has been found that plasma levels of Heparin Binding Protein (HBP) are elevated in systemic inflammatory conditions. In this study, we aimed to demonstrate the diagnostic value of HBP in patients with acute appendicitis (AA). Material and Method: Sixty patients with acute appendicitis and 27 healthy subjects were included in the study. Plasma HBP levels were measured in the patient groups and control groups and the results were compared.Results: The average HBP level in the 60 patients with acute appendicitis (AA) was 9.63 ± 3.64 ng/ml, while the average HBP value of the healthy group was 7.65 ± 2.52 ng/ml. When the groups were compared, the HBP serum levels were significantly lower (p = 0.02) in the healthy control group. The area under the curve (AUC) was 0.785 in the ROC curve for diagnosis of acute appendicitis using HBP. Discussion: This study has significance as the first study to investigate the HBP level in patients with acute appendicitis, and HBP may be a potential new marker for the diagnosis of acute appendicitis.

Keywords: Acute Appendicitis; Heparin Binding Protein; Inflammation

Full Text
Introduction

Acute appendicitis (AA) is the most frequent cause of acute abdominal pain with a lifetime risk of 7%, representing an important proportion of emergency surgical procedures. In the US, approximately 300 000 people undergo appendectomies annually in acute care hospitals [1,2]. An AA diagnosis is usually based on a combination of clinical information including symptoms (e.g. right lower quadrant abdominal pain, nausea and/or vomiting, high fever (38°C), abdominal rigidity and painful urination), physical examination findings, traditional biomarkers such as white blood cell count (WBC), mean platelet volume (MPV), absolute neutrophil count and C-reactive protein (CRP) and radiographic imaging (e.g. ultrasound and computed tomography scans) [3-5]. Clinical diagnosis of AA is often difficult even for experienced surgeons, and the rate of negative explorations can reach 20%–30% [6-7]. Delays in the diagnosis of AA may lead to perforation and the development of other complications. Therefore, there is a need for new laboratory methods that are both easy and inexpensive to perform for the diagnosis of AA.

Heparin-binding protein (HBP), also known as azurocidin or CAP37, is stored in secretory vesicles and azurophilic granules of neutrophils and is released early upon neutrophil adhesion and during neutrophil extravasation. Bacterial products induce the release of HBP leading to increased vascular leakage by acting on endothelial cells through unknown mechanisms [8]. In clinical investigations, the release of HBP has been demonstrated to be caused by a wide array of bacteria in various infectious diseases [9-11]. However, a search of the medical literature did not find a study about the place of HBP as an inflammatory marker in patients with AA. In this study, we aim to demonstrate the diagnostic value of HBP in patients with AA.

Material and Method

This study was carried out at the General Surgery Clinic of Erzurum Regional Education and Research Hospital between September 2016 and November 2016 in 60 patients who were diagnosed with acute appendicitis and in 27 healthy control individuals. The present study was approved by the Erzurum Regional Training and Research Hospital Institutional Review Board (approval number: 2015/10-105). A written informed consent from the patient was waived because the present study was performed prospectively.

The healthy control group was selected from healthy persons who came to the hospital without any complaints, just for purposes of a routine checkup in the Infection Diseases Clinic, and who did not conform to the exclusion criteria.

Inclusion and Exclusion Criteria:

All of the patients underwent operations for appendicitis based on their history, physical findings, and relevant clinical data. Postoperatively, the removed appendix was sent for histopathological examination. Cases, where the histopathology was not consistent with appendicitis, were excluded from the study. The exclusion criteria for entry into the study were heart failure, peripheral vascular disease, hematological disorders, acute or chronic infection, cancer, prior antibiotic therapy, age < 10 years, pregnancy, hepatic diseases, and other known inflammatory conditions. None of the patients had received prior anticoagulant medications, nonsteroidal anti-inflammatory drugs or oral contraceptives.

Biochemical Analysis:

Venous blood samples were obtained from the patient group and the control group and were collected into hemogram test tubes containing EDTA. The samples were centrifuged at 4000 rpm for 10 minutes, and then, they were stored at −80°C until the day the analysis was performed. Plasma levels of HBP were measured by a Human azurocidin ELISA kit (Bioassay Technology Laboratory Cat. China) using a microplate reader (Bio-Tek Power Wave XS).

Statistical Analysis:

All statistical analyses of the data were performed with the Statistical Package for Social Sciences (SPSS) 16.0 for Windows (SPSS Inc. Chicago, IL, USA). Data distribution was evaluated using the Kolmogorov–Smirnov test. Continuous variables are expressed as mean ± standard derivations (SD) and categorical variables as frequencies (percentages). The significance of each difference between continuous variables was explored with the Mann-Whitney U-test. The significance of each difference between categorical variables was compared using Pearson’s Chi-squared test. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cut-offs of the WBC, CRP, and HBP, for which specificities, sensitivities, positive and negative predictive values and overall accuracies, were calculated. A p-value <0.05 was considered to reflect statistical significance.

Results

Of the 60 patients who underwent appendectomies, 36 were males, and 24 were females, and of the healthy group, 12 were males, and 15 were females. Demographic and clinical characteristics concerning age, gender distribution, WBC, CRP, and HBP levels are presented in Table 1.

The HBP, WBC, and CRP results for patients and control groups are shown in Figure 1. The average HBP level in the 60 patients with AA was 9.63 ± 3.64 ng/ml, while the average HBP value of the healthy group was 7.65 ± 2.52 ng/ml. When the groups were compared, the HBP serum levels were significantly lower (p = 0.02) in the healthy control group (Figure 1). The average WBC level in the 60 patients with AA was 14400 ± 4670 ng/ml, while the average WBC value in the healthy group was 7.43 ± 1.14 ng/ml. When the groups were compared, the WBC serum levels were significantly lower (p < 0.001) in the healthy control group (Figure 2). The average CRP level in the 60 patients with AA was 3.91 ± 5.77 ng/ml, while the average CRP value in the healthy group was 0.33 ± 0.03 ng/ml. When the groups were compared, the CRP serum levels were significantly lower (p < 0.001) in the healthy control (Figure 3). In the ROC curve analysis, sensitivity rates for HBP, WBC, and CRP rate were 86.7%, 64.4%, 66.7%, respectively, while specificity rates were 71,4%, 76.2% and 76.2%, respectively (Figure 4) (Table 2). In addition, the distribution of HBP levels in patients and in the control group is shown in Table 2. For HBP, the area under the curve (AUC) was 0.785 in the ROC curve for the diagnosis of acute appendicitis.

Discussion

The aim of this study is to evaluate the diagnostic value of plasma HBP levels in patients with suspected AA.

Acute appendicitis (AA) is one of the most commonly encountered emergency presentations to general surgical services and requires emergency surgical intervention [12]. In the pathogenesis of acute appendicitis, bacterial invasion of the appendicular wall occurs, and the consequent inflammatory reaction leads to purulent infection. In many cases, appendices are surgically removed due to inadequate diagnostic laboratory evidence. Unnecessary removal of the appendix due to a lack of reliable laboratory data has not only

become a burden on healthcare systems and increased suffering in patients but also it has reduced quality of life in patients [13]. For this reason, the need is great for new, easily applied and inexpensive diagnostic tools that have high diagnostic value for AA and little operator dependence.

HBP is included in azurophilic granules and secretory vesicles of neutrophils and is released upon fusion of azurophilic granules and secretory vesicles with the plasma membrane. The basal release of HBP is augmented upon β 2 integrin-dependent adhesion of neutrophils to the vascular endothelium during inflammation [14,15]. At the site of infection, it is also secreted from azurophil granules during phagocytosis, where it exhibits antimicrobial activity and is responsible for the recruitment and activation of monocytes and other inflammatory mediators. It is also internalised by monocytes to prolong survival and enhance cytokine production [16]. Therefore, HBP directly contributes to the maintenance and progression of inflammation [17].

In a recent study, increased HBP was shown to be associated with increased permeability and ARDS in human sepsis. In addition, unfractionated heparin and low molecular weight heparins are potential drugs to prevent excessive HBP-induced increases in vascular leak in sepsis [18]. Linder et al. [11] reported that plasma HBP levels in patients with septic shock or sepsis were significantly higher than those in non-septic patients in the intensive care unit, and HBP correlated with severity of illness. It has also been observed that elevated HBP during admission to the hospital is associated with increased risk of death. Therefore, it is suggested that repeated HBP measurement in the intensive care unit can help to monitor treatment and predict the outcome in patients with severe infections. In another study in intensive care patients, it was shown that a high concentration of HBP in plasma on admission to the intensive care unit is associated with not only respiratory and circulatory

failure later during the intensive care unit care period, but also with increased 30-day mortality [19].

In a study of patients with urinary tract infections, urinary HBP levels were found to be higher in patients with urinary tract infection compared with healthy subjects [20]. In a similar study, plasma HBP levels were found to be significantly higher in patients with pediatric acute pyelonephritis [21]. In a recent study, it was shown that plasma HBP levels in acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) patients were significantly higher compared with cardiogenic pulmonary edema patients, and they have suggested that this is a strong indicator for short-term mortality in ALI/ARDS patients. It also suggests that HBP levels may both guide clinical management and shed light on appropriate treatment in this group of patients [22].

In a study on central nervous system infections, it was shown that HBP levels in the Cerebrospinal fluid in patients with acute bacterial meningitis increased significantly compared with other central nervous system infected patients [10]. HBP levels also increased significantly in inflammatory diseases caused by Leishmania chagasi, influenza (H1N1) virus and Leptospira interrogans [23,24,25].

In our study, HBP levels were significantly higher in patients with acute appendicitis compared with the control group. We have also found that HBP is more sensitive than WBC and CRP in confirming the disease in the ROC curve for both sensitivity and specificity in the diagnosis of acute appendicitis. In addition, in the AA group, the value of the AUC was as high as 0.785. For this reason, the utility of HBP in diagnosing acute appendicitis is considered high.

Conclusion

Worldwide, AA is one of the most common surgical pathologies. When the correct diagnosis is not made, both complications, such as perforation, and negative surgical procedures can occur. Additional laboratory tests are needed to confirm the diagnosis to reduce these complications and negative appendectomies. This study has significance as the first study to investigate HBP levels in patients with acute appendicitis, and to suggest that HBP may be a potential new marker for the diagnosis of AA. Therefore, HBP can be used as a diagnostic marker for AA because HBP levels are significantly higher in patients with AA.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

Referances

1. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990; 132(5): 910-25.

2. De Lissovoy G, Fraeman K, Hutchins V, Murphy D, Song D, Brian B, et al. Surgical site infection: incidence and impact on hospital utilization and treatment costs. Am J Infect Control. 2009; 37(5): 387-97.

3. Albayrak Y, Albayrak A, Celik M, Gelincik I, Demiryılmaz I, Yıldırım R, et al. High mobility group box protein-1 (HMGB-1) as a new diagnostic marker in patients with acute appendicitis. Scand J Trauma Resusc Emerg Med. 2011; 20(19): 27.

4. Kharbanda AB, Taylor GA, Fishman SJ, Bachur RGA. Clinical Decision Rule to Identify Children at Low Risk for Appendicitis. Pediatrics. 2005, 116: 709.

5. Albayrak Y, Albayrak A, Albayrak F, Yıldırım R, Aylu B, Uyanık A, et al. Mean Platelet Volume: A New Predictor in Confirming Acute Appendicitis Diagnosis. Clin Appl Thromb Hemost. 2011; 17(4): 362-6.

6. Andersson RE, Hugander A, Thulin AJ. Diagnostic accuracy and perforation rate in appendicitis: association with age and sex of the patient and with appendicectomy rate. Eur J Surg. 1992; 158(1): 37-41.

7. Yang HR, Wang YC, Chung PK, Chen WK, Jeng LB, Chen RJ, et al. Laboratory tests in patients with acute appendicitis. ANZ J Surg. 2006; 76(1-2): 71-4.

8. Gautam N, Olofsson AM, Herwald H, Iversen LF, Lundgren-Akerlund E, Hedqvist P, et al. Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Nat Med. 2001; 7: 1123 – 7.

9. Linder A, Christensson B, Herwald H, Bjorck L, Akesson P. Heparin-binding protein: An early marker of circulatory failure in sepsis. Clin Infect Dis. 2009; 49: 1044–50.

10. Linder A, Akesson P, Brink M, Studahl M, Björck L,Christensson B. Heparin-binding protein: A diagnostic marker of acute bacterial meningitis. Crit Care Med. 2011; 39: 812–17.

11. Linder A, Åkesson P, Inghammar M, Treutiger CJ, Linner A, Cullberg JS. Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock. Crit Care. 2012; 16. DOI: 10.1186/cc11353

12. Nance ML, Adamson WT, Hedrick HL. Appendicitis in the young child: a continuing diagnostic challenge. Pediatr Emerg Care. 2000; 16(3): 160–2.

13. Flum DR, Koepsell T. The clinical and economic correlates of misdiagnosed appendicitis: nationwide analysis. Arch Surg. 2002; 137(7): 799–804.

14. Gautam N, Olofsson AM, Herwald H, Iversen LF, Lundgren-Akerlund E, Hedqvist P, et al. Heparin-binding protein (HBP/CAP37): A missing link in neutrophil-evoked alteration of vascular permeability. Nature Med. 2001; 7 (10): 1123 – 7.

15. Tapper H, Karlsson A, Morgelin M, Flodgaard H, Herwald H. Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles. Blood. 2002; 99 (5): 1785 – 93.

16. Heinzelmann M, Mercer-Jones MA, Flodgaard H, Miller FN. Heparin-binding protein (CAP37) is internalized in monocytes and increases LPS-induced monocyte activation. J Immunol. 1998; 160: 5530-6.

17. Linder A, Soehnlein O, Akesson P. Roles of heparin-binding protein in bacterial infections. J Innate Immun. 2010; 2(5): 431-8.

18. Bentzer P, Fisher J, Kong HJ, Mörgelin M, Boyd JH, Walley KR, et al. Heparin-binding protein is important for vascular leak in sepsis. Intensive Care Med Exp. 2016;4(1): 33.

19. Tydén J, Herwald H, Sjöberg F, Johansson J. Increased plasma levels of heparin-binding protein on admission to intensive care are associated with respiratory and circulatory failure. PloS one. 2016; 11(3): DOI: 10.1371/journal.pone.0152035

20. Kjölvmark C, Påhlman LI, Åkesson P, Linder A. Heparin-binding protein: a diagnostic biomarker of urinary tract infection in adults. In Open forum infectious diseases. 2014; 1: DOI: 10.1093/ofid/ofu004.

21. Lertdumrongluk K, Thongmee T, Kerr SJ, Theamboonlers A, Poovorawan Y, Rianthavorn P, et al. Diagnostic accuracy of urine heparin binding protein for pediatric acute pyelonephritis. European journal of pediatrics. 2015; 174(1): 43-8.

22. Lin Q, Shen J, Shen L, Zhan Z, Fu F. Increased plasma levels of heparin-binding protein in patients with acute respiratory distress syndrome. Critical Care. 2013; 17(4): DOI: 10.1186/cc12834

23. Martins T V F, de Carvalho TV, de Oliveira CVM, de Paula SO, Cardoso SA, di Oliveria LL, et al. Leishmania chagasi heparin-binding protein: Cell localization and participation in L. chagasi infection. Molecular and biochemical parasitology. 2015; 204(1): 34-43.

24. Kaukonen KM, Linko R, Herwald H, Lindbom L, Ruokonen E, Ala-Kokko T, et al. Heparin-binding protein (HBP) in critically ill patients with influenza A (H1N1) infection. Clinical Microbiology and Infection. 2013; 19(12): 1122-8.

25. Ching ATC, Fávaro RD, Lima SS, Chaves A, de Lima MA, Nader HB, et al. Lepstospira interrogans shotgun phage display identified LigB as a heparin-binding protein. Biochemical and biophysical research communications. 2012; 427(4): 774-9.

PDF

Download attachments: JCAM_6004.pdf

How to Cite

Temiz A, Altınkaynak K, Albayrak Y, Özdemir Y, Şebin SÖ, Tanrıkulu CŞ. Prognostic importance of plasma heparin binding protein in the diagnosis of acute appendicitis. Ann Clin Anal Med 2019;10(4): 491-5

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Vitamin D status and association with disease activity and quality of life in patients with rheumatoid arthritis

Senem Şaş 1, Fatmanur Aybala Koçak 2, Emine Eda Kurt 2, Hatice Rana Erdem 2, Figen Tuncay 2

1 Department of Physical Medicine and Rehabilitation Ahi Evran University Training and Research Hospital, 2 Department of Physical Medicine and Rehabilitation, Ahi Evran University School of Medicine, Kırşehir, Turkey

DOI:10.4328/ACAM.5967 Received: 15.07.2018 Accepted: 28.08.2018 Published Online: 05.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 462-5

Corresponding Author: Senem Şaş, Department of Physical Medicine and Rehabilitation, Ahi Evran University Training and Research Hospital, Kirsehir, Turkey. T.: +90 3862134515-1169 GSM: +905055520451 E-Mail: senemsas@gmail.comORCID ID: https://orcid.org/ 0000-0002-5616-5723

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: The aim of this study is to determine the vitamin D level in patients with RA (Rheumatoid Arthritis) and association with clinic and laboratory param-eters and quality of life. Material and Method: Out of 111 patients with RA and 107 healthy controls who were admitted to Ahi Evran University Training and Research Hospital were included in this study. Patients underwent clinical, laboratory, functional, and quality of life examination. Laboratory tests used for patient evaluations included complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP). Disease activity was calculated by DAS28 (Disease Activity Score) and functional and quality of life was examined by RAQoL (Rheumatoid Arthritis Quality of Life), HAQ (Health Assessment Questionnaire). Larsen score was calculated to assess the radiographic damage. Results: There was no significant difference between the patient and control groups regarding age, sex and vitamin D level (p > 0.05). There were no correlation between vitamin D and Larsen score, RAQoL, HAQ, ESR, and CRP (p > 0,05). We found negative correlation between DAS28 (Disease Activity Score) and vitamin D (r = -0,416, p = 0,014). We found negative correlation between morning stiffness and vitamin D (r = -0,454, p = 0,007). Patients with RA were divided into two groups with D vitamin deficiency (0-19 ng / mL) and vitamin D ( > 20 ng / mL). There was a negative correlation with morning stiffness in the group with vitamin D deficiency (r = -0,454, p = 0,007). There was a negative correlation between DAS28 score and vitamin D deficien-cy (r = -0.416, p = 0.014). Discussion: This study presents a negative correlation between serum vitamin D level and DAS28. Since vitamin D has autoimmune roles, deficiency or inadequacy can cause flaring in patients with RA. In the light of these findings, we recommend vitamin D supplementation.

Keywords: Rheumatoid Arthritis; Vitamin D; Disease Activity; Deficiency; Autoimmune Role

Full Text

Introduction

Rheumatoid Arthritis (RA) is a chronic systemic autoinflammatory disease that involves predominantly joints. The typical course of the disease presents synovial inflammation, cartilage damage and bone resorption [1]. The pathogenesis of RA is not still fully understood but some susceptibility factors may include genetic factors, environmental triggers, and activation of the acquired and natural immunity [2].

Vitamin D is a hormone that plays a major role in regulation of bone metabolism and its insufficiency causes rickets in children and osteomalacia in adults. The 25-hydroxy-vitamin D (25-OH-D) has been mentioned to inhibit T-cell expansion and down-regulate inflammatory cytokines and 1,25-dihydroxy vitamin D3 [1,25 (OH)2D3] discourage IFN-У and IL-12 secretion [2,3]. Data indicate that sufficient vitamin D levels have a protective role against autoimmunity through inhibiting T cell expansion and inflammatory mediators in inflammatory rheumatic diseases including RA [4-6].

Also, some studies reported the association between seasonal variations in serum levels of vitamin D, disease activity and latitude in patients with RA [7,8]. Furthermore, it has been showed increasing vitamin D had no association to relative risk of developing RA [10]. However, contradictory results have been published in the literature about vitamin D and RA activity [7-24]. It has been reported that vitamin D has a negative correlation between DAS28, CRP and HAQ values [25]

Therefore, the aim of the present study was to evaluate the vitamin D level in patients with RA and association with clinic and laboratory parameters and quality of life.

Material and Method

Patients

Out of 111 patients (aged between 30 and 84 years) with RA and 107 healthy controls who were admitted to Ahi Evran University Training and Research Hospital were included in this study.

The inclusion criteria were to be a volunteer patient with a rheumatoid arthritis disease. Exclusion criteria were the presence of chronic medical disorders requiring medical treatments, fractures, infectious diseases, malignant tumors, unstable hypertension, severe cardiovascular problems, major hepatic and renal insufficiency, hemorrhagic diseases, serious anemia, pregnancy, psychiatric disorder, and systemic inflammatory disease except RA.

All the patients were diagnosed by the same physician (SS) at the Physical Medicine and Rehabilitation clinic. Laboratory tests used for patient evaluations included complete blood count, erythrocyte sedimentation rate, C-reactive protein level, fasting blood glucose level, hepatic and renal function tests, rheumatoid factor, and thyroid function tests. The patients who met the inclusion and exclusion criteria were admitted to the hospital outpatient clinic.

The patients were fully informed about the nature and purpose of the study. Written informed consents were obtained. The study was approved by the ethics committee (Approval number: 2017-04/31).

Outcome Measures

Demographic and clinical features and measurements were performed before participation. Patient data, included age, gender, smoking history, disease duration, health assessment questionnaire (HAQ), Rheumatoid arthritis quality of life (RAQoL), disease activity score (DAS28), Larsen score, Hemoglobin, platelet, white blood cell, rheumatoid factor, sedimentation (ESR), C-Reactive protein (CRP), serum vitamin D level, number of tender joints, number of swelling joints.

Disease activity was examined by disease activity score (DAS28) including 28 joints, ESR, patient VAS (visual analogue scale) (0-100), where O = best and 100 = worst, and both swollen and tender joint number. DAS28 scores is defined high ( > 5,1), moderate (3,2 < 5,1) and slightly active disease ( ≤ 3,2) respectively [26]. It is calculated as follows:

DAS28 (ESR) = 0.56*!(TJC28) + 0.28*!(SJC28) + 0.014*GH + 0.70*ln (ESR)

TJC = tender joint count and SJC = swollen joint count.

Larsen score was analyzed by the same physician from hand radiography. Wrist, 2-5 proximal interphalangeal and 2-5 metacarpophalangeal joint were assessed. Radiography was scored 0 to 5 points, where 0 = no abnormalities, 1 = slight abnormalities, 2 = small but define erosions, 3 = medium erosions, 4 = severe destructive abnormalities, 5 = mutilating abnormalities [27].

Health status was measured by HAQ. HAQ includes 20 activities of daily living with four answers (0 = any difficulty, 1 = some difficulty, 3 = much difficulty, 4 = inability) were classified into eight groups. The score is assigned to the highest point in each group. Patients were asked to use any device or aids, or help from another person [28].

Life quality was assessed by RAQoL in patients with Rheumatoid arthritis. RAQoL was formed of 30 items with a yes/no (1/0) response [29].

All the measurements were taken by the same physician. All patients received medical immunosuppressive treatment. The patients did not receive vitamin D supplementation.

Statistical analyses

Descriptive statistical methods including frequency distribution tables, graphs, central and distribution tendencies were utilized to analyze the data. Kolmogorov-Smirnov test was utilized to check the normality of data distribution. Comparing the qualitative values of the two groups was carried out using independent-samples t-test or its non-parametric equivalent. Chi-square test was employed to examine the relationship between qualitative variables. The significance level was defined at p < 0.05. Data analysis was performed using SPSS version 20.0 Software.

Results

The demographic features of the patient and control group were displayed in Table 1. There was no significant difference between the patient and control groups regarding age, sex and vitamin D level (p > 0.05). There was no correlation between vitamin D level and Larsen score, RAQoL, HAQ, ESR and CRP (p > 0,05). The negative correlation was found between DAS28 and vitamin D level (r = -0,416, p = 0,014). We found negative correlation between morning stiffness and vitamin D (r = -0,454, p = 0,007).

Patients with RA were divided into two groups with D vitamin deficiency (0-19 ng / mL) (n = 34) and D vitamin ( > 20 ng / mL). There was a negative correlation with morning stiffness in the group with vitamin D deficiency (r = -0,454, p = 0,007) and a negative correlation between DAS28 score and D vitamin deficiency (r = -0.416, p = 0.014).

Discussion

This study investigated vitamin D level and association with disease activity and quality of life in patients with RA and healthy controls. The results indicated that there is no significant difference in vitamin D levels in patients with RA compared with healthy controls. And also in the RA group, there was a negative correlation between DAS-28 and morning stiffness. This negative correlation also persisted when vitamin D was lower than 20 ng / mL. But we didn’t note any correlation between acute-phase reactants, life quality scales, number of tender joints, number of swollen joints, disease duration, patient, and doctor global assessment and hemogram parameters. Patients with RA were not under vitamin D supplementation.

Vitamin D deficiency is a widespread health condition. It has been recommended, as a routine procedure for measuring serum vitamin D level in patients with RA. It has been estimated that 25 (OH) D level of above 30 ng/mL (75nmol/L) is optimal by various groups including Endocrine Society [30].

It was published that more vitamin D intake reduces the prevalence of RA in Northern Europe compared with Southern Europe [7]. Also, a report including data of 15 different countries confirms variation of serum D vitamin levels [31]. This difference is explained due to the differences in people such as ethnic variation, climate, sun exposure, dressing style or latitude [7, 31]. Since this study was performed in a rural area of Turkey, ethnic variations were not noted.

Turhanoglu et al. reported that there is a negative correlation between DAS28 and vitamin D. They also found that there is no difference in vitamin D levels in RA and healthy controls. Serum 25-OH vitamin D levels were correlated inversely with DAS28, CRP, and HAQ [25]. We didn’t find any correlation with vitamin D and health status, health quality, and acute phase reactants. Similar to this study, there was no difference between the patient and the control group.

Comparable results have been demonstrated by various studies [7-24]. Besides, Cutolo et al. reported a negative correlation between vitamin D and RA disease activity showing a circadian rhythm [8].

Contradictory results were also published. Baker et al. and Feser et al. reported that there is no correlation between serum vitamin D level and RA disease activity [10, 32]. Furthermore, Saseli et al. found non-significant improvement in the effect of oral vitamin D supplementation in active RA patients receiving methotrexate treatment [33]. Our study results suggest vitamin D intake to improve the DAS28 score. All patients were taking immunosuppressive treatment.

The progress of RA is influenced by various environmental and genetic factors. Actually, it has been shown in murine models that vitamin D may suppress incidence and development of collagen-induced arthritis [34]. Furthermore, vitamin D receptor (VDR) agonists may prevent collagen-induced arthritis [35]. VDR gene polymorphism can affect serum vitamin D levels and function and RA development [36]. VDR is found at high levels in immune system cells such as dendritic cells, macrophages and activated T and B lymphocytes [37]. Vitamin D prevents inflammatory process by adaptive immune responses through binding VDR. Vitamin D also changes the balance between Th1 to Th2 and T regulatory cells [38]. Inhibiting the proliferation of Th1 cells can induce inflammation, generate bone loss leading to osteopenia or osteoporosis [39]. However, vitamin D decreases acute-phase response rather than causing inflammation [40].

There are some limitations in our study. First, the patient’s long-term follow up was not conducted. Second, we did not note clothing, sun exposure and season. Third, we did not measure vitamin D receptors.

In conclusion, this study presents a negative correlation between serum vitamin D level and DAS28. This study concluded that serum vitamin D can be measured as an alternative marker in patients with RA.

Since vitamin D has autoimmune roles, deficiency or inadequacy can cause flaring in patients with RA. In the light of these findings, we recommend vitamin D supplementation.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Scott DL, Steer S. The course of established rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2007; 21: 943-67.

2. Choi SJ, Rho YH, Ji JD, Song GG, Lee YH. Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford). 2006; 45(2): 166-70. 

3. Cantorna MT. Why do T cells express the vitamin D receptor? Ann N Y Acad Sci. 2011; 1217: 77-82.

4. Kamen DLAranow C. The link between vitamin D deficiency and systemic lupus erythematosus. Curr Rheumatol Rep. 2008; 10(4): 273-80.

5. Cutolo MPaolino SSulli ASmith VPizzorni CSeriolo B. Vitamin D, steroid hormones, and autoimmunity. Ann N Y Acad Sci. 2014; 1317: 39-46.

6. Gallone GHaerty WDisanto G, Ramagopalan SVPonting CPBerlanga-Taylor AJ. Identification of genetic variants affecting vitamin D receptor binding and associations with autoimmune disease. Hum Mol Genet. 2017. DOI: 10.1093/hmg/ddx092.

7. Vojinovic J, Tincani A, Sulli A, Soldano S, Andreoli L, Dall’Ara F, et al. European multicentre pilot survey to assess vitamin D status in rheumatoid arthritis patients and early development of a new Patient Reported Outcome questionnaire (D-PRO). Autoimmunity Reviews. 2017; DOI:10.1016/j.autrev.2017.03.002

8. Cutolo MOtsa KLaas KYprus MLehtme RSecchi ME, et al. Vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol. 2006; 24(6): 702-4.

9. Gatenby PLucas RSwaminathan A. Vitamin D deficiency and risk for rheumatic diseases: an update. Curr Opin Rheumatol. 2013; 25(2): 184-91.

10. Feser MDerber LADeane KDLezotte DCWeisman MHBuckner JH, et al. Plasma 25,OH Vitamin D Concentrations Are Not Associated with Rheumatoid Arthritis (RA)-related Autoantibodies in Individuals at Elevated Risk for RA. The Journal of Rheumatology. 2009; 36 (5): 943-6. DOI: https://doi.org/10.3899/jrheum.080764

11. Grazio S, Naglic DB, Anic B, Naglic DB, Anic B, Bakula M, et al. Vitamin D serum level, disease activity and functional ability in different rheumatic patients. Am J Med Sci. 2015; 349: 46-9.

12 .Brance ML, Brun LR, Lioi S, Sanchez A, Abdala M, Oliveri B. Vitamin D levels and bone mass in rheumatoid arthritis. Rheumatol Int. 2015; 35: 499-505.

13. Sharma R, Saigal R, Goyal L, Mital P, Yadav RN, Meena PD, et al. Estimation of vitamin D levels in rheumatoid arthritis patients and its correlation with the disease activity. J Assoc Physicians India. 2014; 62: 678-81.

14. Hong Q, XU J, Xu S, Lian L, Zhang M, Ding C. Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokines and bone loss in patients with rheumatoid arthritis. Rheumatology (Oxford). 2014; 53: 1994-2001.

15. Chen J, Liu W, Lin Q, Chen L, Yin J, Huang H. Vitamin D deficiency and low bone mineral density in native Chinese rheumatoid arthritis patients. Int J Rheum Dis. 2014; 17: 66-70.

16. Gheita TA, Sayed S, Gheita HA, Kenawy SA. Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome. Int J Rheum Dis. 2014; 19(3): 294-9.

17. Sahebari M, Mirfeizi Z, Rezaieyazdi Z, Rafatpanah H, Goshyeshi L. 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR). Caspian J Intern Med. 2014; 5: 148-55.

18. Atwa MA, Balata MG, Hussein AM, Abdelrahman NI, Elminshawy HH. Serum 25-hydroxyvitamin D concentration in patients with psoriasis and rheumatoid arthritis and its association with disease activity and serum tumor necrosis factor-alpha. Saudi Med J. 2013; 34: 806-13.

19. Yazmalar L, Ediz L, Alpayci M, Hiz O, Toprak M, Tekeoglu I. Seasonal disease activity and serum vitamin D levels in rheumatoid arthritis, ankylosing spondylitis and osteoarthritis. Afr Health Sci. 2013; 13: 47-55.

20. Baykal T, Senel K, Alp F, Erdal A, Ugur M. Is there an association between serum 25-hydroxyvitamin D concentrations and disease activity in rheumatoid arthritis? Bratisl Lek Listy. 2012; 113: 610-1.

21. Kostoglou-Athanassiou I, Athanassıou P, Lyraki A, Raftakis I, Antoniadis C. Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab. 2012; 3: 181-7.

22. Attar SM. Vitamin D deficiency in rheumatoid arthritis. Prevalence and association with disease activity in Western Saudi Arabia. Saudi Med J. 2012; 33: 520-5.

23. Cutolo M, Otsa K, Laas K, Prus M, Lehtme R, Secchi ME, et al. Circannual vitamin D serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol. 2006; 24: 702-4.

24. Wen HY, Luo J, Lı XF. Vitamin D levels and associations with disease activity in Chinese Han patients with early rheumatoid arthritis. J Clin Rheumat. 2015; 21: 276-7.

25. Turhanoğlu AD, Güler H, Yönden Z, Aslan F, Mansuroglu A, Ozer C. The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis. Rheumatol Int. 2011; 31(7): 911-14.

26. Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol. 2005; 23: 93–9.

27. Solymossy C, Dixey J, Utley M, Gallivan S, Young A, Cox N, et al. Larsen scoring of digitized X-ray images. Rheumatology. 1999; 38(11): 1127-9.

28. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: a review of its history, issues, progress and documentation. J Rheumatol. 2003; 30: 167-78.

29. De Jong Z, van der Heijde D, McKenna SP, Whalley D. The reliability and construct validity of the RAQoL: a rheumatoid arthritis-specific quality of life instrument. Br J Rheumatol. 1997; 36: 878–83.

30. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2001; 96: 1911–30.

31. Hajjaj-Hassouni N, Mawani N, Allali F, Rkain H, Hassouni K, Hmamouchi I, et al. Evaluation of Vitamin D Status in Rheumatoid Arthritis and Its Association with Disease Activity across 15 Countries: “The COMORA Study”. International Journal of Rheumatology.  2017. DOI: /10.1155/2017/5491676

32. Baker JF, Baker DG, Toedter G, Shults J, Von Feldt JM, Leonard MB. Associations between vitamin D, disease activity, and clinical response to therapy in rheumatoid arthritis. Clin Exp Rheumatol. 2012; 30 (5): 658–64.

33. Salesi M, Farajzadegan Z. Efficacy of Vitamin D in patients with active rheumatoid arthritis receiving methotrexate therapy. Rheumatology international. 2012; 32(7): 2129-33.

34. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. The Journal of nutrition. 1998; 128(1):68–72.

35. Adorini L. Intervention in autoimmunity: the potential of vitamin D receptor agonists. Cellular immunology. 2005; 233(2):115–24. DOI: 10.1016/j.cellimm.

36. Tizaoui K, Hamzaoui K. Association between VDR polymorphisms and rheumatoid arthritis disease: Systematic review and updated meta-analysis of case-control studies. Immunobiology. 2014. doi: 10. 1016/j.imbio.2014.12.013 37.

37. Ceglia L, Niramitmahapanya S, da Silva Morais M, Rivas DA, Harris SS, Bischoff-Ferrari H, et al. A randomized study on the effect of vitamin D(3) supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. The Journal of clinical endocrinology and metabolism. 2013; 98(12): DOI: 10.1210/jc.2013-282038.

38. Guillot X, Semerano L, Saidenberg-Kermanac’h N, Falgarone G, Boissier MC. Vitamin D and inflammation. Joint, bone, spine: revue du rhumatisme. 2010; 77(6):552–7. DOI: 10.1016/j.jbspin.39.

39. Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Annals of the rheumatic diseases. 2007; 66(9):1137–42.

40. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O’Reilly DS, et al. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. The American journal of clinical nutrition. 2011; 93(5): 1006–11. DOI: 10.3945/ajcn.110.Control (n=107)

PDF

Download attachments: JCAM_5967.pdf

How to Cite

Şaş S, Koçak FA, Kurt EE, Erdem HR, Tuncay F. Vitamin D status and association with disease activity and quality of life in patients with rheumatoid arthritis. Ann Clin Anal Med 2019;10(4): 462-5.

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

ASTYM® versus massage in the treatment of chronic exertional anterior compartment syndrome of the lower leg: a randomized controlled trial

Ibrahim Mohammed Ragab 1, Olfat Ibrahim Ali 2, Hamada Ahmed Hamada 3, Rafik Radwan 3, Dalia Mosaad 4

1 Lecturer of Orthopedic Physical Therapy, Faculty of Physical Therapy, Beni- Suef University, Egypt, 2 Department of Basic Science, Faculty of Physical Therapy, Cairo University, Egypt & Batterjee Medical College, KSA, 3 Department of Biomechanics, Faculty of Physical Therapy, Cairo University, Egypt, 4 Department of Basic Science, Faculty of Physical Therapy, Cairo University, Egypt

DOI:10.4328/ACAM.5986 Received: 04.08.2018 Accepted: 02.09.2018 Published Online: 05.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 470-4

Corresponding Author: Hamada Ahmed, Lecturer of Biomechanics, Faculty of Physical Therapy, Cairo University, Cairo, Egypt. T.: 00201117893697 E-Mail: Hamada.Ahmed@pt.cu.edu.eg ORCID ID: https://orcid.org/0000-0002-661-3948

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: Chronic exertional anterior compartment syndrome (ant-CECS) is a major cause of lower leg pain. Surgical fasciotomy is still the main treatment given with high success rate. Thorough physical therapy attempts as a non-operative treatment depends on manual therapy, modalities, and proper orthotic wear. Hence, there is a paucity of literature that compares the effects of two manual techniques on patients with ant-CECS. So, the purpose of this study was to compare the effects of Astym therapy and massage in patients with chronic exertional anterior compartment syndrome of the lower leg. Material and Method: This study was a prospective, randomized, single-blind, pre–post-test, controlled trial. The study was conducted at Beni-Suef University, Egypt. A total of thirty participants with chronic exertional anterior compartment syndrome pain enrolled in experimental and control groups. The outcomes were measured post- treatment to compare the effect of both interventions. Results: Mixed design MANOVA was used to compare the tested variables of interest. Post-treatment comparison showed a significant reduction in pain in favor of Astym group with significant differences in both lower extremity functional score and passive ankle dorsiflexion. (p > 0.05). Discussion: Pain and disability typically associated with ant-CECS reduced greatly after treatment of ant-CECS using ASTYM or massage. ASTYM treatment is more effective than massage therapy in reducing pain, improving overall functional level for patients with ant-CECS.

Keywords: Anterior Compartment Syndrome; ASTYM; Leg Pains; Massage

Full Text

Introduction

Chronic exertional anterior compartment syndrome (ant-CECS) of the lower leg occurs when the elevated pressure within a small unyielding anterior fascial compartment precipitates chronic lower leg pain [1, 2]. It constitutes 27-33% of the causative factors [3, 4]. This syndrome most commonly occurs in young adults, athletes subjected to high lower limb stresses (uphill and distance runners, basketball and football players, gymnasts and hurdlers) and military personnel where pain may briefly persist after termination of exercise [2, 5]. Symptoms either subside within minutes to hours when the activity stops or worsen over time [6].

A major revision of diagnostic criteria is necessary, and the differential diagnoses include patient’s history, physical examination and if necessary radiographs, compartmental pressure measurements, arteriograms, angiography, bone scans and MRI [7]. Other diagnoses such as medial tibial stress syndrome, stress fracture, popliteal artery and common peroneal nerve entrapment may need to be excluded [1]. The anterior compartment contains the deep peroneal nerve, tibialis anterior muscle, and long toe extensors. Increased pressure in this compartment can cause signs of loss of sensation to the first web space and weakness with dorsiflexion of the toes and ankle. Physical exam may also include an assessment of gait or gait analysis because pronation is a common physical finding [8]. Because the syndrome primarily affects the venous system, arterial pulses are normally intact. To quantify the severity in patients with ant-CECS, a few investigators used visual analog scales [6, 9]. An ordinal scaled CECS specific measure has been introduced to grade the functional limitations resulting from pain provoked by CECS [9].

Fasciotomy is a surgical procedure to release the intracompartmental tension by severing the fascia covering the muscle compartment. However, a great range of surgical decompression is unsuccessful. Regarding outcome, results on operative intervention are good in the short term but these studies are limited with respect to follow up duration, involved many operative techniques, and the use of outcome measures [9]. Generally, nonsurgical treatment involves four treatment choices: massage, gait modification, chemo-denervation, and ultrasound-guided (USG) fascial fenestration [10]. Noninvasive interventions include arch support orthotics, ice massage to reduce swelling and pain, myofascial release, deep tissue massage, stretching before exercise, and training load modification [11]. These modalities are successful to modify the intra-compartmental pressures for short-term [12]. Conservative treatment methods include avoidance of running on hard terrains, footwear modification, alleviating the biomechanical techniques of running, and discontinuing the activity that elicits symptoms or decreasing the intensity of training. Massage therapy can also help alleviate symptoms by reducing the chronic muscular tension where patients are able to do more exercise without pain [11]. Astym® therapy is a manual technique with specific strokes used to enhance tissue healing, alleviate pain, and facilitate mobility hence, muscle performance improves through the application of specialized instruments that have shown evidence of stimulating soft-tissue healing [13, 14], and improving impairments such as pain, limitations in mobility, and muscle weakness that may accompany musculoskeletal pathology[15]. However, sinceAstym therapy and massage should theoretically reveal acceptable results, there is a dearth of literature that compare effects of these two techniques for patients with CECS. Therefore, the purpose of this study was to determine whether Astym therapy or massage applied to the lower leg would result in alleviation in pain, soft tissue mobility and ankle dorsiflexion.

Material and Method

The study was designed as a prospective, randomized, single-blind, pre–post-test, placebo-controlled trial. Ethical approval was obtained from the institutional review board at the Faculty of physical therapy, Beni-Suef University before study commencement [No: BSUPT04/25/07/2017]. The study followed the Guidelines of the Declaration of Helsinki on the conduct of human research. The study was conducted between July 2017 and November 2017.

Convenient samples of thirty patients recruited from the outpatient clinic of the faculty of physical therapy, Beni-Suef University were enrolled and assessed for their eligibility to participate in the study. All subjects of the study have read and signed an informed consent form approved by the Beni-Suef University. This study included participants diagnosed clinically with bilateral exertional anterior compartment syndrome of the lower leg. Their ages ranged from 18 to 35 years, they had ant-CECS for more than 3 months ago, with a Visual analog scale (VAS) Pain score > 4.All patients had no history of previous trauma to their legs and demonstrated normal roentgenograms of the tibia and fibula findings. Only patients with gradual cessation of the offending activity were involved. For individualsinsisting on continuing their exertional activities, surgical treatment (fasciotomy) is the choice. Exclusion criteria involved medical history of hemophilia or other blood coagulation disorders, medical history of cardiovascular disease including those with previous cardiovascular surgery and uncontrolled hypertension, current use of prescription blood thinners, a history of metastatic disease, neuropathy of the lower extremity, an active infection (or taking medication for an infection), conditions affecting both lower extremities and previous treatment that included fasciotomy, massage or Astym [16]. Bilateral involvement was reported in 60% to 90% of the time.

Each patient signed a consent form after explaining the scope, objectives, and value of the study, informing them about the right to refuse or withdraw at any time, and reassuring them about the confidentiality of information. Data coding assured anonymity. Patients allocated randomly into Astym and massage treatment groups by a blinded and an independent research assistant who opened sealed envelopes containing a computer-generated randomization card. No subjects dropped out of the study after randomization.

Participants were randomly assigned into two experimental groups (Group A) received ASTYM therapy (Figure 1) and the other group (Group B) received intermittent massage (effleurage and cross fiber frictions) (Figure 2) for 8 sessions over a four-week period healing [13-15]. Physiotherapy program for both groups included ice (20 minutes), ultrasound on the lower lateral leg (5 minutes 2 days/week), with an intensity of 1.5 w/cm2with a frequency of 1 Hz continuous mode of application [11], stretching before exercise (calf muscles, anterior tibial group) and strengthening exercises (dorsiflexors and evertors, core stability exercises). Exercise programs were individually designed based on the patient’s examination and clinical findings. Subjects were blinded to whether they received the Astym® treatment or massage treatment intervention. After a 5-minute warm-up on a lower leg, Astym® treatment starts. End-feel assessment is an integral part of the examination as a hard end feel may be indicative of joint dysfunction or soft tissue restriction and can help guide intervention.

The study outcomes were measured before starting the treatment program and at the end of the program. A subjective pain sensation as a primary outcome measure was assessed by scoring in the 10-point visual analog rating scale; zero indicates no pain while 10 represents the worst pain. While the secondary outcomes were the ankle dorsiflexion, lower extremity functional scale [17]. Measuring the range of motion of dorsiflexion as an objective measure is the third outcome.

Sample size and Statistical analysis

Sample size calculation prior to the study using G*POWER statistical software (version 3.1.9.2; Franz Faul, Universitat Kiel, Germany) reflected that the appropriate sample size for this study was n=30, which gave observed power equal to 0.85. Calculations made using alpha = 0.05, beta = 0.15 and large effect size. For comparing subject characteristics between both groups t-test was conducted. Then, normal distribution of data was checked using the Shapiro-Wilk test for all variables, hence Levene’s test for homogeneity of variances was conducted to test the homogeneity between groups. Mixed MANOVA was performed to compare within and between groups effects of treatment on VAS, functional scale and dorsiflexion ROM between the group A and B as between group comparison and between pre and post-treatment in each group as within-group comparison. Partial squared eta was considered as the effect size. Post-hoc tests using the Bonferroni correction were carried out for subsequent multiple comparisons. The level of significance for all statistical tests was set at p < 0.05. All statistical analysis was conducted through the statistical package for social studies (SPSS) version 19 for Windows (IBM SPSS, Chicago, IL, USA).

Results

A total of 30 patients with chronic exertional anterior compartment syndrome pain enrolled in experimental and control groups (fig 3). Table 1 showed the subject characteristics of both groups. There was no significant difference between both groups with respect to the mean age, weight, height and BMI (p < 0.05). Also, there was no significant difference in blood pressure between groups (p < 0.5). Mixed MANOVA revealed that there was a significant interaction of treatment and time (Wilks’ Lambda = 0.64; F (4,25) = 3.48, p = 0.02, η2= 0.35). There was a significant main effect of time (Wilks’ Lambda = 0.06; F (4,25) = 93.62, p = 0.0001, η2= 0.93). There was no significant main effect of treatment (Wilks’ Lambda = 0.8; F (4,25) = 1.51, p = 0.22, η2 = 0.19). Table 2 showed descriptive statistics of VAS, lower extremity functional scale and dorsiflexion ROM as well as the significant level of comparison between groups and the significant level of comparison between pre and post-treatment in each group. There was no significant difference between the Group A and B in all variables pre-treatment (p > 0.05). Post-treatment there was a significant increase in lower extremity functional scale, right and left dorsiflexion ROM of Group A compared with that of the group (p > 0.05). Also, there was a significant decrease VAS of Group A compared with that of Group A post-treatment (p > 0.05). There was a significant increase in the lower extremity functional scale, right and left dorsi flexion ROM post treatment compared with pre-treatment in both groups (p = 0.0001). However, both groups showed a significant decrease in VAS post-treatment compared with that pre- treatment (p = 0.0001).

Adverse events

There are no adverse events occurred during the study.

Discussion

The Osseo-fascial boundary of the anterior compartment could limit the swelling of the muscle in chronic exertional anterior compartment syndrome. Fronek et al. [5] stated the presence of different mechanisms explaining the cause of this swelling.The use of a non-operative approach to the treatment of CECS would be valuable when it could prevent the risk, complications, and costs related to surgical intervention. This study designed to compare the effects of Astym therapy and massage in patients withbilateral chronic exertional anterior compartment syndrome of the lower leg. Fronek et al. stated that the nonsurgical treatment of CECS was successful when it could prevent patients with CECS to develop an acute compartment syndrome through the ischemic producing mechanism as many acute cases with acute compartment syndrome superimposed on CECS.

There was a diversity of mechanisms precipitating muscle hypertrophy within a confined Osseo-fascial boundary. Canale et al. [18] postulated that isometric or isotonic muscle contraction, vigorous exercises through increasing muscle mass by 20%. While Brown et al. [19] explained that increased muscle blood volume was the causative mechanism. Sejersted [20] found that the compression of the interstitial fluid is another mechanism. Jacobbson et al. [21] revealed that post-exercise muscle swelling increases blood flow and fiber swelling which may reach up to 20 times more than the resting level and fluid retention. Therefore, the increase of intramuscular pressure could diminish venous return leading to capillary occlusion and consequently compartment ischemia. The ultimate Intracompartmental pressures render the muscle in the non-contractile state where the balance between intramuscular compartment pressure and the microvascular pressure determined the patency of perfusion and hence, the oxygen supply of the muscle. Scheer et al. [22] emphasized the importance of treatment type in providing tactile pressures and shear forces to stimulate tissue healing at a cellular level.

Results of the current study revealed that Astym had more pronounced effect than massage in the treatment of ant-CECS. Collins et al. [23] demonstrated that patients with CECS may have some improvement following manual therapy [24-26].Sevier et al. [24], Laudner et al. [25] and Loghmani et al. [26] showed that Astym therapy could induce leakage from dysfunctional capillaries that ends up with increased fibroblast activity, macrophage phagocytosis, and local growth factors released that enhanced more fibroblast recruitment, reduced pain and restored function in people with musculoskeletal pathologies including epicondylosis.

The study results are consistent with the conclusion of Mc Cormack [27]who revealed significant pain reduction with the improvement of the lower limb function in the patient with high hamstring tendinopathy. The finding of Chughtai [28] proved a significant gain in knee joint ROM in patient who underwent Astym therapy compared with standardized physical therapy program following total knee arthroplasty. Chughtai [28]and Paker [29] proved that the joint pain and ROM might be related to effects of Astym on the biomechanical properties of the injured tissues with enhancement of blood flow and possible angiogenesis in the vicinity of these tissues

Patients with Ant-CECS might have transient or permanent low-grade foot drop as a result of the weakness of dorsiflexors with or without paresthesia on the dorsum of the foot. Rest or cessation of exercise relieved symptoms by 85% of athletes. The involved muscles may be tender or not relying on whether the patient is symptomatic or not. Findings of Detmer [30] revealed that the majority of patients were symptomatic. Findings of our study contradict with Diebal 2012 [3] as they confirmed the failure of non-surgical management (anti-inflammatory drugs, stretching, prolonged rest, decreasing or avoiding the problematic activity, orthotics, and massage) to address symptoms.

There are some limitations of the current study that should be recognized. The main limitation of our study was the fact that the conventional program, which was prescribed for the two groups, is already effective by itself. Therefore, the results of this study failed to prove the independent effects of Astym or massage therapy alone. In addition, this study only reported the short-term effects of ASTYM or massage, so we cannot generalize about long-term effects.

Conclusion

Pain and disability typically associated with ant-CECS reduced greatly after the treatment of ant-CECS using ASTYM or massage. ASTYM treatmentis more effective than massage therapy in reducing pain, improving the overall functional level and ankle dorsiflexion for patients with ant-CECS.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Tucker AK. Chronic exertional compartment syndrome of the leg. Curr Rev Musculoskelet Med. 2010; 3(1-4): 32-37.

2. Van Zantvoort APM, de Bruijn JA, Winkes MB, Hoogeveen A R, Teijink J A W, Scheltinga M R. Role of repeat muscle compartment pressure measurements in chronic exertional compartment syndrome of the lower leg. Orthop J Sports Med. 2017; 5(6): 1-6.

3. Diebal AR, Gregory R, Alitz C, Gerber JP. Forefoot running improves pain and disability associated with chronic exertional compartment syndrome. Am J Sports Med. 2012; 40(5): 1060-7.

4. Franklyn-Miller A, Roberts A, Hulse D, Foster J. Biomechanical overload syndrome: defi ning a new diagnosis. Br J Sports Med. 2012:1-3.

5. Fronek J, Mubarak SJ, Hargens AR, Lee YF, Gershuni DH, Garfin SR, et al. Management of chronic exertional anterior compartment syndrome of the lower extremity. Clin Orthop Relat Res. 1987; (220): 217-27.

6. Howard JL, Mohtadi NG, Wiley JP. Evaluation of outcomes in patients following surgical treatment of chronic exertional compartment syndrome in the leg. Clin J Sport Med. 2000; 10: 176–84.

7. Roscoe D, Roberts A. Intramuscular Compartment Pressure Measurement in Chronic Exertional Compartment Syndrome: New and Improved Diagnostic Criteria. Am J Sports Med. 2014; 20(12): 1-7.

8. Frontera W. Essentials of physical medicine and rehabilitation. Canada: Hanley and Belfus; 2002. p. 256–61.

9. Schepsis AA, Fitzgerald M, Nicoletta R. Revision surgery for exertional anterior compartment syndrome of the lower leg: technique, findings, and results. Am J Sports Med. 2005; 33(7): 1040-7.

10. Rajasekaran S, Hall MM. Nonoperative Management of Chronic Exertional Compartment Syndrome: A Systematic Review. Curr sports Med Rep. 2016;15(3): 191-8

11. Gill CS, Halstead ME, Matava MJ. Chronic exertional compartment syndrome of the leg in athletes: evaluation and management. Phys Sports Med. 2010; 38(2): 126-32.

12. Matsen FA, Winquist RA, Krugmire RB. Diagnosis and management of compartmental syndromes. J Bone Joint Surg. 1980; 62(2): 286-91.

13. Pandit A. Study of Complication Profile in Type 2 Diabetes Mellitus Patients at First Visit to Tertiary Care Clinic in Central Indian Context. IJHSR. 2016; 6(6): 46-9.

14. De Oliveira RR, Lemos A, de Castro Silveira PV, Da Silva RJ, De Moraes SR. Alterations of tendons in patients with diabetes mellitus: a systematic review. Diabetic Medicine. 2011 ;28(8): 886-95.

15. Tajik A, Shokri E, Ghanbari A. The Effect of Kinesio Taping of Quadriceps Muscle on the Balance of Non-Elite Football Players After a Local Fatigue Induced Protocol. J Rehab Sci Res. 2016;16; 3(1): 5-10.

16. Kivlan BR, Carcia1 CR, Clemente1 FR, Phelps AL, Martin RL. The effect of Astym® therapy on muscle strength: a blinded, randomized, clinically controlled trial. BMC Musculoskelet Disord. 2015; 16: 325

17. Binkley JM, Stratford PW. The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network. Phys Ther. 1999; 79(4): 371-83.

18. Canale S. Campbell’s operative orthopaedics. 9th ed. Philadelphia: Elsevier; 1998. p. 405–1411.

19. Brown Am, Stubbs DW. Medical physiology. New York: Wiley medical. 1983; p.284

20. Sejersted OM, Hargens AR. Regional pressure and nutrition of skeletal muscles during isometric contraction. In Hargens A.R (ed.): Tissue nutrition and viability. New York:Springer-Verlag. 1996; p. 263-83

21. Jacobbson S, Kjellmer I. Flow and protein content of lymph in a resting and exercising skeletal muscle. Acta Physiol, Scand. 1964; 60: 278.

22. Scheer NA, Alstat LR, Van Zant RS. Astym therapy improves bilateral hamstring flexibility and Achilles tendinopathy in a child with cerebral palsy: a retrospective case report. Clin Med Insights: Case Reports. 2016; 9:95-8.

23. Collins CK, Gilden B. A non-operative approach to the management of chronic exertional compartment syndrome in a triathlete: A case report. Intern J Sport phys. 2016; 11(7):1160-76.

24. Sevier TL, Stegink-Jansen CW. Astym treatment vs. eccentric exercise for lateral elbow tendinopathy: a randomized controlled clinical trial. Peer J. 2015; 19: 3:DOI: 10.7717/peerj.967. 

25. Laudner K, Compton BD, McLoda TA, Walters CM. Acute effects of instrument assisted soft tissue mobilization for improving posterior shoulder range of motion in collegiate baseball players. Int J Sports Phys Ther. 2014; 9(1): 1.

26. Loghmani MT, Warden SJ. Instrument-assisted cross fiber massage increases tissue perfusion and alters microvascular morphology in the vicinity of healing knee ligaments. BMC Complement Altern Med. 2013; 13(1): 240.

27. McCormack JR. The management of bilateral high hamstring tendinopathy with ASTYM® treatment and eccentric exercise: a case report. J Man Manip Ther. 2012; 20(3): 142–6.

28. Chughtai M, McGinn T, Bhave A, Khan S, Vashist M, Khlopas A, et al. Innovative multimodal physical therapy reduces incidence of repeat manipulation under anesthesia in post–total knee arthroplasty patients who had an initial manipulation under anesthesia. J Knee Surg. 2016; 29(8): 639-44.

29. Packer J D, Day MS, Nguyen JT, Hobart SJ, Hannafin JA, Metzl J D. Functional outcomes and patient satisfaction after fasciotomy for chronic exertional

compartment syndrome. Am J Sports Med. 2013; 41(2): 430-6.

30. Detmer DE, Sharpe K, Sufit RL, Girdley FM. Chronic compartment syndrome: diagnosis, management, and outcomes. Am J Sports Med. 1985; 13:162-70.

PDF

Download attachments: JCAM_5986.pdf

How to Cite

Ragab IM, Ali OI, Hamada HA, Radwan R, Mosaad D. ASTYM versus massage in the treatment of chronic exertional anterior compartment syndrome of the lower leg: a randomized controlled trial. Ann Clin Anal Med 2019;10(4): 470-4

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Relationship between glomerular filtration rate with uric acid and neutrophil to lymphocyte ratioin diabetic patients

Yasemin Kaya 1, Ahmet Karataş 2, İlhan İrende 3

1 Department of Internal Medicine, Ordu University Medical School, Ordu, 2 Department of Nephrology, Ordu University Medical School, Ordu, 3 Department of Medical Biology, Karadeniz Teknik University Medical School, Trabzon, Turkey

DOI:10.4328/ACAM.5953 Received: 27.06.2018 Accepted: 17.08.2018 Published Online: 27.08.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 436-40

Corresponding Author: Yasemin Kaya, Department of Internal Medicine, Ordu University Medical School, 52000, Ordu, Turkey. T.: +90 452 2252342 F.: +90 452 2250190 E-Mail: ysmnkcmz@gmail.com ORCID ID: https://orcid.org/0000-0001-7360-8090

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: In this study we aimed to investigate the relationship between uric acid (UA) and neutrophil-lymphocyte ratio (NLO) with glomerular filtration rate (GFR) in diabetic patients. Material and Method: 355 diabetic patients were included in this study. Patients with gout, liver fatigue, coronary artery disease, heart fail-ure, cancer disease, polycythemia, hypothyroidism, sarcoidosis, obesity, rheumatic diseases and active infection were excluded from the study. The biochemis-try and complete blood count tests were recorded.GFR were calculated by the formula of Modification of Diet in Renal Disease. 24-hour urine microalbumin and protein levels were measured. Results:The patients with estimated GFR<60 werecompared to the patients with e-GFR>60.The patients with e-GFR>60were older and had higher NLR ratio, UA levels; more proteinuria-microalbuminuria. The age, UA levels and microalbuminuria was determined as e-GFR independent predictors.It was detected that when UA value was taken as >5.70mg/dl, e-GFR<60 ml/min/1.73m2 was demonstrated by the sensitivity of 80% and the specifity of 75% (AUC:0.863, 95%CI 0.785-0.941, p<0.001). Discussion: The high level of UA can be used as one of the independent predictors of e-GFR<60 ml/min/1.73 m2 in patients with DM. Although there is significant negative correlation between e-GFR and NLR, this doesn’t predict e-GFR<60 mL/min/1.73m2.

Keywords: Neutrophil Lymphocyte Ratio; Uric Acid; Diabetic Nephropathy

Full Text

Introduction

Diabetic nephropathy has a growing importance today as the most common cause of end-stage renal failure. It is known that the diabetic nephropathy develops in 20-40% of the patients with diabetes around the world [1].  

Uric acid is the end product of purine catabolism in humans. At the same time, it is suggested as a result of the studies performed that the uric acid is a protective antioxidant against the oxidative stress [2,3].However, while it is expected that the uric acid, which is known to be an anti-oxidant in the diabetic patients, corrects the renal damage, it is said that it increases the renal damage [4-6].

It is acknowledged that the oxidative stress develops in diabetes, and this oxidative stress contributes to the formation of both the disease and the complications [7-11]. It is also showed in the studies performed that the inflammation plays a role in the etiopathogenesis of diabetes and its complications [12,13].The neutrophil-lymphocyte ratio (NLR) is an easily measurable systemic inflammatory marker and is showed to have a close relationship with morbidity and mortality in numerous diseases [14].

We aimed in this study to investigate the relationship of uric acid (UA) and NLR with the estimated glomerular filtration rate (e-GFR) in diabetic patients, and whether or not they can be used as clinical markers to show the changes in e-GFR.  

Material and Method

In this retrospective longitudinal study, our study consisted of a population of non-selected 466 patients, who visited our clinic from January to August 2014.   The exclusion criteria were gout disease (n=5), hepatic steatosis (n:20), coronary artery disease (n=21), heart failure (n=11), sarcoidosis (n=1), obesity (n=15) , cancer disease (n=5), rheumatic diseases (n=4), inflammation which may cause a systemic infection in the body (n=12), polycythemia (n:1), and hypothyroidism (n=16). Finally, the study population consisted of 355 patients. All participants gave an informed consent and the study was approved by the local ethics committee.    

After 12 hours of fasting, the blood samples were taken from all patients, who underwent a detailed physical examination,for the routine biochemical parameters and the complete blood count tests.

The blood samples were collected in gel tubes that did not include anticoagulant to measure the fasting glucose, urea, creatine, albumin, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL C), and uric acid (A). The blood samples were centrifuged at 1800*g for 15 minutes, and the plasma and the serum samples were obtained. The fasting glucose, total cholesterol, TG, HDL-C, LDL-C, and UA, urea, creatine and the albumin levels were measured cholorometrically using an Abbott original reagent on Abbott Architect 8000 auto analyzer.They were measured by the method of HbA1cHigh Performance Liquid Chromatography (HPLC) on the device of Automatic Glycohaemoglobin Analyzer ADAMS A1c HA-8160 (Arkray).

The venous blood is routinely collected in a tube containing EDTA for the measurement of hemoglobin, total WBC, neutrophils, lymphocytes were determined using an automated blood cell counter by an Abbott Cell-Dyn 3700 Hematology in all patients .    

GFR of the patients were calculated considering the serum creatinine, age, race and gender based on Modification of Diet in Renal Disease (MDRD) formula [14].For the staging of chronic kidney disease; stage 1 was described as GFR ≥90 mL / min / 1.73 m 2, stage 2 as GFR = 60-89 ml / min / 1.73 m 2, stage 3 as GFR = 30-59 ml / min / 1.73 m 2, stage 4 as GFR = 15-29 mL / min / 1.73 m2, stage 5 as GFR <15 mL / min / 1.73 m2 or as undergoing dialysis.

All patients were explained the 24-hour urine collection method and the samples were collected as described and transported to the laboratory [15]. The microalbumin and the protein levels in the urine collected were studied by the immunoturbidimetric technique on the device of Abbott Architect 8000 auto analyzer. The results were defined as following: normoalbuminuria<30 mg / day; microalbuminuria 30-200 mg / day; macroalbuminuria, ≥300 mg/day, proteinuria> 150 mg / day [1].   

Statistical analysis

The quantitative variables are expressed as mean ± SD, and the categorical variables are expressed as percentage. In order to test the differences of the numerical variables between the groups, Student’s t test or Mann-Whitney U test was used.In order to test the differences of the categorical variables between the groups, Chi-square test was used.Pearson or Spearman correlation test was used for the correlation analysis between the variables. Multiple linear regression analysiswas used for the detection of the independent predictors of the estimated GFR (what is found significant in the univariate analysis: the age,hemoglobin (HB), red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), uric acid (UA), albumin, fasting blood glucose, and microalbuminuria). ROC analysis was used to determine the best predictive value in the estimation of the estimated GFR (e-GFR). A P value of <0.05 was accepted as the limit of significance. SPSS 20.0 (SPSS Inch., Chicago, Illinois) software package was used for all statistical analysis. 

Results

A total of 355 diabetic patients were included in the study. The mean age of the patients was 57 ± 10 and 42.9% of them were men. E-GFR was measured as > 90 in 54.5% of the patients, 60-89 in 27% , 30-59 in 6.5%, 15-29 in 1%, , and <15 in 11%.When E-GFR was categorized according to 60, it was measured as >60in81.6% of the patients, and <60in18.4%of the patients. The number of the patients undergoing dialysis in the entire group was 10.8%. The other clinical and the biochemical variables of the entire population are summarized in Table 1.

The ones with e-GFR <60, compared to the ones with e-GFR >60, were older, had a higher male gender ratio, lower albumin levels, lower hemoglobin levels, higher RDW and NLR, more proteinuria and microalbuminuria, and higher levels of UA (Table 2). There was no difference between groups in terms of hypertension (p= 0,58 ) The age (r = -0,416, p <0.001), HB (r = 0.314, p <0.001), and RDW (r = -0,485, p <0.001), NL (r = -0,316, p <0.001) , A (r = -0,515, p <0.001 were observed by e-GFR.A negative correlation was found between between GFR and UA (figure 1) and NLR . A positive correlation was found between albumin (r = 0.382, p <0.001), fasting blood glucose (r = 0.632, p <0.001), microalbuminuria (r = -0315, p <0.001)

In order to detect the independent variables of e-GFR, multiple linear regression analysis was used.Accordingly, the age, UA level and the amount of microalbuminuria were determined as the independent predictors of e-GFR (Table 3).In ROC analysis carried out to predict e-GFR <60, UA level >5.70 is showed with a sensitivity of 80% and a specificity of 75% (AUC: 0.863, 95% CI 0.785 to 0.941, p <0.001) (Figure 2).

Discussion

In this study, we found that there was a negative correlation between GFR value and UA and NLR; UA was one of the independent predictors of GFR <60 mL/min/1.73m2; and NLR didnot predict GFR decline.

Lipid peroxidation, one of the most important causes of cell damage, is initiated by free oxygen radicals (FOR) and formed as a result of the oxidative degradation of unsaturated fatty acids in the cell membrane structure.It accumulates in the body as a result of the increase in the production of FOR occurred physiologically or a defect in the anti-oxidant defense system which eliminates the free radicals.Free oxygen radicals, interacting with lipids, proteins, and nucleic acids may lead to the loss of membrane integrity, the structural or functional changes in proteins and the genetic mutations [16].

It is reported in the studies that free oxygen radicals and lipid peroxidation significantly increases in diabetic patients; and the oxidative stress has an important role in the formation and the progression of diabetes [17]. It is also mentioned that the oxidative stress plays a role in the development of chronic complications of diabetes. The imbalance between the formation rate of free radicals and the antioxidant defense capacity cause to the chronic complications of diabetes meaning that hyperglycemia leads to the oxidative stress and therefore damages organs [18-21].

It has been reported that uric acid cleans up the toxic reactants at normal levels and is protective against the oxidative stress [2].

It has been demonstrated in the studies that the level of increased serum UA is related to type 2 DM and uric acid is one of the independent predictors of type 2 diabetes.In addition,in certain studies it is reported that hyperuricemia is common in the patients with chronic renal failure and has an important role in the development and progression of chronic renal disease; it is related to persistent macroalbuminuria and microalbuminuria in diabetic patients [4,23], can contribute to the formation of diabetic nephropathy and is one of the independent risk factors of renal dysfunction in diabetic patients [5]. It has also been demonstrated in the studies that a high level of serum uric acid which is reported to be harmful to the kidneys, induce the endothelial dysfunction and leads to glomerular hypertension and renal hypertrophy; and it decreases the renal perfusion by stimulating the vascular smooth muscle cells in arterioles[5,24,25].It was found in the studies that UA, which was known as antioxidant, caused renal damage although it was expected to have positive effects on the renal functions.In our study, we also found that the increased serum UA levels has a negative correlation with GFR, and are one of the independent predictors of GFR <60 mL / min / 1.73 m2.

It is mentioned in some studies that the antioxidants may act as the prooxidants in certain cases [23,26]. It is also known that uric acid acts as an antioxidant in the early stages of atherosclerotic process, and is the most powerful predictor of plasma antioxidant capacity [5,26]. However, the case of being antioxidant in the late stages of atherosclerotic process paradoxically turns into being prooxidant.This paradoxical situation depends on several environmental factors such as the process, tissue andsubstrate localization, acidity, oxidative environment, the other local antioxidant depletion and the release and presence of oxidants and enzymes to the medium[26].Diabetic nephropathy and GFR decline are seen in the advanced stages of diabetes.It is also reported in some studies that UA may act as a pro-oxidant if it increases 1/3 or more than the normal levels.Uric acid may turn into prooxidant in the patients with diabetes in which the complications develop like in the atherosclerotic process [27].Zapolski et.al also report as a result of their studies that a high level of uric acid is related to the pro-inflammatory markers; and the relation with inflammation may cause to renal dysfunction in the patients with metabolic syndrome and coronary artery disease [28].There isa need for studies to explain the etiopathogenesis of renal damage uric acid causes in the patients with diabetes.

Many studies show that inflammation plays an important role in the development of diabetic nephropathy .The inflammatory cytokines play an important role at every stage from the development of acute renal failure to the chronic renal disease.The destructive enzymes released as a result of the stimulation of the inflammatory cells (macrophages, natural cellar, neutrophils, etc.) for any reason (ischemia, exposure to sepsis or nephrotoxic agents) lead to the structural and the functional changes in endothelial and tubular epithelium; and the inflammatory pathways have an important role in the progression of renal damage as well as in harming the vascular permeability and the endothelial functions and inducing the acute renal damage[11-13,29].In a number of studies in recent years, it is detected that NLR is a non-specific marker of the systemic inflammation and related to many cardiac and non-cardiac diseases.[30]Azab et al.suggest that NLR is not only a marker of presence of nephropathy but a factor in the pathogenesis of the disease [31]. In another study, it was found that NLR predicts albuminuria in diabetic patients [32]. On the other hand, it was observed in another study that no correlation existed between the inflammatory marker of CRP levels and diabetic nephropathy (GFR 60 mL / min / 1.73 m2) [31]. In this study, we found that when compared the ones with the estimated GFR <60 with the ones with GFR >60, NLR significantly increased in the ones with the estimated GFR <60, but didnot independently predict the estimated GFR <60.Considering the fact that the onset and the progression of diabetic nephropathy is related to many mechanisms, we think that there is a reason for NLR was not found to be an independent predictor in our study.

Diabetic nephropathy is one of the major complications of diabetes and is formed with many complex pathophysiological mechanisms.It was demonstrated in the studies that oxidative stress and inflammation can stimulate each other [33,34]. It is difficult to know which pathophysiological mechanismis dominant in which patient.This makes difficult the early prediction of diabetic nephropathy, and therefore the treatment decision.In the view of these results, we believe that the application of treatments with anti-inflammatory and anti-oxide from the properties may be worthy for further investigation in the prevention of early intervention or progression of DM nephropathy. 

Limitations

This is an observational, single-institution study that had a relatively small sample size and thus was subject to various unaccounted confounders inherent in such an analysis. Additionally, we could not compare NLR with other inflammatory markers, CRP, fibrinogen, or myeloperoxidase, because they were not routinely measured in our study population.

Conclusion

A high level of UA may be used as one of the independent predictor of diabetic nephropathy in the patients with DM (GFR <60 ml / min / 1.73 m2). Although there is a significant negative correlation betweenGFR and NLR, NLR does not predict GFR <60 mL / min / 1.73 m2, .There is need for more studies to explain the etiopathogenesis of diabetic renal damages.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Amerıcan Dıabetes Assocıatıon. Standards Of Medical Care İn Diabetes.Dıabetes Care. 2010; 33:11-61.

2. Nakatani ANakatani SIshimura EMurase TNakamura TSakura Met al. Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients. Sci Rep. 2017;7:15416.

3.Choromańska MKlimiuk AKostecka-Sochoń PWilczyńska KKwiatkowski MOkuniewska Net al. Antioxidant Defence, Oxidative Stress and Oxidative Damage in Saliva, Plasma and Erythrocytes of Dementia Patients. Can Salivary AGE be a Marker of Dementia? Int J Mol Sci. 2017;18:1-16.

4. Hovind PRossing PTarnow LJohnson RJParving HH. Serum Uric Acid as a Predictorfor Development of Diabetic Nephropathy in Type 1 Diabetes. Diabetes 2009;58:1668–1671.

5. Behradmanesh S, Horestani MK, Baradaran A,  Nasri H.. Association of serum uric acid with proteinuria in type 2 diabetic patients. J Res Med Sci 2013;18:44-6.

6.Bonakdaran S, Hami M, Shakeri MT. Hyperuricemia and Albuminuria in Patients With Type 2 Diabetes Mellitus. Iran J Kidney Dis. 2011;5:21-4.

7. Araszkiewicz A, Zozulinska-Ziolkiewicz D. Retinal Neurodegeneration in the Course of Diabetes-Pathogenesis and Clinical Perspective Current Neuropharmacology 2016; 14: 805-809

8. Wang WXLuo SBJiang PXia MMHei ALMao YH et al. Increased Oxidative Damage of RNA in Early-Stage Nephropathy in db/db Mice. Oxid Med Cell Longev. 2017;2017:1-12.

9. Liu WYLiou SSHong TY,  Liu IM. Protective Effects of Hesperidin (Citrus Flavonone) on High Glucose Induced Oxidative Stress and Apoptosis in a Cellular Model for Diabetic Retinopathy. Nutrients. 2017;2:9-12.

10. Castro-Correia CMaia MLNorberto SCosta-Santos CBarroso MFCarvalho Aet al. Can Antioxidative Status Be Involved in Type 1 Diabetes? J Clin Med Res. 2017;9:998-1001.

11. Rani AJMythili SV. Study on Total Antioxidant Status in Relation to Oxidative Stress in Type 2 Diabetes Mellitus. Journal of Clinical and Diagnostic Research 2014; 8: 108-110.

12. Sohrab GNasrollahzadeh JZand HAmiri ZTohidi MKimiagar M.. Effects Of Pomegranate Juice Consumption On İnflammatory Markers İn Patients With Type 2 Diabetes: A Randomized, Placebo-Controlled Trial. J Res Med Sci 2014; 19:215-220.

13. Zhang MChen PChen SSun QZeng QCChen JY,,et al. The Association Of New İnflammatory Markers With Type 2 Diabetes Mellitus And Macrovascular Complications. A Preliminary Study European Review For Medical And Pharmacological Sciences 2014; 18: 1567-1572.

14. Kaya AKaya YTopçu SGünaydin ZYKurt MTanboğa IHet al. Neutrophil to Lymphocyte Ratio Predicts Contrast Induced Nephropathy in Patients Undergoing Primary Percutaneous Coronary Intervention. Angiology 2014; 65: 51-56.

15.Levey AS, Coresh J, Greene T, Stevens LA, Zhang Y, Hendriksen S. et al. Using standardized serum creatinin evalues in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145:247–54.

16.Turk HM, Sevinç A, Camcı C. Plasma lipid peroxidation products and antioxidant enzyme activities in patients with type 2 diabetes mellitus. ActaDiabetol 2002; 39:117-122.

17.Kulkarni R,Acharya J, Ghaskadbi S, Goel P. Thresholds of oxidative stress in newly diagnosed diabetic patients on intensive glucose-control therapy. PLoSOne 2014; 9: 1-8.

18. Sifuentes-Franco SPacheco-Moisés FPRodríguez-Carrizalez AD,  Miranda-Díaz AG. The Role of Oxidative Stress, Mitochondrial Function, and Autophagy in Diabetic Polyneuropathy. J Diabetes Res. 2017;1-15

19. Butaeva SGAmetov ASBugrov AV,  Dolgov VV. Glycemic variability and oxidative stress in patients with type 2 diabetes mellitus during combined glucose-lowering therapy.Ter Arkh. 2017;89: 36-39.

20. Kurosaki YImoto AKawakami F,  Yokoba MTakenaka TIchikawa Tet al. Oxidative stress increases megalin expression in the renal proximal tubules during the normoalbuminuric stage of diabetes mellitus. Am J Physiol Renal Physiol. 2018;314:462-470.

21.Lipinski B. Pathophysiology of oxidative stress in diabetes mellitus. Journal of Diabetes and Its Complications 2001; 15: 203–210.

22.Kramer CK, M¨Uhlen DV,Jassal SK,  Barrett-Connor E. Serum Uric Acid Levels Improve Prediction Of IncidentType 2 Diabetes İn Individuals With Impaired Fasting Glucose. Diabetes Care 2009; 32:1272–1273.

23.Yan L, Xiao-mu L, Xin G. Cross-sectionalassociation of serum C-reactive protein anduricacidwithalbuminuria in Chinesetype 2 diabeticpatients. ChinMed J.2013;126: 4023-4029.

24.Behradmanesh S, Horestani MK, Baradaran A, Nasri H. Association of serum uric acid with proteinuria in type 2 diabetic patients. J ResMedSci.2013; 18:44-6.

25.Khosla UM, Zharikov S, Finch JL, Nakagawa TRoncal CMu Wet al. Hyperuricemia induces endothelial dysfunction. KidneyInt. 2005;67: 1739-1742.

26.Naghavi M, John R, Naguib S,  Siadaty MSGrasu RKurian KCet al. pH Heterogeneity of human and rabbit atherosclerotic plaques; a new in sight into detection of vulnerable plaque. Atherosclerosis 2002; 164:27-35.

27.Nan H, Dong Y, GaoW, Tuomilehto JQiao Q. Diabetes associated with a low serum uric acid level in a general Chinese population. Diabetes Res Clin Pract.2007;76: 68–74.

28. Hayden MR, Tyagi SC. Uricacid A newlook at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: Theurateredoxshuttle. Nutr Metab.2004; 1: 1-10.

29.Navarro-Gonza´ lez JF, Mora-Ferna´ ndez C. The Role of Inflammatory Cytokines in Diabetic Nephropathy. J Am Soc Nephro 2008; l19:433–442.

30.Kaya A, Kurt M, Tanboğa İ.H,  Işık TGünaydın ZYKaya Yet al. Relation of Neutrophil to Lymphocyte Ratio With the Presence and Severity of Stable Coronary Artery Disease. Clinical and Applied Thrombosis/Hemostasis 2013; 23;20: 473-477.

31.Azab B, Daoud J, Naeem FB,  Nasr RRoss JGhimire Pet al. Neutrophil-to-Lymphocyte Ratio as a Predictor of Worsening Renal Function in Diabetic Patients (3-Year Follow-UpStudy).Renal Failure 2012; 34: 571–576.

32. Akbas EM, Demirtas L, Ozcicek A,  Timuroglu ABakirci EMHamur Het al. Association of epicardial adipose tissue, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with diabetic nephropathy .Int J Clin Exp Med 2014; 7:1794-1801

33. Gupta SGambhir JKKalra OGautam AShukla KMehndiratta M, et al. Association of biomarkers of inflammation and oxidative stres with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. Journal of Diabetes and Its Complications 2013; 27: 548–552.

34. Kuhad, A, Chopra K. Attenuation of diabetic nephropathy by to cotrienol: Involvement of NFkB signalling pathway. Life Sciences 2009; 84:296–301.

PDF

Download attachments: JCAM_5953.pdf

How to Cite

Kaya Y, Karataş A, İrende İ. Relationship between glomerular filtration rate with uric acid and neutrophil to lymphocyte ratioin diabetic patients. Ann Clin Anal Med 2019;10(4):436-40

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Comparison of the intraocular pressure measurements with the tono-pen and the goldman applanation tonometer and the effect of central corneal thickness on measurements

Mehmet Serdar Dervişoğulları 1, Cengiz Akarsu 2, Ahmet Ergin 3

1 Başkent University, Ophthalmology Department, Adana, 2 Dünya Göz Hospital, Antalya, 3 Balıkesir University, Ophthalmology Department, Balıkesir, Turkey

DOI:10.4328/ACAM.5996 Received: 04.08.2018 Accepted: 14.09.2018 Published Online: 17.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 479-84

Corresponding Author: Mehmet Serdar Dervisogullari, Ophthalmology Department, Başkent University Medical School, Adana Dr. Turgut Noyan Clinic and Research Center, Adana, Turkey. T.: +90 3223272727 F.: +90 3223271274 Gsm: +905327720616 E-Mail: serdarderv@hotmail.com ORCID ID: https://orcid.org/ 0000-0003-2006-2906

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: Incorrect values of applanation tonometers according to varying corneal thickness were investigated many times. In this study, we aimed to compare intraocular pressure (IOP) measurements of the Tono-Pen and Goldman applanation tonometer (GAT) in eyes with normal corneas of various thicknesses.Material and Method: IOP was measured with Tono-Pen and GAT respectively in 255 patients’ eyes with normal corneas. Only the right eyes were analyzed for statistical purposes. Central corneal thickness (CCT) was measured using an ultrasound pachymeter after all IOP determinations had been made. Re-sults: With both instruments, IOP varied with CCT. Readings with Tono-Pen showed a mean increase in IOP with increasing CCT of 0,18 mmHg/10μm and an increase of 0,16 mmHg/10 μm with the GAT. The Tono-Pen consistently recorded comparatively higher IOPs than the GAT (p<0,05). Discussion: In our study, the difference between the Tono-Pen and GAT measurements is statistically insignificant and 60% of this difference is within the 1 mmHg range. Although it is thought that Tono-Pen may be less affected by corneal thickness due to the measurement from a smaller area we did not obtain data that Tono-Pen is less affected by corneal thickness as a result of linear regression analysis.The Tono-Pen is more affected by CCT when used to measure IOP in eyes with normal corneas. This is contrary to expectations, based on the theory that Tono-Pen is least affected by the CCT because it needs smaller applanation area.

Keywords: Tono-Pen; Goldman Applanation Tonometer; Intraocular Pressure; Central Corneal Thickness

Full Text

Introduction

Glaucoma is an ocular disease characterized by optic neuropathy which is caused by mechanisms connected to vascular and mechanical factors and is among the leading causes of preventable blindness in the world. Elevated intraocular pressure (IOP) is the most common risk factor. In the pathogenesis of glaucoma, blood flow in the eye, optic disc structure and ganglion cell degeneration are also important but the most important factor in diagnosis and treatment of the disease is IOP. Many instruments such as Schiotz indentation tonometry, Goldman applanation tonometry (GAT), McKayMarg tonometry, noncontact and contact pneumotonometers have come to the fore with the historical process in IOP measurements made from smooth corneal surfaces. Among them only McKay-Marg tonometry can measure irregular corneal surfaces due to scarring, edema or surgery [1] but it is not in production today. GAT developed by Goldman in 1957 according to the Imbert-Fick law has been accepted as the gold standard today. According to the Imbert-Fick law the pressure to flatten the wall of an elastic full of water, for example a balloon, is equal to the applied force divided by the application area. In fact, this law recognizes that cornea is a structure that does not resist other forces than the internal pressure force against fine, applied gentleness in perfect elasticity. Goldman and Schmidt stated that although the device is calibrated according to the standard corneal thickness (520 μm), it may theoretically be affected by corneal thickness changes [2]. There are many factors that can affect the IOP measurements made with this device. The accuracy of the measurement is expected to increase with the application of the appropriate measurement technique in large scale. [3] As for the negative aspects of GAT, this device, which is developed with constant corneal thickness and higher values above the value, may cause lower measurements at lower thicknesses, and corrections between 1 and 6.8 mmHg are also made for a 0.1 mm change in corneal thickness. [4] Glaucoma prevalence, which is high in myopic patients, and the increase in refractive surgical procedures that change corneal thickness in recent years have made the relationship between IOP and corneal thickness more important [5]. In addition to differences in race, age and gender, central corneal thickness (CCT) and corneal curvature and IOP and curvature associations are also discussed in corneal thickness [6]. Medeiros et al. have shown that ocular hypertensive cases with early glaucomatous defects with perimeter have lower CCT values than those without a defect [7].
In this context, the use of devices such as Tono-Pen, which is thought to be less affected by corneal surface irregularities and thickness in recent years, has come to the fore. Tono-Pen works according to the McKay-Marg principle, which expresses the conversion of mechanical energy into electrical energy. The measurement area measures from a smaller area (diameter of 1.02 mm) than the GAT (diameter of 3.06 mm) with a transducer movement as small as 10 μm, which may be considered to be less affected by corneal thickness. The positive aspects of the device are that it is easier to measure IOP in situations such as corneal irregularity, lid edema, narrow palpebral aperture, infant, small children, bedridden or wheelchair patients, head tremor or nystagmus patients.
CCT can be measured by optic or ultrasonographic methods. Ultrasonic pachymetry is a more reliable, precise method than optic pachymetry, with repeated measurements of the observer and less variability between different observers [8].
In this study, we aimed to investigate the effect of CCT on the IOP measurements of GAT and Tono-Pen devices. According to our hypothesis corneal thickness does not make a difference in IOP measurements between the Tono-Pen and the GAT.

Material and Method

This study was performed in adherence with the tenets of the Declaration of Helsinki and was approved by the Kırıkkale University Medical Faculty Ethics Committee (14.01.2004/2004106). Informed consent was obtained from all of the study participants. Participants with less than 2D spherical and 1D astigmatic refraction were enrolled. Two hundred and fifty-five patients who did not have any contact lens and volunteered to participate in the study were prospectively included in the study. Patients with a history of intraocular surgery history, unilateral anophthalmia, any corneal pathology or scarring and evidence of anterior segment inflammation were excluded. Visual acuity, refraction, biomicroscopy and fundoscopy examinations were performed on both eyes of the participants. The age and sex of the participants were recorded. The participants’ ages ranged from 10 to 80 (average 40.86). There were 109 males and 146 females. In all examinations the right eye was first evaluated. All examinations and measurements were made between 09:00 and 14:00 hours. In response to the possibility of the GAT dropping the IOP and causing the lower values that can be measured with the Tono-Pen, the GAT and IOP measurement examination was first applied to 128 participants. Measurements with GAT (Zeiss Co, Zurich, Switzerland) were performed on the patients looking at a target at a distance of 6 m, in the primary position, with a drop of 0.25% fluorescein in both eyes subconjunctivally as a mixture of 0.45% oxybuprocaine hydrochloride (Benoxinate, Alcon Couvreur, Puurs, Belgium) and fluorescein (Fluoroscite 10%, Alcon, Texas, USA). Participants were asked not to move their eyes and to breathe regularly. The blue light was turned on until the end and was brought to an angle of 45 degrees with the eye in the horizontal plane. The arithmetic averages were obtained by the experienced practitioner by performing 3 measurements within the limit of 1 mmHg (MSD). In the study, the same GAT was used regularly with annual calibration. The IOP measurements were then repeated with the Tono-Pen (Tono-Pen XL, Mentor Ophthalmics, CA, USA) instrument in a sitting position, looking at the target 6 m away in the primer position, Measurements with Tono-Pen were performed after the drop of 0.45% oxybuprocaine hydrochloride was applied to the lower conjunctival fornix of both eyes. For each patient, a new latex membrane (Mentor OcuFilm Type Covers) was placed on the transducer. After Tono-Pen was activated and the ‘beep’ sound was heard the transducer was contacted gently to the cornea, waiting for at least 1 second until the ‘beep’ sound indicating successful measurement. The procedure was repeated until two measurement results with reliability of 5% were obtained on the liquid display. All the IOP measurements with Tono-Pen were performed by the same practitioner (MSD). Tono-Pen was calibrated every morning in line with the manufacturer’s recommendation. After the measurement with Tono-Pen or GAT, the measurement with the other instrument was made 15 minutes apart. After IOP measurements were completed by both methods, central corneal thickness (CCT) was measured with an ultrasonic pachymeter (Optikon 2000 S.p.A., Rome, Italy). After dropping 0.45% oxybuprocaine hydrochloride to each lower conjunctival sac, the patient was held in the primary position, the probe was held perpendicular to the cornea and 3 measurements were taken from the undiluted pupil center and averaged. The participant was asked to blink between measurements. Pachymeter measurements were all made by the same person (MSD). Measurements were made in both eyes, and only right eyes were included in the study. Since the measurements are made with corneal contact, the possible complication is keratitis. Therefore antibiotic drops were applied to the eyes after the measurement.

When the alpha value (confidence interval) was 0.05 and the number of participants was 255, the power of the study was determined to be 80% to show a 2% difference between the two instruments’ measurements. IOP measurements of both devices were evaluated by the Student t- test. Simple linear regression analysis (dependent on IOP measurement with Tono-Pen or GAT, corneal thickness as an independent variable) was used to determine the measurement averages of both devices in relation to the corneal thickness and regression equations were found. The increase in measured IOP by 10 μm in CCT is calculated from the graphs for each of the Tono Pen and GAT devices. For this statistical evaluation, SPSS Ver. 11.0 (SPSS Inc, Chicago, USA) program was used. The values of p<0.05 were considered statistically significant.

Results

There was no statistically significant difference in the measurements of Tono-Pen (p = 0.352), GAT (p = 0,203) and CCT (p = 0,734) (P <0.05) according to the gender. (Table 1) Using Tono-Pen and GAT, a total of 255 values were determined. In the measurements, the mean of the Tono-Pen measurements (± SD) was 16.71 (±3.09) mmHg (8-30 mmHg) and the mean of the GAT measurements was (± SD) 16.10 (±3.07) mmHg (7-26mmhg). The measurement difference between the two devices was statistically significant (p <0.05) and Tono-Pen measurements were higher. Tono-Pen and GAT measurements differed from 0,6 to 1 mmHg (Figure 1). According to the point distribution graph and the regression curve for the comparison of the thickness of the cornea with Tono-Pen, the regression equation is y = 6,812 + 0,018x (r2: 0.041), where y = IOP measured by Tono-Pen, x = CCT. An increase of 0, 18 mmHg was observed in the IOP measurement made with Tono-Pen in every 10 μm increase in CCT (Figure 2). According to the results of linear regression analysis, GAT is less affected by corneal thickness (An increase of 0, 16 mmHg was observed in the IOP measurement made with GAT in every 10 μm increase in CCT).

In Table 2 and Figures 1, 2 and 3 we can see that the Tono-Pen measurements are higher than the GAT measurements. This difference in measurement was statistically significant (p<0.05). The mean CCT (± SD) was 547 (± 34.50 μm)( range of 451.60-650 μm) (Figure 4).
The regression equation is y = 7,448 + 0,016x (r2 = 0,032), where y = the IOP value measured with GAT and x = the CCT value. According to the point distribution graph for the CCT comparison of GAT and the regression curve, the IOP measurement value with GAT increased by 0.16 mmHg at a 10 μm increase in thickness (Figure 3). There was no statistically significant difference between measurements performed with Tono-Pen (p = 0.411) or with GAT (p = 0.579) (Table 2).

Discussion

Glaucoma is one the most important cause of blindness in the world and the only currently accepted treatment is the reduction of IOP. For this reason, correlations of IOP measuring devices with each other have always been the subject of research. Today GAT is accepted as the gold standard in IOP measurement but many factors are thought to affect its measurement results. Opinions have been reported that changes in corneal thickness, which is the determinant of corneal rigidity, will affect measurements. [9] In some studies in which invasive IOP measurement methods were used, the values obtained with the applanation method were normal with the corneal thickness increase. [3] Recep et al. have shown that noncontact tonometers are also affected by corneal thickness. [10] Feltgen and colleagues found that Tono-Pen and Perkins applanation tonometry measurements are correlated with manometric measurements and did not require any correction.[11] Comparison of GAT with the first sample of Tono-Pen (Tono-Pen-1) was made in 1987 by Minckler et al. and reported that Tono-Pen showed higher values at higher IOP and lower values at lower IOP. [13] Hessemer et al. compared manometric measurements with TonoPen and reported that Tono-Pen showed lower values at 17 mmHg below and higher at 17 mmHg [14] and Foster et al.observed a deviation of 2 mmHg (between -8 and +4) with Tono-Pen compared to the manometric measurements in their 23 eyes performed phacoemulsification but this deviation could not be correlated with corneal thickness.[15] Similar results were reported in similar studies on rabbits and rats. [16] Eisenberg et al. reported that they measured very well with the Tono-Pen’in laboratory conditions but they found a decrease in the accuracy of the measured values compared with intraocular measurements [17]. Feltgen et al. reported that Tono-Pen and Perkins applanation tonometers were correlated with each other and their measurement results were not affected by corneal thickness in their studies comparing applanation tonometry measurements with manometric measurements according to corneal thickness [11].

It has been shown that the cornea is thinner in pseudoexfoliation glaucoma cases [10]. In order to avoid detection of false low IOP values in lower CCT, IOP measuring devices are required to minimize the effect of corneal thickness and make measurements close to true IOP values. It is known that changes in IOP measurements after surgery compared to the preoperative period are determined due to the decrease of corneal thickness after excimer laser photorefractive keratectomy in myopia cases. The incidence of increased glaucoma in myopic patients and the increase in refractive surgery applied to myopia today are considered to be significant. In some previous studies, Tono-Pen has been shown to make precise measurements in the eye bank eyes [18]. However in vivo studies have identified some data suggesting that Tono-Pen and GAT measurements are incompatible with the clinic. For example Tono-Pen reported inconsistent results on measurements over 30 mmHg [19] did not reflect IOP fluctuation and did not make precise measurements that could be used in glaucoma diagnosis and follow-up [20]. It is thought that the inaccuracies of in vitro studies are related to the absence of precorneal tear film, live corneal epithelium, normal corneal thickness and rigidity, extraocular muscle function, fluctuating blood pressure,respiration and even patient anxiety [21],

In our study the difference between the Tono-Pen and GAT measurements is statistically insignificant and 60% of this difference is within the 1 mmHg range. Our sample size and standardized measurement procedures did not allow statistical uncertainty.
Although it is thought that Tono-Pen may be less affected by corneal thickness due to the measurement from a smaller area we did not obtain data that Tono-Pen is less affected by corneal thickness as a result of linear regression analysis. We also observed slightly higher values with Tono-Pen as the thickness increased and found increases of 0.18 mmHg with TonoPen and 0.16 mmHg with GAT in 10 μm CCT increase. Earlier studies in which Dohadwala et al. evaluated Tono-Pen’s measurements of various corneal thicknesses reported increases in IOP of 0.29 mmHg in males and 0.12 mmHg in females with an increase in corneal thickness of 10 μm [22]. Bhan et al obtained 0,10 mmHg / 10 μm and 0,23 mmHg / 10 μm IOP increments in their studies investigating the relationship between Tono-Pen and GAT corneal thickness [23]. In our study we did not observe a statistically significant difference in Tono-Pen, GAT and CCT values according to sex.

It is known that astigmatism, refraction and visual acuity do not affect corneal thickness. The effect of corneal curvature on IOP measurements has been shown to be negligible. [24] For this reason, we did not evaluate the corneal curvature in our study.
In our study we did not divide our values into subgroups, but we performed our measurements within the range of 11-20 mmHg in patients who applied to the eye policlinic for the routine eye examination and observed that the Tono-Pen measurements were higher than the GAT measurements. We have not compared our measurements with manometric measurements but nowadays it is thought that even manometric measurements have some disadvantages because the applied paracentesis leads to changes in anterior chamber structure and volume, aqueous production, endothelial function and ocular temperature.
The advantages of Tono-Pen compared to GAT are light, portable, easy to learn, able to measure from a smaller surface easier to measure IOP in corneal irregularities, uncooperative cases and pediatric patients. The measurement made with the Tono-Pen is reflected in the resultant liquid crystal screen and is not open to interpretation. In addition sterile latex tip covers maintain an advantage in postoperative cases and ocular or systemic infections (hepatitis, HIV, prion diseases). The use of the TonoPen in corneal pathology is important in several ways: It can be used in cases of corneal edema, scarring or band keratopathy. The latex allergy caused by Tono-Pen latex tip cover should be questioned before the measurement.
Other portable tonometers are also available. Measurements with Schiotz tonometry make the patient more uncomfortable and the values can be influenced by the elastic properties of the eye and the corneal curvature. With Draeger, Kowa and Perkins tonometric measurements to be more precise, you need to gain experience for quality measurements. The McKay-Marg tonometry can also provide more accurate measurements, but its transport is more difficult and is no longer produced. The appearance of the optic disc and the evaluation of the visual field are much more important than the assessment of the corneal thickness in order to make the decision to start treatment FOR glaucoma. Corneal thickness should be assessed in addition to IOP measurements in cases of ocular hypertension and normotensive glaucoma in our findings. Corneal thickness measurements are especially important when the clinically determined IOP value is inconsistent and target IOP evaluation needed after the treatment.

Conclusion

In summary, the slightly higher values were seen in the Tono-Pen measurements. This did not appear to cause problems clinically because Tono-Pen also has the above-mentioned characteristics. Although GAT is still the gold standard for IOP measurement and is used as the most preferred tonometer, Tono-Pen is portable, it can be used in corneal pathologies and animal experiments and its sterility properties are superior.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Tierney JP, Rubin ML. A clinical evaluation of the electronic applanation tonometer. Am J Ophthalmol. 1966; 62: 263-71.

2. Goldman H. Schmidt T. Weiterer Beitrag zur Applantionstonometrie. Ophthalmologica. 1961; 141: 441-56.

3. Dielemans l, Vingerling JR, Hofman A, Groebe DE, DeJong PTVM. Reliability of intraocular pressure measurement with the Goldman applanation tonometer in epidemiological studies. Graefes Arch Clin Exp Ophthalmol. 1994; 232: 141-4.

4. Argus WA. Ocular hypertension and central corneal thickness. Ophthalmology. 1995; 102: 1810-12.

5. Rashad KM, Bahnassy AA. Changes in intraocular pressure after laser in situ keratomileusis. J Refract Surg. 2001; 17: 420-3.

6. Mark HH. Corneal curvature in applanation tonometry. Am J Ophthalmol. 1973; 74: 223-4.

7. Medeiros FA, Sample PA, Weinreb RN. Corneal thickness measurements and visual function abnormalities in ocular hypertensive patients. Am J Ophthalmol. 2003; 135: 131-7.

8. Giasson C, Forthomme D. Comparison of central corneal thickness measurements between optical and ultrasound pachometers. Opt Vis Sci. 1992; 69: 236-41.

9. Whitacre MM, Stein R. Sources of error with use of Goldman-type tonometers. Surv Ophthalmol. 1993; 38: 1-30.

10. Recep ÖF, Hasıripi H, Çağıl N, Sarikatipoğlu H. Relation between corneal thickness and intraocular pressure measurement by noncontact and applanation tonometer. J Cataract Refract Surg. 2001; 27: 1787-91.

11. Feltgen N, Leifert D, Funk J. Correlation between central corneal thickness, applanation tonometry and intracameral readings. Br J Ophthalmol. 2001; 85: 85-7.

12. Minckler DS, Baerveldt G, Heuer DK, Quillen-Thomas B, Walonker AF, Weiner J. Clinical evaluation of Oculab Tono-Pen. Am J Ophthalmol. 1987; 104: 168-73.

13. Bordon AF, Katsumi O, Hirose T. Tonometry jm pediatric patients:A comparative study among Tono-Pen, Perkins and Schiotz tonometers. J Pediatr Ophthalmol Strabismus. 1995; 32: 373-7.

14. Hessemer V, Rössler R, Jacobi K. Comparison of intraocular measurements with the Oculab Tono-Pen vs manometry in humans shortly after death. Am J Ophthalmol. 1988; 105: 678-82.

15. Foster PJ, Wong JS, Wong E. Acurracy of clinical estimates of intraocular pressure in Chinese eyes. Ophthalmology. 2000; 107: 1816-21.

16. Mermoud A, Baerveldt G, Minckler DS, Lee MB, Rao NA. Intraocular pressure in Lewis rats. Invest Ophthalmol Vis Sci. 1994; 35: 2455-60.

17. Mermoud A, Baerveldt G, Minckler DS, Lee MB, Rao NA. Measurement of rabbit intraocular pressure with the Tono-Pen. Ophthalmologica. 1995; 209: 275-7.

18. Eisenberg DL, Sherman BG, McKeown CA, Scuman JS. Tonometry in adults and children:a manometric evaluation of pneumotonometry, applanation and Tono-Pen in vitro and in vivo. Ophthalmology. 1998; 105: 1173-81.

19. Boothe WA, Lee DA, Panek WC, Pettit TH. The Tono-Pen: a manometric and clinical study. Arch Ophthalmol. 1988; 106: 1214-17.

20. Moses RA, Arnzen RJ,. instanteneous tonometry. Arch Ophthalmol. 1983; 101 :249-52.

21. Lim JI, Blair NP, Higginboham EJ, Farber MD, Shaw WE, Garretson BR. Assesment of introcular pressures in gas-containing eyes. Arch Ophthalmol. 1990; 108: 648-88.

22. Khan J, Davis M, Graham CE, Trank J, Whitcre M. Comparison of Oculab Tono-Pen readings obtained from various corneal and scleral locations. Arch Ophthalmol. 1991; 109: 1444-6.

23. Dohadwala AA, Munger R, Damji KF. Positive correlation btween Tono-Pen intraocular pressure and central corneal thickness. Ophthalmology. 1998; 105: 1849-54.

24. Bhan A, Browninig AC, Shah S, Hamilton R, Dave D, Dua I-IS. Effect of corneal thickness on intraocular pressure measurements with the pneumotonometer, Goldman applanation tonometer and Tono-Pen. Invest Ophthalmol Vis Sci. 2002; 43: 1389-92.

25. Matsumoto T, Makino H, Uozato H, Saishin M, Miyamoto S. The influence of corneal thickness and curvature on the difference between intraocular pressure measurements obtained with a non-contact tonometer and those with Goldman applanation tonometer. J Jpn Ophthalmol Soc. 2000; 104: 317-23.

PDF

Download attachments: JCAM_5996.pdf

How to Cite

Dervişoğulları MS, Akarsu C, Ergin A. Comparison of the intraocular pressure measurements with the tono-pen and the goldman applanation tonometer and the effect of central corneal thickness on measurements. Ann Clin Anal Med 2019;10(4): 479-84

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Comparison of the effects of levetiracetam and valproic acid on neural tube defect formation in the chick embryo: an experimental study

Ziya Asan 1, Mediha Eser 2, Taner Tanrıverdı 3, Cihan Isler 3, Faruk Alkan 4, Pamir Erdıncler 3

1 Department of Neurosurgery, Faculty of Medicine, Ahi Evran University, Kirsehir, 2 Department of Histology and Embriology, Faculty of Medicine, Istanbul University Cerrahpasa, Istanbul, 3 Department of Neurosurgery, Faculty of Medicine, Istanbul University Cerrahpasa, Istanbul, 4 Department of Histology and Embriology, Faculty of Medicine, Halic University, Istanbul, Turkey

DOI:10.4328/ACAM.5964 Received: 07.07.2018 Accepted: 08.08.2018 Published Online: 05.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 453-7

Corresponding Author: Ziya Asan, Beyin ve Sinir Cerrahisi Kliniği, Ahi Evran Üniversitesi, Eğitim ve Araştırma Hastanesi, 40100, Kırşehir, Türkiye.GSM: +905336502641 E-Mail: ziyaasan@gmail.com ORCID ID: https://orcid.org/0000-0001-8468-9156

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: The aim of this study is to compare the dosage-related effects of levetiracetam and valproic acid on neural tube defect formation in chick embryos, when applied as monotherapy and in combination. Material and Method: A total of 360 fertilized pathogens-free white-Leghorn eggs were used in the study. The eggs were allowed to incubate for 72 hours. Total of six groups were formed where each medication was administered in low (250 mcg) and high (500 mcg) doses and in combination. Results obtained from the control and sham groups were compared. Results: The prevalence of NTD was found to be significantly lower in the group that received levetiracetam compared to the group that was treated with valproic acid. It was determined that NTD prevalence increased with a dosage increase in both groups. The prevalence of NTD was found to be significantly higher in groups where the two medications were administered in combination compared to the groups that received a single medication. Discussion: Both levetiracetam and valproic acid have the potential to create NTD. Valproic acid has a higher potential of creating NTD compared to levetiracetam. The likeliness of causing NTD significantly increases depending on dosage for both medications. Both medications have the potential to create NTD during pregnancy and must be used with caution.

Keywords: Neural Tube Defect; Levetiracetam; Valproic Acid; Teratogenity

Full Text

Introduction

Central nervous system anomalies are among the most prevalent anomalies [1,2]. The most common anomalies within this group are those of neural tube formation. Certain factors are known to be involved in the etiology of neural tube formation anomalies. The fact that the same anomalies have been detected in embryos that were not exposed to these known factors suggests the existence of other factors involved in the etiology [1,3].

Folic acid deficiency is one of the most prominent environmental factors in the etiology of NTD formation [3], and it could be suggested that the folic acid metabolism is in turn affected by the environmental factors that commonly result in NTD. The use of anti-epileptic medications during pregnancy is also known to have a role in the development of congenital anomalies [4].

Many antiepileptics that are commonly used today are considered teratogens and it is recommended to use antiepileptics either at lower doses during pregnancy or substituted by other medications [5,6].

In this experimental study, the teratogenic effects of levatiracetam and valproic acid during pregnancy when anti-epileptic medications are required have been comparatively evaluated in the chick embryo. It was investigated whether the development of neural tube defects was associated with the dosage of levatiracetam and valproic acid used in the study (dosage comparison). The effects of combined levatiracetam and valproic acid therapy on NTD prevalence was evaluated in comparison to monotherapy.

Material and Method

Total of 360 specific pathogen-free (SPF), zero- day fertile, white-Leghorn eggs were obtained from the Bornova Veterinary Control Institute under cold chain for the purpose of comparative analysis of the effects of levetiracetam and valproic acid in terms of causing NTD in the chick embryo.

The eggs, which were obtained at different periods, were distributed into 3 main groups of 100 eggs each, 1 control group with 50 eggs, and 1 sham group with 10 eggs. Each of the three main groups with 100 eggs was evaluated under two subgroups with 50 eggs, where normal and high doses of medications were administered. Each egg was numbered and the obtained results were recorded (Table 1).

Parenteral forms of levatiracetam (Keppra) and valproic acid (Depakine) were obtained to be injected into the eggs. Each medication was diluted with physiological serum and the normal and high doses were ensured to be of an equal volume of 0,1 ml. Medication concentrations of 250 mcg were used as the normal dose, and 500 mcg as high dose.

The site of injection was cleansed with alcohol and Betadine prior to injection. The prepared medications were developed with physiological serum in appropriate concentrations and homogenization was ensured by centrifugation. Medication material (0,1 ml) was injected under the embryonic disc in the egg with a 31- gauge needle. In order to prevent contamination at the injection site, this area was sealed with paraffin. Each egg prepared to be incubated was kept under cold chain again, ensuring that the development of the embryos would be suppressed by the outer temperature and the eggs would begin incubation simultaneously. After all eggs were prepared, they were incubated in a Cimuka brand incubator at 37.8 °C and 60-70% relative humidity. Each egg in the incubator was rotated at 6- hour intervals so that the embryo material would not stick to different tissues within the egg. The eggs were left to incubate for 72 hours and were allowed to reach stage 18-20 according to the Hamburger-Hamilton stages. At the end of 72 hours, all eggs were removed from the incubator and were introduced to cold chain in order to suppress their development due to the effect of the outer temperature.

As the eggs were being removed from the incubator, they were cracked open in laboratory conditions and the embryo materials were revealed. The embryos were isolated from the surrounding tissues and were investigated under loop with 4x magnification in a petri dish; other tissues attached to the embryo were removed with microforceps (Figure 1). Each embryo was then transferred and preserved in containers that contained 10% formol for the purpose of carrying out microscopic assessments later on.

Whole embryos that were not yet sectioned were also evaluated under a microscope with various lighting effects to obtain better images. Whole embryos that were evaluated were embedded in paraffin blocks and 5-micron sections were taken from the regions that manifested NTD. The sections that were stained with hematoxylin-eosin, were inspected under microscope at various levels of magnification (Figure 2,3). The sections were investigated under the Olympus BX61 brand microscope after staining and their images were captured.

(Ethics committee approval was obtained from Istanbul University Animal Research Local Ethics Committee: 23/07/2009-99/90)

Statistical Analysis

The number of embryos obtained at the end of the experiment and the presence of neural tubes was recorded in the Excel software. A chi-square test and Fisher’s exact test (two-tailed; nonparametric) were used to assess the differences between the groups with respect to major developmental anomalies. A p-value < 0.05 was considered statistically significant.

Results

It was determined that embryo loss increased as drug concentration increased in all groups, regardless of whether the drugs were administered separately or in combination. Moreover, the prevalence of NTD was also found to increase depending on the dose in all groups (Table 1).

A total of 46 embryos were obtained from the eggs evaluated within Group 1a, which received 250 mcg levetiracetam. No embryos were found in 4 eggs. NTD was detected in 5 of the 46 obtained embryos. Fifty eggs evaluated within Group 1b were administered 500 mcg levetiracetam. Forty-five embryos were obtained in total. No embryos were found in 5 eggs. NTD was detected in 7 of the 45 obtained embryos.

Valproic acid (250 mcg) was administered to the 50 eggs evaluated within Group 2a. A total of 40 embryos were obtained. No embryos were found in 10 eggs. NTD was detected in 10 of the 40 obtained embryos. Valproic acid (500 mcg) was administered to the 50 eggs evaluated within Group 2b. Forty embryos were obtained in total. No embryos were found in 10 eggs. NTD was detected in 12 of the 40 obtained embryos.

Fifty eggs evaluated within Group 3a were administered with 250 mcg levetiracetam and valproic acid. Forty-three embryos were obtained in total. No embryos were found in 7 eggs. NTD was detected in 11 of the 43 obtained embryos. Fifty eggs evaluated within Group 3a were administered with 500 mcg levetiracetam and valproic acid. Thirty-nine embryos were obtained in total. No embryos were found in 11 eggs. NTD was detected in 14 of the 39 obtained embryos.

Fifty eggs evaluated within the control group (Group 4) were administered with 0,1 cc physiological serum. Forty-seven embryos were obtained in total. No embryos were found in 3 eggs. No NTDs were detected in the 47 obtained embryos. No drugs were administered to the 10 eggs evaluated within the sham group. These eggs underwent all experimental procedures including injections. Ten embryos were obtained in total. No NTDs were detected in the obtained embryos.

The comparison of results from Group 1a and Group 2b, which were treated with levetiracetam, revealed that the prevalence of neural tube defects was significantly higher in the group that received a higher dose of the drug (Group 1b) (p = 0.007). Similarly, the comparison of results from Group 2a and Group 2b in Group 2, which was treated with valproic acid, revealed that the prevalence of neural tube defects was significantly higher in the group that received a higher dose of the drug (Group 2b) (p = 0.00001).

In Group 3, we investigated the effect of administering combined levetiracetam and valproic acid on neural tube defect formation in the chick embryo. The comparison of results from Group 3a, which was the group that received low-dose medication, and Group 3b, which was the group that received high-dose medication, revealed that the prevalence of neural tube defects was significantly higher in Group 3b; the group that received high-dose medication (p = 0.00001).

The comparison of the group that was administered normal-dose levetiracetam (Group 1a) with the group that received normal-dose levetiracetam and valproic acid in combination (Group-3a) revealed that the prevalence of neural tube defects was significantly higher in the group that received both medications (p = 0.007).

The comparison of the group that was administered high-dose levetiracetam (Group 1b) with the group that received levetiracetam and valproic acid in combination (Group 3b) revealed that the prevalence of neural tube defects was significantly higher in the group that received both medications (p = 0.00001). The prevalence of neural tube defects was found to be significantly higher in groups that were administered with levetiracetam and valproic acid when compared to the control group.

It was determined that the prevalence of NTD and embryo loss increased in all groups at higher doses of the medications (Figure 4-7).

Discussion

The old generation medications used today as the first line treatments still make up the primary step of anti-epileptic treatment despite their known toxic and teratogenic effects [1,4,7,8]. There has been an increasing tendency to prefer new generation anti-epileptic medications over this group of medications referred to as the old generation anti-epileptics [8]. Numerous retrospective and prospective clinical studies have tried to reveal the mechanisms underlying the toxic and teratogenic effects of older generation anti-epileptics and the rates at which these effects are manifested [7]. Information regarding the levels and rates of similar effects associated with new generation anti-epileptics are scarce in the literature.

Valproic acid is among medications with established teratogenic effects when used during pregnancy [9]. Associated congenital anomalies, including NTD have been shown in many retrospective and prospective studies [10,11]. A study by G.L.Barnes et al. investigated the relationship between the teratogenic effect of VA on somites in the chick embryo and PaxC1 gene expression [12]. In this study, various doses of VA were administered, and it was concluded that the survival rate of the embryos decreased as the dose increased.

Among older generation anti-epileptics, carbamazepine, and phenytoin, although at a relatively low rate, have been shown to cause neural defects [9,13]. The fact that administering these two medications at the same dosage resulted in different rates of neural tube defect suggests that the affected biochemical paths are different [8]. Therefore, it would make sense to consider while trying to reveal the mechanism underlying any congenital anomaly, particularly those that appear during the embryonic stage, that it is not a single biochemical mechanism that is affected but the primary morphological processes that initiate fetal development. First of all, it must be considered that the teratogenic effect brought about by the use of anti-epileptics or any other teratogens in the first trimester would affect the differentiation of the endoderm, mesoderm, and ectoderm embryonic germ layers.

The most well-known external factor that result in a high prevalence of neural tube defect is a folic acid deficiency [14,15]. For this reason, the teratogenic agents that cause neural tube defect are believed to affect the folic acid metabolism. However, the fact that the known teratogenic agents manifest this teratogenic effect of varying levels suggests that these agents either affect the folic acid mechanism at varying levels are also affected different biochemical paths.

Similar studies done previously also have shown that levetiracetam causes NTD [16,17]. In the experimental study conducted by Ozer et al. on chick embryos, it was shown that levetiracetam led to midline defects and a reduction in cell proliferation [16]. Ozgural et al. reported that the concentration of calcium ions were affected and NTD prevalence increased depending on the dosage; and emphasized that genetic and developmental factors also needed to be considered alongside teratogenic effects [17]. The same effects were found to appear via the Fibroblast Growth Factor-2 in a study conducted by Duransoy et al [18]. This study, on the other hand, compared valproic acid, which is known to have a high potential for causing NTD, and levetiracetam, the effects of which are not as well-known, and allowed comparison of the risk potentials of these two anti-epileptics in terms of causing NTD.

In this study, although levetiracetam presented a weaker teratogenic effect in terms of causing neural tube defect when compared to valproic acid, its teratogenic effect was significantly higher in comparison to the control group. Moreover, it was determined that survival decreased and the prevalence of neural tube defect increased with an increasing dose in eggs injected both with levetiracetam and valproic acid. Similarly, survival rates associated with the combination of the two medications were lower compared to the groups that were administered a single medication, and neural tube defects were more prevalent in the case of combined use.

It was concluded that levetiracetam, despite resulting in higher survival and a lower prevalence of neural tube defect than valproic acid, had a significantly higher teratogenic effect when compared to the control group. The combination of the two medications has a potential negative effect on NTD prevalence and survival.

Conclusion

In our experimental study, we intended to reveal the neural tube defect rates associated with levetiracetam compared to valproic acid. Both medications were applied at equal doses across groups and the results were evaluated by comparing. Both medications were evaluated statistically in terms of causing NTD in chick embryos in comparison to the control group and the results were significant. Furthermore, the higher prevalence of NTD resulting from the combined use of the two medications compared to the NTD rate associated with their use as monotherapy was considered statistically significant. It was concluded that, when used in combination, LVT and VA increased each other’s teratogenic effect in the etiology of NTD.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Moore KL, Persaud TVN, Torchia MG. The Developing Human: Clinically oriented embryology. 8th ed. W.B. Saunders; 2007. p. 381-92.

2. Lee H, Bush KT, Nagele RG. Time-lapse photographic study of neural tube closure

defects caused by xylocaine in the chick. Teratology. 1988; 37(3): 263-9.

3. Rosenquist TH, Ratashak SA, Selhub J. Homocysteine induces congenital defects of

the heart and neural tube: effect of folic acid. Proc Natl Acad Sci U S A. 1996; 93(26): 15227-32.

4. Samren EB, van Duijn CM, Koch S, Hiilesmaa VK, Klepel H, Bardy AH, et al. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia. 1997; 38(9): 981-90.

5. Frey L, Hauser WA. Epidemiology of neural tube defects. Epilepsia. 2003; 44 (Suppl.3): 4-13.

6. Holmes LB, Harvey ES, Brown KS, Hayes AM, Khoshbin S. Anticonvulsant teratogenesis: I. A study design for newborn infants. Teratology. 1994; 49(3): 202–7.

7. Tureci E, Asan Z, Eser M, Tanriverdi T, Alkan F, Erdincler P. The effects of valproic acid and levetiracetam on chicken embryos. J Clin Neurosci. 2011; 18(6): 816-20.

8. Hernández-Díaz S, Smith CR, Shen A, Mittendorf R, Hauser WA, Yerby M, et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012; 78(21): 1692-99.

9. Werler MM, Ahrens KA, Bosco JL, Mitchell AA, Anderka MT, Gilboa SM, et al. Use of antiepileptic medications in pregnancy in relation to risks of birth defects. Ann Epidemiol. 2011; 21(11): 842-50.

10. Greene ND, Copp AJ. Neural tube defects. Annu Rev Neurosci. 2014; 37: 221-42. DOI: 10.1146/annurev-neuro-062012-170354.

11. Barboza-Argüello Mde L, Umaña-Solís LM, Azofeifa A, Valencia D, Flores AL, Rodríguez-Aguilar S, et al. Neural tube defects in Costa Rica, 1987-2012: origins and development of birth defect surveillance and folic acid fortification. Matern Child Health J. 2015; 19(3): 583-90.

12. George L, Barnes JR, Brian D, Rocky S.Wan. Valproic acid-induced somite

teratogenesis in the chick embryo: relationship with Pax-1 gene expression. Teratology. 1996; 54(2): 93-102.

13. Afshar M, Moallem SA, Houshang Mohammadpour A, Shiravi A, Majid Jalalian S, Jafar Golalipour M. Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice. Cutan Ocul Toxicol. 2010; 29(1): 10-5.

14. Imbard A, Benoist JF, Blom HJ. Neural tube defects, folic acid and methylation. Int J Environ Res Public Health. 2013; 10(9): 4352-89.

15. Denny KJ, Jeanes A, Fathe K, Finnell RH, Taylor SM, Woodruff TM. Neural tube defects, folate, and immune modulation. Birth Defects Res A Clin Mol Teratol. 2013; 97(9): 602-9.

16. Ozer FD, Demirel A, Yilmaz DO, Aydin M, Ozdemir N, Uyanikgil Y, et al. Effects of levetiracetam on neural tube development and closure of the chick embryos in ovo. Childs Nerv Syst. 2012; 28(7): 969-76.

17. Ozgural O, Armagan E, Bozkurt M, Eroglu U, Kahilogullari G, Unlu A. The effect of levetiracetam on midline closure in early chicken embryos. Turk Neurosurg. 2015; 25(5): 681-4.

18. Duransoy YK, Simsek T, Ozturk F, Mete M, Tuglu MI, Selcuki M. The effects of fibroblast growth factor-2 blocking on development of chick cervical vertebra and relationship with oxidative stress and apoptosis. J. Neurol. Sci. [Turk]. 2014; 31(1): 188-96.

PDF

Download attachments: JCAM_5964.pdf

How to Cite

Asan Z, Eser M, Tanrıverdı T, Isler C, Alkan F, Erdıncler P. Comparison of the effects of levetiracetam and valproic acid on neural tube defect formation in the chick embryo: an experimental study. Ann Clin Anal Med 2019;10(4): 453-7

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Prognosis of the decompressive craniectomy for stroke according to preoperative computed tomography

Gonul Guvenc 1, Ceren Kızmazoglu 2, Inan Uzunoglu 1

1 Department of Neurosurgery, Katip Celebi University Ataturk Research and Training Hospital, 2 Department of Neurosurgery, Dokuz Eylül University School of Medicine, Izmir, Turkey

DOI:10.4328/ACAM.5951 Received: 27.06.2018 Accepted: 25.07.2018 Published Online: 29.07.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 431-5

Corresponding Author: Ceren Kizmazoglu, Department of Neurosurgery, Dokuz Eylül University School of Medicine, Balçova, Izmir, 35340, Turkey. GSM: +905058737619 F.: +90 2324123301 E-Mail: ceren.kizmazoglu@gmail.com ORCID ID: https://orcid.org/0000-0001-6146-0842

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Aim: The aim of this study was to investigate the preoperative clinic and radiologic signs which affect the prognosis after decompressive craniectomy for stroke. Material and Method: We retrospectively analyzed the demographic and radiological images of patients who underwent decompressive craniectomy for internal carotid artery (ICA) and middle cerebral artery (MCA) strokes. Seventeen patients analyzed retrospectively between January 2012 and December 2015 at our hospital. Results: A total of 17 decompressive craniectomies were performed for supratentorial ischemic strokes: 3 (17.6%) ICA and 14 (82.4%) MCA stroke patients. There were 11 (64.7%) males and 6 (35.3%) females with a mean age of 59.35 ± 15.39 years (range 20-83 years). There were 10 (58.9%) mor-talities. Seven patients were discharged home. The patients’ Glasgow Coma Scale, infarct type, dominant hemisphere side, preoperative cranial tomography shift, hemorrhagic transformation, basal cistern, transcalvarial herniation were analyzed. Basal cisterns of 8 (47.1%) patients were open, of 9 (52.9%) patients were closed before decompressive craniectomy. There was a statistically significant difference between mortality rate between open cistern versus closed basal cistern (p=0.029). Discussion: In our study, open cisterns were associated with good outcomes. Larger studies should be performed in the the future.

Keywords: Basal cistern; Decompressive Craniectomy; Mortality; Stroke

Full Text

Introduction

Acute ischemic stroke is one of the destructive neurologic emergencies. Despite new therapies, about half of stroke patients have important morbidities, they need a long period of rehabilitation [1,2]. Life-threatening brain edema occurs between 2 and 5days after onset of stroke in 1-10% of supratentorial infarct patients [3]. Clinical worsening occurs within first 24 hours in 1/3 of the patients [4]. Prognosis in malign middle cerebral artery infarcts is poor, mortality is about 80% in intensive care series [5].

Wide ischemic region related to infarct with cytotoxic edema called malign infarct theoretically. This may be proportional to the volume of infarcted brain tissue and seen with increased intracranial pressure (ICP). Despite early intravenous thrombolytic treatment, the development of infarcted brain tissue in patients will continue. Successful reperfusion of ischemic and swollen vessel walls cause parenchymal blood extravasation and leads to hemorrhagic transformation. The prevalence and type of hemorrhagic transformation show the neurologic deterioration degree [6]. Decompression surgery for traumatic brain injury was for the first time described by Kocher in 1901 [7] and then was encouraged for severe acute ischemic attacks [8]. Decompressive hemicraniectomy (DCH) is a surgical treatment option for patients with malign infarct who are unresponsible to medical therapy, to prevent parenchymal brain congestion and to gain space for brain tissue recovery [3,9,10]. Trauma requires a large craniotomy, such as a bone flap. The dura on the hemisphere is expanded, and ICP is reduced by duraplasty. Anterior-medial temporal lobectomy is another surgical option to reduce the brain’s pressure on vital brainstem structures when the intracranial pressure is too high [2].

As a result of three randomized controlled trials, hemicraniectomy and a decompressive surgery with duraplasty significantly reduces mortality and morbidity in patients with malignant MCA infarction [11-13]. Cranioplasty can be perfromed within 1-3 months after intracranial pressure reduction and recovery of malignant infarction area [10,14].

The aim of this study was to investigate the preoperative clinic and radiologic signs which affect the prognosis after decompressive craniectomy for stroke.

Material and Method

Patients with acute ischemic stroke who had supratentorial decompression surgery at our university hospital between January 2012 and December 2015 were analyzed retrospectively. Medical records, patients’ files, and radiological images were evaluated. Hospital records kept during hospitalization period and the data obtained at the periodic routine controls were examined. Clinical characteristics, preoperative and postoperative early and late physical and neurological examination data were analyzed retrospectively. Ethical approval was obtained from our institution (31829978-050.01.04-E.1700048196 and decision number 107).

Patients with regression in Glasgow Coma Scale (GCS) or with an increase in midline shift in control computed tomography scan (CT) while undergoing medical treatment due to acute ischemic stroke in the stroke unit of our hospital, were enrolled in emergency decompression surgery.

Patients were positioned supine with a small support under the ipsilateral shoulder and the head positioned facing to the opposite side. After the sterile surgery field was covered, a large question mark incision was made, starting at 2 cm in the midline, up to the posterior parieto-occipital area and up to the posterior-inferior ear area and down to the zygoma level up to 5 mm in front of the ear. Superficial temporal artery was protected carefully to provide adequate blood flow for the skin flap. The temporal muscle was dissected and the bone was removed from the flap and hung on the frontal surface with hooks. Bone flap was removed with appropriate fronto-parietal-temporal craniectomy. The middle meningeal artery, bone surfaces, and sphenoid wing hemorrhages were stopped with bipolar cautery and bone wax. Dura opened with envelope-style, duraplasty was performed with right fascia lata, the drain was placed at the epidural space, and the bone flap was buried in the right leg. Lobectomy was performed in none of the cases. Patients with early postoperative CT were taken to the intensive care unit. Transcalvarial herniation measurements of the patients were performed as the method which was done by Flint et al. [15].

Chi-square and Mann-Whitney U tests were used for statistical calculations. P-values < 0.05 were considered statistically significant. Statistical analysis of the data was performed on a statistical package program for Statistical Package for Social Sciences for Windows 15.0 (SPSS Inc. Chicago, Ilinois, USA).

Results

Decompression surgery was performed for a total of 17 patients as follows: 3 (17.6%) with internal carotid artery (ICA) infarct and 14 (82.4%) with middle cerebral artery (MCA) infarct between years 2012 and 2015. Mean age was 59.35 ± 15.39. Eleven (64.7%) of patients were male and 6 (35.3%) were female (Table 1).

Four of operated patients were under 50 years old, 8 of them between 50-70 years old, 5 of them were above 70 years old. Preoperative infarct types of patients were evaluated by diffusion MRG sequences ,and by cranial CT according to artery feeding area. For assessment of brainstem compression and herniation in the cranial CT, the presence of compression findings in basal cisterns (Quadrigeminal, ambient, perimesencephalic) was evaluated. Before the decompressive craniectomy, eight of the basal cisterns (47.1%) were open, and nine (52.9%) were closed. At the same time, hemorrhagic field was also evaluated in cranial CT (Figure 1). In the surgical procedure applied to the patients, temporal craniectomy was performed in 15 patients including the sphenoid wing and temporal pole. Two patients were decided not to undergo extensive craniectomy involving the sphenoid wing and temporal pole as a result of preoperative observation and the operation was completed by frontoparietotemporal craniectomy.

One of the operated patients had undergone ventriculoperitoneal shunt due to acute hydrocephaly at the postoperative 2nd month, and cranioplasty operation had performed in 1 patient at the postoperative 6th month. Other patients did not accept cranioplasty operation. No significant value has been found between GCS, infarct type, hemisphere side, pre-post- operative midline shift, hemorrhagic transformation, transcalvarial herniation, operation time, modified ranking scale and mortality. However, it was statistically significant between basal cistern closed and mortality (p = 0,029)(Table 2).

Discussion

Duraplasty with decompressive hemicraniectomy supports edema enlargement to the outside of the neurocranium and thereby, prevents lethal internal displacement and subsequent herniation of brain tissue. Decompressive hemicraniectomy is particularly useful in patients with malignant middle cerebral artery infarction [13].

Analysis of three prospective studies (DECIMAL, DESTINY I, HAMLET) showed that decompressive craniectomy significantly reduced mortality by about 50% in patients under 60 years of age [16]. Uhl et al. in the study of 188 patients under 50 years of age, evaluated decompression surgery as promising [17]. Juttler et al. in their study of 112 middle cerebral artery infarct patients over 60 years of age, showed significantly increased survival rates when decompressive craniectomy was performed within the first 48 hours (early surgery) [13]. Vahedi et al. in a study of 93 patients older than 50 years old, had 80% mortality rate [3]. In our study, the mean age was 59.35 ± 15.39 years (range 20-83 ). Patients were separated as follows: under 50 years, 50-70 years and over 70 years of age, but mortality rates were not significantly different.

Palival et al. showed that in 75 patients with moderate cerebral artery infarction who were treated by decompressive craniectomy, early surgery within 48 hours increased survival rates regardless of age [1]. Both DECIMAL and DESTINY trials showed that for patients who were treated by surgery within 48 hours after symptoms start, early and long-term mortality rates were decreased and neurologic results improved [18,19]. In the study by Foerch et al. of 36 cases, time of decompressive craniectomy had no effect on mortality and functional outcomes [20]. In our study, there were no significant differences between the first 24 hours, 24-48 hours, 48-72 hours, and 72 hours after the onset of symptoms and surgery time and there were no significant differences between patients’ ages and survival rates. Both in the study by Foerch et al. [20] and our study, as well as the small number of patients is thought to result in the absence of an effect on the outcome of the surgical timing.

Recently, 4 points in modified ranking scale has been considered favorable for evaluating survival of patients, but in the last period modified Rankin scale (mRS) ≤ 3 was considered more favorable [1]. In our study, mRS was 4 in 2 of 6 survivors, 5 was in 3, and 3 was in 1 patient.

In the studies related to patients who underwent decompression surgery due to MCA infarction, right MCA was more frequent than left side [1,13,18,21]. Paliwal et al. stated that right MCA infarction rate was 70% [1]. In our study, righ MCA infarction rate was 64.3%.

The expected amount of postoperative brain herniation varies according to the patients. The maximum extracranial herniation was reported by Fletcher et al. [22] and Flint et al. [15] as 20-40 mm. The difference between measurements occurs due to many factors. Both studies are used to measure herniation in traumatic brain-damaged patients, so the amount of herniation is high. In our study, transcalvarial herniation values were between 0-23 mm. There was no significant difference between the amount of transcalvarial herniation and mortality in our study. A study of Kouvarellis et al. with 141 pediatric cases with traumatic brain injury, resulted in an increase in intracranial pressure in patients with close basal cistern and lower survival rates [23]. Nourallah et al. revealed that evaluation of basal cisterns in brain CT was directly related to brain stem pressure independent of other parameters (such as age, midline sp shift) in assessing premorbid findings in traumatic brain injury [24]. Uncal, parahippocampal, and central transtentorial herniation reflect the pressure effects of a wider range of compartments, and basal cistern pressure can be detected earlier, radiologically [24]. In the literature, radiological signs have been tried to be defined as pre-herniation findings indicative of urgent decompressive craniectomy to help to diagnos and treat brain stem damage that will be developed secondary to malignant MCA infarction. In some studies, a larger infarct region more than 50% of the MCA irrigation area in cranial CT or larger than 145 cm³ infarct area showed urgent need for decompressive craniectomy. [3,18,21]. Significant results were obtained in our study between the appearance of open baseline cisterns in cranial CT and survival rates of the patients (p = 0.029). The results of our study showed that preoperative evaluation of basal cisterns on cranial CT may be useful in predicting prognosis, and patients with preoperative open baseline cisterns on cranial CT may have better prognosis..

The limiting factor in our study is the small number of patients. In our study, although there was no significant difference between decompression timing and mortality, early decompression surgery was found to have better results in many studies [1,3,13].

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Funding: None

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Paliwal P, Kazmi F, Teoh HL, Yeo LLL, Seet RCS, Yeo TT et al. Early Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Infarction in Asian Patients: A Single-Center Study. World neurosurgery. 2018; 111: 722-8.

2. Al-Jehani H, Petrecca K, Martel P, Sinclair D, Sirhan D. Decompressive Craniectomy for Ischemic Stroke: Effect of Hemorrhagic Transformation on Outcome. Journal of stroke and cerebrovascular diseases. The official journal of National Stroke Association. 2016; 25(9): 2177-83.

3. Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. The Lancet Neurology. 2007; 6(3): 215-22.

4. Qureshi AI, Suarez JI, Yahia AM, Mohammad Y, Uzun G, Suri MF et al. Timing of neurologic deterioration in massive middle cerebral artery infarction: a multicenter review. Critical care medicine. 2003; 31(1): 272-7.

5. Berrouschot J, Sterker M, Bettin S, Koster J, Schneider D. Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under conservative intensive care. Intensive care medicine. 1998; 24(6): 620-3.

6. Fiehler J, Remmele C, Kucinski T, Rosenkranz M, Thomalla G, Weiller C et al. Reperfusion after severe local perfusion deficit precedes hemorrhagic transformation: an MRI study in acute stroke patients. Cerebrovascular diseases (Basel, Switzerland) 2005; 19(2): 117-24.

7. Guerra WK, Gaab MR, Dietz H, Mueller JU, Piek J, Fritsch MJ. Surgical decompression for traumatic brain swelling: indications and results. Journal of neurosurgery 1999; 90(2):187-96.

8. Gupta R, Connolly ES, Mayer S, Elkind MS. Hemicraniectomy for massive middle cerebral artery territory infarction: a systematic review. Stroke. 2004; 35(2): 539-43.

9. Adeoye O, Hornung R, Khatri P, Ringer A, Kleindorfer D. The rate of hemicraniectomy for acute ischemic stroke is increasing in the United States. Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 2011; 20(3): 251-4.

10. Stoner KE, Abode-Iyamah KO, Grosland NM, Howard MA, 3rd. Volume of Brain Herniation in Patients with Ischemic Stroke After Decompressive Craniectomy. World neurosurgery. 2016; 96: 101-6.

11. Morley NC, Berge E, Cruz-Flores S, Whittle IR. Surgical decompression for cerebral oedema in acute ischaemic stroke. The Cochrane database of systematic reviews 2002; (3). DOI: 10.1002/14651858.CD003435.

12. Schwab S, Steiner T, Aschoff A, Schwarz S, Steiner HH, Jansen O et al. Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke. 1998; 29(9): 1888-93.

13. Juttler E, Unterberg A, Woitzik J, Bosel J, Amiri H, Sakowitz OW et al. Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke. The New England journal of medicine. 2014; 370(12): 1091-100.

14. Wang Z, Su N, Wu RL, Zhang YS, Zhang XJ, Qi JJ et al. Decompressive Craniectomy With Bifrontal Coronal Incision in the Management of Fronto-Temporal Contusion and Laceration for Early Cranioplasty. The Journal of craniofacial surgery. 2017; 28(6): 1442-4.

15. Flint AC, Manley GT, Gean AD, Hemphill JC, 3rd, Rosenthal G. Post-operative expansion of hemorrhagic contusions after unilateral decompressive hemicraniectomy in severe traumatic brain injury. Journal of neurotrauma. 2008; 25(5): 503-12.

16. Zweckberger K, Juettler E, Bosel J, Unterberg WA. Surgical aspects of decompression craniectomy in malignant stroke: review. Cerebrovascular diseases (Basel, Switzerland). 2014; 38(5): 313-23.

17. Uhl E, Kreth FW, Elias B, Goldammer A, Hempelmann RG, Liefner M et al. Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction. Journal of neurology, neurosurgery, and psychiatry. 2004; 75(2): 270-4.

18. Juttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke 2007; 38(9): 2518-25.

19. Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke. 2007; 38(9): 2506-17.

20. Foerch C, Lang JM, Krause J, Raabe A, Sitzer M, Seifert V et al. Functional impairment, disability, and quality of life outcome after decompressive hemicraniectomy in malignant middle cerebral artery infarction. Journal of neurosurgery. 2004; 101(2): 248-54.

21. Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB et al. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. The Lancet Neurology. 2009; 8(4): 326-33.

22. Fletcher TL, Kolias AG, Hutchinson PJ, Sutcliffe MP. A new improved method for assessing brain deformation after decompressive craniectomy. PloS one 2014; 9(10): DOI: 10.1371/journal.pone.0110408.

23. Kouvarellis AJ, Rohlwink UK, Sood V, Van Breda D, Gowen MJ, Figaji AA. The relationship between basal cisterns on CT and time-linked intracranial pressure in paediatric head injury. Child’s nervous system: ChNS: official journal of the International Society for Pediatric Neurosurgery. 2011; 27(7): 1139-44.

24. Nourallah B, Menon DK, Zeiler FA. Midline Shift is Unrelated to Subjective Pupillary Reactivity Assessment on Admission in Moderate and Severe Traumatic Brain Injury. Neurocritical care. 2018; DOI: 10.1007/s12028-018-0526-8.

PDF

Download attachments: JCAM_5951.pdf

How to Cite

Guvenc G, Kızmazoglu C, Uzunoglu I. Prognosis of the decompressive craniectomy for stroke according to preoperative computed tomography. Ann Clin Anal Med 2019;10(4): 431-5

Citations in Google Scholar

Citations in Google Scholar: Google Scholar


Case Report

Cervical destructive spondyloarthropathy due to the dialysis-related amyloidosis: imaging findings

Hale Turnaoglu 1, Kemal Murat Haberal 1, Oğuzcan Ünal 1, Ozlem Isiksacan Ozen 2, Ahmet Muhtesem Agildere 1

1 Department of Radiology, 2 Department of Pathology, Baskent University Faculty of Medicine, Ankara, Turkey

DOI: 10.4328/ACAM.6068 Received: 05.11.2018 Accepted: 08.12.2018 Publihed Online: 10.12.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 525-8

Corresponding Author: Hale Turnaoglu, Department of Radiology, Baskent University, Faculty of Medicine, 06490 Bahcelievler, Ankara, Turkey.GSM: +905323106920 F.: +90 3122237333 E-Mail: haletrn@yahoo.com ORCID ID: https://orcid.org/0000-0002-0781-0036

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Dialysis-related amyloidosis that occurs secondary to the deposition of amyloid fibrils containing beta-2-microglobulin, is a type of amyloidosis affecting patients undergoing long-term hemodialysis. It involves the osteoarticular system predominantly. Destructive spondyloarthropathy, is a type of dialysis-related spondyloarthropa-thy, which frequently involves the cervical spine, have been reported only sporadically. We describe a case of a destructive spondyloarthropathy, in a 43-year-old long-term hemodialysis patient, presenting with myelopathy with particular interest to cervical computed tomography and magnetic resonance imaging findings.

Keywords: Dialysis-Related Amyloidosis; Destructive Spondyloarthropathy; Myelopathy; Magnetic Resonance Imaging; Computed Tomography

Full Text

Introduction

Dialysis-related amyloidosis that consists of the deposition of amyloid fibrils containing beta-2-microglobulin, is a type of amyloidosis affecting patients undergoing long-term hemodialysis. It affects the osteoarticular system predominantly. The most common manifestations are arthropathy of the axial skeleton, knees, shoulders, hips and carpal tunnel syndrome [1]. Dialysis-related spondyloarthropathy has been divided into three types: destructive spondyloarthropathy (DSA), amyloid deposition in spinal ligaments, and pseudotumor of the craniocervical junction (amiloidoma). DSA, which frequently affects the cervical spine, have been reported only sporadically. We describe a case of a DSA, in a long-term hemodialysis patient, presenting with myelopathy with particular interest to cervical computed tomography (CT) and magnetic resonance imaging (MRI) findings.

Case Report

A 43-year-old man who had chronic renal failure secondary to unknown etiology presented with loss of strength in the legs and disturbances while walking. He had been receiving hemodialysis for 29 years. Cervical vertebral computed tomography (CT) scans showed narrowing in the cervical 2 (C2) – cervical 3 (C3) intervertebral space, and osteolytic areas with peripheral sclerosis in the laminae and pedicules of the various vertebrae (Figure 1). Magnetic resonance imaging (MRI) showed thickening and decreased signal intensity on both T1and T2-weighted images, in the posterior longitudinal ligament and ligamentum flavum. Scattered increased signal intensity of the spinal cord was seen secondary to compression of thickened ligaments and narrowing of the spinal canal (Figure 2). No contrast was given because of the patient’s poor glomerular filtration rate. The patient was operated. Histopathological examination revealed amyloid deposits and the presence of intense beta-2-microglobulin fibrils (Figure 3). Informed consent was obtained from the patient for using his data.

Discussion

DSA is characterized by erosions of the anterosuperior and/or anteroinferior aspects of the vertebral body, severe narrowing of the intervertebral disk space and erosions and cysts of adjacent vertebral plates, with absence of significant osteophyte formation, radiographically. In advanced stages of the disease, subluxation, listhesis, or vertebral body collapse may occur [2]. CT is the best modality for detecting osseous erosion or small

areas of osteolysis in cortical bone. CT can demonstrate the distribution and extent of the destructive changes [2]. In the case presented here, areas of osteolysis with peripheral sclerosis in the cervical vertebral bodies, laminae, and pedicles were demonstrated by CT (Figure 1). MRI shows the extent and distribution of osseous, articular, spinal cord and soft-tissue involvement, adding to the information obtained from radiographic and CT images. MRI may show amyloid deposits in the intervertebral disk, in the synovium of apophyseal joints, and in the ligaments. Although bone lesions show decreased signal intensity on T1-weighted images in most patients, T2-weighted images show various signal intensity patterns that range from hypointense to hyperintense. The variability in signal intensity is probably caused by the combination of amyloid deposits and fluid collection within the subchondral lesions. Identification of an intraosseous lesion with low signal intensity on both T1- and T2-weighted images is helpful in the diagnosis of amyloidosis. After the gadolinium-based contrast material injection, the bone lesions usually show moderate enhancement [3]. Compression of the spinal cord and myelopathy caused by extradural deposition and thickening of ligaments may occur [3]. MRI is well suited, as in the case presented here, for assessing the compression of the spinal cord and myelopathy, caused by the thickening of ligamentum flavum and posterior longitudinal ligament (Figure 2).

The diseases of the differential diagnosis usually includes spondylodiscitis, metastatic malignancy, multiple myeloma, secondary hyperparathyroidism (renal osteodystrophy), ossification of the posterior longitudinal ligament, and cervical spondylosis. In some cases, it can be difficult to differentiate changes secondary to dialysis-related amyloidosis from spondylodiscitis. In spondylodiscitis, involved structures show decreased signal intensity on T1-weighted MR images and in most cases increased signal intensity on T2-weighted and STIR images. Low signals present in T2-weighted images helps the exclusion of an infection [3]. Brown tumors of hyperparathyroidism are sometimes difficult to differentiate from amyloid cysts in dialysis patients. The location of the bone lesions is helpful [4]. Also, cysts tend to increase in number and size associated with the duration of dialysis [3]. In the metastatic disease, lesions are more diffuse and less circumscribed compared with dialysis-related amyloidosis. Multiple myelomas can be differentiated from dialysis-related amyloidosis by urine and serum protein electrophoresis. A bone scan may be used for detecting other locations, and magnetic resonance imaging has been recommended to assist with the diagnosis [5]. Ossification of the posterior longitudinal ligament can be recognized by the presence of calcifications on the plain radiography and/or CT [6]. In the cervical spondylosis, features related to the cervical spine and intervertebral space, such as osteophyte formation and intervertebral space narrowing are evident.

The gold standard of the diagnosis is the histological identification of beta-2-microglobulin, a major constituent of amyloid fibrils, in the material which is obtained by surgery. The pathology diagnosis is made with hematoxylin-eosin and Congo red. Under polarized light, these areas exhibit characteristic apple-green birefringence [1] (Figure 3).

In the treatment, medical therapy is limited to symptomatic approaches to reduce pain and inflammation. In the patients suffering from cervical pain may be referred for surgical evaluation. For relieving of the pain, surgical procedures, such as circumferential reconstructive surgery involving pedicle screw fixation, anterior strut bone grafting, posterior and/or anterior decompression, posterior nerve root decompression or spinous process wiring may perform, due to the severity and involvement of the disease [8]. The best treatment of hemodialysis-related amyloidosis is renal transplantation. Renal transplantation can provide a very rapid symptomatic relief and prevents the progression of the disease. However, the effect of transplantation on existent amyloid depositions is controversial [7].

Conclusion

In the long-term dialysis patients, imaging diagnosis is necessary for the evaluation of dialysis-related amyloidosis before serious complications arise. The changes of the vertebral body, ligaments, facet joints and intervertebral spaces in dialysis-related amyloidosis and the complications due to these changes, can recognize and identify by CT and MRI.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Moslavac S, Dzidic I, Kejla Z, Tomas D. Hemodialysis associated amyloidosis with cervical spinal cord compression and incomplete tetraplegia: a case report. Spinal Cord. 2007; 45(12): 799-801.

2. Oruckaptan H, Karli Oguz K, Isikay I, Ruacan S. Amyloidoma of the temporal bone and upper cervical spine; presentation of a rare clinical entity with a brief literature review. Turk Neurosurg. 2009; 19(2): 159-62.

3. Kiss E, Keusch G, Zanetti M, Jung T, Schwarz A, Schocke M, et al. Dialysis-related amyloidosis revisited. AJR Am J Roentgenol. 2005; 185(6): 1460-7.

4. Yamamoto S, Gejyo F. Historical background and clinical treatment of dialysis-related amyloidosis. Biochim Biophys Acta. 2005; 1753(1): 4-10.

5. Schiffl H. Impact of advanced dialysis technology on the prevalence of dialysis-related amyloidosis in long-term maintenance dialysis patients. Hemodial Int. 2014; 18(1): 136-41.

6. Choi BW, Song KJ, Chang H. Ossification of the posterior longitudinal ligament: a review of literature. Asian Spine J. 2011; 5(4): 267-76.

7. Mourad G, Argilés A. Renal transplantation relieves the symptoms but does not reverse beta 2-microglobulin amyloidosis. J Am Soc Nephrol. 1996; 7(5): 798-804.

8. Abumi K, Ito M, Kaneda K. Surgical treatment of cervical destructive spondyloarthropathy (DSA). Spine. 2000; 25(22): 2899-905.

PDF

Download attachments: JCAM_6068.pdf

How to Cite

Turnaoglu H, Haberal KM, Ünal O, Ozen ÖI, Agildere AM. Cervical destructive spondyloarthropathy due to the dialysis-related amyloidosis: imaging findings. Ann Clin Anal Med 2019;10(4): 525-8

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

A rare case of interrupted inferior vena cava with azygos continuation

Neslihan Özçelik 1, Bilge Yılmaz Kara 1, Songül Özyurt 1, Oğuzhan Özdemir 2, Ünal Şahin 1

1 Department of Chest Diseases, 2 Department of Radiology, Recep Tayyip Erdoğan University, Rize, Turkey

DOI:10.4328/ACAM.5950 Received: 28.06.2018 Accepted: 01.08.2018 Publihed Online: 02.08.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 510-2

Corresponding Author: Neslihan Özçelik, Department of Chest Diseases, Recep Tayyip Erdoğan University, 53200, Rize, Turkey. GSM: +905308958083 E-Mail: ozcelik.nesli@gmail.com ORCID ID: https://orcid.org/0000-0002-4672-6179

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

The identification of vascular pathologies of the mediastinum is very important for the prevention of complications during the interventional procedure. A rare devel-opmental anomaly of inferior vena cava (IVC): the interrupted IVC continues with azygos vein in thorax. And then, the azygos vein merges with the superior vena cava (SVC) and pours into the right atrium. The incidence is reported to be 0.6%. It is a crucial application to distinguish the enlarged azygos vein from the right paratracheal mass and lymph node radiologically and clinically.

Keywords: Vena Cava Inferior; Azygos; Variation

Full Text
Introduction

The IVC is a single vessel that is located in the right side of abdominal aorta. If disorder occurs during embryogenesis, it can cause congenital anomalies of the IVC. Vascular anomalies of IVC are not common and are often recognized incidentally during radiological and surgical procedures. The incidence is reported to be 0.6% [1]. In the absence of cardiac abnormalities, the incidence of the variations or anomalies of IVC has been reported to be 0.3% in the normal population [2]. We hereby present an asymptomatic case of IVC with azygos continuation without cardiac comorbidity.

Case Report

A 29-year-old male patient was admitted to our outpatient clinic with chest pain. THe was completely healty with no chronic disease history. The physical examination was normal. Chest x-ray showed mediastinal widening with enlargement of azygos arch and right hilus (Figure 1). On contrast-enhanced computed tomography (CT) images, a right sided azygos vein and an enlarged IVC with no hepatic segment was observed. The hepatic veins were pouring in right atrium. Additionally, the azygos vein was prominently dilated. There was no obvious abnormality in the hemiazygos vein (Figure2-3-4). Informed consent form was received from the patient.

Discussion

The IVC is one of the largest vein in the body. It is responsible for the venous drainage of the abdomen. It ascends through the abdominal and then the thoracic cavity and finally drains into the right atrium. Embryogenesis of IVC comprises complex relations with other abdominal and thoracic structures. These unknown conditions lead to the development of IVC anomalies. The anatomical variations are usually discovered incidentally as clinically silent. But in some cases collateral vessels provide physiological compensation for venous circulation and they present with deep venous thrombosis, atypical lower back pain, recurrent venous thromboembolism and hematoma [2]. IVC formation during embryogenesis occurs at 4-8 weeks of gestation. IVC is the result of several anastomoses made by three group of embryological veins: the supracardinal, the posterior and the subcardinal [3]. During this complex formation, many variations may develop due to various step changes. The most common anomalies include: duplication, transposition, interruption, and left renal veins that is located in a retro or circumaortic region [4-5]. Another IVC anomaly is interruption type with azygos continuation. Abnormal fusion of hepatic and prerenal parts of the IVC results in the infrahepatic hypoplasia or interruption type azygos continuation and compensatory enlargement [6]. IVC continues with azygos vein into the thorax then the azygos vein merges with the SVC and pours to the right atrium (Figure 5). The incidence of this condition was reported as 0.6% [7] in correlation with congenital heart disease, polysplenia and rarely with asplenia [8]. Generally, 0.3% of the population is faced with anomalies and variations of IVC with no cardiac comorbidity [3-4]. Our patient did not have any additional pathology.

Normally, the azygos vein locates on the intersection of right vena lumbalis ascendens and right vena subcostalis that passes in the thorax along the aortic hiatus. It ascends through the anterolateral surface of the thoracic vertebrae and arches ventral to right major bronchus at T5–6 and pours in SVC and uncommonly, into the right brachiocephalic vein, right subclavian vein, intrapericardial SVC or right atrium [9-10]. The enlarged azygos vein can be defined as mediastinal enlargement on chest radiography and may be confused with a right sided paratracheal adenopathy and mediastinal mass [11-12].

Conclusion

It is important to recognize and confirm this abnormal condition with radiologic tools for the purpose of preventing complications ie. hemorrhage, before performing invasive procedures.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Folger GM. Plain film identification of failure of Inferior Vena Caval – right atrial continuity. Cath. Cardiovasc. Diag. 1977; 3: 267-77.

2. Spentzouris G, Zandian A, Cesmebasi A, Kinsella C. R, Muhleman M, Mirzayan N. et al. The clinical anatomy of the inferior vena cava: a review of common congenital anomalies and considerations for clinicians. Clinical anatomy. 2014; 27(8): 1234-43.

3. Hashmi Zubair A, Smaroff Gregory G. Dual inferior vena cava: two inferior vena cava filters. The Annals of thoracic surgery, 2007; 84(2): 661-3.

4. Balzer K. M, Pillny M, Luther B, Grabitz K, Sandmann W. Spontaneous rupture of collateral venous aneurysm in a patient with agenesis of the inferior vena cava: a case report. Journal of vascular surgery. 2002; 36(5): 1053-7.

5. Cho B. C, Choi H. J, Kang S. M, Chang J, Lee S. M, Yang D. G. et al. Congenital absence of inferior vena cava as a rare cause of pulmonary thromboembolism. Yonsei medical journal, 2004; 45(5): 947-51.

6. Schneeweiss A, Bidden L. C, Deutsch V, Shem-Tov A, Neufeld H. N. Uninterrupted inferior vena cava with azygos continuation. Chest. 1981; 80(1): 114-15.

7. Ovalı G. Y, Örgüç Ş, Serter S, Göktan C, Pekindil G. Bilgisayarlı tomografide vena kava inferior anomalileri. Türk Göğüs Kalp Damar Cer Derg. 2006; 14: 169-71.

8. Okur A, Intepe Y. S, Serin H. I, Yıldırım U, Mavili E. Recurrent pulmonary embolism in an asthmatic patient who had interrupted inferior vena cava with azygous continuation. Turk Kardiyol Dern Ars. 2014; 42(3): 277-80.

9. Demos T. C, Posniak H. V, Pierce K. L, Olson M. C, Muscato M. Venous anomalies of the thorax. American Journal of Roentgenology. 2004; 182(5): 1139-50.

10. Geley T. E, Unsinn K. M, Auckenthaler T. M, Fink C. J, Gassner I. Azygos continuation of the inferior vena cava: sonographic demonstration of the renal artery ventral to the azygos vein as a clue to diagnosis. AJR. American journal of roentgenology. 1999; 172(6): 1659-62.

11. Lee S. Y, Kuo H. T, Peng M. J, Lin F. J, Shih S. C, Sheu C. Y. et al. Azygos vein varix mimicking mediastinal mass in a patient with liver cirrhosis: a case report. Chest. 2005; 127(2): 661-4.

12. Lee K. S, Kim Y, Han B. K, Yoon H. K, Ro D. W, Choe Y. H. et al. Mediastinal Interfaces and Lines: Clinical Significance and Radiographic-CT Correlation. Journal of the Korean Radiological Society. 1997; 36(5): 777-86.

PDF

Download attachments: JCAM_5950.pdf

How to Cite

Özçelik N, Kara BY, Özyurt S, Özdemir O, Şahin Ü. A rare case of interrupted inferior vena cava with azygos continuation. Ann Clin Anal Med 2019;10(4): 510-2

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Restrictive factors for detection of responsible agent in perioperative anaphylaxis: a case report

Hacı Yusuf Güneş 1, Abdulmenap Güzel 2

1 Private Akdamar Hospital, Department of Anaesthesiology and Reanimation Van, 2 Department of Anaesthesiology and Reanimation, Dicle University, Diyarbakir, Turkey

DOI:10.4328/ACAM.6005 Received: 17.08.2018 Accepted: 24.09.2018 Publihed Online: 25.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 517-21

Corresponding Author: Abdulmenap Güzel, Department of Anesthesiology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey. T.: +90 4122488001/4328 GSM: +905052165597 F.: +90 4122488440 E-Mail: dr.amenap@gmail.com ORCID ID: https://orcid.org/0000-0003-2261-0072

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Perioperative anaphylaxis is a type I hypersensitivity reaction, which rapidly develops with severe and variable clinical findings and can be fatal even in previously healthy patients. Early diagnosis and appropriate treatment are required but identifying the responsible agent is difficult. After anaphylaxis developed in our case, we did not have a healthy and adequate knowledge about the following questions. When should we get the blood sample, how much blood and to which tubes? Which tests can we work for detection of the responsible agent, where and in which laboratories? When we were communicating with the centers and laboratories which are given as references, we could not reach to standard information. Therefore, when perioperative anaphylaxis develops, it would be beneficial to have a set of perioperative anaphylaxis management guideline, including contact information of a national center for feedback and a reference anesthetic allergy testing center that could identify the responsible agent.

Keywords: General Anesthesia; Diagnostic Tests; Anaphylaxis; Perioperative Period

Full Text

Introduction

Anaphylaxis is an immunoglobulin E (IgE) mediated type I hypersensitivity reaction, which occurs with the release of primary mediators from basophils and mast cells into the circulatory system. Anaphylaxis is a type of vasogenic shock that can be life threatening, and is accompanied by a series of symptoms and findings ranging from mild acute respiratory distress to circulatory shock and collapse. Perioperative anaphylaxis is a clinical condition involving multiple organ systems that usually develops in response to anesthetic drugs or medical materials used in surgery [1–3]. Anaphylaxis may also occur during primary exposure due to cross-reactivity between many commercial products and drugs [4]. True anaphylaxis associated with anesthetic agents is rare, with anaphylactoid reactions being much more common. Muscle relaxants are the most common cause of anaphylaxis during anesthesia [2]. The clinical manifestations according to the Clinical Severity Scale of Immediate Hypersensitivity Reactions adapted from Ring and Messmer vary widely, from skin manifestations including erythema, edema, pruritus, and angioedema to the involvement of multiple organ systems and cardiac arrest [3]. When anaphylaxis occurs, allergy and immunological evaluations are important to identify the responsible agent and prevent relapse. Because there are no strategies for prophylactic treatment [3], early diagnosis and proper treatment management are the first two steps to achieving a successful outcome [4].

Here, we describe our experience regarding restrictive factors in the detection of the responsible agent and our clinical practices.

Case Report

A 28-year-old male patient weighting 85 kg with acute appendicitis was hospitalized for an emergency appendectomy. There were no food or drug allergies in his history. He reported only sun allergy in the summer months. Physical examination revealed no unusual features other than pain in the right lower quadrant. Findings consistent with acute appendicitis were obtained on the abdominal ultrasound. There were no abnormal findings on routine laboratory tests other than a C-reactive protein (CRP) level of 36 mg dL–1. The patient, who had no previous history of illness, was the American Society of Anesthesiologists’ physical status 1E. The antecubital vein was cannulated with an 18 G cannula for crystalloid infusion and an emergency appendectomy was planned under general anesthesia. After receiving written and verbal informed consent of the patient, premedication of midazolam (0.02 mg kg)–1was given. Routine monitoring showed a pulse rate of 80 beats per minute, noninvasive blood pressure of 110/70 mmHg, and peripheral capillary oxygen saturation (SpO2) of 98. After induction with 2 µg kg–1fentanyl, 3 mg kg–1propofol, and 0.5 mg kg–1rocuronium, endotracheal intubation was performed using a size 7.5 spiral cuffed tube. A mixture consisting of 50% O2+ 50% N2O + 2% sevoflurane was used for maintenance of anesthesia.

Within 2–3 min after induction, while surgical skin preparation was being performed using povidone iodine and the patient was being covered with sterile surgical covers; urticarial eruptions were noted on the upper side of the neck and chest with erythema and edema on the face. There was a slight increase in airway pressure and a decrease in SpO2to 87–90. As this was thought to indicate an allergic reaction, the patient was immediately given 100% oxygen while other anesthetic gases were stopped. Prednisolone (75 mg) was given intravenously. When hypotension (80/45 mmHg) and arrhythmia began to develop, adrenaline was administered at a dose of 0.2 mg intravenously, and the fluid replacement rate was increased. For arrhythmia, lidocaine hydrochloride 100 mg (Aritmal 2% ampoule) was administered intravenously. The cutaneous signs were mild but persisted. Therefore, dexamethasone 8 mg (Dekort amp 4 mg/mL; Deva, Istanbul, Turkey), the antihistaminic H1antagonist pheniramine maleate 45.5 mg (Avil amp; Sandoz, Istanbul, Turkey), and the H2antagonist ranitidine hydrochloride 50 mg (Ulcuran ampoule) were administered intravenously. The patient’s blood pressure, arrhythmia, and oxygenation began to improve, and the erythema on the face decreased. The urticarial eruptions on the neck and upper chest lessened (Figures 1–2). Examination of the events after the patient’s clinical condition had improved suggested that the patient may have suffered from anaphylaxis. Surgery was allowed to continue because of the urgent nature of the case and because the clinical findings of the patient improved after the emergency treatment. A blood sample was taken for detection of the responsible agent. We did not encounter other problems during the intraoperative period. Neuromuscular block was antagonized with 100 mg of sugammadex sodium (Bridion 200 mg/2 mL) after surgery without an additional dose, and the patient was awakened and extubated smoothly. The patient was monitored closely in the postoperative period but no problems occurred. The patient’s relatives were informed of the incident. The next day, the patient was discharged with allergy-immunology polyclinic referral for further examination and differential diagnosis.

Discussion

Perioperative anaphylaxis is an important cause of anesthesia-related mortality and morbidity. The actual incidence is unknown and it is a rare event, although possibly underreported. All medicines and medical materials can cause allergic reactions in patients in the perioperative period [5]. It is difficult to estimate the worldwide rate of allergic reactions during anesthesia, but the reported rates are 1:35,006 in Canada, 1:60,002 in Norway, 1:10,000 to 1:200,007 in Australia, and 1:340,008 in the United States. Anaphylaxis reportedly has a mortality rate of 3.5–10% depending on the source of the data [6].

Anaphylaxis during anesthesia can lead to life-threatening consequences if not diagnosed and treated in a timely manner. Perioperative anaphylaxis has a number of unique aspects. Early signs and mild symptoms are not noticed, and skin signs are not visible or are noticed late because the patient is anesthetized or obscured under a surgical cover. The severity of anaphylaxis may be underestimated by anesthesiologists, and cardiovascular manifestations may initially be attributed to general anesthesia or central block. Therefore, when a severe anaphylaxis crisis is noticed, there is little time for treatment. As more than one drug is given to the patient in a short time during surgery, the responsible agent can only be estimated during the crisis. Allergenic agents are not limited to intravenous drugs or fluids, but also include other materials used in the operating room such as skin disinfectants, latex gloves, and catheters [6]. The three most common causes of perioperative anaphylaxis in patients under anesthesia are muscle relaxants (70%), latex (20%), and antibiotics 15%. Among the muscle relaxants, succinylcholine, atracurium, vecuronium, and pancuronium are the primary agents responsible for anaphylaxis. Anaphylaxis has also been reported for opioid drugs, but the incidence is extremely rare. Propofol is responsible for 1.2–2% of perioperative anaphylactic reactions. Isopropyl groups found in skin-care products can induce IgE sensitization with subsequent cross-reactivity with the isopropyl groups of the propofol molecule [6]. It is not a simple matter to define propofol as a triggering agent because perioperative anaphylaxis due to propofol hypersensitivity is so rare that the predictive capacities of individual tests and test combinations are not at the same level as for many other drugs. The intradermal test is thought to be more reliable than the skin prick test in diagnosing propofol allergy [7]. Since thiopental is rarely used these days, reports of reactions to it are very rare too. The incidence of thiopental allergy is 1: 30000. Ketamine allergy is very rare, and etomidate is considered the “most immunologically safe drug” in anesthesia. Anaphylaxis in response to benzodiazepines is extremely rare. There have been no reported anaphylactic reactions to any of the volatile anesthetics. Colloids used as volume expanders during surgery and trauma are responsible for 2.5% of all intraoperative anaphylactic reactions [6].

Povidone-iodine (betadine) is the most commonly used topical antiseptic solution in the surgery [8]. It may cause hypersensitivity associated with IgE by inducing histamine release. It can only affect the local area or whole body if it is widely applied [9].

The initial diagnosis of anaphylaxis relies on clinical grounds and should be followed by retrospective confirmation via skin testing and serology. The summary of the clinical severity scale of immediate hypersensitivity reactions during anesthesia is shown in Table 1 [6]. Early diagnosis and rapid treatment of anaphylaxis are very important to prevent adverse outcomes. Anaphylaxis should be considered if it is accompanied by skin findings, bronchospasm, or hypotension. The decision to continue or discontinue surgery is determined by the urgency of the surgery, the degree of anaphylaxis, and the underlying comorbidities of the patient [10].

As a primer for perioperative anaphylaxis treatment (Table 2), it is necessary to stop the medication or serum, call for help, inform the surgeon, place the patient in the supine position as soon as possible, adopt the Trendelenburg position if hypotension is evident, take the airway under control and provide the patient with 100% oxygen. Adrenaline (epinephrine) is administered in mild to moderate anaphylaxis (Grades 1 and 2) as a 5–10 μg bolus, in severe anaphylaxis (Grades 3 and 4) as a 0.5–1 mg bolus or infusion of 0.05–1 μg kg–1min–1and 20 mL kg–1bolus of crystalloid or colloid fluid treatment. Adequate fluid resuscitation with adrenaline (epinephrine) therapy is a critical step in the management of hypotension, as it has been shown that 35–70% of the blood volume may extravagate in 10–15 min [6,10].

Perioperative anaphylaxis can present as cardiac arrest, most commonly pulseless electrical activity. The Australian Resuscitation Council and the New Zealand Resuscitation Council recommendations for nonshockable rhythms are 1 mg adrenaline administered immediately and then repeated every 4 min. The 2015 recommendation from the American Heart Association is 1 mg adrenaline every 3–5 min. In secondary treatment, antihistamine (H1antagonist, promethazine 0.3–1 mg kg;–1H2antagonist, ranitidine 0.5–1 mg kg)–1, corticosteroids (hydrocortisone 50 mg kg)–1, and β 2agonist nebulization (salbutamol 5–10 μg) are recommended [6,10]. We applied these treatments according to this protocol in our case.

To detect the responsible agent when perioperative anaphylaxis develops, serum tryptase, histamine, and IgE levels should be investigated immediately and skin tests should be performed as later exposure can seriously increase the risk for mortality. Histamine is a preformed inflammatory mediator contained in granules of mast cells and basophils. An early increase in plasma histamine concentration indicates activation of mast cells and/or basophils, and is observed via allergic and nonallergic mechanisms; conversely, the absence of histamine increase does not preclude an immunological or non-immunological mechanism. The plasma half-life of histamine is assumed to be very short (15–20 min). Blood samples for histamine measurement should therefore be drawn within 30 min after a Grade I or II reactions, and within 2 h after severe reactions (Grades III and IV). The biological half-life of tryptase is about 2 h, with the peak level usually reached after 15–120 min from the start of the reaction. The level of tryptase decreases slowly in the following 3–6 h. The return to baseline can be measured 24 h after the reaction. Therefore, blood samples may be drawn within 15 and 60 min in Grade I or II reactions and within 30 min and 2 h in Grade III or IV reactions. The increase in serum tryptase is considered a reliable indicator of mast cell degranulation, and serum tryptase levels tend to be elevated in IgE-mediated and non-IgE mediated anaphylaxis. Tryptase concentrations may also increase in relation to late onset, biphasic anaphylaxis, or underlying mastocytosis. Serial measurements of serum tryptase are recommended, including the baseline value. In addition, histamine and tryptase concentrations are correlated with the severity of allergic reactions, and some groups have suggested that combined histamine and tryptase measurements should be performed for diagnosis of sudden reactions [3,10,11].

Specific IgE tests seem to be less sensitive than skin tests, and serum IgEs provide a possible explanation for the mechanism but do not confirm that the drug or agent was responsible for the reaction. Skin tests continue to be the gold standard for detection of IgE-mediated reactions. As premedication with antihistamine or corticosteroids does not prevent anaphylaxis, skin tests are helpful to identify the responsible agent and provide protection against future risks. Due to mast cell depletion, it should be done 4–6 weeks after the reaction to prevent false negative test results [3,10,11]. In our case, after vital signs had stabilized, a blood sample was taken to determine the responsible agent. However, we could not reach a reference anesthetic allergy testing center capable of identifying the responsible agent. The anaphylaxis reaction developed within 2–3 min after induction. There were no cutaneous signs on the povidone-iodine applied area and its surroundings. Therefore, we do not consider povidone-iodine as a responsible agent. Latex-induced anaphylaxis usually occurs for 30–60 min after surgery [3],so it is unlikely that latex was the responsible agent in our case, and we did not use antibiotics. One or more of the agents used for induction (fentanyl, propofol, and rocuronium) may have been the responsible agent. The use of sugammadex in the anaphylaxis following to administration of rocuronium is not recommended [10]. However, the neuromuscular block was successfully antagonized by sugammadex. Whole blood collected in a covered test tube was separated into blood cells and plasma by centrifugation, and serum was analyzed immediately. We considered these four agents as antigens and dropped two drops of each drug onto serum and whole blood samples to examine agglutination both macroscopically and microscopically. We observed both macroscopic and microscopic agglutination of serum and blood samples into which propofol was dropped. The findings obtained using both in vitro methods and the conventional method implies that propofol may have been the responsible agent in our case. However, this was not a definite diagnosis.

Conclusions

In conclusion, when perioperative anaphylaxis occurs, it would be beneficial to have a set of perioperative anaphylaxis management guidelines, including the contact information of a national center for feedback, and reference anesthetic allergy testing centers able to identify responsible agents. The feedback of data regarding these cases to a national center would make it easier to reach the correct conclusion and would prevent the repetition of anaphylactic events in the future.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Demirsoy S. Anaphylaxis. Turkiye Klinikleri. Journal of Pediatric Sciences. 2005; 1(9): 1-12.

2. Butterworth J, Mackey DC, Wasnick J. Anesthetic Complications. Morgan and Mikhail’s Clinical Anesthesiology. 5th ed. Chapter 54. New York: McGraw-Hill Medical; 2013;1217-22

3. Dewachter P, Faivre CM, Charles W. Emala CW. Anaphylaxis and Anesthesia. Anesthesiology. 2009; 111(5): 1141-50

4. Ahmed A, Kumar A. Severe Anaphylactic Reaction at Induction of Anesthesia. J Pak Med Assoc. 2007; 57(9): 463-6.

5. Mota AC, Pereira F, Guimaraes J, Neves E, Sa P, Paiva M, et al. Propofol Induced Anaphylaxis-A Case Report. J Allergy Ther. 2015; 6: 209. DOI: 10.4172/2155-6121.1000209.

6. Dippennaar JM, Naidoo S. Allergic Reactions and Anaphylaxis During Anesthesia. Current Allergy and Clinical Immunology. 2015; 28(1): 18-22.

7. Harper NJH. Propofol and Food Allergy. British Journal of Anesthesia. 2016; 116 (1): 11–3. DOI:10.1093/bja/aev401.

8. Mali S. Anaphylaxis during the perioperative period. Anesthesia, Essays and Researches. 2012; 6(2): 124-33. DOI:10.4103/0259-1162.108286.

9. Altın F, Aydın S, Eygi B, Güneş T, Erkoç K, Kutas B, et al. An Allergic Reaction (Anaphylaxis) Observed Before Open Heart Surgeryin the Operating Room. Kosuyolu Heart J. 2013; 16(3). DOI: 10.5578/kkd.4720.

10. Kolawole HMarshall SDCrilly HKerridge RRoessler P. Australian and New Zealand Anaesthetic Allergy Group/Australian and New Zealand College of Anaesthetists Perioperative Anaphylaxis Management Guidelines. Anaesth Intensive Care. 2017; 45(2): 151-8.

11. Meng J, Rotiroti G, Burdett E, Lukawska JJ. Anaphylaxis during general anaesthesia: experience from a drug allergy centre in the UK. Acta Anaesthesiologica Scandinavica. 2017; 61(3): 281-9. DOI: 10.1111/aas.12858.

PDF

Download attachments: JCAM_6005.pdf

How to Cite

Güneş HY, Güzel A. Restrictive factors for detection of responsible agent in perioperative anaphylaxis: a case report. Ann Clin Anal Med 2019;10(4): 517-21

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the bladder: a case report

Recep Bedir

Department of Pathology, Recep Tayyip Erdogan University, Medical Faculty, Rize, Turkey

DOI:10.4328/ACAM.6006 Received: 17.08.2018 Accepted: 17.09.2018 Publihed Online: 20.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 522-4

Corresponding Author: Recep Bedir, Department of Pathology, Recep Tayyip Erdogan University of Medical Faculty, Rize, Turkey. T.: +90 4642130491 GSM: +905057331695 E-Mail: bedirrecep@gmail.com ORCID ID: https://orcid.org/0000-0001-8247-3781

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the urinary bladder is a rare tumor. This tumor, known as carcinosarcoma has a poor prognosis. The present study reports a rare case of sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation in the badder of a 71-year-old man.

Keywords: Bladder; Sarcomatoid Carcinoma; Chondrosarcomatous Differentiation

Full Text

Introduction

Sarcomatoid urothelial carcinoma is a very rare variant of urothelial carcinoma and it is generally detected in the bladder [1]. It constitutes 0.2-0.6% of all the histological subtypes of urothelial carcinomas found in bladder [2]. The malign heterologous elements such as chondrosarcoma and osteosarcoma may accompany these tumors, which are also known as carcinosarcoma [3]. The prognosis of these tumors having an aggressive course is worse than other urothelial carcinomas [4]. In the present study, we present a 71-year-old male patient’s sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation detected in bladder transurethral resection (TUR) material which is rarely seen.

Case Report

A 71-year-old male patient applied to our clinic with the complaint of hematuria for 15-20 days. In computed tomography (CT) imaging, a mass infiltrating the bottom-right edge of the urethra, extending towards adjacent fatty tissues, and having 8x4cm size was found in the right posterior wall of the bladder. The patient underwent TUR. In the macroscopic analysis of TUR material with 15x10x7cm size, the high-grade urothelial carcinoma foci consisting of papillary structures and the sarcomatoid zones showing differentiation towards chondrosarcoma consisting of spindle mesenchymal cells with the apparent nucleolus and large hyperchromatic nucleus, and having a pleomorphic appearance with highly mitotic activity were observed (Figure 1-3). In addition, the tumor was observed an undifferentiated element composed of small cells (Figure 4). No invasion analysis could be performed since no muscularis propria was observed in the tumor. In immunohistochemical analysis, the positive staining with both cytokeratin 7 (CK7) and vimentin were observed in sarcomatoid areas and positive staining with S-100 in chondrosarcomatous areas. Based on these findings, the case was diagnosed with invasive sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation. Since the patient didn’t accept the surgical therapy, he received chemotherapy for only 3 months and then died 1 year later because of widespread metastases. The written informed consent was obtained from the patient before the aforementioned work was carried out.

Discussion

Sarcomatoid urothelial carcinoma is a different histologic variant of urothelial carcinoma and the term “invasive urothelial carcinoma, sarcomatoid variant” was preferred in the 2004 World Health Organization Classification Tumors of the Urinary System [5]. The risk of metastasis is high in urothelial carcinomas with sarcomatoid differentiation and the most frequently seen metastases are those in bones, liver, lung, and lymph nodes [6]. The large majority of these tumors are histologically high-grade [7]. In sarcomatoid carcinomas, the metaplastic changes such as chondroid and osseous metaplasia or the more aggressive histological findings such as pseudo-carcinomatous stroma may be seen [4]. In these tumors, the epithelial component consists of urothelial carcinoma, urothelial carcinoma in situ, small-cell carcinoma, adenocarcinoma, and squamous cell carcinoma, whereas the sarcomatous component consists of leiomyosarcoma, chondrosarcoma, and osteosarcoma [5]. The differential diagnosis of these tumors includes the pseudo-sarcomatous stromal reaction with low mitotic activity and minimal atypia but deficit in apparent malignity criteria.

In these tumors having bad prognosis resistant to radiotherapy, the main therapy option is surgical resection and it is recommended to perform total cystectomy. The adjuvant radiotherapy and chemotherapy were observed to have no positive effect on the prognosis [7-9]. Since he denied surgical therapy, our patient received only the chemotherapy.

In conclusion, understanding the sarcomatoid urothelial carcinoma is important from therapeutic and prognostic aspects. These tumors should be accepted as high-grade invasive urothelial carcinoma with a high level of sarcomatous differentiation, which may include malign heterologous components such as chondrosarcoma. The pseudosarcomatous stromal reaction, which may be confused with these tumors in the histopathological analysis, should be kept in mind.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Lu W, Wang Y, Li Y, Cao Y, Han H, Zhou F. Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the ureter: A case report and review of the literature. Oncol Lett. 2017; 13: 1331-7.

2. Cho MH, Kim SH, Park WS, Joung JY, Seo HK, Chung J, et al. Bladder chondrosarcoma plus urothelial carcinoma in recurred transitional cell carcinoma of the upper urinary tract: a case report and literature review. World J Surg Oncol. 2016; 20: 270.

3. Darko A, Das K, Bhalla RS, Heller D. Carcinosarcoma of the ureter: Report of a case with unusual histology and review of the literature. Int J Urol. 2006; 13: 1528-31.

4. Nicolas MM, Nazarullah A, Guo CC. Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the ureter: A case report. Anal Quant Cytopathol Histpathol. 2014; 36: 111-16.

5. Eble JN, Sauter G, Epstein J, Sesterhenn I, editors. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. 3rd ed Vol. 7. Lyon: IARC Press; 2004.

6. Johnin K, Kadowaki T, Kushima M, Ushida H, Koizumi S, Okada Y. Primary heterologous carcinosarcoma of the ureter with necrotic malignant polyps. Report of a case and review of the literature. Urol Int. 2003; 70: 232-5.

7. Perimenis P, Athanasopoulos A, Geragthy J, Speakman M. Carcinosarcoma of the ureter: A rare, pleomorphic, aggressive malignancy. Int Urol Nephrol. 2003; 35: 491-3.

8. Wang X, MacLennan GT, Zhang S, Montironi R, Lopez-Beltran A, Tan PH, et al. Sarcomatoid carcinoma of the upper urinary tract: Clinical outcome and molecular characterization. Hum Pathol. 2009; 40: 211-17.

9. Yilmaz E, Birlik B, Arican Z, Guney S. Carcinosarcoma of the renal pelvis and urinary bladder: A case report. Korean J Radiol. 2003; 4: 255-9

PDF

Download attachments: JCAM_6006.pdf

How to Cite

Bedir R. Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the bladder: a case report. Ann Clin Anal Med 2019;10(4): 522-4

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Removal of foreign bodies from maxillary sinus: A report of three cases

Onur Şahin 1, Onur Odabaşı 2, Toghrul Aliyev 1, Birkan Tatar 1

1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, İzmir Katip Çelebi Universty, İzmir, 2 Department of Oral and Maxillofacial Surgery, Ministry of Health, Mamak Mouth and Dental Centre, Ankara, Turkey

DOI:10.4328/ACAM.5992 Received: 03.08.2018 Accepted: 04.09.2018 Publihed Online: 05.09.2018 Printed: 01.07.2019 Ann Clin Anal Med 2019;10(4): 513-6

Corresponding Author: Onur Şahin, Department of Oral and Maxillofacial Surgery, İzmir Katip Çelebi Universty, Faculty of Dentistry, İzmir, Turkey GSM: +905054410192 F.: +90 2323252535 E-Mail: onursahin43@hotmail.com ORCID ID: https://orcid.org/0000-0001-7816-1443

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

The maxillary sinus is the largest paranasal sinuses and displacement of foreign bodies into it is rarely reported in literature. It is necessary to know how to treat this kind of situation. The treatment for this complication is the surgical removal of the foreign bodies. We report three cases of foreign bodies (implant, impacted third molar and root) displaced into the maxillary sinus. The foreign bodies were removed soon after their migration, using the Caldwell-Luc approach, through lateral wall of the maxillary sinus. The operations were performed under local anesthesia and postoperative recoveries were uneventful, without any signs of postoperative sinusitis for both of the patients. In conclusion, Caldwell-Luc technique is a simple approach for the removal of foreign bodies into the maxillary sinus. The great advantage of this technique is that it is performed under local anesthesia and provides direct visualization.

Keywords: Maxillary Sinus; Migration; Caldwell-Luc; Dental Implant; Impacted Third Molar

Full Text

Introduction

Largest of paranasal sinuses, maxillary sinuses are the pyramidal shaped cavities localized within the maxillary bone bilaterally. This pyramidal base, an apex of which pointing toward the zygomatic process forms by the lateral wall of the nasal cavity. The upper wall is bounded by the base of the orbit, and the lower wall is bounded by maxilla’s processus alveolaris [1]. The lowest part of the lower wall is 3-5 mm below the nasal cavity and close to the first molar and the second premolar. Maxillary sinus volume has a natural tendency to increase among life, and especially when premolars and molar teeth are extracted, maxillary sinus may expand downward [1]. Factors that play role in the process of pneumatization of the maxillary sinus are absence of tooth roots after tooth extraction and atrophic resorption of maxillary alveolar crest [2]. Resorption of the bones can occur in the toothless alveolar crest with wide maxillary sinuses. In such cases, dental implant application is needed together with the sinus lift procedure [2].

Migration of foreign bodies to paranasal sinuses is a rare but significant condition. Among the reasons for this condition are; clinicians or surgeons with less experience in surgery, perforations during sinus wall lift procedures, implants placed without sinus floor elevation in the excessively pneumatized maxillary sinus, false graft technique, poor anatomical knowledge and maxillary teeth closely related to the maxillary sinus [3].

In this case report, we describe the removal of a dental implant, an impacted third molar and a tooth root with the Caldwell-Luc approach in three different patients with maxillary sinus displacement.

Case Reports

Case 1

An eighteen-year-old healthy female patient was referred to our department for the assessment of maxillary right third molar which was accidentally displaced into the maxillary sinus. According to the patient’s history, the patient underwent an unsuccessful surgical procedure under local anesthesia performed by a clinician for removal of her impacted right maxillary third molar. The localization of the tooth was detected in the right maxillary sinus with panoramic radiography. (Figure 1A-1B) The cone beam computed tomography (CBCT) taken the next day showed that the tooth was in the apical region of the molar teeth (Figure 1C). The surgical procedure was performed under local anesthesia. The surgical intervention began with the Caldwell-Luc lateral wall approach and the elevation of a trapezoidal full-thickness mucoperiosteal flap was performed. (Figure 1D) The buccal aspect of the flap was raised to access the maxillary sinus bony wall. A low-speed straight hand-piece with a circular diamond bur was used to perform spherical osteotomy. Immediately afterward, the upper third molar was identified and removed with a surgical aspirator and a clamp (Figure 1E). The postoperative healing was uneventful 3 month follow-up period.

Case 2

A 59-year-old male was referred to our department for the removal of a dental implant that had been displaced to the left maxillary sinus. While the healing cap was being attached, the implant displaced to sinus because of a successful primary stabilization did not occur. The clinical findings were supported by radiological examination and it was seen that the implant was at the apex of the left upper second molar. (Figure 2A) Because the patient did not have an acute infection, surgical removal of the implant under local anesthesia was decided. The surgical procedure was performed under local anesthesia. The crestal incision and vertical relaxing incisions were made for Caldwell-Luc operation. After removal of the full thickness flap, a rectangular window was removed on the lateral wall of the sinus with a round bur under irrigation of saline solution. (Figure 2B) The granulation tissues inside the sinus were removed with a sinus curette. The implant was removed with surgical aspirator and hemostat (Figure 2C). The postoperative recovery was uneventful 3 month follow-up period.

Case 3

A forty-five-year-old female patient was referred to us for her maxillary sinus displaced root after tooth extraction. According to the patient’s history, it has been learned that the left maxillary sinus area has pain and pressure sensation. Vestibular sulcus has sensitivity in palpation. Oroantral fistula findings were not found. Radiological examination revealed root presence in the left maxillary sinus. (Figure 3) It was determined that there was no acute condition in the patient and it was decided to remove the root with the Caldwell-Luc approach under local anesthesia. The surgical procedure was performed under local anesthesia. The surgical intervention began with the Caldwell-Luc access bilaterally and the elevation of a trapezoidal full-thickness mucoperiosteal flap. The buccal aspect of the flap was raised to access the maxillary sinus bony wall. The rectangular bone window was removed with the help of piezo-surgery (Figure 4A). The sinus membrane is perforated and the root is reached. (Figure 4B) L-PRF was applied to the surgery area and the removed bone piece was fixed with the aid of a mini screw (Figure 4C-4D). Postoperatively, amoxicillin 1000mg, naproxen 550mg, cetirizine 5mg, pseudoephedrine 125mg, % 0,12 chlorhexidine mouth rinse twice a day were prescribed for a week. The postoperative course was uneventful and the patient was asymptomatic in the three months period of follow-up.

Discussion

Because of the anatomical proximity of the upper teeth and dental implant placement in this area, maxillary sinuses are the most important among the paranasal sinuses for clinicians and surgeons in dentistry. Because of this close anatomic relationship, a careful clinical and radiological examination is needed before surgeries made in this area [3]. Maxillary sinus-related complications in dentistry are maxillary sinusitis, oroantral fistula formation and migration of foreign bodies into maxillary sinus [4]. The displacement of foreign bodies into the paranasal sinuses is a rare condition, and migraine usually occurs into the maxillary sinus. However, case reports about migrated implants into ethmoid and sphenoid sinuses are also available in the literature [5]. In such cases, sometimes no symptoms may be observed and this can occur with routine radiographic examinations. Sometimes it causes an infection in maxillary or other paranasal sinuses [6]. The causes of this complication include the incorrect extraction technique, poor anatomical information, reduced visualization of the surgical field, and complications experienced during sinus lifting operation [7]. In the treatment, there are the following methods as standard Caldwell-Luc operation, transoral functional endoscopic sinus surgery, transnasal functional endoscopic sinus surgery [8].

Surgeries using the standard Caldwell-Luc approach are under local anesthesia. With this method, sinusoid approach is essential by opening a window on the lateral wall of the maxillary sinus. The approach is direct from the opened window and this method is advantageous for the experienced clinician. Comparing the Caldwell-Luc surgery with endoscopic sinus surgery, the main disadvantage of endoscopic sinus surgery is the need for general anesthesia. If the foreign bodies are close to the anterior or inferior wall of the maxillary sinus, it is almost impossible to obtain these objects with a transnasal approach [8]. In this case report, we preferred to receive foreign bodies from the maxillary sinus via Caldwell-Luc operation under local anesthesia.

Conclusion

As a result, migration of foreign bodies to maxillary sinuses as a result of the surgical procedures performed is an undesirable complication. Careful clinical and radiological examination is necessary to avoid such complications. The Caldwell-Luc lateral wall approach is a simple method for removing maxillary sinus displaced foreign bodies. The biggest advantage is that it is performed under local anesthesia and provides direct visualization.

Scientific Responsibility Statement

The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.

Animal and human rights statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.

Conflict of interest

None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.

References

1. Costa FSBellotti AFarah GJDaniel ANCamarini ETRezende de Moraes Ferreira AC. Surgical management of impacted teeth using three-dimensional computed tomography. J Craniofac Surg. 2011; 22(6): 2344-7.

2. Tung TCChen YRSantamaria EChen CTLin CJTsai TR. Dislocation of anatomic structures into the maxillary sinus after craniofacial trauma. Plast Reconstr Surg. 1998; 101(7): 1904-8

3. Chanavaz M. Maxillary sinus: Anatomy, physiology, surgery and bone grafting related to implantology eleven years of sugical experience (1979-1990). J Oral Implantol. 1990; 16: 199-209.

4. Jung JH, Choi BH, Zhu SJ, Lee SH, Huh JY, You TM, et al. The effects of exposing dental implants to the maxillary sinus cavity on sinus complications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102: 602–5.

5. Haben CM, Balys R, Frenkiel S. Dental implant migration into the ethmoid sinus. J Otolaryngol. 2003; 32: 342–44.

6. Galindo-Moreno P, Padial-Molina M, Sánchez-Fernández E, Hernández-Cortés P, Wang HL, O’Valle F. Dental implant migration in grafted maxillary sinus. Implant Dent. 2011; 20: 400-5.

7. González-García A, González-García J, Diniz-Freitas M, García- García A, Bullón P. Accidental displacement and migration of endosseous implants into adjacent craniofacial structures: a review and update. Med Oral Patol Oral Cir Bucal 2012; 17: 769-74.

8. Felisati G, Lozza P, Chiapasco M, Borloni R. Endoscopic removal of an unusual foreign body in the sphenoid sinus: an oral implant. Clin Oral Impl Res. 2007; 18: 776–80.

PDF

Download attachments: JCAM_5992.pdf

How to Cite

Şahin O, Odabaşı O, Aliyev T, Tatar B. Removal of foreign bodies from maxillary sinus: A report of three cases. Ann Clin Anal Med 2019;10(4): 513-6

Citations in Google Scholar

Citations in Google Scholar: Google Scholar


Original Image

Eosinophilic granuloma of the femur with its radiological and histopathological images

Zülfü Birkan, Erhan Kaymaz

Radyoloji, Silivri Devlet Hastanesi, İstanbul, Turkey

DOI: 10.4328/ACAM.5738 Received: 30.01.2018 Accepted: 14.05.2018 Publihed Online: 14.05.2018 Printed: 01.07.2019

Corresponding Author: Zülfü Birkan, Radyoloji, Silivri Devlet Hastanesi, İstanbul, Turkey GSM: +905303201704 E-Mail: drzulfubirkan@yahoo.com.tr

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

One of the three clinical presentations of Langerhans cell histiocytosis, Eosinophilic Granuloma (EG) develops as a result of the benign inflammatory reaction to an etiological agent, with an undetermined cause. It is commonly seen in children and young adults. Most common locations in the body are primarily the skull, followed by diaphyses of long bones, such as costae and femur. In this report, we have aimed to present a 12- year old case we diagnosed with EG with the aid of imaging techniques, that had presented with pain in his femoral area for a period of time, along with the review of relevant literature (Figure 1, 2, 3 and 4).

Full Text

One of the three clinical presentations of Langerhans cell histiocytosis, Eosinophilic Granuloma (EG) develops as a result of the benign inflammatory reaction to an etiological agent, with an undetermined cause. It is commonly seen in children and young adults. Most common locations in the body are primarily the skull, followed by diaphyses of long bones, such as costae and femur. In this report, we have aimed to present a 12- year old case we diagnosed with EG with the aid of imaging techniques, that had presented with pain in his femoral area for a period of time, along with the review of relevant literature (Figure 1, 2, 3 and 4).

PDF

Download attachments: JCAM_5738.pdf

How to Cite

Zülfü Birkan, Erhan Kaymaz. Eosinophilic granuloma of the femur with its radiological and histopathological images. Ann Clin Anal Med 2019, DOI: 10.4328/ACAM.5738

Citations in Google Scholar

Citations in Google Scholar: Google Scholar

Severe melasma image presentation

Gülşah Öztürk 1, Onur Öztürk 2

1 Asarcık Devlet Hastanesi, Aile Hekimliği Kliniği, 2 Asarcık Meydan Aile Sağlığı Merkezi, Aile Hekimliği Kliniği, Samsun, Turkey

DOI: 10.4328/ACAM.6019 Received: 12.09.2018 Accepted: 01.10.2018 Publihed Online: 02.10.2018 Printed: 01.07.2019

Corresponding Author: Onur Öztürk, Aile Hekimliği Uzmanı, Asarcık Meydan Aile Sağlığı Merkezi, Biçincik Mah. Esen Sk. No:15/A Kat:1, Asarcık, Samsun, Turkey GSM: +905547536566 E-Mail: dr.onurozturk@yahoo.com

Abstract
Full Text
PDF
How to Cite
Citations in Google Scholar
Abstract

The changes in pigmentation during pregnancy are mostly physiological; and bioactive molecules released from estrogen, progesterone and placenta are known to play a role in this process. The increase in pigmentation progresses during pregnancy, but it is expected that the skin will return to its original appearance after pregnancy [1,2]. Melasma (chloasma or the mask of pregnancy) describes gray-brown hypermelanosis on the face and rarely on the neck and forearms, which are well-circumscribed, symmetrical and tend to unite. It has been reported in more than half of pregnant women. Pigmentation changes rarely reach pathological dimensions and cause cosmetic problems. Due to being a cosmetic problem, it can lead to emotional changes. Maxillary melasma constitutes one-fifth of all types of melasma [1,2]. A 25-year-old woman in her 39th week of pregnancy presented with complaint of discoloration on her face. It was learned that she had her first pregnancy in her medical history and she has received vitamin D and iron replacement. Her examination revealed severe maxillary melasma (Figure 1). There was no additional complaints and features in her mdical history and in family medical history. Laboratory tests and other health check ups were normal. Sun protection was recommended. Control examination after the pregnancy was suggested.

Full Text

The changes in pigmentation during pregnancy are mostly physiological; and bioactive molecules released from estrogen, progesterone and placenta are known to play a role in this process. The increase in pigmentation progresses during pregnancy, but it is expected that the skin will return to its original appearance after pregnancy [1,2]. Melasma (chloasma or the mask of pregnancy) describes gray-brown hypermelanosis on the face and rarely on the neck and forearms, which are well-circumscribed, symmetrical and tend to unite. It has been reported in more than half of pregnant women. Pigmentation changes rarely reach pathological dimensions and cause cosmetic problems. Due to being a cosmetic problem, it can lead to emotional changes. Maxillary melasma constitutes one-fifth of all types of melasma [1,2]. A 25-year-old woman in her 39th week of pregnancy presented with complaint of discoloration on her face. It was learned that she had her first pregnancy in her medical history and she has received vitamin D and iron replacement. Her examination revealed severe maxillary melasma (Figure 1). There was no additional complaints and features in her mdical history and in family medical history. Laboratory tests and other health check ups were normal. Sun protection was recommended. Control examination after the pregnancy was suggested.

References

1. Durmazlar SPK, Atacan D, Eskioğlu F. Gebelikde fizyolojik ve biyolojik deri değişiklikleri: derleme. Kadın doğum dergisi. 2007; 6(1): 1331-4.

2. Bilaç C, Şahin MT, Öztürkcan S. Melazmada Güncel Tedavi Yaklaşımları. Bezmialem Science. 2018; 6: 54-62.

PDF

Download attachments: JCAM_6019.pdf

How to Cite

Gülşah Öztürk, Onur Öztürk. Severe melasma image presentation. Ann Clin Anal Med 2019; DOI: 10.4328/JCAM.6019

Citations in Google Scholar

Citations in Google Scholar: Google Scholar