May 2022
Assessment of platelet reactivity after the anthracyclinebased chemotherapy via mean platelet volume: Does it act on anthracycline-induced cardiotoxicity?
Gokmen Aktas 1, Tulay Kus 2, Emre Kuş 3, Murat Sucu 4, Handan Haydaroglu Sahin 5, Mustafa Pehlivan 5
1 Department of Internal Medicine, Division of Medical Oncology, Kahramanmaraş Sütçü İmam University, School of Medicine, Kahramanmaraş, 2 Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Faculty of Medicine, Gaziantep Oncology Hospital, Gaziantep, 3 Department of Cardiology, Sehitkamil State Hospital, Gaziantep, 4 Department of Cardiology, University of Gaziantep, School of Medicine, Gaziantep, 5 Department of Hematology, University of Gaziantep, School of Medicine, Gaziantep, Turkey
DOI:10.4328/JCAM.5499 Received: 12.12.2017 Accepted: 23.01.2018 Published Online: 25.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 183-6
Corresponding Author: Gokmen Aktas, Department of Internal Medicine, Division of Medical Oncology, Kahramanmaraş Sütçü İmam University, School of Medicine, Kahramanmaraş, Turkey. GSM: +905076969249 E-Mail: aktas_gokmen@hotmail.com
Aim: Anthracycline-induced cardiotoxicity is the most frequent dose-limited toxicity. There has been numerous hypothesis about this matter. As an indicator of platelet size, mean platelet volume (MPV) is correlated with platelet reactivity, aggregation, and long-term atherosclerosis. We aimed to study whether the anthracycline triggers the elevation of MPV.
Material and Method: Patients who had breast carcinoma and received anthracycline-based chemotherapy for only adjuvant setting were included. Age, disease stage, history of diabetes mellitus (DM), hypertension (HT) and body mass index (BMI) were recorded. Patients with systemic inflammatory rheumatic disorders, the symptoms of infectious diseases, cytopenia after the chemotherapyand, BMI over 40 and metastatic disease were excluded. Blood samples were collected for initial MPV value and after four cycles of adjuvant anthracycline treatment. Statistical significance of the associations was analyzed using Pearson correlation, Student’s t, ANOVA tests and Wilcoxon signed-rank test.
Results: Three hundred operated breast cancer patients were recruited in this study. Mean age was 49.1 (20-77). There was no significant correlation between age and initial MPV (r=-1.111, p=0.056) or between BMI and initial MPV (r=0.023, p=0.697). Stage, DM, and HT did not affect initial MPV levels. Initial median MPV was 9.1 (6.2-12.8), and the last median MPV was 9.2 (6.1-12.9). According to Wilcoxon signed ranks test, positive ranks were found in 151 patients (p=0.003, Z=-3,002, based on positive ranks) after anthracycline therapy.
Discussion: Anthracycline causes elevation in MPV value which is a marker of thrombocyte reactivation and atherosclerosis. This might be responsible for the possible long-term cardiotoxicity of anthracyclines.
Keywords: Platelet Reactivation; Doxorubicin; Cardiotoxicity; Mean Platelet Volume
Introduction
The mechanisms of the antiproliferative and cytotoxic effects of the anthracycline antibiotics are DNA synthesis inhibition, free radical formation, DNA binding and alkylation, cross-linking, interference with DNA strand separation, direct membrane damage via lipid oxidation, and inhibition of topoisomerase II [1]. Anthracycline-induced cardiotoxicity is a dose-limited toxicity, and it presented classically with congestive heart failure vascular toxicity, and rarely as acute cardiotoxicities, such as electrocardiogram changes, arrhythmias, pericarditis and myocarditis syndromes [2]. Since there are no known effective protective agents and it leads to irreversible toxicity, it is managed based on preventive strategy according to cumulative dose. Also, it was known that increasing age is associated with increased risk of doxorubicin-related cardiotoxicity [3].
Although multiple mechanisms have been proposed for anthracycline-induced cardiotoxicity, it remains unclear which of these are effective in clinical context since most of the studies are on animals or in-vitro studies. Known mechanisms of the anthracyclines-induced cardiotoxicity are based on produced oxidative stress with membrane damage via lipid peroxidation, and inactivation of nitric oxide synthase. This ultimately leads to myocyte cell death even within hours after the anthracycline infusion according to human studies and cardiac remodeling develops with changing the extracellular matrix in the long-term [4-6]. Also, suppression of DNA, RNA, and protein synthesis triggers the cardiac sarcopenia, apoptosis, and necrosis in the heart tissue as in cancer cells [7]. On the other hand, decreased beta-adrenergic receptor stimulation after the anthracycline infusion contributes to decrease in the cardiac contractility [8].
Other explanations of cardiotoxicity have been proposed as some mediators such as platelet-activating factor, thromboxane A2 (TxA2), adenosine diphosphate (ADP), prostaglandins, histamine, and calcium according to in vivo and rat studies [9]. Mean platelet volume (MPV) is a significant marker showing a platelet activation. Larger platelet size is associated with more platelet function and activation which plays a crucial role in the pathophysiology of atherosclerotic disease and ultimately long-term cardiotoxicity. Thrombocyte activation and aggregation leads to proliferation and migration of smooth muscle cells from the media to endothelium in early stages of atherogenesis [10-12]. In this regard, we aimed to study whether the anthracycline-based chemotherapy triggers a higher MPV that indicates the platelet activity.
Material and Method
This retrospective study was designed to evaluate whether the anthracycline chemotherapy leads to platelet activation assessing through the measurement of MPV. A total of 300 operated breast cancer patients recruited in this study. All patients received anthracycline-based chemotherapy and were treated in the Gaziantep University Department of Medical Oncology between September 2011 and June 2016. The protocols were reviewed and approved by the Independent Ethics Committee of Gaziantep University Hospital.Patients were eligible for the study if they were over 18 years old, female, diagnosed with pathologically confirmed breast carcinoma, and received anthracycline-based chemotherapy for only in adjuvant setting. Other eligibility criteria were; an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, adequate hematologic and biochemical function, patients without hematologic disorders and without other malignancy, patients who did not receive any chemotherapy before.Patients with systemic inflammatory rheumatic disorders, the symptoms of infectious diseases (high C-reactive protein or white blood cell [WBC]), missing measured MPV before and after chemotherapy, cytopenia after the chemotherapy and body mass index (BMI) over 40, more than two times of upper limit of ALT and metastatic disease were excluded. Age, disease stage, history of diabetes mellitus (DM), hypertension (HT) and BMI were recorded. HT was defined as history of HT and/or systemic blood pressure measurements exceeding 140/90 mmHg. DM was defined as history or presence of diabetes and/or a fasting plasma glucose level higher than 7.0mmol/l (126 mg/dl) on two separate occasions, or a random glucose value of more than 11.1mmol/l (200 mg/dl) before administered anthracycline. BMI was calculated by dividing the weight in kilograms by the height in meters squared. Obesity was defined as BMI of 30 or greater. Due to retrospective design, we could not reach the history of smoking and lipid profile.
In all patients, blood samples for complete blood count analyses were collected in 3.0 ml tubes containing ethylene dinitro tetraacetic acid (EDTA) and evaluated within 30 minutes before every administration of the anthracycline. Initial MPV values and initial WBC of all patients were recorded. Also, last platelet count and MPV values were noted after four cycles of adjuvant anthracycline treatment.All patients received intravenous (IV) 60 mg\m2 doxorubicin with 600 mg\m2 cyclophosphamide once every three weeks or IV 60 mg\m2 doxorubicin with 600 mg\m2 cyclophosphamide once every two weeks for four cycles.All statistical analyses were performed using SPSS version 16.0. MPV levels before first chemotherapy cycle and after the last chemotherapy cycle were recorded as continuous variables. Continuous variables were presented as mean±SD and compared using independent sample t-test between two groups. One-way ANOVA was used to compare three groups. Pearson correlation test was used to assess the relationship between two variables. Comparisons between parameters before and after anthracycline therapy were tested with the Wilcoxon signed-rank test. All P values were reported as two-tailed, with an accepted significance at less than 0.05.
Results
Three hundred operated breast cancer patients were recruited in this study. Mean age was 49.1 (20-77). There was no significant correlation between age and first MPV (r=-1.111, p=0.056). Respectively 9% (n=27), 42.7% (n=128) and 48.3% (n=145) of patients were stage I, II and III. There was no statistically significant difference between three groups according to first MPV levels. Stage I mean MPV was 9,46±1,27, stage 2 mean MPV was 9,23±1,23, and stage III mean MPV was 9,25±1,04 (p=0.568). There were 40 (13.3%) patients who have DM. First MPV of the patients with and without DM was 9,45±1,18 and 9,228±1,145 respectively (p=0.258). There were 20 (6.6%) patients who have HT. First MPV of patients with and without HT was 9,57±1,6 and 9,23±1,1 respectively (p=0.203). BMI of 163 (54.3%) patients was under 30, and 137 (45.7%) were over 30. First MPV of patients with BMI under and over 30 was 9,22±1.17 and 9,29±1,13 respectively (p=0.633). There was no significant correlation between BMI and first MPV (r=0.023, p=0.697).
Initial median MPV was 9.1 (6.2-12.8), and last median MPV was 9.2 (6.1-12.9). According to Wilcoxon signed ranks test, positive ranks were found in 151 patients, and negative ranks were found in 149 patients P value was 0.003 (Z value:-3,002) based on positive ranks.
Discussions
The most common known vascular cardiotoxic agents are anti-metabolites (5-fluorouracil) and the anti-tumor antibiotics (bleomycin, doxorubicin). These agents affect not only tumor-associated endothelial cells but also endothelial cells of other tissues. This causes vascular toxicity such as pulmonary veno-occlusive disease, hepatic veno-occlusive disease, myocardial ischemia and infarction, cerebrovascular attacks, venous thromboembolic events [13]. Activation of coagulant factors, endothelial dysfunction, stimulation of fibroblasts and increase in levels of prothrombotic microparticles originating from endothelial cells or platelets could cause the direct vascular damage after the administration of anticancer drugs [14]. Biomarkers rise such as troponin-T, troponin-I, brain natriuretic peptide (BNP) and inactive amino-terminal pro-BNP (NT-pro-BNP) and phosphorylation of the histone H2A variant H2AX (termed γ-H2AX) is sensitive in detecting early asymptomatic cardiotoxicity in order to guide imaging assessment [15-17]. However, platelet activation has been not studied as a biomarker in the pathogenesis of chemotherapy-induced vascular toxicity and atherosclerosis in a humans study, until now. We, for the first time, evaluated the effect of doxorubicin on platelet reactivity through elevation of MPV after the chemotherapy in breast cancer patients. And we showed that anthracycline triggered an elevation in MPV.
Platelets play a crucial role in the pathogenesis of atherosclerosis and acute myocardial infarction (MI). Young platelets are characterized by an increased platelet volume, and more reactive platelet activity metabolically and enzymatically. They can lead to more platelet adhesion, aggregation, and acute vascular events. As an indicator of platelet size, MPV is correlated with platelet reactivity and aggregation [18]. Increased MPV is an independent risk factor for MI, stroke, and mortality from coronary artery disease and it has a poor prognosis after the MI and the coronary artery intervention especially patients with DM and HT [19-23]. Larger and more reactive platelets secrete a variety of mediators of inflammation, thrombosis, and coagulation such as neutrophil-activating peptide 2, interleukin-1, interleukin-6, P-selectin, intercellular adhesion molecule 2, Toll-like receptors, CD40, thromboxane A2 (TxA2), ADP and all of these mediators trigger platelet aggregation, inflammatory response, and tissue injury [9].
MPV, indicating a marker both inflammation and platelet reactivity, is also prognostic and predictive on recurrence in some cancer types via some mediators mentioned above. In malignant tumors, platelets can lead to tumor progression and angiogenesis. High MPV is associated with uncontrolled and metastatic disease [24-29]. Therefore, in this study, we excluded the un-operated and metastatic patients due to a probable rise in MPV value. In addition to patients with acute or chronic inflammatory disease and patient with a history of MI, and with an ejection fraction lower than 55% were excluded. After excluded conditions which might be the cause of platelet reactivity, we found increased MPV levels after completion of doxorubicin chemotherapy.
As previously shown in preclinic studies anthracyclines may cause a rise in the level of prostaglandins, thromboxanes, and leukotrienes through altering arachidonic acid metabolism [30]. And also preliminary data suggested that PAF may contribute to anthracycline toxicity. PAF is a strong activator for thrombocytes aggregation and a strong inducer of granules secreted from the thrombocytes [31]. Active thrombocytes release TxA2 and ADP, and this mediates the primary aggregation of the other pro-coagulation factors. Both granules are secreted from thrombocytes and appeared the TxA2 via released arachidonic acid from the cell membrane leading to irreversible thrombocyte aggregation. In this regard, the main question of this study is “Could MPV, which is an indicator of activated thrombocyte, be a predictive biomarker in anthracycline-induced platelet reactivity and long-term atherosclerosis”. According to our study anthracycline treatment had a positively increasing effect on the level of MPV. Therefore, anthracycline may cause long-term atherosclerosis and cardiotoxicity through thrombocyte reactivation when evaluated with present preclinic studies. Also, metabolic syndrome parameters related to atherosclerosis were previously shown to get worse in the breast cancer patients receiving adjuvant anthracycline [32]. When our study is evaluated with previous studies, we have suggested that anthracyclines may cause long-term cardiotoxicity by provoking atherosclerosis.
The major limitations of this study are the retrospective design and hereby lack of assessment of other cardiac biomarkers together. At the same time, there is also a need for clinical and radiological demonstration of the development of atherosclerosis that may develop many years later. However, this study has importance to be the first clinical study showing increased MPV after the anthracycline chemotherapy. This study can pave the way for designing new prospective studies in this manner.
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.
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Aktas G, Kus T, Kuş E, Sucu M, Sahin HH, Pehlivan M. Assessment of platelet reactivity after the anthracycline-based chemotherapy via mean platelet volume: Does it act on anthracycline-induced cardiotoxicity? J Clin Anal Med 2018;9(3): 183-6.
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Neonatal septicemia in tertiary hospitals in Konya, Turkey
Nuriye Tarakcı 1, Murat Konak 2
1 Department of Neonatology, Dr. Faruk Sukan Women and Children’s Diseases Hospital, 2 Department of Neonatology, Selcuk University, Konya, Turkey
DOI: 10.4328/JCAM.5774 Received: 19.02.2018 Accepted: 04.03.2018 Published Online: 09.03.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 187-91
Corresponding Author: Nuriye Tarakcı, Department of Neonatology, Dr. Faruk SukanWomen andChildren’s Diseases Hospital, 42060 Konya, Turkey. T.: +90 3322380931 F.: +90 3322376025 E-Mail: nuriyetarakci@hotmail.com ORCID ID: 0000-0003-2444-4724
Aim: Neonatal sepsis is one of the leading causes of mortality and morbidity in the developing world. The present study aims to determine the incidence and risk factors of neonatal sepsis in a single center over a four-year period.
Material and Method: This is a retrospective study of all cases of culture-proven neonatal sepsis admitted in the neonatal intensive care unit of a single center between January 2013 and December 2016. Clinical features, risk factors, microbiological and biochemical results, and mortality rates were recorded. Associations between risk factors and mortality were investigated.
Results: The prevalence rate of neonatal sepsis was 2.7 per 1000 live births (94/30545) and 9.3 per 1000 neonatal admissions (94/10133). Low birth weight (≤ 2500g) was recorded in 79 (84%) neonates with sepsis. There was at least one risk factor in all cases. Gram-negative bacteria were more frequently isolated than gram-positive bacteria (63.8% (60/94) vs. 29.7% (28/94)). Klebsiella pneumonia was predominant in both early-onset sepsis and late-onset sepsis (53% (16/30), 29.7% (19/64) respectively). Late-onset sepsis episodes attributed to Klebsiella pneumonia were associated with the highest sepsis-related mortality (41.7%).
Discussion: Klebsiella pneumonia was found to be the most common agent in neonatal sepsis and responsible for sepsis-related mortality in this study. Prevalence of neonatal sepsis, its pathogens and risk factors differ in different parts of the world. Region-specific strategies to prevent new infections should be encouraged.
Keywords: Neonatal Sepsis; Neonatal Intensive Care Unit
Introduction
Neonatal sepsis is a clinical syndrome that occurs during the first months of life and is associated with a high rate of mortality when the diagnosis is delayed [1]. In spite of recent advances in health care units, neonatal sepsis is still an important cause of death and morbidity in the neonatal intensive care unit (NICU). Signs and symptoms of neonatal sepsis are often non-specific thus making its clinical diagnosis challenging. Isolation of a bacterial pathogen from the bloodstream is the gold standard for diagnosis. However, due to the difficulty with growing pathogenic microorganisms in the blood, assistive diagnostic methods based on clinical and laboratory findings have been proposed in addition to blood cultures [2].
The frequency of neonatal sepsis, risk factors, and resistance against antimicrobial agents may be different in each unit [2]. Causative microorganisms differ from one group to the other and can vary over time even in the same clinical setting [3]. Recently, the most frequently reported causative organisms for neonatal sepsis are gram-positive bacteria followed by gram-negative bacteria such as Klebsiella pneumonia and Escherichia coli. Fungal etiologies are less commonly reported [4].
The aim of the present study was to evaluate the incidence of neonatal sepsis, characterize the etiological agents of neonatal sepsis, and determine risk factors for sepsis in the NICU of a single center.
Material and Method
The medical records of all neonates who were admitted to the NICU of a single center between January 1, 2013 and December 31, 2016 were reviewed. During the study period, all exposed neonates with clinical signs and symptoms of sepsis at the time of admission or who developed sepsis during their hospital stay were assessed and included in the study.
Cases of sepsis were classified according to the infant’s age, the growth of potentially pathogenic organisms from blood at the time onset of clinical and laboratory findings consistent with infection symptoms: early-onset sepsis (EOS) (≤ 72 hours of life) and late-onset sepsis (LOS) (> 72 hours of life) [5]. Blood cultures were taken routinely when the baby was admitted to the NICU with the suspicion of having an infection.
Demographic characteristics, clinical and microbiological variables at the onset of a septic episode were collected retrospectively from patient charts. The following variables were collected: age, NICU stays, antimicrobial therapy exposure (yes/no), additional interventions (surgery, invasive intubation, or use of a ventilator, use of umbilical and central venous catheters or total parenteral nutrition, orogastric feeding tube, urinary catheter, thorax tube), and response to treatment.
Hematological (white blood cell (WBC) count, platelet count), biochemical (C-reactive protein (CRP), blood glucose) and microbiological findings (blood culture, urine culture) of the patients in both groups were recorded and compared.
Statistical Analysis
Summary of measures was reported as the mean ± standard deviation (SD) for continuous variables and percentages for categorical variables. For group comparison, the Mann-Whitney U-test was used for quantitative variables. Categorical data were tested using the Chi-square test. P value ≤ 0.05 was considered statistically significant. All the statistical analyses were performed using SPSS 20 (SPSS Inc., Chicago, IL, USA).
Results
Out of 30,545 babies who were born at the center, 10,133 NICU admissions were recorded during the study period. Of these, 94 neonates diagnosed with sepsis were enrolled. They included 55 (58.5%) females and 39 (41.5%) males. Deliveries were by caesarean section in 54 (57.4 %) cases and vaginal in 40 (42.6%) cases. The mean gestational age (GA) of patients was 30.3 ± 3.8 weeks and mean birth weight (BW) was 1647.1 ± 772.7 g. Seventy-nine (84%) septic neonates had low birth weight (≤ 2500g). Subgrouping identified 48 (51%) with very low birth weight (VLBW) (≤ 1500 g). Mean hospitalization time was 43.6 ± 34.4 days (Table 1). Among the sick newborns, EOS was present in 30 (31.9 %) cases and LOS in 64 (68.1%).
All septic babies had at least a risk factor for neonatal sepsis (Table 2). All patients with EOS had received at least an antibiotic. Total parenteral nutrition (TPN) and mechanical ventilation (MV-CPAP) were the most common risk factors in both EOS and LOS groups. For EOS patients, umbilical venous catheter was found in 23 (76.7%), TPN in 19 (63.3%), MV and CPAP in 23 (76.6%). For LOS babies, MV or CPAP was present in 27 (42.1%), and 18 (28.1%) patients had TPN (Table 2). 19 (29.7%) patients with LOS had received one or more antibiotics before a septic attack.
The median skin temperature was 36.6ºC (interquartile range [IQR]: 0.90). Minimum and maximum skin temperatures were 36.0ºC and 39.4ºC respectively. Besides, 55 (58.5%) cases had normal temperature, 34 (36.2%) had hyperthermia, and 5 (5.3%) had hypothermia (1). Median skin temperatures between EOS and LOS groups were comparable (for EOS, 36.80C; for LOS, 36.70C).
Abnormal leukocyte counts were seen in 36 (38.3%) cases. Abnormalities in the complete blood count such as leukopenia (WBC <5,000/mm3), leukocytosis (WBC > 20,000/mm3), and thrombocytopenia (platelets <150,000/mm3) were seen in 24 (25.5%), 12 (12.8%), and 42 (44.7%) patients, respectively (Table 3). Thrombocytopenia was more common among EOS cases but similar to leukocytosis and leukopenia, there were no significant differences between EOS and LOS groups (p=0.30, p=0.06, p=0.13, respectively).
CRP levels were measured in all 94 cases and were found to be positive (>8mg/L) in 55 (58.5%) cases. CRP positivity was not significantly different in the EOS and LOS groups (p=0.48). Blood glucose levels were not significantly associated with the incidence of sepsis (p=0.19).
Table 4 shows the most common causative organisms of neonatal sepsis (early or late-onset sepsis). Ninety-four microorganisms were identified in blood cultures. These consisted of 35 (37.2%) Klebsiella pneumonia, 8 (8.5%) Staphylococcus haemolyticus, 6 (6.4%) Staphylococcus epidermidis, 6 (6.4%) Serratia marcescens, 5 (5.3%) Enterococcus faecium, 4 (4.3%) Pseudomonas aeruginosa, and 4 (4.3%) Enterobacter cloacae. Candida was grown in the blood of six patients (all LOS patients). Among all cases of LOS, Klebsiella pneumonia were the most common organisms isolated with 19 cases (29.7%), followed by coagulase-negative staphylococci (CoNS) 18 (28.1%), Staphylococcus haemolyticus 7 (11%), Staphylococcus epidermidis 6 (9.4%), Staphylococcus hominis 1 (1.6%), other 4 (6.3%), Serratia marcescens 6 (6.4%) and Candida 6 (6.4%) (Table 4). Similarly, Klebsiella pneumonia was the most common organism, with 16 ( 53.3%) isolated in the cases of EOS.
On average, LOS occurred on the day of life 40.3±35.2. Rates of LOS, death and sepsis-related death were inversely proportional to GA and BW (Table 1). LOS episodes attributed to Klebsiella pneumonia were associated with the highest sepsis-related mortality (41.7%), followed by Staphylococcus haemolyticus (33.3%), Enterobacter spp (8.3%), and Candida (8.3%).
Discussion
This study aimed to investigate the incidence of culture-proven EOS and LOS in the state of Konya, a region in Turkey, to identify the primary causative organisms of neonatal sepsis, and to highlight the complex interaction of factors involved in the outcome of neonatal sepsis.
Neonatal sepsis is the leading cause of mortality in the neonatal intensive care units [6]. Its prevalence rate in the present study was 2.7 per 1000 live births (94/30545) of 9.3 per 1000 neonatal admissions (94/10133). Nikkhoo et al. [3] have reported a prevalence rate of 6.4% for sepsis. The prevalence of sepsis in their study was twice that of ours. Similar to what has been reported in developed countries [7], the incidence of EOS was 0.98 per 1000 live births. The incidence of LOS was 2.1 per 1000 live births, which is less than that reported from developing countries [8].
In premature newborns, the risk of sepsis and sepsis-related mortality increase as birth weight decreases [9]. In our study, the mortality rate was significantly high among patients with birth weights less than 1500 g. The rate of death was 13.8% below 1500g but decreases to 6.4% above 1500g. In a study by Turhani et al. [2], low birth weight was found to be significantly associated with mortality rates of neonatal sepsis. Sepsis-related mortality was found to be 36.3% in babies with a birth weight <1000g, and 15% in babies with a birth weight >1000g.
According to previous studies conducted in Turkey on neonatal sepsis, mortality rates are higher for EOS patients than LOS patients [10]. Conversely, the present study reported higher death rates among LOS patients than EOS patients (12.8 % for LOS, 7.4% for EOS). A greater proportion of patients with BW <1500g within the LOS group can explain this different finding.
In the present study, premature rupture of the fetal membranes (PROM), meconium-stained liquor, low birth weight, prematurity, active resuscitation required in the labor room, urinary tract infection in the mother, MV or NCPAP, TPN, orogastric tube, vesical catheter, previous antibiotics, chest tube, and central catheter were associated with neonatal sepsis. Similar findings have been reported in previous studies [11, 12, 13]. Of note, PROM, active resuscitation required in labor room, TPN and MV were significant risk factors for early sepsis, but not for late sepsis. The most important neonatal factor predisposing to neonatal sepsis is prematurity and LBW [3]. Low birth weight and prematurity were major risk factors for early and late sepsis in our study.
The incidence and microbiology of neonatal sepsis vary from region to region. In developed countries, Group B Streptococcus is most significant cause of neonatal sepsis [14]. However, in the present study, gram-negative bacteria were more frequently isolated than gram-positive bacteria. These results were consistent with the findings of many previous studies [15,16]. Similarly, the most commonly isolated agents in EOS from different units in Turkey include gram (-) bacilli [17]. In this study, Klebsiella pneumonia is reported as the common isolate in both EOS and LOS, followed by coagulase-negative staphylococci in LOS and Enterococcus faecalis and Pseudomonas aeruginosa in EOS. Most of the studies performed in developing countries have shown Klebsiella pneumonia as the most implicated gram-negative bacteria for neonatal sepsis [18, 19].
Body temperature, blood glucose level, and various serologic markers such as CRP, WBC counts, and thrombocyte count are often used to support the diagnosis of sepsis [20]. In a study by Ahmad et al. [5], most cases of culture-proven and probable neonatal sepsis found the normal axillary temperature. Similar findings were seen in this study. CRP is an acute phase reactant which is used very frequently in the diagnosis of neonatal sepsis [20]. In this study, CRP levels were found to be high in EOS and LOS. But there was no statistically significant difference in CRP elevation between these two groups. Thrombocytopenia was observed in 55.3% of the patients. This finding supported the results of Turhan et al. [2]. In our study, the thrombocyte count was found to be lower in the babies who were EOS compared to the LOS. But there was no statistically significant difference in thrombocytopenia between these two groups. Turhan et al. [2] found the neutrophil count to be lower in the babies who were lost because of sepsis compared to the mortality from non-sepsis. In our study, there was no statistically significant difference in white blood cell count between these two groups.
There are many metabolic changes during severe sepsis and septic shock, and among the metabolic changes, blood glucose level is the most important [21]. Studies by Ahmad et al. [22] found that blood sugar levels below 40 mg / dL and above 200 mg / dL had higher mortality rates. However, in our study, there was no relationship between blood glucose level and sepsis.
In conclusion, Klebsiella pneumonia was the most commonly found organism in this study and was responsible for the mortality associated with sepsis in this study. This study has demonstrated an increased incidence of sepsis in VLBW and premature babies. Prevalence of neonatal sepsis, its pathogens, and risk factors are different across the world. In each NICU, strategies aimed at prevention of neonatal infection such as reinforcement of infection control policies, selecting correct antibiotics, and providing information regarding the frequently isolated organisms and their drug resistance patterns should be implemented.
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. M.S. Edwards and C.J.Baker, “Sepsis in the newborn,”in Krugman’s Infectious Diseases of Children, A.A. Gershon, P.J.Hotez, and S.L. Katz, Eds. p.545, Mosby, Philadelphia, Pa, USA, 2004.
2. Turhan EE, Gürsoy T, Ovalı F. Factors which affect mortality in neonatal sepsis. Turk Pediatri Ars. 2015; 50 (3): 170-5.
3. Nikkhoo B, Lahurpur F, Delpisheh A, Rasouli MA, Afkhamzadeh A. Neonatal blood stream infections in tertiary referral hospitals in Kurdistan, Iran.Ital J Pediatr. 2015; 41: 43.
4. García H, Torres-Gutiérrez J, Peregrino-Bejarano L, Cruz-Castañeda MA. Risk factors for nosocomial infection in a level III Neonatal Intensive Care Unit.Gac Med Mex. 2015; 151 (6): 711-9.
5. Ahmad MS, Ali N, Mehboob N, Mehmood R, Ahmad M, Wahid A. Temperature on admission among cases of neonatal sepsis and its association with mortality. J Pak Med Assoc. 2016; 66 (10): 1303-1306.
6. Robinson D, Kumar P, Cadichon S. Neonatal Sepsis in the Emergency Department. Pediatr Emerg Med. 2008; 9 (3): 160–8.
7. Bizzarro MJ, Shabanova V, Baltimore RS, Dembry LM, Ehrenkranz RA, Gallagher PG. Neonatal sepsis 2004-2013: the rise and fall of coagulase-negative staphylococci.J Pediatr. 2015; 166(5): 1193-9.
8. Thaver D, Zaidi AK. Burden of neonatal infections in developing countries: a review of evidence from community-based studies. Pediatr Infect Dis J 2009; 28:S3–9.
9. Hornik CP, Fort P, Clark RH, et al. Early and late onset sepsis in very low birth weight infants from a large group of neonatal intensive care units. Early Hum Dev 2014; 88: S69-74.
10. Ovalı F. Bakteriyel enfeksiyonlar. İçinde: Dağoğlu T, Ovalı F, (yazarlar) . Neonatoloji. 2. baskı. İstanbul, Nobel Tıp Kitabevleri, 2007.p.765-810.
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13. Elster T, Beata Czeszyńska M, Sochaczewska D, Konefał H, Baryła-Pankiewicz E. Analysis of risk factors for nosocomial infections in the Neonatal Intensive Care Unit of the Pomeranian Medical University in Szczecin in the years 2005–2008. Ginekol Pol. 2009; 80 (8): 609–14.
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15. Topuz S. Yenidoğan sepsisinin tanı ve izleminde C-Reaktif Protein ile prokalsitonin değerlerinin karşılaştırılması. Nobel Medicus 2012; 8: 6-72.
16. Payaslı MÖ. Neonatal sepsisli hastalarda polimorfonükleer lökosit elastaz düzeylerinin değerlendirilmesi. Uzmanlık tezi. İstanbul, Haseki Eğitim ve Araştırma Hastanesi Çocuk Sağlığı ve Hastalıkları Kliniği, 2007.
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20. Ng PC and Lam HS. Diagnostic markers for neonatal sepsis. Curr Opin Pediatr 2006; 18: 125-131.
21. Hirasawa H, Oda S, Nakamura M: Blood glucose control in patients with severe sepsis and septic shock. World J Gastroenterol 2009, 15: 4132-4136.
22. Ahmad S, Khalid R. Blood glucose levels in neonatal sepsis and probable sepsis and its association with mortality.J Coll Physicians Surg Pak. 2012; 22 (1):15-8.
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Tarakcı N, Konak M. Neonatal septicemia in tertiary hospitals in Konya, Turkey. J Clin Anal Med 2018;9(3): 187-91.
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A comparison of serum alpha-1-antitrypsin and vitamin B12 levels in patients with vitamin B12 deficiency
Yılmaz Sezgin 1, Mehtap Kartal 2, Azize Dilek Güldal 2
1 Department of Family Medicine, University of Health Science, İstanbul Educational Research Hospital, İstanbul, 2 Department of Family Medicine, Dokuz Eylül University, İzmir, Turkey
DOI: 10.4328/JCAM.5629 Received: 19.12.2017 Accepted: 05.01.2018 Published Online: 08.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 192-4
Corresponding Author: Yılmaz Sezgin, Department of Family Medicine, University of Health Science, İstanbul Educational Research Hospital, 34098 Fatih, İstanbul, Turkey. GSM: +905383425644 E-Mail: drysezgin@gmail.com
Aim: Alpha-1-antitrypsin (A1AT) loses its antiprotease activity as a result of oxidation of the methionine in its structure. Vitamin B12 plays an active role as a co-factor during methionine synthesis. Thus, we think that vitamin B12 deficiency may lead to decreased A1AT.
Material and Method: The research was planned as an observational study. One hundred eighty patients were enrolled. The levels of serum A1AT and vitamin B12 were compared based on demographic characteristics of the patients. Twenty-seven patients’ -who have accomplished therapeutic protocol and who have come to control visits- A1AT levels were controlled after treatment and compared with the before treatment levels.
Results: The levels of serum A1AT could not be found statistically significantly different according to the level of vitamin B12. However, in patients using any medication because of a chronic disease, the levels of serum A1AT were found higher in the group with high level of vitamin B12, than the group with the low level of vitamin B12. Serum A1AT levels were found significantly lower in obese than non-obese participants. Following treatment with vitamin B12, the levels of serum A1AT (pre-treatment 121.67±13.884, post-treatment 138.04±16.922, P=0.001) were found to be increased.
Discussion: This study’s results suggest that the level of vitamin B12 may have a significant role in the synthesis of A1AT.
Keywords: Vitamin B12; Alpha 1-Antitrypsin; Obesity
Introduction
A1AT acts as an antioxidant due to its methionine content, and its deficiency causes chronic diseases such as emphysema. It is the main inhibitor of the serine protease in human plasma and inhibits trypsin and other proteases such as elastase [1]. It is synthesized by hepatocytes, macrophages, and intestinal and bronchial epithelial cells, and it has a plasma half-life of five days [2-4]. It is estimated that the ratio of development of emphysema in patients with genetic A1AT deficiency is approximately 5%, but autopsy studies reveal that there is significant lung injury in approximately 70% of the patients with the genetic deficiency [3]. It is highlighted that the risk of developing emphysema is increased when serum level of A1AT falls below 80 mg/dl [5]. The mechanisms of the environmental factors that play a role in the development of Chronic Obstructive Pulmonary Disease are suggested to be secondary to their action as free radicals oxidizing A1AT. The oxidation by free radicals of the methionine sulfide groups at the 351st and 358th amino acids of the peptide chain lead to loss of the antiprotease activity of A1AT [3,6]. A1AT deficiency may be seen particularly in pulmonary involvement with diseases such as emphysema, bronchiectasis, and chronic bronchitis, and also in liver involvement in clinical situations such as neonatal cholestasis, chronic hepatitis, and cirrhosis and hepatocellular carcinoma. It is reported that in the deficiency of A1AT the risks of necrotizing panniculitis and multisystem vasculitis are increased [7,8].
Vitamin B12 mainly acts as a cofactor in two enzyme systems in the body. There is methylmalonyl-CoA-mutase which converts methylmalonyl-CoA to succinyl-CoA. On the other hand, there is methionine synthase which converts homocysteine, a methionine residue formed by methylation reactions back to methionine where vitamin B12 transfers the methyl group taken from folate [9]. Epidemiological studies point out that cobalamin deficiency ranges between 5% and 60% and this difference is correlated with age [10,11]. Framingham reported that prevalence of cobalamin deficiency among elderly is 12% [12]. Interestingly, a significant deficiency of vitamin B12 is observed in smokers and alcohol users. There are several studies reporting an association between cigarette as a free radical source and reduced vitamin B12 serum levels [13,14].
The amino acid methionine is one of the building stones of A1AT, and since it is not synthesized in the body, it should be taken from the environment. One of the principal functions of methionine is to participate in methylation reactions by S-adenosyl methionine molecules [15]. A large part of homocysteine produced by methylation reactions is converted to methionine by the enzyme methionine synthase which has vitamin B12 as a cofactor. A stable level of methionine in the body is provided by the maintenance of this transformation in an uninterrupted manner. To evaluate this relation, we investigated whether serum A1AT levels were affected by the level of vitamin B12.
Material and Method
This study was designed as an observational study. The study was approved by Dokuz Eylul University (DEU) Ethical Committee. The sample size was calculated to be at least 144 according to the formula n = t2pq / d2. In determining the sample size the values were accepted as follows: p = 0.12, the q = 0.88, d = 0.05, α error level = 0.05 and t = 1.96 according to error level, respectively.
A total of 5743 serum samples for vitamin B12 tests ordered between April and July 2011 by DEU Hospital outpatient and inpatient clinics were examined with the help of the central laboratory operating system. The serum samples of the 180 patients who accepted to participate in the study and have inclusion criteria were stored. The serum levels of vitamin B12 were categorized into two groups; the high group was up to 220pg/ml, and the low group was below 220pg/ml. The levels of serum A1AT and vitamin B12 were compared based on demographic characteristics of the patients.
Exclusion criteria: Pregnant women, children, patients whose folate levels were not measured or detected to be higher or lower than normal, the ones with iron deficiency anemia, liver disease, kidney failure, infection, trauma history, and tissue necrosis pathologies.
Among one hundred eighty patients, only twenty-seven patients -who have accomplished therapeutic protocol and who have come to control visits- A1AT levels were controlled after treatment and compared with the before treatment levels.
Windows SPSS statistical software package (PASW Statistics for Windows, Version 16.0 Chicago: SPSS Inc.) was used in analyzing the data. Chi-square test was used to compare percentages. In the comparison of the mean values of the two groups, the independent-samples t-test was used for independent variables, and paired samples t-test was used for dependent variables.
Results
Of the 180 patients enrolled in the study; 101 (56.1%) were females, and 79 (43.9%) were males. There were no significant differences between the two vitamin B12 groups, regarding weight, height, age, gender, and use of cigarette, alcohol, and drugs.
The levels of serum A1AT could not be found statistically significantly different according to the level of vitamin B12. However, in patients using any medication because of a chronic disease, the levels of serum A1AT were found higher in the group with high level of vitamin B12, than the group with the low level of vitamin B12 (Table 1).
Serum A1AT levels were found significantly lower in obese participants than non-obese. In addition, vitamin B12 levels were lower in obese than non-obese (Table 2).
The mean serum A1AT level before treatment was 121.67 ± 13.884 mg/dl, and the post-treatment mean level was 138.04 ± 16.922 mg/dl. A statistically significant increase was observed in the A1AT levels after Vitamin B12 replacement therapy (P = 0.001) (Table 3).
Discussion
The levels of serum A1AT could not be found statistically significantly different according to the level of vitamin B12. Serum A1AT level is affected by many genetic or individual-related physiological factors. However, in patients using any medication because of a chronic disease, the levels of serum A1AT were found higher in the group with high level of vitamin B12, than the group with the low level of vitamin B12. These data indicate that there is a relation between serum A1AT and vitamin B12 levels in some certain conditions, and in groups that have certain specifications. It was mentioned in one study that hepatocellular carcinoma risk increases in A1AT deficiency, and in another study, it was stated that using S-adenosyl-methionine is beneficial for treating hepatocellular carcinoma [16,17]. This brings in to mind the thought that there might be a relationship between A1AT and S-adenosyl-methionine, and this relationship can be related to vitamin B12.
Serum A1AT levels were found to be lower in obese participants. Serum A1AT levels were found significantly lower in obese participants than non-obese. In addition, vitamin B12 levels were lower in obese participants than non-obese. There are studies claiming an increased obesity frequency in subjects with vitamin B12 deficiency [18,19]. Since there are no accessible studies citing the relationship between serum A1AT level and obesity, we may claim that our results mentioned a relationship may be a new data. The demonstrated decrease in serum A1AT levels in obese individuals may account for the obesity, which is observed more frequently in vitamin B12 deficiency. Both vitamin B12 and A1AT play roles in the etiopathogenesis of obesity, either independently, or A1AT synthesis affected by serum vitamin B12 levels.
In this study, acceleration was detected on serum A1AT levels on participants who attended the therapy protocol and showed up at control visits. This finding suggests that owing to a steady plasma methionine level provided by vitamin B12 treatment, A1AT synthesis is accelerated.
Conclusion
As a conclusion; this study’s results suggest that the level of vitamin B12 may have a significant role in the synthesis of A1AT. However, further studies are needed to support our results.
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. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Chapter 50; Plasma Proteins & Immunoglobulins, Harper’s Illustrated Biochemistry, 28th Edition. The McGraw-Hill Companies; 2009. P.566-82.
2. Teckman JH, Lindblad D. Alpha-1-antitrypsin deficiency: Diagnosis, pathophysiology, and management. Current Gastroenterology Reports. 2007; 8: 14-20.
3. Perlmutter DH, Daniels JD, Auerbach HS, De Schryver-Kecskemeti K, Winter HS, Alpers DH. The Alpha-1-antitrypsin gene is expressed in a human intestinal epithelial. J Biol Chem. 1989; 269: 15957-60.
4. Cichy J, Potempa J, Travis J. Biosynthesis of alpha-1-proteinase inhibitor by human lung-derived epithelial cells. J Biol Chem. 1997; 272: 8250-5.
5. Alves CC, Santos C. Alpha-1-antitrypsin deficiency. The experience of Pulido Valente Hospital with augmentation therapy. Rev Port Pneumol. 2009; 15: 473-82.
6. Taggart C, Cervantes-Laurean D, Kim G, McElvaney NG. Oxidation of either methionine 351 or methionine 358 in alpha-1-antitrypsin causes loss of anti-neutrophil elastase activity. The Journal of Biological Chemistry. 2000; 275: 27258-65.
7. Gross B, Grebe M, Wencker M, Stoller JK, Bjursten LM, Janciauskiene S. New findings in PiZZ alpha-1-Antitrypsin deficiency-related panniculitis demonstration of skin polymers and high dosing requirements of intravenous augmentation therapy. Dermatology. 2009; 218: 370-5.
8. Takii Y, Inoue H, Karashima E, Akahoshi M, Furugo I, Hattori S, et al. Systemic vasculitis associated with alpha-1-antitrypsin deficiency. Intern Med. 2003; 42: 619-23.
9. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Chapter 44; Micronutrients: Vitamins & Minerals, Harper’s Illustrated Biochemistry, 28th Edition. The McGraw-Hill Companies; 2009. P.467-81.
10. Dali-Youcef N, Andres E. An update on cobalamin deficiency in adults. QJM. 2009; 102: 17-28.
11. Allen LH. How common is vitamin B12 deficiency? Am J Clin Nutr. 2009; 89: 693-6.
12. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population, Am J Clin Nutr. 1994; 60: 2-11.
13. Pivathilake HJ, Macaluso M, Hine RJ, Richards EW, Krumdieck CL. Local and systemic effects of cigarette smoking on folate and vitamin B12. Am J Clin Nutr. 1994; 60: 559-66.
14. Mcgarry JM, Andrews J. Smoking in pregnancy and vitamin B12 metabolism. British Medical Journal. 1972; 2: 74-7.
15. Takemoto C, Spremulli LL, Benkowski LA, Ueda T, Yokogawa T, Watanabe K. Unconventional decoding of the AUA codon as methionine by mitochondrial tRNAMet with the anticodon f5CAU as revealed with a mitochondrial in vitro translation system. Nucleic Acids Res. 2009; 37: 1616-27.
16. Perlmutter DH. Alpha-1-antitrypsin deficiency: diagnosis and treatment. Clin Liver Dis. 2004; 8: 839-59.
17. Lu SC, Mato JM. S-Adenosylmethionine in cell growth, apoptosis, and liver cancer. J Gastroenterol Hepatol. 2008; 23: 73-7.
18. Pinhas-Hamiel O, Doron-Panush N, Reichman B, Nitzan-Kaluski D, Shalitin S. Obese children and adolescents, a risk group for low vitamin B12 concentration. Arch Pediatr Adolesc Med. 2006; 160: 933-6.
19. Karatela RA. Sainani GS. Plasma homocysteine in obese, overweight, and normal weight hypertensives and normotensives. Indian Heart J. 2009; 61: 156-9.
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Sezgin Y, Kartal M, Güldal AD. A comparison of serum alpha-1-antitrypsin and vitamin B12 levels in patients with vitamin B12 deficiency. J Clin Anal Med 2018;9(3): 192-4.
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Publication rate of abstracts presented in national congress of Turkish society of anesthesiology
Kutlu Hakan Erkal, Yucel Yuce
Anaesthesiology and Reanimation Department, University of Health Sciences Kartal Dr. Lutfi Kirdar Education and Research Hospital, Kartal, Istanbul, Turkey
DOI: 10.4328/JCAM.5630 Received: 19.12.2017 Accepted: 19.01.2018 Published Online: 25.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 195-9
Corresponding Author: Yucel Yuce, Anaesthesiology and Reanimation Department, University of Health Sciences Kartal Dr. Lutfi Kirdar Education and Research Hospital, Kartal, Istanbul, Turkey. T.: +90 2164583000 F.: +90 21635200 E-Mail: dryyuce@gmail.com
Aim: This study aimed to determine the rate of conversion to scientific publication of abstracts presented at the annual congress of Turkish Society of Anesthesia and Reanimation (TARD) between the period of 2011-2013.
Material and Method: The abstracts presented at TARD Congresses in 2011, 2012, 2013 and published in various peer-reviewed medical journals were identified using PubMed and Google Scholar. In a retrospective study design, the abstracts were divided into either oral presentations(OP) or poster presentations(PP), type of the study; trial design, first author’s name and affiliated institution, mean publication time and journal name were analyzed.
Result: From a total of 2417 abstracts, 114(4.7%) were found to be published as a scientific full-text article. While the conversion rate of OP was; 24 of 187(12.8%), for PP it was 90 of 2230(4%), and the difference was statistically significant (p<0.001). Experimental studies had the highest publication rate compared to clinical studies and case reports. The publication rate of university-related anesthesia programs was higher than other hospitals. The mean time of publication after the abstract presentation was 14.4±11.4 months.
Discussion: This is the first study evaluating the publication rates of abstracts presented at TARD congress. Our study results show that conversion to publication rate of TARD congress presentations is 4.7% and this rate is relatively lower than those presented at national congress for other clinical specialties held in Turkey.
Keywords: Congress; Anesthesia; Publication; Abstract; Full-Text Article; Pubmed; Google Scholar
Introduction
In a scientific congress, the scientists share the results of their studies as abstracts, and they share their ideas about these findings. The findings of these studies presented at the congresses and symposiums have an important role for scientific improvement. For distribution of these new findings to all our colleagues working in the anesthesiology field, the reported findings need to be published in medical journals to be able to distribute reliable reports related to the study design, methods, and outcomes. Finally, colleagues who have no chance to join these scientific platforms will have an opportunity to reach up-to-date knowledge related to new research data [1,2].
Even today, there are limited number of articles which evaluate the conversion rate of the abstracts into scientific articles in national congresses organized in Turkey. Recently, data on the national congresses of different other clinical fields such as; gynecology, rheumatology, radiology, and plastic reconstructive-aesthetic surgery national congresses were reviewed, and it has been reported that the conversion rate of abstracts into peer-reviewed scientific publications were between 5.7% and 28.6% [3-6]. No similar studies have been reported about the national congress and scientific meetings in the field of anesthesiology and reanimation in Turkey.
The Society of Anaesthesiology in Turkey was founded in 1956, and it was named as Turkish Anaesthesiology and Reanimation Society (TARD) in 1972. TARD is the only legal nongovernmental organization in Turkey in the field of anaesthesiology, perioperative care medicine, pain medicine, and critical care and it is a member of the World Anesthesiology Federation. TARD organizes national congress during the last 50 year period each year and publishes a monthly scientific journal in the field of anesthesiology and reanimation. This society provides communication of physicians with colleagues throughout the world and develops guidelines depending on new scientific knowledge. Improving education of students in anesthesiology and reanimation in hospitals in Turkey, and setting accreditation certificates and board exams are other activities.
This study aims to determine the rate of conversion to scientific full-text articles publication of abstracts presented at the annual congress TARD between the period of 2011-2013.
Material and Method
To obtain the reports published in the peer-reviewed journals, we identified all oral presentations (OP) and poster abstracts accepted to the TARD, which was held in 2011, 2012 and 2013. All data of the reports presented at the congress were obtained using the congress booklet provided to the participants during these three congresses. A period of minimum 36 months was selected for follow-up of the abstracts for publication as it was accepted as adequate time for the editorial process [7]. Therefore, we decided that July 2017 would be a cut-off date.The study was conducted in a retrospective study design. An investigation of databases were performed with the help of the PubMed database [8] and Google Scholar [9] electronic search engines by each author of this research. The search was conducted by entering the name and surname of the first and second authors along with the title in English and Turkish languages. If search did not give a result for the abstract, it was assumed that the study was not published in a journal. The investigation related to a full publication includes; the year of national congress abstract document publication, the presentation type as oral or poster of abstract, study type (clinic study, experimental study, case presentation), study design (prospective, retrospective) and the affiliated institution (university hospital, training and research hospital, state hospital and private hospital) were recorded. The institution of the first author was considered as where the study was mainly performed when it is found that there are several institutions related to the authors working addresses. The date of publication according to the month and year, the name of the journal, and the index of the journal (Science Citation Index(SCI), Science Citation Index-Expanded(SCIE), national journals) were also noted.As patient data was not used and there was no need for informed consent of patients, approval of ethics committee was not required.After the data was entered into a computer, the Statistical Package for the Social Sciences version 20.0 software (SPSS Inc., Chicago, IL, USA) was used to analyze the data. A descriptive analysis was initially performed. Numerical variables were presented as average, and standard deviation and categorical variables were presented as percentages. The Mann Whitney U-test was used to compare continuous variables, and the Pearson chi-square test and Fishers-Exact test were used to compare categorical variables. A p value of <0.05 was considered statistically significant with 95% confidence interval (%95 CI).
Results
There were a total of 2417 accepted abstracts at 2011, 2012, and 2013 of which 187(7,73%) were OPs, 2230(92.3%) were poster presentations (PP). Of these presentations, 114(4.7%) were published in the various medical journals. The distribution of publication rate according to years was found as 663/37(5.58%) in 2011, 739/43(5.81%) in 2012, and 891/34(3.81%) in 2013(Table 1) (Figure 1).According to the type of presentation, 24(12.8%) of the OPs and 90(4%) of PPs were published in either national or international peer-reviewed journals. The publication rate for OP was higher than PP, and the difference was statistically significant (p<0.001) (Table 2).
According to the type of institution, proceedings from the universities had the highest ratio of publication (53.4%), followed by studies from training and research hospitals (41.1%), multi-centered studies (4%), and state hospitals (1.5%). There were no significant differences between the distribution of oral and PPs according to the institution types. There was no statistical difference in the rate of publication of presentations between universities and training and research hospitals (p=0.412). But; there was a statistical difference in the rate of publication of presentations from universities and training and research hospitals between multi-centered and state hospitals (p=0.623, p=0.741, p=0.701) with respect to the institution types in which presentations were converted into publications. In 2011 and 2012 no publication was produced from proceedings of state hospitals and private hospitals, but in 2013 only one proceeding ended with publication.
When the types of publications were reviewed; 1388(57.4%) abstracts were clinical studies, 987(40.8%) were case series or case reports presentations, and 42(1.8%) were experimental studies. When clinic studies were compared according to their prospective and retrospective nature; among the 1242(50.2%) of the clinical studies were prospective studies whereas 604(49.8%) were retrospective in nature, the rate of publication was higher in prospective clinical studies than retrospective studies, and significant difference was founded between two groups (p=0.643).When the publication rate was examined according to type of abstract, it was seen that experimental abstracts had the highest rate (73%) of being published and case reports had the lowest publication rate (2.4%)5; publication rates according to study type were statistically significantly different (p<0.001), as shown in Table 3.
The duration between the date of Congress and the publication date of abstract as an article was 14,4±11.4 months (range 3 to 72 months), this duration was 13,5±15.1, 14,6±13.6 and 17,4±11.2 months for the years of 2011, 2012, and 2013 respectively (p=0,321, p= 0,356, p=0,422) (Table 4). Publishing time for OPs was relatively longer compared PPs, but no significant difference was observed (p=0.18). When training and research hospitals were compared to university hospitals, presentations from training and research hospitals identified to be published earlier than other institutions (p=0.062). Analysis of publication rate and publication duration according to the subject, there was not a significant difference between three fields (p=0.68, p=0.59, p=0.78).
When it was evaluated according to the abstract subject of published articles, “pain’’ ranked first, ‘’intensive care’’ field the second and “anesthesia” third (n= 58, n=31 and n=25).Of all the reports published in 63 different national or international medical journals. While 42(36.8%) abstracts that have been published as an article in international journals, 72(63.2%) were published in national journals. The percentages of the publications are low in international journals, and there was a significant difference between national journals (p<0.05). The first five journals that were listed by databases in which the articles were mostly published are Turkish Journal of Anesthesia and Reanimation(n=13), Pain(n=9), Anaesthesia and Analgesia(n=9), Acta Anaesthesiologica Scandinavica(n=8), European Journal of Anaesthesiology(n=4).
Discussion
To our knowledge, this study is the first study to determine publication rates of the abstracts presented at the Annual Congress of the TARD. The main result showed that 4,7% of the abstracts, were converted to manuscripts and published in the peer-reviewed journals within the subsequent three years. Scientific research shared at the congresses provide a very important effect in scientific improvement. New studies shared with the medical community after the congresses may develop by the contributions of the colleagues [10]. When these reports are accepted for publication in medical journals, we can think that the researchers conducted these studies by scientific methods ending with reliable results. In addition, publication of these studies in the journals is the best way of intercommunication with a wide range of colleagues worldwide rapidly, and the scientific quality of a congress may be evaluated by the publication rate of abstracts [11,12]. For this purpose, there is a need for an evaluation of the conversion of abstracts into full-text peer-reviewed, and indexed articles in national and international journals and the evaluation would also provide data on the quality of these publications which can be assessed by citation rates, h-index, and publication in science citation indexed journals. In a Cochrane meta-analysis published in 2007, after review of the 30,000 reports, the conversion rate of abstracts to scientific articles was reported as 44.5% [13].
National meetings for clinical sciences had different publication rates for different clinics. The main reason for this difference in national congress results were the used methodology, search engine and the properties of the published journal as national or international. The publication rate of national congress proceedings in different medical branches was reported as significantly low in recent studies [14].
Our study included the most comprehensive national meeting about Anesthesiology and Intensive Care in which nearly 1500 participants attend annually in Turkey. Similarly, in the same field report from in The Indian Society of Anaesthesiologists national congress that is the primary conference of anesthesia in India the publication rate of presentations was 5% [15]. No similar studies were found in Turkey about Anaesthesiology and Reanimation, but when different clinical branches were compared, our rate is relatively lower than those presented at national congress for clinical specialties held in Turkey and other countries [3-5,16].
According to our results, we determined that OPs presented at TARD congresses had higher publication rate than the PPs and the difference was statistically significant (12.8% vs. 4%, p<0.001). Commonly in the scientific view, studies with better methodology and design are expected to be an OP in congresses. Consequently, when the type of proceedings are examined OPs have statistically significantly higher rates of publication as articles when compared with posters. After OPs, the critics made by the participants of the Congress attribute to the completion of the deficiencies before the publication. It was reported that OP of the more qualitative studies was the most important cause [17]. In our study, although the number of proceedings about ‘pain’ is lower than other subjects, the publication rate of this subject is the highest. Balasubramanian et al. reported that; a treatment alternative, experimental studies, and large-scale studies had a higher chance of being converted into full-text publications [18]. There was no significant difference between the publication rates of OP and PP in a study [19], but in a similar study, some authors reported that the publication rate of OP was higher than PP [20].
It was determined that clinic studies (57.4%) constituted the biggest percentage and case reports second biggest (40.8%) percentage of studies that were presented at the TARD Congress, but experimental studies (1.8%) have the highest publication rate as an article in peer-reviewed journals 4.2%, 2.4%, and 73%, respectively. The highest publication rate was in the experimental group, and this may be due to the higher diligence of the investigators or the higher predisposition of acceptance of the studies (Table 3).
The highest ratio of presentations (n=61,53.4%) was from the universities when the type of the affiliated institutions were compared. The publication rate of presentations from training and research hospitals was lower. Less time given for academic studies due to workload when compared to universities may be a reason, and the change of the institutions of the physicians of training and research hospitals may be another reason. Weber et al. in their questionnaire-based study reported the reasons for not publishing as some pessimistic belief about acceptance, lack of confidence about the importance of the results and low priority of submitting a manuscript for the authors [21].
There is a certain time for submission and evaluation processes, so the reports published in several journals were sent to the journals without losing considerable time after the Congress. The publication interval for abstracts presented at national meetings varied from 14.9 months to 30.72 months [22]. This higher rate of the publication may be attributed to the type of the Congress as international. It should be noted that clinical studies may take longer time for evaluation, maturation, data collection, interpretation, and inscription. Time intervals for publication may be affected due to the quality of the study classified as randomization status of the study and the statistical methods used [23]. In our study, the mean time for publication was found 14,4±13.8(range 2 to 40) months. PP publication time were found shorter compared to OP. (Mean value:12 months (2-23) vs. 23 months (6-40); p=0,062) (Table 4). Similar to our study; PPs were often case reports and were sent to peer-reviewed journals sooner than the other types. The length of publication time was comparable with that of other medical societies congresses [24]. In a study, it was reported that 90% of the abstracts that have been published as articles were published within four years [25]. In our study; 90% of these proceedings were published as articles in first two years and 10% in after two years.
When it was evaluated according to the abstract subject of published articles, “pain’’ ranked first with 58(8%) abstracts, ‘’intensive care’’ field ranked the second with 31(7.4%) abstracts and “anesthesia” the third with 25(3.37%) abstracts (Table 5). Although our study is the first trial on publication rates of abstracts presented in the TARD, it still has some limitations. First of all, computerized search for full-text articles was carried out manually so the chances of human error cannot be ruled out. Additionally, our search strategy did not enable us to identify full publications in the journals indexed in the other databases (Thomson Reuters, Scopus, OvidSP, EBSCO). So the abstracts that were accepted by journals and not indexed in these two big databases may have been missed. In a study, it was reported that the title changed in 40% from abstract to the publication [24]. We considered this situation also as a limitation of our study.
In conclusion, we found the publication rate of the reports presented at the Annual Congress of the TARD relatively lower compared to the rates at other national congresses in Turkey.Our study results show that OPs were more frequently converted to publications than PPs; the time to convert into a publication was significantly shorter in PPs, and the highest conversion rate of publications was from universities.We think more selective and qualitative rather than quantitative acception of the proceedings before congresses may increase the publication rates of the abstracts. Also, we think that restriction of the case reports may increase the publication rates.
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
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2. Schulte TL, Trost M, Osada N, Huck K, Lange T, Gosheger G, et al. Publication rate of abstracts presented at the Annual Congress of the German Society of Orthopaedics and Trauma Surgery. Arch Orthop Trauma Surg. 2012; 132(2): 271-80.
3. Ersoy GŞ, Eken M, Öztekin D, Çöğendez E, Eroğlu M. The International publication rates of abstracts presented in The National Gynecology and Obstetrics Meetings in the field of reproductive endocrinology and infertility. Zeynep Kâmil Tıp Bülteni. 2015; 46(2): 63–8.
4. Kalyoncu U, Çınar M, Demirağ MD, Yılmaz S, Erdem H, Kiraz S, et al. The assessment of abstracts presented in National Rheumatology Congresses: where do we stand? RAED Dergisi. 2011; 3(1): 6–10.
5. Seçil M, Uçar G, Şentürk Ç, Karasu Ş, Dicle O. Publication rates of scientific presentations in Turkish national radiology congresses. Diagn Interv Radiol. 2005; 11(2): 69–73.
6. Ersoy B. What is the Ultimate Fate of Presented Abstracts? Conversion Rates of Presentations to International Publications from the 31st National Congress of Plastic, Reconstructive, and Aesthetic Surgery. Turk J Plast Surg. 2016; 24(1): 8-18.
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8. National Library of Medicine, Bethesda, Maryland, USA (PubMed Health [database on the Internet] Bethesda (MD): National Library of Medicine (US); [updated 2011 Jan 1; cited 2015 Sep 9]. Available from: https://www.nlm.nih.gov
9. Google Scholar [database on the Internet] Mountain View (CA): c2004 Google Inc; [cited 2015 Sep 9]. Available from: https://scholar.google.com.tr
10. Cartwright R, Khoo AK, Cardozo L. Publish or be damned? The fate of abstracts presented at the International Continence Society Meeting 2003. Neurourol Urodyn. 2007; 26(2): 154-7.
11. Ozbilgin S, Hanci V. Turkish Publications in Science Citation Index and Citation Index-Expanded Indexed Journals in the Field of Anaesthesiology: A Bibliographic Analysis. Turk J Anaesthesiol Reanim. 2017; 45(1): 26–35.
12. Yılmaz S, Bakış M. Anesteziyoloji Alanında Türkiye ve Dünyada Yapılan Bilimsel Yayınların Bibliyometrik Analizi. Turkiye Klinikleri J Anest Reanim. 2014; 12(3): 143–7.
13. Scherer RW, Langenberg P, von Elm E. Full publication of results initially presented in abstracts. Cochrane Database of Syst Rev. 2007; 18(2): MR000005.
14. Gerlach B, Shah AM, Lee MT, Wong CA, Sullivan JT, Toledo P. Publication Rate of Abstracts Presented at the Society for Obstetric Anesthesia and Perinatology Annual Meetings 2010-2014. Anesth Analg. 2017; 124(3): 887-9.
15. Tyagi A, Chugh V, Kumar S, Sethi AK. Presentation of research in anesthesia: Culmination into publication? J Anaesthesiol Clin Pharmacol. 2013; 29(2): 216-20.
16. Peng PH, Wasserman JM, Rosenfeld RM. Factors influencing publication of abstracts presented at the AAO-HNS Annual Meeting. Otolaryngol Head Neck Surg. 2006; 135: 197-203.
17. Knobloch K, Yoon U, Rennekampff HO, Vogt PM. Quality of reporting according to the CONSORT, STROBE and Timmer instrument at the American Burn Association (ABA) annual meetings 2000 and 2008. BMC Med Res Methodol. 2011; 29(11): 161.
18. Balasubramanian SP, Kumar ID, Wyld L, Reed MW. Publication of surgical abstracts in full text: a retrospective cohort study. Ann R Coll Surg Engl. 2006; 88(1): 57-61.
19. Ugarte-Gil C, Schmucker C, Meerpohl JJ. Authors report lack of time as main reason for unpublished research presented at biomedical conferences: A systematic review. J Clin Epidemiol. 2015; 68(7): 803-10.
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21. Weber EJ, Callaham ML, Wears RL, Barton C, Young G. Unpublished research from medical specialty meeting: why investigators fail to publish. JAMA. 1998; 280(3) :257–9.
22. Schulte TL, Trost M, Osada N, Huck K, Lange T, Gosheger G, et al. Publication rate of abstracts presented at the Annual Congress of the German Society of Orthopaedics and Trauma Surgery. Arch Orthop Trauma Surg. 2012; 132(2): 271-80.
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24. Macdonald AL, Parsons C, Davenport M. Outcome of abstracts presented at the British Association of Paediatric Surgeons congresses (1999-2008). J Pediatr Surg. 2012; 47(2): 386-90.
25. Waldorff FB, Petersen K, Vinther S, Sandholdt H, Siersma V, Andersen JS. Full journal publication of abstracts presented at the Nordic Congress of General Practice in 2009 and 2011. Scand J Prim Health Care. 2017; 35(1): 84–8.
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Erkal KH, Yuce Y. Publication rate of abstracts presented in national congress of Turkish society of anesthesiology. J Clin Anal Med 2018;9(3): 195-9.
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Evaluation of reasons for rejecting candidates for living donor liver transplantation
Ali Ozer 1, Hikmet Aktaş 2, Meltem Güner 3, Ercument Gurluler 1, Remzi Emiroglu 1
1 Organ Transplantation Department, Acibadem Atakent University Hospital, Istanbul, 2 Organ Transplantation Department, Acibadem Bursa Hospital, Bursa, 3 Anesthesiology Department, Acibadem Atakent University Hospital, Istanbul, Turkey
DOI: 10.4328/JCAM.5635 Received: 22.12.2017 Accepted: 05.01.2018 Published Online: 09.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 200-2
Corresponding Author: Ali Özer, Acibadem Atakent University Hospital, Turgut Ozal Bulvarı, Halkalı, Küçükçekmece, Istanbul,Turkey. GSM: +905332122324
Aim: The shortage of cadaveric donors has sparked an interest in living donor transplantation in Eastern countries. Obtaining an optimal graft for a recipient and avoiding jeopardizing the health of a donor is the main concern in this procedure.
Material and Method: A three-step assessment protocol was used to select the appropriate donor. The reasons for rejected candidates were analyzed to refine donor selection and minimise complications.
Results: Between January 2016 and October 2017, 290 volunteers were evaluated for living liver donation, and 88 were rejected. At each step of donor evaluation, the individuals were excluded based on laboratory, imaging or liver biopsy results. Volumetric measurement results were the most detected reason (40.9%) to reject a candidate.
Discussion: Ensuring donor safety in living donor liver transplantation is fundamental for transplant teams. Therefore, using systematic evaluation is the principal concern in this procedure.
Keywords: Donor Selection, Living Donor, Liver Transplantation
Introduction
Although there has been a partial improvement in organ donation, the scarcity of deceased organs is still a problem in our country, and the frequency of living donor liver transplantation (LDLT) is increasing for expanding the donor pool and reducing waiting list mortality. The donor and recipient outcomes in LDLT have become substantial in the last decade due to advances in surgical techniques and the sophisticated evaluation process of living donor candidates. However, the procedure still poses an undeniable risk for the healthy organ donor that leads to concerns about the ethical dilemma. The early surgical complication rate reported in the literature is 12–29%, with a mortality rate of 0.1–0.8%. Beyond any doubt, donor safety is the prime concern and, therefore, a definitive international consensus has been composed to emphasize the importance of evaluating the psychosocial and medical suitability of a live donor [1].
In Eastern countries, including our country, deceased donor organs are rare, and patients come to transplant centers with their last hope regarding LDLT. However, to obtain an optimal graft for a recipient and to avoid jeopardizing the health of a donor, a systematic approach to the evaluation of the living donor is necessary [2,3]. With these concerns, a distinct preoperative assessment has been practiced compared to conventional patient care in our center.
Despite the many patients and their donor candidates who are mostly relatives that apply with a great motivation for LDLT, we refuse some of them for conditions in which LDLT is unsuitable. In this report, we analyzed the reasons for refusing live donors in different stages of evaluation.
Material and Method
The study was approved by the Institutional Review Board at Acibadem University. We evaluated the individuals who were rejected as donors for LDLT between January 2016 and October 2017 in our center.
We have a strict three-step assessment process, starting from potential donors’ application. Satisfactory results on all tests at each step were required before proceeding to the next step. The assessments must uncover any unknown medical condition that might pose any risk for the donor.
The recipient and the donor candidate are informed in detail about the evaluation process and the procedure. A transplant coordinator conducts the first interview for a basic assessment. According to the law, individuals within four degrees’ consanguinity are allowed to be organ transplant donors. In case of other candidates willing to be an organ donor, the approval of an authorized ethical committee is required. If the donor is married, the written consent of conjoint is essential. The minimal age for acceptance is 18, and the upper age limit is 55. ABO blood group compatibility is investigated, and non-invasive tests are performed for first-step evaluation. The potential risks, success, and morbidity-mortality rates are explained to both the recipient and donor by a physician. Before progressing to the next step, a psychiatric assessment is performed for all candidates. In addition, an independent psychologist called a ’’patients’ rights defender’’ interviews recipients and donors at certain intervals to support them throughout the entire process.
If doubtful results are detected from the standard protocol, more testing and consulting may be necessary. In the second step, detailed laboratory tests are performed. Additionally, candidates older than 40 years undergo cardiologic and pulmonary assessments routinely while the others are only evaluated in case of a suspected cardio-pulmonary disease. Endoscopy is performed depending on the presence of a questionable medical history, test results and physical examination findings. Then the radiological examination begins with ultrasonography (US) to assess the liver and the other abdominal organs and continues with computerized tomography (CT) angiography to evaluate the liver vascular structure and, more importantly, to make volumetric measurements for a graft and remnant liver. We take notice of the percentage of remnant liver volume to total liver volume (> 30%) and graft to recipient body weight ratio (GRBW) aiming for > 0.8. If the volumetric assessment is eligible for both the donor and recipients, then magnetic resonance cholangiopancreatography (MRCP) is performed to evaluate the biliary structure.
In the third and last step, a liver biopsy is applied to all donor candidates to investigate steatosis and possibly other covered liver diseases. US-guided liver biopsies are evaluated by the same experienced pathologist. We consider ≤ 20% steatosis acceptable in association with GRBW.
While practicing all three steps, the candidates can be rejected for any of these aforementioned reasons. Our donor evaluation protocol is presented in Table 1. Absolute exclusion criteria were withdrawing the willingness to donate, ABO incompatibility, serious co-morbidities that can pose risks for donors, recent detected illness, positive hepatitis serology, inadequate liver volume and/or calculated GRBW <0.8, significant steatosis and/or fibrosis, underlying liver disease detected by laboratories and liver biopsy.
Results
We evaluated 290 candidates and 88 of them were considered improper donors for LDLT. Some recipients had more than one rejected candidate. Sixty-four candidates were male, and 24 were female.
The mean age was 34.1 years (19–55). Of 88 candidates, 60, 24 and 4 were first-, third- and second-degree relatives, respectively.
The most established reason preventing donation was lower GRBW (23 candidates). Thirteen candidates had an inadequate graft size for the recipient. Eight candidates had steatosis, and 10 candidates had steatosis and fibrosis. Vascular and/or biliary variation preventing a safe hepatectomy was detected in seven candidates. In four candidates, their hepatitis B virus serology was positive. Nine candidates changed their mind about donation, and two candidates of this group did not give their consent. Four candidates were rejected due to ABO blood group incompatibility. Unfortunately, two oncologic disorders were demonstrated in two candidates (lymphoma and renal cell carcinoma). All the reasons leading to the rejection of the candidate were listed in Table 2.
Discussion
The scarcity of cadaveric donors remains an unsolved problem that leads to increasing LDLT in our country. Donor safety is recognized as an absolute prerequisite in LDLT, and a well-designed system to evaluate potential donors is essential [4].
Donor candidates must be legally competent, have the capacity for autonomous decision-making and enter the donation process of their own free will. The donation involves a complex interplay of psychosocial and family dynamics; therefore, an explicative information by the transplant team plays a key role in proceeding with the process. Respect for the autonomy and free will of the candidate is fundamental [5]. Following an initial interview, a psychiatric consultation is routinely performed in our center, and a psychologist supports the candidates during the entire process. In our study, four of nine refuser candidates have decided not to donate after a psychiatric consultation that emphasizes the importance of the autonomy of the decision.
In the present study, the most detected reason for rejection depends on radiological assessment (36 cases, 40.9%). The graft size is inversely related to the risk of small for size syndrome. Moreover, the ratio of the remnant liver volume to the total liver volume is an important predictive risk factor.
Most transplant centers still consider >35% a safe percentage [6,7], but a great number of studies have presented >30% as an acceptable ratio [8,9]. Our current limit of GRBW is 0.8 like the literature, although some recent studies have recommended 0.6 [10].
It is supposed that each percentage of fat in the graft decreases the functional liver mass by 1%. Up to 12% of donor candidates have been rejected due to biopsy findings alone. The threshold of steatosis has not been conclusively established, and the decision should be given regarding multi-factors such as donor age, graft size and GRBW [11,12]. We routinely performed liver biopsies in our center, and 18 of 88 (20.4%) rejected cases were based on biopsy results, which are >20% steatosis and/or fibrosis.
Conclusion
In our country, the demand for LDLT will continue due to a shortage of cadaveric donors. Donor safety is of paramount importance in LDLT. It is obviously necessary to maintain a systematic donor assessment involving the highest medical and ethical standards to achieve optimal outcomes for both donors and recipients.
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. Barr ML, Belghiti J, Villamil FG, Pomfret EA, Sutherland DS, Gruessner RW, et al. A report of the Vancouver Forum on the care of the live organ donor: lung, liver, pancreas, and intestine data and medical guidelines. Transplantation. 2006; 81:1373–85.
2. Yamahiki N, Sugawara Y, Tamura S, Kaneko J, Nojiri K, Omaya M, et al. Selection of liver-transplant candidates for adult-to-adult living donor liver transplantation as the only surgical option for end-stage liver disease. Liver Transpl. 2006;12(7):1077-83.
3. Marcos A, Fisher RA, Ham JM, Olzinski AT, Shiffman ML, Sanyal AJ, et al. Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation. 2000;69(11):2410-5.
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5. de Villa VH, Lo CM, Chen CL. Ethics and rationale of living-donor liver transplantation in Asia. Transplantation. 2003 15;75(3 Suppl):2-5.
6. Reichman TW, Sandroussi C, Azouz SM, Adcock L, Cattral MS, McGilvray ID, et al. Living donor hepatectomy: the importance of the residual liver volume. Liver Transpl. 2011;17(12):1404-11.
7. Imamura H, Makuuchi M, Sakamoto Y, Sugawara Y, Sano K, Nakayama A, et al. Anatomical keys and pitfalls in living donor liver transplantation. J Hepatobiliary Pancreat Surg. 2000;7(4):380-94.
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9. Reichman TW, Sandroussi C, Azouz SM, Adcock L, Cattral MS, McGilvray ID, et al. Living donor hepatectomy: the importance of the residual liver volume. Liver Transpl. 2011;17(12):1404-11.
10. Uemura T, Wada S, Kaido T, Mori A, Ogura Y, Yagi S, et al. How far can we lower graft-to-recipient weight ratio for living donor liver transplantation under modulation of portal venous pressure? Surgery. 2016; 159(6):1623-30.
11. Minervini MI, Ruppert K, Fontes P, Volpes R, Vizzini G, de Vera ME, et al. Liver biopsy findings from healthy potential living liver donors: Reasons for disqualification, silent diseases and correlation with liver injury tests. J Hepatol. 2009; 50(3): 501-10.
12. Ryan CK, Johnson LA, Germin BI, Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl. 2002;8(12):1114-22.
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Ozer A, Aktaş H, Güner M, Gurluler E, Emiroglu R. Evaluation of reasons for rejecting candidates for living donor liver transplantation. J Clin Anal Med 2018;9(3): 200-2.
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Can eight weeks of stabilization exercise change the amount of knee flexion and anterior shear force?
Faraj Fatahi 1, Gholamali Ghasemi 1, Mohamadtaghi Karimi 2, Ramin Beyranvand 3
1 Department of Sports Injuries and Corrective Exercises, Faculty of Sport Sciences, University of Isfahan, Isfahan, 2 Department of Orthotics and Prosthetics, School of Rehabilitation Sciences, Shiraz University of Medical Sciences, Shiraz, 3 Department of Sports Injuries and Corrective Exercises, Faculty of Sport Sciences, Shahid Bahonar University of Kerman, Kerman, Iran
DOI: 10.4328/JCAM.5638 Received: 24.12.2017 Accepted: 05.01.2018 Published Online: 09.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 203-8
Corresponding Author: Faraj Fatahi, Darvazeh Shiraz Square, University of Isfahan, Isfahan, Iran. T.: +989163188344 E-Mail: farajfatahi92@yahoo.com; faraj.shahamiri@yahoo.com
Aim: This study aimed to evaluate the effect of eight-week stabilization training on knee flexion and anterior shear force during a single leg drop landing to prevent ACL injury.
Material and Method: Thirty basketball athletes were randomly assigned to a training group (n = 15) and a control group (n = 15). Training group performed the Core stability training for 8 weeks, but control group did not perform these exercises. Lower extremity kinetics and kinematics variables during single-leg drop landing were collected by motion analysis and force plate in pre and post-test. Data were analyzed by using mixed ANOVA repeated measure test with significance level of P≤0.05.
Results: The results showed that the amount of knee flexion significantly increased after conducting the 8 weeks of core stability training (P< 0.05), while there was no significant decrease in anterior shear forces (P> 0.05).
Discussion: Based on the results, the core stability training by increasing the core stability can improve the core muscles recruitment during landing. Therefore, it can be concluded that core stability training can reduce the ACL injury risks during the dynamic movements.
Keywords: Stabilization Training; Kinetics; Kinematics; Single Leg Drop Landing; Acl Injury
Introduction
Anterior cruciate ligament (ACL) injury is known as one of the most common injuries not only in athletes but also in active non-professionals [1]. ACL injury can lead to long-term disability [2]. Children and youth are more prone to ACL injury [3]. Moreover, athletes who play team sports such as football, volleyball, and basketball are four to six time more at the risk of ACL injury due to jump, cutting and rotational movements [4]. At least 70% of ACL injuries occur in non-contact conditions [3]. Research findings confirm that the condition of lower extremities during high-risk activities such as running, cutting maneuver, rotation, and landing may be predisposing risk factors for ACL injuries [5,6]. It is believed that lower extremities condition which affects directly the force applied to the ACL, plays a vital role in increasing the risk of ACL injury. Most non-contact ACL injuries happen during sports which include single-leg landing [7]. Single leg drop landing is a common maneuver which is an important part of the majority of sports such as basketball, volleyball, handball, badminton, and football [8].
The single leg-drop landing needs too much motion in short time. Sudden movements and high amounts of loads during landing can cause injuries in the knee and ankle joints [9]. Studying the mechanism of injury and kinematic analysis shows that the movements and body condition can increase the risk of injury [10]. For instance, previous studies showed the increase of knee valgus angle [11,12], the decrease of the knee flexion [11,13], and reducing of the hip flexion angle [6,8] during the landing can cause more damage to the ACL. Indeed, the common movement (motion) pattern of non-contact ACL injuries includes the decrease of the knee, hip, and trunk flexion along with the increase of knee valgus and the tibia rotation [14,15]. Although knee valgus angle and rotation of the knee increase the ACL strain [16], quadriceps muscle contraction increases much more ACL strain by creating anterior proximal shear force [17,18]. Research findings show that anterior shear force is the main mechanism for the load applied to the ACL [16]. There is a kinetic relationship between proximal lower extremities and the knee movements. Therefore, changes in the kinematics of proximal part and their muscles movement (motion) pattern may affect the moments and forces applied on the tibiofemoral joint. Although the core muscles do not act directly on the knee joint, its muscle activities can affect the lower extremities alignment and load-bearing capacity of the knee.
Studies showed that the core muscles stabilize the pelvis during single leg stand and play an important role in the kinematic control of the hip joint [1]. Ineffectiveness or weakness of core during landing may cause increase adduction and internal rotation which can lead to increase the ACL moments and strain. Moreover, inadequate neuromuscular control of trunk (body) or core stability may affect the dynamic stability of lower extremities and increase the knee ligaments strain. The increased strain in ligaments can bring about some injuries [19]. Yu et al. showed that the angular velocity of the hip joint could change the anterior shear force during landing [8]. Therefore, it is possible that proximal muscles affect the force applied to the knee joint.
It seems that core stability training can reduce the risk of non-contact ACL injury[20]. Hewett et al. showed that lower limb and trunk strength and neuromuscular control of lower extremities and body can be boosted by neuromuscular training [21]. Researchers used various intervention trainings to change lower extremities and body mechanics during dynamic activities [22]. Meyer et al. found that neuromuscular trainings which are included balance and core stability trainings reduce the forces applied to the knee [23]. They mentioned that plyometric trainings cannot reduce the knee forces. Despite emphasizing the implementation of intervention training to improve core stability [24], the effects of trunk intervention and especially core stability training have not been specified. According to the previous studies, it seems that the core muscles can play a key role to reduce the forces applied to ACL during landing. Therefore, due to the lack of information about the effect of stability training on the reduction of the injury risk, this study aimed to evaluate the effect of 8 weeks stability training on knee flexion and anterior shear force during single-leg landing.
Material and Method
This study was a quasi-experiment study with selective sampling and pre-posttest design. Based on previous studies and the fact that in quasi-experiment studies usually 20 or 30 samples are used [25], 30 professional basketball players have been recruited for this study. Subjects were divided randomly into a training group (n=15) and control group (n=15). All 30 athletes were enrolled voluntarily, and before entering the study, informed consent and demographical information was obtained from each subject. Ethical approval for this study has been granted by the ethics committee of Musculoskeletal Research Center of the Isfahan University of Medical Science. The selection criteria were: Not having any musculoskeletal disorders such as previous ankle sprain, neuromuscular disorder, pes planus and pes cavus. Lower extremity injuries were also defined as injuries which lead to the absence of more than one day of physical activities [26].
Subjects were asked to perform one jump from 40 cm height box to the force platform (5060, Kistler, Switzerland) with a single leg. The initial contact onto the ground was defined as the moment which the magnitude of vertical reaction forces is more than 30N [27]. Each jump task was performed 3 times, and there was 1 minute of rest between each jump in order to eliminate neuromuscular fatigue [28].
The 3D kinematic data were collected using a 7-camera optoelectronic motion capture system (Proreflex, Qualysis, Savedalen, Sweden); Therefore 34 reflecting skin markers with 4 mm diameter were placed on two sides of the body based on Visual 3D marker set [29] (over first and fifth metatarsal, medial and lateral malleolus, heel, lateral and medial epicondyle, great trochanter, anterior and posterior superior iliac spine (ASIS and PSIS respectively), iliac crest, sacrum, wrist, elbow joint, acromioclavicular joint (AC), sternum, C7 and on the vertex of the head). Also, four rigid plastic clusters containing three markers on each cluster were placed on the shin and thigh for tracing the segmental movements [30].
After warming up, each participant was instructed to jump from box to force plate with single leg drop landing. They should perform the single leg drop landing with the preferred (premier) leg.
The box height was 40cm, located 10 cm behind the force plate (figure 1). The subjects stood in balance condition close to the edge of the box in such a way that the preferred (premier) foot is suspended in the air. Kinematic data and the forces were collected at 200 Hz [31] and were filtered by using a low-pass filter (fourth-order zero-lag Butterworth filter) with the cut-off frequency of 6 Hz. Then, the lower extremity joint kinematics and kinetics were calculated using OpenSim (v.3.0.2, Stanford University) software. The posterior ground reaction force obtained from force platform was used to calculate maximum posterior reaction force for each subject. The forces were normalized to be unbiased based on the subjects weights. Moreover, in the coordination system of the laboratory, x, y and z axis belong to anterior-posterior, internal-external and vertical directions, respectively.
The training protocol included 8 weeks of (3 sessions in each week and each session 25-50 minutes) core stability training under the supervision of researchers for training group and ordinary training for the control group. In this study the training protocol of Willardson et al. and Araujo et al. were employed [32,33] (Table 1).
Statistical analysis: The data were statistically analyzed by using SPSS v22.0. For data distribution analysis, the Shapiro-Wilk test was used. For knee flexion angle, and anterior shear force comparison the mixed repeated measure ANOVA test was employed. Assessment assumption was made with 95 percent significance and α≤0.05.
Results
Demographical variables obtained from 30 professional basketball players are presented in table 2. Also, mean values and standard deviations of knee flexion angles and anterior shear forces during single-leg landing at the moment of touching the ground are presented in table 3.
Table 2 Table 3 The mean values of knee flexion angle in training and control group before and after participation in core stability training increased 5.24 degree in the training group and decreased 0.06 degree in the control group. The results of mixed repeated measure ANOVA test dedicated significant difference before and after training (F=17.88, P=0.003). The results also showed a significant difference between 2 groups (F=0.14, P=0.039). Moreover, these results highlighted a significant interactive effect of time before and after intervention for both training and control groups (F=32.37, P=0.01). The results of mixed repeated measure ANOVA test for knee shear force showed that there was no significant difference before and after training (F=11.8, P=0.12) and between groups (F=12.9, P=0.09). The results also showed there was no significant interaction between the time before and after intervention for both groups (F=0.05, P=0.81).
Discussion
This study aimed to evaluate the effect of 8 weeks core stability training on the knee flexion angle and anterior shear force during single-leg landing. Since the tibia proximal anterior shear force has the most significant effect on ACL loading [34], this was chosen as a variable to study and was considered as the maximum posterior force of the ground reaction force. Yu et al. explained how the tibia proximal anterior shear force can be regarded as the ACL force [8]. The results of this study showed there was a significant increase in knee flexion angle while there was no significant drop in anterior shear force during single-leg landing after conducting the 8 weeks of core stability training.
To decrease the ground reaction force, the body has to predict and prepare itself for landing. This can be achieved by the muscle contraction. The body disability in contraction generation and also disability in movement prediction can increase the ground reaction force dramatically [35].
Based on previous studies the increase of knee flexion angle leads to decrease in proximal anterior shear force [8,10]. Also, these studies showed that the maximum knee extensor moment corresponds to the knee anterior shear force [8]. Shelburne et al. demonstrated that when the anterior shear force is high enough, the force applied on the ACL is also very high [36].
There are some studies that assessed the mechanism of the ACL injury and reported the single leg drop landing is one of the most common mechanisms of ACL injury [11,12]. The body acceleration increases and the lower limb muscles contract eccentrically during landing to support the body weight and acceleration. Therefore, these muscle forces can increase the anterior shear force by extensor mechanism [10]. Co-contraction of the lower limb muscles can absorb the forces applied on the knee, and as a result, it can reduce the forces applied on the knee ligaments [5].
Using lower limb muscles and knee flexion decrease the anterior shear force [37]. Gastrocnemius and quadriceps muscles contribute to the increase of the anterior shear force while the Hamstring muscles try to decrease these force [37-40]. The abilities of these muscles to affect the cruciate ligaments force can be changed by the knee flexion angle [41,42]. Therefore, the ability of quadriceps muscles increases for anterior force generation in low knee flexion angles when the ability of hamstring muscles decreases to neutralize the force generated [10].
The core stability trainings increase the trunk flexion ability and muscle recruitment strategy of the core muscles by increasing the stability of the core. Trunk flexion during single-leg landing potentially reduces the ability of quadriceps muscle utilization which can result in decreasing of its loading on the ACL upon touching the ground by foot. Also, Trunk flexion during landing compared to a landing posture with trunk flexion leads to more flexion in hip and knee joint and results in the lower limb position which has less risk of ACL rupture [43]. In addition, the trunk flexion increases by the hamstring muscle utilization and consequently decreases the force applied on cruciate ligaments. Kulas et al. reported that Hamstring muscle activation by trunk flexion leads to tibia shear force [44].
The increase of knee flexion brings about the decrease of force applied on cruciate ligaments and the increase of energy absorption during landing. During functional activities especially landing, the range of knee motion most likely offers better functions [45,46]. Previous studies confirm that the core feed forward muscles are employed before distal muscles [47]. As an example Hodges et al. made efforts to demonstrate that the trunk muscles activities are prior to limb muscles, while this state cannot be correct for subjects with disabilities [48,49]. This has been thought that the core feed forward muscles recruitment can provide the body with better neuromuscular function. The trunk muscles can act as feedforward muscles and work prior or with mover’s muscles to reduce the moments resulted from disturbances [50]. The postural adjustment can provide distal movement with proximal stability. The increased stiffness in body produces proximal stability for lower and upper limbs and also distal force absorption [51]. Kulas et al. reported that the feedforward muscles control during landing is based on abdominal muscles before touching the ground by foot. They concluded that the trunk muscles activities aimed to prepare the body for landing [52]. Iida et al. showed an increase in the activities of external oblique, rectus abdominis and Gastrocnemius muscles before touching the ground by foot. They claimed that those muscles so as to prepare the body for landing, are activated by the increase of ankle joint stiffness and can act as a predictive postural control to absorb the force [53]. There are some other studies that considered the neuromuscular control in pelvic as an effective criterion for knee joint kinematics [24,54-56]. Following the interpretation of knee flexion during core preparation as distal mobility, the results of current study verify the proximal stability theory which improves the distal mobility of limbs. Whereas, the importance of the core muscles on the lower limb movement was not understood properly. Matthew et al. showed that the using of core muscles can increase knee flexion angle [57]. The core muscles activities affect the injury risk of cruciate ligaments. Following a decrease of trunk movement to carry the body weight, the activity of the quadriceps muscle increases to preserve the stability of the body [57]. Regarding the landing, the vertical forces in sagittal plane are oriented in the direction of hip to knee which results in producing moments in these joints [58]. The core activities can increase absorbed energy and decrease the force applied on the knee during landing [59]. Stevens et al. assessed the core stability lumbar training on the pattern of muscle recruitment in healthy subjects and showed that there was an increase at the level of local abdominal muscle activities and also a slight change in the global muscle activities [60]. They revealed that the pattern of muscle recruitment can change by using a training program which emphasizes on neuromuscular control. Tsao and Hodges also confirmed that there was a recovery in patients with back pain after 8 weeks training with transverse abdominis activities [61].
Following points above, it can be concluded that the core stability training used in this study had a positive effect on the feedforward muscles activities and force absorption by increasing the core stability.
Conclusion
The current study results showed the core stability training increases the knee angle flexion while it does not have a significant effect on the anterior shear force. Therefore, these trainings can act as a support for anterior cruciate ligament and the increase of core activities leads to decrease of the load applied on cruciate ligaments. These results can help sports coaches and physiotherapists to design the training programs.
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.
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Cochlear implantation surgery experience of a tertiary clinic
Ahmet Mutlu 1, Mete Iseri 2, Merve Durgut 3, Murat Topdag 4, Selvet Erdogan 3, Murat Ozturk 3
1 Department of Otolaryngology, Uskudar State Hospital, Istanbul, 2 Private Practice, Kocaeli, 3 Department of Otolaryngology, Kocaeli University Faculty of Medicine, Kocaeli, 4 Department of Otolaryngology, Acibadem University Faculty of Medicine, Istanbul, Turkey
DOI: 10.4328/JCAM.5639 Received: 24.12.2017 Accepted: 05.01.2018 Published Online: 10.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 209-12
Corresponding Author: Ahmet Mutlu, Barbaros Mahallesi, Veysi Pasa Sokak No:14, 34672, Uskudar, Istanbul, Turkey. GSM: +905355003650 F.: +902164747912 E-Mail: ahmutlu1988@gmail.com
Aim: Cochlear implantation (CI) is a commonly performed procedure for severe to profound deafness in patients. It has been widely used for this purpose, and it becomes more complicated than expected for new institutes. In this report, we aimed to discuss the patient features, surgery indications, results of the CI surgeries in the experience of a single center.
Material and Method: We retrospectively analyzed 65 patients who were underwent CI in a tertiary hospital. Hearing loss etiologies, hearing results and postoperative complications were assessed.
Results: Sixty-five patients were evaluated within in two groups as 0-6 years-old and over 7 years-old. Twenty-nine patients were placed in 0-6 years-old group, and 36 patients were placed in over 7-years-old group. In 0-6-years-old group; 27 patients hearing loss remained idiopathic, but 1 patient had Cogan syndrome, and 1 patient had a cochlear malformation. Hearing gain of the entire group was found statistically significant (p<0.000). In over 7-years-old group; 1 patient underwent CI for each of indications: traumatic hearing loss, iatrogenic cochlear damage, Meniere’s disease, chronic otitis media, electrode renewing. The etiology of the 31 patients were not revealed in the over 7-years-old group. The hearing gain of the group was found statistically significant (p<0.000). One patient had a dural injury, and 1 patient had a round window gusher. Six patients had postoperative vertigo. Post-implantation facial nerve stimulation was revealed in 1 patient.
Discussion: CI is a very revolutionary technic for the hearing-impaired patients. The implant success is strongly related to the patient management and appropriate surgical technics
Keywords: Cochlear Implantation; Hearing Loss; Complication; Indication
Introduction
Cochlear implantation (CI) has developed into a commonly performed procedure for severe to profound deafness in patients. The development of the audiological test batteries eased to obtain the hearing impairments, and the newborn hearing screening made early detection of hearing loss [1]. The early detection of the deafness in children affects the development of speech perception, language, and reading skills [2]. The appropriate management of the hearing loss decreases the morbidity and contribute to the country’s economic aspects. CI has a great value for the profound hearing loss, however surgical procedures are still challenging for the physicians and patients. The complex anatomy, naive structures, and inappropriate surgical interventions may cause the complications. But developing operative technics and new instruments pioneer the improvement of the CI success.
In this report; we aimed to discuss the indications, hearing results of the CI surgeries with the data of CIs recipients and management of the complications due to a tertiary clinic experience.
Material and Method
This study is designed as an observational, descriptive study and the data was collected retrospectively from the patient records. Sixty-five patients, who received CI surgery in XXX Otorhinolaryngology department between 2012 and 2015, were the main subjects.
The following data has been studied: hearing and medical history, the age of implantation, deafness etiology, radiological images (computerized tomography and magnetic resonance images), intraoperative findings, and postoperative complications.
Population: Patients were divided into the two subgroups according to their lingual, prelingual and postlingual development. Twenty-nine (44%) children were evaluated in the prelingual group and age distribution of CI was 0-60 months (mean: 26,2; median: 8; min: 14; max: 52 months). Sixteen (55%) patients were girls, and 13 (45%) were boys. Thirty-six (56%) patients were classified in the postlingual group, and CI age of individuals differed from 10 to 65 years. Mean age was 34,1 years (median: 21; min: 10, max: 65 years). Gender distribution was as 21 (58%) males, 15 (42%) females. Three different CI systems (Clarion®, Medel®, Nucleus®) were used in different numbers.
Hearing Tests: The prelingual group was assessed with visual reinforcement or conditioned play audiometry (Interacoustics® AS DK-5610 Assens, Denmark) in the preoperative period. Postoperative hearing with the CI was monitored with a warble tone free field audiometry test. Hearing levels and gains were recorded at 250, 500, 1000, 2000, 3000, 4000, 6000, 8000 Hz frequencies.
The postlingual group was tested on mentioned frequencies with pure tone audiometer without hearing aid. Free field levels with hearing aids were recorded before the CI and during the postoperative period.
All statistical analyses were performed using SPSS v.20.0 (SPSS, IBM®, Chicago, IL, USA). Kolmogorov-Smirnov tests were used to detect the normality of data distribution. Related variables were expressed as mean, standard deviation (normal distribution) and median, 25th-75th percentiles (non-normal distribution). Comparisons of groups were performed using the Wilcoxon and Friedman and Dunn’s test (Non-normal distribution). Statistically, significance was accepted for p-values < 0.05.
Ethics Statement: The local ethics committee of the XXX approved this clinical study (XXX). The participants or their parents gave their informed consent for evaluating the data for this study.
Results
Total of 65 patients were evaluated within in two groups as 0-6 years-old and over 7-years-old. Twenty-nine patients were placed in 0-6 years-old group, and 36 patients were placed in over 7-years-old group. In 0-6 years-old group; 1 patient with Cogan syndrome and 1 patient with cochlear anomaly underwent CI, and 27 patients who received CI remained idiopathic (Figure 1). Hearing gain of the entire group was found statistically significant (p<0.001) (Figure 2).
The group which is over 7-years-old contained various reasons for the profound hearing loss. One patient (2.7%) had a traumatic hearing loss, 1 patient (2.7%) had iatrogenic cochlear damage, 1 patient (2.7%) had severe Meniere’s disease, 1 patient (2.7%) had hearing loss secondary to long-term chronic otitis media. One (2.7%) patient was undergoing electrode renewing, and etiology of the 31 patients was not revealed clearly (Figure 1). Hearing gain of the whole group was found statistically significant (p<0,000) (Figure 3).
The analyzed data of the 65 patients showed moderate intraoperative complications in 2 patients (3%). One patient (1.5%) had a dural injury. One patient (1.5%) had a round window gusher. Six patients (9%) had postoperative vertigo. Post-implantation facial nerve stimulation was seen in 1 patient (1.5%).
Discussion
CI improved the auditory skills of the patients who did not benefit from hearing aid use however the outcome of the surgery depends on a number of variables. Swami et al. reported the duration of auditory deprivation, parental education, and cochlear morphology have a direct impact on the outcomes of CI [3]. In our study, patients received CI surgery in 9.2 months after the first diagnosis. It is related to the conventional hearing aid usage period (6 months) and preoperative evaluation (radiological, psychiatric assessment). After considering these reasons patients received a great hearing gain in our study.
Cogan syndrome was defined as the interstitial keratitis, and bilateral audiovestibular disorders (hearing loss, dizziness, etc.) and the literature mentioned that the patients with Cogan syndrome might benefit from the CI [4]. Due to the literature, implantation was performed, and our patient benefitted from the CI in the long term.
Meniere’s disease is inner ear disorder which demonstrates with vertigo episodes, progressive fluctuating hearing loss and patients can be affected bilaterally. Long-term progression can end up with a profound hearing loss [5], and a CI is a treatment option for these patients [6]. We also performed a CI surgery to a patient, who had a profound hearing loss because of the Meniere’s disease, and the patient had a great hearing gain after all.Idiopathic sudden sensorineural hearing loss (ISSNHL) is a sensorineural hearing loss of more than 30 dB in 3 adjacent frequencies in less than 3 days, and hearing loss can vary from e mild to profound hearing loss [7]. CI is currently an effective treatment option in spite of the proper medical treatment, and Lee et al. suggest CI 3 months after the hearing loss [8]. In our study; 3 patients, who suffer from ISSNHL in their only hearing ear, received the implantation for this purpose and all of the patients regained hearing significantly.CI in chronic otitis media is still a debate in the current literature. Electrode implantation with sterile conditions and recreation of a non-infected middle ear are vital on this purpose. Suppuration in chronic otitis media may lead to electrode array to be lost, and it is better to perform CI after the eradication of the disease [9]. Two-step surgery is suggested in chronic otitis with cholesteatoma, the first step is the eradication of the disease (tympanoplasty, mastoidectomy, etc.) and the second step is CI [10]. We followed two patients, who underwent intact canal mastoidectomy for a year, and implantation was performed after that. Nor complication neither disease recurrent occurred, and patients were satisfied with their hearing results.Vertigo after the CI surgery may be caused by the loss of the perilymph and diminish in the short term. Persistent vertigo may be related to a perilymphatic fistula [11]. Another study revealed that the benign positional vertigo could be found more frequently in these patients than normal population [12]. In our study, 5 patients recovered spontaneously after few weeks but 1 patient, who had severe Meniere’s disease, had mild vertigo after the surgery and no additional treatment was required by the patient.Facial nerve stimulation after the CI is a frequent and well-known complication. The sclerotic cochlea, malformations and ascending stimulation levels are some of the causes of this clinical entity. Fitting modifications and reducing the electrode stimulations can eradicate mostly [13]. In our study, a patient faced an uncomfortable the post-implantation facial nerve stimulation, and responsible electrodes were canceled with a minimum influence on speech recognition.Cerebrospinal gusher is a frightening complication for the physicians, and anatomical variations or cochlear malformations may result in this clinical situation [14]. The common cavity is a malformation which has a cerebrospinal gusher risk [15]. In our study; cerebrospinal gusher occurred in 1 patient, who had a common cavity malformation, and the leakage was obliterated with soft tissue (temporalis muscle fascia).
Conclusion
CI is a very revolutionary technic for the hearing-impaired patients because of the gain levels. The implant success is strongly related to the patient management and appropriate surgical technics.
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. Tarkan O, Tuncer U, Ozdemir S, Surmelioglu O, Çetik F, Kıroglu M, et al. Surgical and medical management for complications in 475 consecutive pediatric cochlear implantations. Int J Pediatr Otorhinolaryngol. 2013; 77(4): 473-9.2. Dunn CC, Walker EA, Oleson J, Kenworthy M, Van Voorst T, Tomblin JB, et al. Longitudinal speech perception and language performance in pediatric cochlear implant users: the effect of age at implantation. Ear Hear. 2014; 35(2): 148-60.
3. Swami H, James E, Sabrigirish K, Singh SK, Ohal M. A study to determine factors influencing outcomes of pediatric cochlear implants. Med J Armed Forces India. 2013;69(4):366-8.
4. Bacciu A, Pasanisi E, Di Lella F, Guida M, Bacciu S, Vincenti V. Cochlear implantation in patients with Cogan syndrome: long-term results. Eur Arch Otorhinolaryngol. 2015;272(11):3201-7.
5. Stahle J, Friberg U, Svedberg A. A Long-term progression of Meniere’s disease. Acta Otolaryngol Suppl. 1991;485:78-83.
6. Mick P, Amoodi H, Arnoldner C, Shipp D, Friesen L, Lin V, et al. Cochlear implantation in patients with advanced Ménière’s disease. Otol Neurotol. 2014;35(7):1172-8.
7. Mutlu A, Cam I, Dasli S, Topdag M. Doppler ultrasonography can be useful to determine the etiology of idiopathic sudden sensorineural hearing loss. Auris Nasus Larynx. Doi: 10.1016/j.anl.2017.08.013. [Epub ahead of print]
8. Lee SS, Cho HH, Jang CH, Cho YB. Fate of sudden deafness occurring in the only hearing ear: outcomes and timing to consider cochlear implantation. J Korean Med Sci. 2010;25(2):283-6.
9. Incesulu A, Kocaturk S, Vural M. Cochlear implantation in chronic otitis media. J Laryngol Otol. 2004;118(1):3-7.
10. Andrew KP, Greg B, Joni KD. Cochlear implantation in chronic suppurative otitis media. Operative Techniques in Otolaryngology- Head and Neck Surgery. 2010;21(4):254-60.
11. Steenerson RL, Cronin GW, Gary LB. Vertigo after cochlear implantation. Otology and Neurotology. 2001;22:842-3.
12. Limb CJ, Francis HF, Lustig LR, Niparko JK, Jammal H. Benign positional vertigo after cochlear implantation. Otolaryngology – Head and Neck Surgery. 2005;132:741-5.
13. Berrettini S, Vito DA, Bruschini L, Passetti S, Forli F. Facial nerve stimulation after cochlear implantation: our experience. Acta Otorhinolaryngol Ital. 2011;31(1):11–6.
14. Kamogashira T, Iwasaki S, Kashio A, Kakigi A, Karino S, Matsumoto Y, et al. Prediction of Intraoperative CSF Gusher and Postoperative Facial Nerve Stimulation in Patients With Cochleovestibular Malformations Undergoing Cochlear Implantation Surgery. Otol Neurotol. 2017;38(6):114-9.
15. Sennaroglu L. Cochlear Implantation in Inner Ear Malformations A Review Article Cochlear Implants Int. 2010;11(1):4-41.
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Mutlu A, Iseri M, Durgut M, Topdag M, Erdogan S, Ozturk M. Cochlear implantation surgery experience of a tertiary clinic. J Clin Anal Med 2018;9(3): 209-12.
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The effect of high volume adrenalin solution infiltration on blood loss in reduction mammaplasty
Erkan Orhan
Department of Plastic Surgery, Namik Kemal University, Tekirdağ, Turkey
DOI: 10.4328/JCAM.5641 Received: 25.12.2017 Accepted: 16.01.2018 Published Online: 17.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 213-7
Corresponding Author: Erkan Orhan, Reşat Nuri Sok. No: 71/31 Y.Ayrancı, Çankaya, Ankara, 06510, Turkey. GSM: +905325004192 F.: +90 2822509900 E-Mail: eorhan@yahoo.com
Aim: One of the important complications during and after the reduction mammoplasty operation is blood loss. The most implemented method to decrease the amount of bleeding is adrenaline infiltration, but adrenalin is mostly infiltrated with the fluid in the volume less than 250cc in the clinic. It is expected that adrenaline will accumulate more in the tissue and thus, exhibit more bleeding-reducing effect by increasing the fluid volume used in the infiltration. In this study, it is aimed to indicate the effect of the infiltration of adrenaline with the high volume fluid, on the amount of blood loss occurring due to the reduction mammoplasty operation.
Material and Method: Patients who had undergone bilateral reduction mammoplasty between July 2013 and August 2017 were retrospectively examined. Patients not subjected to infiltration were described as Group 1, patients infiltrated with adrenalin 100cc were described as Group 2, and patients infiltrated with adrenalin 500cc were described as Group 3.
Results: The average decrease in the hemoglobin level (bleeding) after the operation was calculated to be 3.4±0.97 in Group 1, 2.8±0.83 in Group 2, 1.0±0.46 in Group 3 and the average amount of bleeding in Group 2 and Group 3 in comparison with Group 1 and the average amount of bleeding in Group 3 in comparison with Group 2 were statistically significantly lower (p<0.001).
Discussion: The infiltration of adrenaline in the same concentration with a fluid of a higher volume decreases blood loss after the reduction mammoplasty operation.
Keywords: Reduction Mammoplasty; Blood Loss; İnfiltration
Introduction
The reduction mammoplasty operation is one of the procedures frequently performed in plastic surgery [1,2]. There are many techniques described in relation to reduction mammoplasty surgery; however, the common characteristic of these techniques are considerable blood loss during and after the operation [3]. This blood loss causes exhaustion, delayed postoperative recovery, a prolonged stay at the hospital, may require blood transfusion and all of these conditions results in patient morbidity and increased treatment costs [4].The most implemented method to decrease the amount of bleeding after reduction mammoplasty is adrenaline infiltration. There are many prospective and retrospective studies in which it has been indicated that the infiltration of adrenaline and lidocaine mixture into the breast tissue applied before the surgery decreases the need for blood transfusion by reducing the blood loss, and this makes the surgery easier and faster by providing an opportunity for a blood-free operation and increases patient comfort by ensuring intraoperative and early postoperative analgesia [2,5].Although adrenaline infiltration has these positive effects on the reduction mammoplasty operation, adrenaline in the concentration less than 1:100000 is mostly infiltrated with the fluid in the volume less than 250cc in the clinic due to side effects such as circulatory impairment in the pedicle and nipple, this results in rebound bleeding and hematoma in the postoperative period, leading to a delay in wound healing, increasing the risk of infections, and causing necrosis in the breast skin [2,5,6].
The amount of adrenaline accumulated in the breast tissue with infiltration is in direct proportion to the fluid volume infiltrated with adrenaline concentration in the infiltrated solution. It is expected that adrenaline will accumulate more in the tissue and thus, exhibit more bleeding-reducing effect without causing any change in the concentration by increasing the fluid volume used in the infiltration.
In this study, it is aimed to indicate the effect of the infiltration of adrenaline in 1:1000 000 concentration with the high volume fluid on the amount of blood loss occurring due to the reduction mammoplasty operation and side effect level.
Material and Method
In this study, patients who had undergone bilateral reduction mammoplasty in our clinic between July 2013 and August 2017 were retrospectively examined. The ages and preoperative hemoglobin (Hb) and hematocrit (Hct) values of all patients, weight of the breast tissue removed during the surgery, the fact whether infiltration was performed or not, and if performed, adrenaline concentration used, Hb and Hct levels 24 hours after the surgery, the number of blood transfusion performed, the duration of hospitalization and complications occurring in the patients were recorded. Patients with a bleeding problem and receiving anticoagulant and antithrombotic therapy were not included in the study.
At our clinic, the reduction mammoplasty operations were performed without infiltration between July 2013 and September 2014. Due to the significant blood loss and need for blood transfusion in these patients, a solution containing adrenaline at the rate of 1:1000000 has begun to be infiltrated as being 100cc in volume into each breast in the reduction mammoplasty operations since September 2014. Because of blood loss and the ongoing need for blood transfusion, a solution containing adrenaline at the rate of 1:1000000 has begun to be infiltrated as being 500cc in volume into each breast since August 2015. Patients not subjected to infiltration were described as Group 1, patients infiltrated with 100cc were described as Group 2, and patients infiltrated with 500cc were described as Group 3.
All procedures were performed under general anesthesia. All patients underwent single dose prophylactic antibiotic treatment 1 hour before the anesthesia. The patients were laid on the operating table in the supine position. The body was lifted up by 30 degrees, and arms were positioned in abduction. Infiltration was performed in the breast gland and retroglandular region by starting on incision lines with a 50cc injector and 21 gauge needle following putting the chlorhexidine antiseptic solution on the skin. Infiltration was not performed into the pedicle. The surgery was initiated 10 minutes after infiltration. The reduction mammoplasty operation was performed by the same surgeon in all patients in accordance with the vertical mammoplasty technique with the superior and superomedial pedicle and by using electrocautery.The complications were described as follows: hematoma; hemostasis requiring to be drained with a needle or to be surgically explored, wound infection; erythema, strain, cellulite appearance and purulent discharge from the wound, wound healing impairment; partial or complex suture separation from the wound site and secondary healing lasting for longer than 3 weeks, flap necrosis; necrosis on the breast skin flap, nipple necrosis; partial or total necrosis on the nipple areola complex.
Results
The average age of the patients was 38.9±8.4 years in Group 1 (not infiltrated), 37.7±8.6 years in Group 2 (infiltrated with 100cc) and 37.0±9.2 years in Group 3 (infiltrated with 500cc) and there was no statistical difference between the groups (Table 1).
The average preoperative hemoglobin levels were calculated to be 12.1±0.94 g/dl in Group 1 (not infiltrated), 11.7±0.73 g/dl in Group 2 (infiltrated with 100cc) and 11.4±0.97 g/dl in Group 3 (infiltrated with 500cc), and there was no statistically significant difference between the groups (p=0.436) (Figure 1) (Table 2). The average postoperative hemoglobin levels were calculated to be 8.7±1.08 g/dl in Group 1, 9.0±1.01 g/dl in Group 2 and 10.4±1.14 g/dl in Group 3. When the postoperative hemoglobin levels among the groups were compared, there was a statistically significant difference between the groups (p<0.001) (Table 2). When compared to the preoperative period, an average decrease in the hemoglobin level (bleeding) during the postoperative period was calculated to be 3.4±0.97 g/dl in Group 1, 2.7±0.83 g/dl in Group 2 and -1.0±0.46 g/dl in Group 3 and when these differences were compared among the groups, there was s statistically significant difference between the groups (p<0.001) (Table 2).
When the blood transfusion rates among the groups were examined, it was determined that 1 or more units of blood transfusion was performed in 74.4% of the patients in Group 1 (not infiltrated), in 53.5% of the patients in Group 2 (infiltrated with 100cc) and in 3.2% of the patients in Group 3 (infiltrated with 500cc) and there was a statistically significant difference between the groups (p<0.001) (Table 2).
The median amount of the tissue removed from the patients was calculated to be 1400gr (700-3500gr) in Group 1 (not infiltrated), 1500gr (700-2800gr) in Group 2 (infiltrated with 100cc) and 1400gr (700-2900gr) in Group 3 (infiltrated with 500cc), and it was determined that there was no statistical difference among the groups (p: 0.689) (Table 1). It was observed that as the amount of the tissue removed increased in all groups, the hemoglobin level during the postoperative period statistically significantly decreased more when compared to the preoperative period, the amount of the transfused blood statistically significantly increased and the duration of hospitalization statistically significantly increased (Table 3).
When the complications occurring in the patients in the present study were examined, it was observed that there was complication at the rate of 4.7% in all patients, and there was complication at the rate of 5.8% in the Group 1 (no infiltration), at the rate of 4.2% in the Group 2 (infiltrated with 100cc) and at the rate of 4.2% in the Group 3 (infiltrated with 500cc) and when the groups were compared there was no statistically significant difference determined (p>0.05) (Table 4).
When the average duration of hospitalization of the patients was examined, the average duration of hospitalization of the patients was determined to be 3 (2-6) days in Group 1 (no infiltration), 3 days (2-6) in Group 2 (infiltrated with 100cc) and 2 (1-3) days in Group 3 (infiltrated with 500cc). When the duration of hospitalization were compared among the groups, it was identified that the hospitalization duration of the patients in Group 3 was statistically significantly lower in comparison with Group 1 and Group 2 (p<0.001 and p<0.001) and there was no statistically significant difference between Group 1 and Group 2 (p=0.528). (Table 1)
Discussion
A decrease in blood loss occurring in relation to the reduction mammoplasty operation is undoubtfully significant since it ensures the early postoperative recovery of patients, protects patients from the complications of blood transfusion and anemia treatment and decreases the risk of skin and pedicle necrosis occurring due to hypotension [3]. Bretteville-Jensen G. in 1974 demonstrated for the first time that bleeding decreases with the infiltration of solutions containing adrenaline in the reduction mammoplasty and this condition has been supported by further studies [6]. Due to side effects like skin necrosis, decreasing flap viability and increasing the risk of wound site infection, infiltration solutions containing adrenaline at the concentration rates varying between 1:100,000 and 1:1,000,000 are used in reduction mammoplasty, and these liquids are infiltrated in the volume less than 250cc [2,5-7].
Adrenaline causes vasoconstriction in blood vessels, has a bleeding-reducing effect and this effect increases as the amount of adrenaline increases. Thus, it is expected that the amount of bleeding in the breast will decrease as the amount of adrenaline in the breast tissue increases. The amount of adrenaline accumulated in the breast tissue after infiltration is in direct proportion to the concentration of the adrenaline in the infiltration fluid and the amount of the fluid used in infiltration. It is required to increase either the concentration or the amount of the fluid used to increase the amount of adrenaline in the breast tissue. Since it was indicated in many studies that an increase in concentration also increases the prevalence of side effects, the only way to increase the amount of adrenaline in the medium without increasing concentration is to increase the volume of solution used in infiltration [2,5,6].
The first study with the theory that the adrenaline level in the tissue can be increased by increasing the infiltrated fluid volume was conducted by Beveridge and Bell [8]. In their study, the amounts of bleeding in 23 patients not subjected to infiltration, in 20 patients infiltrated with 250cc of the solution in 1:1,000,000 adrenaline concentration, and in 21 patients infiltrated with 10 mg/kg per kilogram of the solution in 1:1,000,000 adrenaline concentration (on average 350cc per person) were compared, and it was observed that as the amount of infiltration increased, the amount of bleeding decreased. However, in another study conducted on 100 patients by Kaplan et al. [2] when the patients who were not infiltrated and infiltrated with 500-1,000cc of the solution containing 1:1,000,000 adrenaline were compared, it was identified that the hemoglobin value decreased on average by 2.4 units in the group subjected to infiltration and on average by 1.9 units in the group not subjected to infiltration, and there was no statistically significant difference among them in terms of the amount of bleeding.In this study, the hemoglobin value decreased on average by 3.4±0.97 g/dl in the Group 1(no infiltration), by 2.8±0.8 g/dl in the Group 2 (infiltrated with 100cc) and by 1.0±0.46 g/dl in the Group 3 (infiltrated with 500cc), and the difference among them was statistically significant. The amount of a decrease in hemoglobin in the group that was not infiltrated and in the group infiltrated with 100cc in this study is consistent with the other studies [7]. In this study, the blood loss considerably decreased in the group infiltrated with 500cc in accordance with the result of the study of Beveridge and Bell and the need for blood transfusion in patients during the postoperative period decreased almost by 30 times together with an increase in the infiltration volume, and it was observed that patients’ recovery during the postoperative period was considerably better and thus, the hospitalization durations of the patients decreased [8].
The reason for the difference between the results of this study and the study of Kaplan et al. can be explained by the way of infiltration [2]. While infiltration was performed into the retroglandular tissue in this study and in the study of Beveridge and Bell [8], it was not performed in the study of Kaplan et al. [2]. Infiltration into the retroglandular region ensures vasoconstriction in intercostal and lateral perforator vessels extending to the breast tissue, and this difference among the studies indicates that vasoconstriction in intercostal and lateral perforator vessels causes a significant decrease in bleeding occurring in the reduction mammoplasty operation [4].
When the complications occurring in the patients in the present study were examined, it was observed that there were complications at the rate of 4.7% in all patients, and there was no statistical difference among the groups in terms of the prevalence of complications. In previous studies in the literature in which infiltration was performed, Steven et al. [9] reported complications at the rate of 14%, Kaplan et al. [2] reported complications at the rate of 4%, DeBono et al. [5] reported complications at the rate of 12.5%, Mandrekas et al. [10] reported complications at the rate of 5.7% in their studies. These results indicate that increasing the adrenaline level in the tissue by increasing the amount of the fluid infiltrated does not increase the rates of complications.
A decrease in the blood loss occurring with high volume fluid infiltration in reduction mammoplasty is ensured not only with an increase in vasoconstriction occurring in relation to an increase in the amount of adrenaline but also with high volume fluid pressure on the local blood vessels in the tissue [11]. However, there may be some disadvantages such as that the fluid in the tissue makes it difficult for electrocautery to work in resections performed especially with electrocautery and that the evaporation of the fluid in the tissue, secondarily to the temperature increase occurring with electrocautery, causes the excessive surgical smoke. In particular, surgical smoke can be very disturbing, and smoke removal is required. However, these disadvantages have not caused any prolongation in any of our patients during the surgery.
Conclusion
The infiltration of adrenaline in the same concentration with a fluid of a higher volume decreases the amount of bleeding, the need for postoperative blood transfusion and the duration of hospitalization and thus decreases patient morbidity and treatment costs. We recommend administering fluid in high doses while performing infiltration, especially in big breasts.
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. Cunningham BL, Gear AJ, Kerrigan CL, Collins ED. Analysis of breast reduction complications derived from the BRAVO study. Plast Reconstr Surg. 2005; 115(6): 1597-604.
2. Kaplan JL, Rotemberg S, Yetman R, Boggs O, Bena JF, Tang AS, et al. Breast reduction: does the tumescent technique affect reimbursement? Plast Reconstr Surg. 2008; 122(3): 693-700.
3. Soueid A, Nawinne M, Khan H. Randomized clinical trial on the effects of the use of diluted adrenaline solution in reduction mammaplasty: same patient, same technique, same surgeon. Plast Reconstr Surg. 2008; 121(3): 30e-3e.
4. Wilmink H, Spauwen PH, Hartman EH, Hendriks JC, Koeijers VF. Preoperative injection using a diluted anesthetic/adrenaline solution significantly reduces blood loss in reduction mammaplasty. Plast Reconstr Surg. 1998; 102(2): 373-6.
5. DeBono R, Rao GS. Vasoconstrictor infiltration in breast reduction surgery: is it harmful? Br J Plast Surg. 1997; 50(4): 260-2.
6. Hardwicke JT, Jordan RW, Skillman JM. Infiltration of epinephrine in reduction mammaplasty: a systematic review of the literature. Plast Reconstr Surg. 2012; 130(4): 773-8.
7. Thomas SS, Srivastava S, Nancarrow JD, Mohmand MH. Dilute adrenaline infiltration and reduced blood loss in reduction mammaplasty. Ann Plast Surg. 1999; 43(2): 127-31.
8. Beveridge M, Bell M. The tumescent technique for bloodless breast reduction. Can J Plast Surg. 1994; 2(3): 121-4.
9. Stevens WG, Gear AJ, Stoker DA, Hirsch EM, Cohen R, Spring M, et al. Outpatient reduction mammaplasty: an eleven-year experience. Aesthet Surg J. 2008; 28(2): 171-9.
10. Mandrekas AD, Zambacos GJ, Anastasopoulos A, Haspas DA. Reduction mammaplasty with the inferior pedicle technique: Early and late complications in 371 patients. Br J Plast Surg. 1996; 49(7): 442-6.
11. Patrick H. Conroy, James O’Rourke. Tumescent anaesthesia. Surgeon. 2013; 11(4): 210-21.
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Risk of sharp injuries and mucocutaneous exposures in healthcare workers: ongoing problem despite prevention programs
Zeliha Haytoglu 1, Ozlem Ozgur Gundeslioglu 2
1 Department of Pediatrics, 2 Department of Pediatrics, Division of Pediatric Infectious Disease, Cukurova University, Faculty of Medicine, Adana, Turkey
DOI: 10.4328/JCAM.5648 Received: 03.01.2018 Accepted: 10.01.2018 Published Online: 11.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 218-21
Corresponding Author: Zeliha Haytoglu, Department of Pediatrics, Cukurova University, Faculty of Medicine, 01130, Adana, Turkey. GSM: +905052540485 E-Mail:zelihahayt@yahoo.com
Aim: The fact that documented cases of sharp injuries and mucocutaneous exposures are still occurring is a reminder of the importance of preventing injuries and of providing services for the prompt and appropriate management of such incidents. Our study provides an overview of the risks associated with needlestick and sharps injuries and lids a light in prevention strategies to protect the healthcare professionals.
Material and Method: Between January 2015 and September 2017 the reports of the occupational injuries in our high-technology hospital that is located in the metropolitan area with 1200 beds and 3300 healthcare workers were examined.
Results: One hundred eighty-five occupational exposures were reported. Percutaneous injuries were the most common exposure (87.5%) (161/185). Mucocutaneous exposures decreased from 16%(9/56) in 2015 to 9.4%(5/53) in 2017. Of all injuries, injuries observed in nursing professions was 49.1%. Twenty-two Hepatitis B surface antigen (HBsAg) positive, 12 Hepatitis C (HCV) and 3 human immunodeficiency virus (HIV) positive source exposures were reported. Seroconversion was not observed in workers exposed to the Hepatitis B (HBV), HCV and HIV. Of 185 workers 75 workers (40.5%) reported that they had sustained injuries without a report. The use of self-protective equipment was poor. When the exposure occurred 22% and 90% of the workers were not using gloves and goggles respectively.
Discussion: The low number of reported exposures suggests that hospital staff are not yet fully informed about possible consequences of their injuries and true number of seroconversion attributable to occupation exposures to HCV and HIV may be potentially underestimated
Keywords: Mucocutaneous Exposures; Needlestick Injuries; Seroconversion
Introduction
Needlestick injuries are common occupational hazards in the hospital setting that expose healthcare workers to the risk of blood-borne infections such as Hepatitis B (HBV), Hepatitis C (HCV) and human immunodeficiency virus (HIV) [1]. Occupational exposures should be considered urgent medical concerns to ensure timely post-exposure management and administration of HBV immunoglobulin, HBV vaccine, and/or HIV post-exposure prophylaxis.
The risk of acquiring HBV from an occupational needlestick injury when the source is Hepatitis B surface antigen (HBsAg) positive ranges from 2% to 40%, depending on the source’s level of viremia [2]. HBV can survive for up to one week under optimal conditions and has been detected in discarded needles [3]. Post-exposure prophylaxis with HBV immunoglobulin and HBV vaccine is effective if provided promptly [4].
The risk of acquiring HCV as a result of an occupational needlestick injury when the source was infected varies from 3% to 10% [2]. Unfortunately, there is no effective post-exposure prophylaxis at present.
The risk of acquisition of HIV from a hollow-bore needle with blood from a known HIV seropositive source is between 0.2% and 0.5% [2]. The risk is increased with the higher viral inoculum, which is related to the amount of blood introduced and the concentration of virus in that blood. Avoiding occupational blood exposures is the primary way to prevent transmission of HBV, HCV, and HIV in health-care settings.The aim of our study was to determine the rate of injuries, to investigate the factors that cause the injuries, and to identify areas in which the prevention program needs improvement, examine the types of exposures, examine the staff involved and collecting data on healthcare workers (HCWs) following significant occupational exposure to HIV, HBV, and HCV in our university hospital.
Material and Method
In this retrospective study, we retrieved all incident reports of our university hospital between January 2015 and September 2017. The outcome data was analyzed using a Statistical Package for the Social Services (SPSS) version 21. Descriptive statistics and chi-square test of independence were used to assess independence or associations between the categorical variations.
Univariate analysis along with 95% CI was calculated to assess factors associated with needlestick injuries. The study protocol was approved by the Ethics Committee of our institution. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Results
Between 2015 and 2017, 185 occupational exposures were reported. Fifty-six exposures were in 2015, 76 were in 2016, 53 were in 2017. Table 1 demonstrates the annual exposures between 2015 and 2017.
Types of exposures: 87% (161/185) of the reported injuries between 2015 and 2017 were percutaneous injuries.
Percutaneous injuries attributed to hollow bore needlestick injuries increased from 89.3% (42/47) in 2015 to 94% (64/68) in 2016, before increasing steadily to 95.8% (46/48) in 2017. As a percentage of the overall number of reports, percutaneous injuries slightly increased from 83.9% in 2015 (47/56) to 89.4% in 2017 (68/76). Sharp injuries attributed to scalpels declined from 8.9%(5/56) in 2015 to 3.8% (2/53) in 2017. Mucocutaneous exposures accounted for 11.9% (22/185) of all exposures between 2015 and 2017.
Exposures by location and time: Occupational exposures reported in the wards were 40% of all exposures between 2015 and 2017. Reported exposures were 27.6% in intensive care units, 8% (15/185) in operating rooms, 5.4% in the emergency unit (10/185) (Figure 1).
Between 2015 and 2017 reported exposures in the emergency unit increased from 1.8% to 13.2%. Of the all reported injuries, 75% (139/185) of the injuries were between at hours of 08:00 and 17:00. In emergency department two peaks of reporting hours of 18.00-24.00 and 03:00-07:00 were observed. In operating rooms, all exposures (100%) were reported between 08:00 and 16:00. In intensive care units exposures were not time-dependent.
Compliance with standard and safety precautions, contributory factors: Waste disposal workers were the subjects in 27.6%(51/185) of all exposures as consequences of nonadherence to safe disposal of sharps and clinical waste.
Twenty-two percent of the HCW did not use gloves also googles and aprons were not used in 90% of the workers in direct contact with blood and/or body fluids.
HCW’s years of experience in the job was categorized into 4 different groups. Group 1 consisted of workers with five years or less experience of the job; group 2 consisted of workers with more than five less than 12 years of experience of the job, group 3 consisted of workers with 12-17 years of experience of job and group 4 consisted of workers with 17-23 years of experience of the job. Of all injuries 62.1% of the injuries, were in workers with five years or less experience in their job (Figure 2). In univariate analysis, odds of having injury was higher among the workers who were: practicing for less than 5 years (OR=6.52, 95% CI: 2.65 – 9.61) (p<0.001).
Overall, of the percutaneous exposures, 57.8% (93/161) occurred during the procedures, 42.2%(68/161) occurred after the procedure. As a contributory factor non-compliance with standard precautions was reported in 86.7% (59/68) of the exposures after the procedure versus in 70.9%(66/93) during the procedure.
Procedure-related contributory factors which are emergency procedures and procedures that are different from rutin practice were the factors in 16% (15/93) of the exposures during the procedure. Health-care worker related contributory factors which are inexperience, tiredness, rushing for the procedure was observed in 12% (12/98) during the procedures.
The most common actions taken after needlestick injuries were compression 22.9% (37/161) and washing the area with soap and water 92.4% (171/185).
The source patient: Of 185 exposures reported between 2015 and 2017; 11.9% involved HBsAg (+) source patients, 1.6% involved HIV (+) and 6.5% involved HCV (+) source exposures. Exposures of HBsAg (+) source patients were 3 in the operating room, 3 in the emergency department, 4 in intensive care units, and 12 in the wards. HIV (+) source exposures were 1 in the operating room, and 2 in the wards. HCV (+) source exposures were 1 in operating room, 2 in intensive care units, and 9 in the wards. Seroconversion was not reported due to exposure of HBsAg (+), HCV (+) and HIV (+) source exposure patients. After HIV (+) source exposures all 3 workers completed 28 days post-exposure prophylaxis of antiretroviral therapy.
At the time when the study was conducted, 88.6% workers were fully vaccinated with three dosages of the vaccine.
Discussion
The awareness of the issue of occupational hazards began many decades ago. Although over fifteen years have passed since the standard precautions have been defined and recommended to be taken by all HCWs when they are in contact with patients, it is a fact that they are often neglected [5]. The absence or insufficiency of basic protective equipment such as masks, gloves, and goggles have been reported as barriers to compliance with standard precautions [6-8]. In our reports, the use of personal protective equipment was poor. When the exposures occurred; 22.2% of the workers were not using gloves, 90% of workers were not using goggles and aprons. As in line with our findings, many studies reported the unavailability of personal protective equipment especially at emergency departments [8,9].
Aside from compliance with the use of personal protective equipment we underline the importance of adhering to protocols for the safe handling and disposal of sharps and clinical waste. In comparing contributory factor categories over time exposures involving non-compliance with proper handling and disposal of clinical waste increased from 64% to 80% from 2015 to 2017.
Of the injuries from 2015 to 2017, the contributory factor was non-compliance with standard precautions in 77.6% (125/161) of the percutaneous injuries. These exposures could have been prevented by compliance with well-known but neglected standard precautions. Non-compliance precautions as a contributory factor include not having sharp at hand, overfull sharps bins, clearing, and disposing of sharps used by someone else. As a part of our local protocol, all healthcare workers attend comprehensive training and education programs 2 times every year on a regular basis. Despite adequate local health policies for occupational exposures, underreporting of exposures remains a distinct problem. Evidence from previous studies suggested that needlestick injuries are underreported [10,11]. Underreporting rates of 22% to 82% have been noted [12,13]. Although in our institution an easily accessible reporting system is provided, 40.5% of the workers reported that they had exposure injuries without reports. In our study underreporting rates were 75% in nurses and 50% in doctors and cleaning workers. In a survey of operating room exposures, it was shown that 91% of nurses compared to 53% of surgeons had reported their injuries [10]. In another study, only 2% of injuries were reported by the surgeons [11]. Although most of the injuries were reported in the wards (40%) in our reports from 2015 to 2017, injuries increased in Emergency Department. Performing procedures under emergency conditions may cause the increased risk of injury. A study conducted in the USA reported that psychiatry, pediatrics, and neonatal units had fewer percutaneous injuries than the medical and surgical wards. In our study, the reported exposures in pediatric wards were at the same percentages in surgical wards although less than the reports in medical wards (29.1% (35/120) versus, 41.6% (50/120). This was not statistically different.
As in line with our study, many studies reported that longer work experience was associated with decreased risk of injury [14,15]. It implies that proper training with professionals is needed especially for workers with less experience in their jobs.
There were no cases of seroconversion amongst the workers exposed to HBV, HCV, and HIV positive source patients. Our hospital has 1200 beds and 3300 HCW located in the metropolitan area and is a high-technology hospital. Between 2015 and 2017, 185 exposures were reported. Underreported exposures were high amongst the healthcare workers in our hospital. Unknown exposures can lead to transmission of HBV, HIV, and HCV.
Conclusions
Preventing injuries is the most effective way to protect workers. A major proportion of these exposures were attributed to non-compliance with the safe handling of sharps and the disposal of clinical waste, and non-compliance with standard precautions. Comprehensive education, training, and promotion of adherence to standard precautions would reduce the exposures. Even though healthcare workers are actively encouraged to report all injuries, injuries are still under-reported. Under-reporting of injuries is a problem and varies by occupation and specialty. As a consequence of underreported injuries seroconversion to HCV and HIV due to occupational injuries may be underestimated. Due to poor use of personal protective equipment supervisors must reinforce the need to wear personal protective equipment correctly and regularly.
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. US Public Health Service. Guidelines for management of Occupational Exposure to HBV, HCV, and HIV and Recommendations for Post-exposure Prophylaxis. MMWR Recomm Rep. 2001; 50: 1-52.
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5. Centers for Disease Control and Prevention (CDC). Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Post-exposure Prophylaxis. MMWR Recomm Rep. 2001; 50: 1-52.
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14. Hanafi MI, Mohamed AM, Kassem MS, Shawki M. Needlestick injuries among health care workers of University of Alexandria Hospitals. EMHJ. 2011; 17: 1-5.
15. Rampal L, Zakaria R, Sook LW, Zain AM. Needlestick and sharps injuries and factors associated among health care workers in a Malaysian hospital. European Journal of Social Sciences. 2010; 13(3): 354–62.
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Cecal diverticulitis mimicking acute appendicitis: Management and short-term results of surgery
Volkan Oter 1, Serdar Oter 2, Mehmet Tolga Kafadar 3
1 Department of Gastroenterological Surgery, Health Sciences University, Mehmet Akif İnan Training and Research Hospital Şanlıurfa, 2 Department of Gastroenterological Surgery, School of Medicine, Mersin Unıversity, Mersin, 3 Department of General Surgery, Health Sciences University, Mehmet Akif İnan Training and Research Hospital Şanlıurfa, Turkey
DOI: 10.4328/JCAM.5650 Received: 30.12.2017 Accepted: 10.01.2018 Published Online: 14.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 222-5
Corresponding Author: Volkan Oter, Department of Gastroenterological Surgery, School of Medicine, Sakarya Unıversity, Serdivan, Sakarya, Türkiye. GSM: +905053366333 F.: +90 2642955032 E-Mail: otervolkan@gmail.com
Aim: Cecal diverticulum is an infrequent cause of acute abdomen, and cecal diverticulitis usually presents in a behavior similar to acute appendicitis. This study aims to review our experience with surgical or nonsurgical management of cecal diverticulitis mimicking acute appendicitis in our department.
Material and Method: From January 2012 to April 2017, fourteen patients were treated for cecal diverticulitis at our clinic. We retrospectively reviewed the patients’ records, imaging modalities, and operative findings.
Results: Nine men and five women with a mean age 43.93 ± 8.95 (range 32 to 65) years were evaluated. Total of nine (64.2%) patients were managed operatively. All patients were urgently operated. The mean hospital stay was 6.11 ± 1.61 days. In the postoperative period, two patients had wound infection, and postoperative mortality was not observed. Nonoperative management was used for the treatment in five (35.7%) patients who were preoperatively diagnosed with cecal diverticulitis, Hinchey stage I or II.
Conclusion: Inflammation of the diverticulum of the cecum is an uncommon disease, but should be kept in mind in the differential diagnosis of pain in the right lower quadrant. Diagnostic laparoscopy can be used in patients and especially in women with atypical presentations of acute appendicitis. Preoperative diagnosis of cecal diverticulitis is very important in order to decide how to manage this condition.
Keywords: Cecum Diverticulitis; Management; Mimicking Acute Appendicitis
Introduction
As a rare clinical entity, the cecal diverticulitis has no certain etiology. The incidence of right colonic diverticula in published studies is low in Western countries (1.5 %), but the incidence rate is substantially higher (55–70 %) in Asian countries [1,2]. A cecal diverticulum is an infrequent cause of acute abdomen, and cecal diverticulitis usually presents in a behavior similar to acute appendicitis [3]. It is extremely difficult to differentiate its preoperative from acute appendicitis, and this kind of distinction is usually made in the operating room [4]. This study aims to review our experience with surgical or nonsurgical management of cecal diverticulitis mimicking acute appendicitis in our department.
Material and Method
From January 2012 to April 2017, fourteen patients were treated for cecal diverticulitis at the General Surgery Department of the Health Sciences University Mehmet Akif İnan Training and Research Hospital. Specific data extracted included presenting complaints and physical signs, preoperative diagnosis, laboratory and radiographic findings, length of symptoms before treatment, indications for operative intervention, surgical treatments, and morbidity and mortality. The severity of diverticulitis was assessed using the modified Hinchey’s classification [5-6].
Data were evaluated with the statistical SPSS package, version 13.0 (Chicago, IL). Data were expressed as mean ± standard deviation (SD) or median (range).
Results
Nine men and five women with a mean age 43.93 ± 8.95 (range 32 to 65) years were evaluated. Demographic and clinical features are shown in Table 1. All patients were admitted to our emergency surgery unit with the complaints of pain in the right lower quadrant of the abdomen, distension, and fever. The clinical presentation of cecal diverticulitis was similar to acute appendicitis. The acute abdominal pain was present in all patients, with an average duration of 2.62± 1.68 days (range 1 to 6 days). Nausea or vomiting occurred in only five (35.7%) patients for an average of 2.1 days (range 1 to 5 days). Right lower quadrant tenderness was the most common physical symptom, found in eleven (78.5%) patients, and this was accompanied by a palpable mass in only three (21.4 %) patients. A low-grade fever of 39.7 °C was often present, along with mild leukocytosis (14.700 WBC). Radiologic studies were performed in patients: plain abdominal x-rays in eight (57.1 %), plain abdominal X-rays revealed no abnormality, computed tomography (CT) scan in eight (57.1 %), and abdominal ultrasound (US) in five (35.7%). A correct radiologic diagnosis was possible in only five patients; all confirmed on CT scan. Depending on these correct radiologic diagnoses, five (35.7 %) patients were managed nonoperatively.
Total of nine (64.2%) patients were managed operatively (Table 2). Emergency surgery was performed for preoperative diagnosis of appendicitis in seven (%50) of the fourteen patients with cecal diverticulitis. In five of this seven patients; the appendix was found in the normal location with a normal appearance, and an inflamed mass was found on the lateral wall of the cecum. Incidental appendectomy and drainage were performed in this patients. In two of this seven patients; the appendix was found in the normal location with a normal appearance, and an inflamed mass was found on the anterior wall of the cecum located between the tenia liberal and plica ileo-cecalis with a paracolic abscess. A diverticulectomy and incidental appendectomy were performed.The other two (14.2 %) of nine patients, the indication for emergency surgery was acute abdomen from a correctable surgical etiology. In these patients, the cecal wall near to the diverticulum were thickened and abnormal, raising the suspicion of underlying carcinoma. Right hemicolectomy with appropriate cancer clearing lymphadenectomy was then performed in these two patients. Histopathology of the resected right colon showed that the lesion was a solitary cecal diverticulum. There were histological features of acute inflammation and gangrene, but no evidence of malignancy. Oral intake of foods was started on a postoperative day three if there was no abdominal pain and blumia. All patients were urgently operated. The mean hospital stay was 6.11 ± 1.61 days. In the postoperative period, two patients had wound infection, and postoperative mortality was not observed. Nonoperative management was used for the treatment in five (35.7%) patients which was preoperatively diagnosed cecal diverticulitis, Hinchey stage I or II. Nonoperative management of these patients included broad-spectrum antibiotics or percutaneous drainage (PCD) in patients with a paracolic abscess. (PCD was only used for one patient because of forming of a right paracolic abscess.) The patients received a combination therapy of second-generation cephalosporin and metronidazole while hospitalized, and they received oral antibiotics for seven days after discharge. Oral intake of foods was started if there was no abdominal pain and blumia.
Discussion
Most patients with inflammation of a solitary diverticulum of the cecum present with abdominal pain and fever that is indistinguishable from acute appendicitis. It accounts for 3,6% of all colonic diverticula with median age incidence of 44 years and male to female ratio is 3:2 [7]. In our study, median age was 42 and male to female ratio was approximately 1,8. Moreover, half of the diverticula seem to be lying anterior to the cecal wall [8]. Cecal diverticula’s can stay asymptomatic for years. They only produce symptoms in the presence of complications like inflammation or perforation. The most frequent clinical symptom of cecal diverticulitis includes abdominal pain in the right lower quadrant, fever, and leukocytosis. With these symptoms, a differential diagnosis should be established not only with acute appendicitis, but also with other conditions such as urinary infection, renal-ureteral colic, gastroenteritis, pelvic inflammatory disease, or inflammatory bowel disease [9,10]. The role of laboratory analysis in making the definitive diagnosis is limited, since that delivers no significant result other than moderate degree leukocytosis. The clinical and the laboratory findings of our cases carry similarity to acute appendicitis.
Radiologic tests prove the most beneficial methods for accurate diagnosis in the preoperative period. The imaging modalities most commonly used to diagnose acute diverticular disease are ultrasound, computed tomography, and magnetic resonance imaging. Water-soluble contrast or barium enema, although effective, have fallen out of favor due to the possible complications of contrast-induced bowel perforation and chemical peritonitis, which have been well documented in the literature [11-13].
Although plain x-rays and the abdominal US yield nonspecific findings, for the most part, CT is reasonably useful in the diagnosis [10]. Cecal diverticulum appears as a hypoechoic pouching, which originated from a broadened segment colonic wall in the US. CT imaging can be used in the diagnosis of acute appendicitis and cecal diverticulum. Thinning of the colonic wall, infiltration of the pericolic fatty, formation of the abscess and presence of extraluminal air might be observed in abdominal CT, which may also be evident in plastron appendicitis, though [10].
The preoperative diagnosis of cecal diverticulitis is difficult. A previous study reports it is only made in 9% of the cases, and most of these patients have had previous appendectomy [14]. The definitive diagnosis of cecal diverticulitis is most commonly justified intra-operatively during exploration for suspected appendicitis [15]. We had already suspected acute appendicitis in our seven cases with no history of prior appendectomy based on the evaluation of nonspecific findings from the US together with the clinical findings and laboratory analysis, yet the definitive diagnosis was only established intraoperatively. The management to be applied is subject to change on the basis of intraoperative findings. When an uncomplicated cecal diverticulitis diagnosis is made before the operation, management should be done conservatively with intravenous antibiotics [16]. However, the majority of the cases are treated surgically because of difficulty distinguishing it from acute appendicitis or excluding a cecal carcinoma. In our study, nine patients were treated surgically, and only five patients were treated non-operatively. Different surgical approaches are defined but a right hemicolectomy is recommended in the presence of an inflammatory mass and when a carcinoma cannot be excluded [17,18]. Moreover, if surgery is needed, elective laparoscopic surgery is preferred to minimize complications and morbidity [19,20].
Conclusion
Inflammation of the diverticulum of the cecum is an uncommon disease but should be kept in mind in the differential diagnosis of pain in the right lower quadrant. The definitive diagnosis can not always be made despite the evaluation of the clinical condition, laboratory findings, and imaging methods. Its diagnosis should especially be suspected in patients with a long history of pain with atypical presentations of acute appendicitis. Diagnostic laparoscopy can be used in patients and especially in women with atypical presentations of acute appendicitis. During the surgical procedure, if the diagnosis of acute appendicitis is in doubt, further exploration should be carried out. Preoperative diagnosis of cecal diverticulitis is very important in order to decide how to manage this condition.
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. Chan CC, Lo KK, Chung EC, Lo SS, Hon TY. Colonic diverticulosis in Hong Kong: distribution pattern and clinical significance. Clin Radiol. 1998; 53(11): 842–4.
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4. Papapolychroniadis C, Kaimakis D, Fotiadis P, Karamanlis E, Stefopoulou M, Kouskouras K, et al. Perforated diverticulum of the caecum. A difficult preopera- tive diagnosis. Report of two cases and review of the literature. Tech Coloproctol. 2004; 8: 116-8.
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patients. Dis Colon Rectum. 1995; 38(6): 627–9.
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13. Gilmore T, Jordan C, Edelstein E. Right-sided diverticulitis mimics appendicitis. J Emerg Med. 2013; 44(1): e29-32.
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17. Park SM, Kwon TS, Kim DJ, Lee YS, Cheung DY, Oh ST, et al. Prediction and management of recurrent right colon diverticulitis. Int J Colorectal Dis. 2014; 29(11): 1355–60.
18. Buluş H, Koyuncu A, Taş A, Köklü S, Soy D, Coşkun A. Caecal diverticulitis mim- icking acute appendicitis. Turk J Gastroenterol. 2013; 24(4): 371-2.
19. Kim TJ, Lee IK, Park JK, Lee YS, Si Y, Jung H, et al. Is conservative treatment with antibiotics the correct strategy for management of right colonic diverticuli- tis? A prospective study. J Korean Soc Coloproctol. 2011; 27(4): 188–93.
20. Lee IK, Lee YS, Kim SJ, Gorden DL, Won DY, Kim HJ, et al. Laparoscopic and open surgery for right colonic diverticulitis. Am Surg. 2010; 76(5): 486–91.
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Oter V, Oter S, Kafadar MT. Cecal diverticulitis mimicking acute appendicitis: Management and short-term results of surgery. J Clin Anal Med 2018;9(3): 222-5.
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Monoblock and twinblock mandibular advancement devices in the treatment of obstructive sleep apnea
Ignazio La Mantia 1, Calogero Grillo 1, Simone Narelli 2, Claudio Andaloro 3
1 Department of Medical Sciences, Surgical and Advanced Technologies, University of Catania, Catania, 2 Dental Unit, ASP Ragusa, Ragusa, 3 Ear Nose and Throat Unit, Santa Marta e Santa Venera Hospital, Acireale, Catania, Italy
DOI: 10.4328/JCAM.5659 Received: 02.01.2018 Accepted: 08.01.2018 Published Online: 10.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 226-30
Corresponding Author: Claudio Andaloro, Ear Nose and Throat Unit, Santa Marta e Santa Venera Hospital, Via Caronia, 95024, Acireale, Catania, Italy. T.: +3909532610274 E-Mail: cla.anda@gmail.com
Aim: Mandibular advancement devices (MADs) are an alternative to continuous positive airway pressure (CPAP) for patients with obstructive sleep apnea syndrome (OSAS). There is conflicting evidence of how different MAD designs may affect OSAS outcomes in certain patients. This study aimed to assess and compare the effectiveness of two different MADs in treating OSAS, based on subjective and objective measurements.
Material and Method: A randomised crossover design trial was carried out on 38 patients with OSAS. A monoblock and a twinblock MAD were tested in each patient. Changes in objective outcomes (apnea-hypopnea index (AHI), total sleep time (TST), oxygen desaturation index >4% (ODI4%), total duration of oxygen saturation with less than 90% (SpO2<90%), total arousal index (TAI) and sleep efficiency) were assessed by polysomnography, changes in subjective outcomes by the Sleep Apnea Quality of Life Index (SAQLI) and Epworth Sleepiness Scale (ESS).
Results: Both MADs proved to be effective in improving several objective parameters from baseline, but when compared there was a significant difference in favor of the monoblock in terms of improving AHI, ODI 4% and total duration with SpO2<90% (p=0.032; 0.046 and 0.043, respectively). Both MADs were efficacious in improving patients’ SAQLI score and ESS score (all p<0.05), but no significant difference was observed between the two MADs.
Discussion: Use of the monoblock MAD should be considered when patients with OSAS choose MAD treatment, as it was more efficient in improving objective OSAS parameters compared to twinblock MAD.
Keywords: Obstructive Sleep Apnea; Mandibular Advancement; Quality of Life
Introduction
The obstructive sleep apnea syndrome (OSAS) is the most common sleep-related breathing disorder. Population-based studies across the world estimate a prevalence of approximately 6% to 49% [1]. Patients suffering from OSAS experience a range of adverse health outcomes such as heart failure, cerebrovascular insult, impaired neuro-cognition, impaired quality of life and social life [2,3].Different treatment options are now available for effective management of this disease, but continuous positive airway pressure (CPAP), after more than three decades from its first use, is still recognized as the treatment of choice to control this disorder [4]. However, its efficacy is highly reliant on patient compliance. Not all patients with OSA tolerate CPAP, some patients complain about some side effects such as dryness of the airway and mouth, increased number of awakenings, blocked up nose, rhinitis, mask pressure and mask leaks [5,6].
Patients were more likely to stop using the CPAP because of poor tolerability, and decreased adherence rates [5]. Oral appliances (OAs) offer a non-invasive treatment option for patients with OSAS. The American Academy of Sleep Medicine (AASM) recommends OAs therapy for patients with mild to moderate OSAS and for those with more severe OSAS who cannot tolerate CPAP and refuse surgery [7]. A variety of OAs is available such as tongue retaining devices, soft palate lifters, and mandibular advancement devices (MADs). These were the most commonly used oral appliance in the treatment of OSAS [8]. The MAD works by increasing the retropalatal and retrolingual spaces while decreasing the length of the soft palate and the angle of mouth opening [9]. Several types of MAD have been created for OSAS treatment. Some appliances have fixed advancements, where the distance of advancement can’t be adjusted, whereas others are adjustable. One study showed that adjustable appliances resulted in a greater reduction in apnea-hypopnea index (AHI) and improvements in Epworth Sleepiness Scale (ESS) compared to fixed appliances [10]. MADs have a variety of side effects with many of them being only temporary: jaw discomfort, tooth tenderness, excessive salivation, and occlusion changes [11].
Understanding which type or design of MAD is most effective and tolerated in the treatment of OSA should be examined for offering the optimum treatment options to patients. However, few studies have investigated this [12]. For this reason, we carried out a study on patients with OSAS to evaluate the efficacy of two different MADs on subjective Sleep Apnea Quality of Life Index (SAQLI), ESS and objective polysomnography (PSG) parameters.
Material and Method
This prospective, randomized cross-over trial was conducted between April 2017 and October 2017 in the Otolaryngology Unit of the Santa Marta e Santa Venera Hospital in Acireale, Catania, Italy, after the approval by the ethical committee of the Unità Operativa Complessa (UOC) Otorinolaringoiatria – ASP 3 CT. The study involved a sample of consecutively adult ASOS patients which had been prescribed treatment with MADs at the Dental Unit of the same hospital.
The criteria for inclusion were: (a) ages of 18 and older; (b) confirmed diagnosis of OSAS by PSG as defined by an AHI score of ≥10; (c) inability to tolerate CPAP or reported noncompliance to CPAP use as defined by CPAP usage for < 4 hours for 70% of the nights; (d)
a score of >10 on the ESS; (e) a body mass index (BMI) <35 kg/m2; (f) complete or functional dentition. Exclusion criteria were: (a) previous surgery to upper respiratory airway; (b) presence of unstable cardiovascular disease, neurological, mental, or psychiatric disorders; (c) pregnancy; (d) presence of temporomandibular joint dysfunction (TMD); (e) unsuitable peridontal or teeth for an oral appliance.
Custom-made MADs were realized following the patient’s anatomic variability and used for each patient. The MADs were: a one-piece (monoblock) and a two-piece (twinblock) appliances made out of a thermal acrylic material. Alginate impressions, a centrical wax bite, and a protrusive wax bite were taken by an orthodontist for the construction of each appliance realized by a dental technician (both not involved in this study). The protrusion and the opening of the bite were individually adjusted for each patient according to a construction bite; in the sagittal plane, MADs were designed to hold the mandible to 75% of the maximal protrusion and in the vertical plane about 6 mm, to ensure retention of the device. The George Gauge, an instrument for bite registration, was used to determine where the bite registration was recorded. Each device was fitted and then reviewed 2-4 weeks later at a second visit to start the study. Patients were taught how to use the MADs every night during sleep properly.
Before the start of the study a biostatistician, who is not involved in the data recruitment nor collection, created the allocation schedule using a computer-assisted random sequence generator. This schedule was used in order to generate the list of patients who will be assigned to the 2 equal treatment groups, where each treatment consists of a sequence of two treatments (AB or BA). Patients assigned to study group AB, received the monoblock MAD first, followed by the twinblock MAD. For those patients assigned to study group BA, this sequence was reversed. At the end of 10 weeks with the first MAD (T1), patients underwent PSG at our hospital to assess the efficacy of the treatment modality. At this appointment, the first MAD was collected from the patient. After that patients have gone through a 2 weeks wash-out period during which patients did not wear any MAD, to avoid any possible effect of the first MAD for the response to the second MAD. The patients were then fitted with the second MAD for 10 weeks (T2). At the end of this study period with the second MAD, patients underwent a final PSG at our hospital and conclusive assessment and data collection. Each patient included in the study underwent a subjective sleep assessment by the SAQLI and the ESS and an objective assessment by PSG at baseline and follow-up data collection points (T1 and T2).
The SAQLI is a disease-specific quality of life (QoL) questionnaire, which was developed in order to detect more subtle effects of sleep apnoea on health-related QoL. Items are scored on a 7-point scale with “all of the time” and “not at all” being the most extreme responses. Item and domain scores are averaged to yield a total composite score between 1 and 7. Higher scores represent better quality of life [13]. The ESS is a validated 8-item questionnaire that measures subjective sleepiness. Each question was answered on a scale of 0 to 3. ESS values ranged from 0 (unlikely to fall asleep in any situation) to 24 (high chance of falling asleep in all 8 situations). Scores of 11 or greater are considered to represent an abnormal degree of daytime sleepiness [14].
A standard overnight full PSG (Sonnoscreen plus-16 channels; Somnomedics, Bellusco, MI, Italy) was performed in our hospital and included the recording of several parameters such as thoracoabdominal movements (detected using respiratory inductance plethysmography), oronasal airflow, bilateral electro-oculography, chin and tibial electromyography, electrocardiography, and the oxygen arterial blood saturation. Obstructive apnea was defined as a 90% drop in respiratory amplitude lasting at least 10 s, associated with continued or increased inspiratory effort. A hypopnoea was defined as a 30% drop of respiratory amplitude lasting 10 s, associated with repeated respiratory effort and (arousals or) oxygen saturation drops of 4%. The AHI was calculated as the number of apnoeas and hypopnoeas per hour of total sleep time. The diagnosis of OSAS was defined as an AHI greater than 5, in accordance with the American Academy of Sleep Medicine recommendations. According to the AHI, the severity of the disease was classified (mild 5–15/h, moderate 15–30/h, and severe greater than 30/h) [15]. All studies were manually reviewed by a medical doctor expert in sleep medicine not involved in the study.
Outcomes of interest were changes both in subjective outcomes by the SAQLI and ESS questionnaires and in objective PSG measurements as AHI, total sleep time (TST), oxygen desaturation index >4% (ODI4%), total duration of oxygen saturation with less than 90% (SpO2<90%), total arousal index (TAI) and sleep efficiency. All subjects gave written informed consent.
In calculating sample size, the principal outcome measure was taken to be the mean ESS score [16]. If there were to be a difference in ESS score of 2.5 (assuming that the standard deviation is 1.2 units) between those patients treated with monoblock and twinblock appliances and setting the significance level at 5% and sample power at 80%, a sample size of 38 subjects would be required.
Data are reported as means ± SD for continuous variables, while categorical variables were expressed as frequencies and percentages. Student t-tests were used to compare the means for continuous data. If the normality test failed, the Mann-Whitney U test was applied. For categorical data, the chi-square test was used. All statistical tests were performed with the MedCalc Statistical Software, v. 9.2.1.0 (MedCalc Software, Belgium) and p values of less than 0.05 were regarded as statistically significant.
Results
Of the 40 patients who met the inclusion criteria and consented to take part in this study, 38 subjects completed both treatment periods. Two subjects (5%), one belonging to the AB group and one belongs to BA group, were lost during washout periods, so a total of 38 patients were included in the final analysis. Patient demographic characteristics were similar between groups as shown in Table 1.
Overall mean score for SAQLI showed significant improvement both with monoblock appliance (p=0.024) and twinblock (p=0.023) when compared to baseline values. On the contrary, no significant difference was observed between the two MADs (p=0.639). Patients’ perceived levels of daytime sleepiness as assessed by ESS was significantly reduced after treatment with the two MADs (p=0.029 for monoblock appliance and p=0.031 for the twinblock appliance). But, also, in this case, no significant difference was observed between monoblock and twinblock treatment (9.4±1.7 vs. 9.8±2.1, p=0.574) (Table 2).
The analysis of objective PSG measurements revealed a highly significant reduction in AHI with the monoblock device from 28.5±5.7 (events/h) to 8.5±3.2 (p<0.001), as well as other indicators such as ODI4% (p<0.001), total duration with SpO2<90% (p=0.009) and TAI (p=0.044). No significant change was observed in TST and sleep efficiency as compared to baseline values. Significant reduction in AHI was also reported after the treatment with the twinblock MAD (p=0.003) as well as in ODI4% (p=0.002) and total duration with SpO2<90% (p=0.022). No significant change was observed for the others PSG parameters. When the PSG results were compared between the two MADs, AHI, ODI4% and total duration with SpO2<90% were found to be reduced in favor of the monoblock treatment (p=0.032; 0.046 and 0.043, respectively) (Table 3).
Discussion
The American Association for Sleep Medicine recommends prescribing OAs to patients with mild to moderate OSAS who prefer OA therapy to CPAP, who do not respond to or are unsuitable for or are unable to tolerate CPAP [6]. As shown in the literature, MADs are the most commonly used oral appliance in OSAS therapy [8]. The compliance rates for MAD are higher than those for CPAPs [17], and they are used on average 1.1 hours a night more than CPAPs [18]. Although MADs are more effective than other types of OAs in treating OSAS [19], it has been emphasized that the design features of the various appliances may have an impact on treatment efficacy [12], so this study aimed to evaluate the objective and subjective efficacy of a monoblock MAD and a twinblock MAD.
The results of this study showed that both MADs proved to be effective in improving objective PSG parameters. These findings are supported by other studies showing a reduction, for the MADs, in several PSG parameters such as AHI scores, arousals during sleep and oxygen desaturation when compared with placebo treatments [20,21].
Moreover, we also showed that the monoblock MAD has proven to be more efficacious than the twinblock as it reduced 4 out of 6 PSG parameters (AHI, ODI4%, total duration with SpO2<90% and TAI) whereas the twinblock only reduced 3 out of 6 (AHI, ODI4% and total duration with SpO2<90%) with also a lighter extent of improvement compared to monoblock treatment. Indeed, when the reduction in PSG parameters was compared between the two MADs, AHI, ODI4% and total duration with SpO2<90% were found to be reduced in favor of the monoblock treatment. This is in contrast to previous findings indicating no difference in any PSG indicators when a one-piece MAD was compared to a two-piece MAD [22].
The evidence for treatment efficacy on OSAS patients’ quality of life is not clear, some studies report improvements in quality of life after treatment with MADs [23,24], however, in others no effect was reported [25,26].
This study showed similar levels of improvement of patients’ quality of life for both MADs, as demonstrated by the increment in total SAQLI score from baseline. Our findings are in agreement with the results of Lam et al. [27], where 34 patients showed a significant improvement in total SAQLI scores after ten weeks of treatment with MADs. When comparing the two MADs, we have not found any difference in SAQLI score between the two devices but, in this case, a comparison of findings of the present study to other literature was not possible because there is no study that compared two MADs and utilized the SAQLI to evaluate the impact on QoL.
Excessive daytime sleepiness is experienced by many patients with OSAS. Treatment of OSAS with MADs has shown to reduce daytime sleepiness [21]. This study showed that the monoblock and the twinblock MAD both reduced ESS scores significantly, but when comparing the efficacy of the two MADs, no significant difference was found in ESS scores. Similar results have been found by other studies [22,28].
The findings of this study must be interpreted in light of some limitations. This study applied a short-term design (about six months) so it is not sufficient in length to monitor the efficacy of MAD therapy in the long-term as OSAS has been shown to deteriorate and MAD efficacy may deteriorate with long-term use. Longer follows up assessments are needed to investigate this. Moreover, improving PSG indices and subjective outcomes may depend on a variety of factors ranging from the severity of OSAS, level of advancement and patient satisfaction. It would be interesting to investigate how these factors may affect our results.
In this study, the efficacy of two differently designed MADs in the treatment of OSA was shown in terms of clinical and subjective outcomes, with a significantly better result for the monoblock MAD in comparison with the twinblock MAD. Long-term follow up assessments would be useful to confirm the continued efficacy of MAD therapy for OSAS.
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.
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Investigation of thiol/disulfide homeostasis in familial mediterranean fever patients
Gokhan Cakirca 1, Muhammet Murat Celik 2, Huseyin Erdal 3, Salim Neselioglu 4, Ozcan Erel 4, Mustafa Kemal Basarali 5, Tuba Damar Cakirca 6
1Department of Biochemistry, Sanliurfa Mehmet Akif Inan Training and Research Hospital, Sanliurfa, 2 Department of Internal Medicine, Mustafa Kemal University, Faculty of Medicine, Hatay, 3 Department of Molecular Biochemistry and Genetics, Mustafa Kemal University, Faculty of Medicine, Hatay, 4 Department of Biochemistry, Yildirim Beyazit University, Faculty of Medicine, Ankara, 5 Department of Biochemistry, Ankara Public Health Institution, Ankara, 6 Department of Infectious Diseases and Clinical Microbiology, Harran University, Faculty of Medicine, Sanliurfa, Turkey
DOI: 10.4328/JCAM.5789 Received: 26.02.2018 Accepted: 11.03.2018 Published Online: 13.03.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 231-4
Corresponding Author: Gokhan Cakirca, Biochemistry Department, Sanliurfa Mehmet Akif Inan Training and Research Hospital, Sanliurfa, Turkey. T.: +90 4143186000 F.: +90 4143186707 E-Mail: cakirca.gokhan@gmail.com ORCID ID: 0000-0003-1526-5899
Aim: To determine the thiol/disulfide homeostasis in patients with familial Mediterranean fever (FMF) and its correlation with the levels of inflammatory markers consisting of white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fibrinogen.
Material and Method: This study was performed in the internal Medicine department of Mustafa Kemal University Hospital in Turkey. A total of 27 FMF patients in the attack period (AP), 33 FMF patients in the attack-free period (AFP), and 36 healthy controls participated in this study. Thiol/disulfide profile parameters were detected using the novel method of Erel and Neselioglu.
Results: Total and native thiol levels of the FMF-AP group were markedly lower than those of healthy controls, while the difference in disulfide level was not statistically significant. Thiol/disulfide levels in the FMF-AFP group were similar to the levels in both the FMF-AP group and healthy controls. Correlation analysis showed a negative correlation between fibrinogen levels and total and native thiol levels, while there was a positive correlation between white blood cell count and disulfide levels in the FMF-AP group.
Discussion: The findings suggest that decreased concentrations of total and native thiol in patients with FMF-AP are likely to be an outcome of inflammation-induced oxidative stress.
Keywords: Familial Mediterranean Fever; Thiol; Disulfide; Oxidative Stress; Inflammation
Introduction
Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease characterized by periodic attacks of fever with serositis, synovitis, and skin rash. This disease is commonly observed in Jewish, Armenian, Arab, and Turkish societies [1,2]. Although the etiopathogenesis of FMF is not fully understood, Mediterranean Fever (MEFV) gene mutation is known to have an important role. The MEVF gene encodes the pyrin/marenostrin protein. The mutation of MEVF in FMF causes the loss of pyrin function, which results in excessive production of interleukin-1β and dysregulation of leukocyte apoptosis that leads to uncontrolled inflammation [3,4]. During the inflammation process, excessive free radical production occurs [5]. Oxidative stress (OS) caused by impaired balance between free radicals and antioxidants has been reported to increase in patients with FMF [6-8]. Thiols are biologically important organic compounds that include the sulfhydryl group. Thiols can be converted to reversible disulfide bonds through oxidation by reactive oxygen species (ROS), after which disulfides can be converted into thiols by reducing agents [9]. Thiol/disulfide redox state is important for the activity and stability of proteins, apoptosis, and as a defense mechanism against ROS [10,11]. Altered thiol/disulfide balance has been found to be associated with the etiopathogenesis of a variety of diseases [12-14].
Until recently, there were no methods available for colorimetrically measuring the thiol-disulfide balance [15]. Today, thiol and disulfide levels can be analyzed with the novel colorimetric method of Erel and Neselioglu [16].
Hence, we investigated the thiol/disulfide homeostasis in FMF patients, besides its correlation with the levels of inflammatory markers including white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen.
Material and Method
In this cross-sectional study, a total of 60 FMF patients diagnosed in accordance with the Tel-Hashomer Criteria [17] and 36 healthy controls were enrolled. FMF patients were divided into two groups as 33 patients during attack-free periods (AFP) and 27 patients during attack period (AP). Diagnosis of attack period was based on the presence of clinical findings such as fever, serositis/arthritis, and skin rash and elevated inflammatory markers. Demographic features and laboratory results of all three groups were recorded. Patients with obesity, diabetes, kidney and liver failure, hematologic diseases, or any malignancy, as well as pediatric patients, pregnant patients, and cigarette/alcohol/drug users were excluded from this study. The local ethics committee has approved the protocol of this study.
Sample collection and analysis
Blood samples for measuring thiol/disulfide homeostasis tests were collected from patients and healthy controls after an 8 to 12 hour fasting period. All blood samples were quickly centrifuged at 1500g for 10 min. The serum samples were then immediately stored at −78°C until assayed. Then, thiol/disulfide profile parameters were analyzed with the novel colorimetric method of Erel and Neselioglu. Also, the (disulfide x100)/native thiol, the (disulfide x100)/total thiol, and (native thiol x100)/total thiol ratios were calculated [16]. The CRP, ESR, fibrinogen levels, and WBC counts were immediately tested using classical methods.
Statistical Analysis
Data analysis was performed using SPSS 22 (SPSS Inc., Chicago, IL, USA). Data normality was examined with the Shapiro-Wilk test. Qualitative data were evaluated using χ² test, while quantitative data were tested using the Kruskal-Wallis and Mann-Whitney U tests. Correlation analysis was evaluated with Spearman test. Data were expressed as mean ± SD or number (%) or median (min–max). P<0.05 was accepted as statistically significant.
Results
The study included 27 (10F, 17M) FM-AP patients, 33 (12F, 21M) FMF-AFP patients, and 36 (14F, 22M) healthy controls. Mean ages were 30.9±10.2 years [median 30 (18–58)] in the FMF-AP patients, 29.9±9.7 years [median 28 (18–51)] in the FMF-AFP patients, and 30.9±10.7 years [median 28 (17–55)] in the healthy controls.There was no marked difference in terms of age and gender distribution among the three groups. Demographic characteristics of the FMF patients are shown in Table1.
Laboratory results of the two FMF groups and the healthy controls are presented in Table 2. The total and native thiol concentrations of the FMF-AP group were significantly lower than those of healthy controls (p=0.016; p=0.003, respectively), (Figures 1 and 2). However, no significant difference was determined regarding disulphide levels and the ratios of thiol/disulphide homeostasis parameters. Thiol/disulfide profile parameters in the FMF-AFP group were similar to the levels in both the FMF-AP group and healthy controls.
The WBC count, CRP, fibrinogen, and ESR levels were markedly higher in the FMF-AP compared to those in the FMF-AFP group (Table 2).
We also evaluated the correlation of the thiol/disulfide profile parameters with the inflammatory markers in the FMF groups. In the FMF-AP group, total and native thiol concentrations were correlated negatively with fibrinogen (r=-0.457, p=0.028 and r=-0.440, p=0.035, respectively), while disulfide levels were correlated positively with WBC count (r=0.449, p=0.028). In the FMF-AFP group, no significant correlations were identified between thiol/disulfide profile parameters and inflammatory markers.
Discussion
FMF is an autoinflammatory disease characterized by periods of exacerbation and remission. During periods of attack, a high level of inflammation with elevated levels of pro-inflammatory cytokines and increased acute phase reactants is observed in FMF patients [18,19]. Subclinical inflammation may continue during the attack-free period that occurs in the intervals between acute attacks [20].
During inflammation, the OS resulting from the excessive production of free radicals and/or reduced antioxidant defense mechanisms may lead to lipid, protein, and nucleic acid damage in the organism [21]. Lipid peroxidation (e.g., conjugated diene and malondialdehyde), protein oxidation (e.g., protein carbonyl), and DNA oxidation markers are used to identify oxidative damage [6,21]. Therefore, these markers are measured to examine the role of OS in the etiopathogenesis of many diseases, including FMF [6,8,22]. Kirkali et al. studied 17 FMF patients and showed marked accumulation of cytotoxic and mutagenic DNA lesions due to overproduction of ROS in polymorph nuclear leukocytes of FMF patients compared to controls [22]. In another study, Ediz et al. found that the protein carbonyl and malondialdehyde levels were significantly higher, and that antioxidant markers, including catalase and glutathione peroxidase levels, were markedly lower in the FMF-AP group compared with healthy controls [8]. Guzel et al. similarly reported high levels of protein carbonyl and conjugated diene, as well as low glutathione peroxidase activity, in FMF patients [6]. These results indicate that FMF is associated with increased OS.
Thiol plays a critical role in the neutralization of reactive oxygen molecules. Thiol-disulfide exchange occurs in case of ROS exposure [9]. Therefore, thiol and disulfide levels may indirectly indicate OS levels. One study reported that total thiol level was markedly higher in the FMF-AFP group compared to healthy controls. However, we could not reach any information about the relationship between high thiol levels and protective or compensatory mechanisms [23]. Guzel et al. reported that thiol levels were similar between FMF patients and controls [6]. In contrast, Omma et al. reported that total and native thiol concentrations were lower, while disulfide concentrations were higher in the FMF-AP group compared to the healthy controls [14]. Similarly, we determined that total and native thiol concentrations of FMF-AP group were significantly lower than those of healthy controls. On the other hand, disulfide concentrations were higher in FMF-AP group but there was no statistical difference. Low thiol levels are expected, since FMF is associated with OS. Thiol groups may play a role in the defense mechanism against OS in the FMF patients, especially during the attack period. Therefore, decreased thiol concentrations may be an indicator of OS in patients with FMF-AP.
In previous studies, increased levels of CRP, ESR, and fibrinogen were detected in the patients with FMF-AP compared to the FMF-AFP group [6,24]. Similarly, we found that CRP, ESR, fibrinogen levels, and WBC count were markedly higher in the FMF-AP group. In the FMF-AP group, fibrinogen levels were found to be negatively correlated with both total thiol and native thiol, and a positive correlation was observed between the WBC count and disulfide. In a recent study, Omma et al. found that CRP and ESR levels in FMF patients correlated negatively with total and native thiol, and positively with disulfide [14].These results indicate that thiol and disulfide levels may be linked to inflammation.
Colchicine is the principal therapy for FMF patients; it suppresses inflammation by reducing release of IL-1β, which is involved in the inflammatory process [25]. In our study, all patients received colchicine. Therefore, the effects of colchicine should be investigated by future studies that include newly-diagnosed FMF patients who are not using this medication.
Limitations
Firstly, this is a cross-sectional study of thiol and disulfide levels in FMF patients. The parameters should also be assessed during the attack and attack-free periods of the same patients. Secondly, this study was carried out at a single center and with a small sample size.
Conclusions
As a conclusion, decreased concentrations of total and native thiol in patients with FMF-AP are likely to be an outcome of inflammation-induced OS. However, to understand the importance of thiol/disulfide balance in FMF patients, it will be necessary to conduct studies with larger sample sizes.
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.
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Cakirca G, Celik MM, Erdal H, Neselioglu S, Erel O, Basarali MK, Cakirca TD. Investigation of thiol/disulfide homeostasis in familial mediterranean fever patients. J Clin Anal Med 2018;9(3): 231-4.
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A case of brainstem encephalitis treated with plasmapheresis
Nagehan Aslan 1, Didar Arslan 1, Dinçer Yıldızdaş 1, Emine Kocabaş 2, Özden Özgür Horoz 1, Özlem Hergüner 3, Derya Alabaz 2, Özlem Özgür Gündeşlioğlu 2
1 Çocuk Yoğun Bakım Bilim Dalı, 2 Çocuk Enfeksiyon Bilim Dalı, 3 Çocuk Nöroloji Bilim Dalı, Çukurova Üniversitesi Tıp Fakültesi, Adana, Türkiye
DOI: 10.4328/JCAM.5390 Received: 26.09.2017 Accepted: 27.11.2017 Publihed Online: 27.11.2017 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 235-8
Corresponding Author: Nagehan Aslan, Çocuk Yoğun Bakım Bilim Dalı, Çukurova Üniversitesi Tıp Fakültesi, Sarıçam, Adana, Türkiye. GSM: +905055499986 E-Mail: nagehan_aslan@hotmail.com
Brain stem encephalitis is a rare disease, which can be triggered by infection, with an unclear etiology, in which infectious and autoimmune mechanisms are thought to play a role in the pathogenesis [1]. Major clinical symptoms are ataxia, muscle weakness and ocular and bulbar dysfunction [2]. Its etiology can vary from infection to autoimmune reasons. Listeria, enterovirus type 71 and Herpes simplex virus are the most common infectious causes. It may also be caused by neurobehcets, Bickerstaff’s encephalitis, autoimmune diseases such as multiple sclerosis and paraneoplastic reasons [3-5]. With those in mind, the underlying etiology is unclear in most cases [2]. Treatment is based on etiology. Immunosuppressive treatment can be tried in brain stem encephalitis patients whose etiology can not be made clear [6]. In this case report, we present a case of brainstem encephalitis which did not respond to the present treatment and was treated with plasmapheresis.
Keywords: Brain Stem Encephalitis; Plasmapheresis
Case Report
The otherwise healthy 16-year-old girl was admitted to an outer center with fever, vomiting, and diarrhea seven days ago. Antibiotherapy and supportive therapies were given to the patient. There were no characteristics in the history of the patient who applied to our hospital due to headache, double vision and unbalanced gait joined her list of complaints. On physical examination, consciousness was present, Glasgow coma score was (GCS): 15, body temperature was: 38.9 ºC, nuchal stiffness, left eye outward gaze restriction and bilateral papillary stasis was present, deep tendon reflexes were normoactive, muscle strength in lower and upper extremities were 5/5, and there was no pathological reflex. Laboratory studies showed, WBC: 11000 / mm3, Hb: 13,6 gr / dL, platelet count: 424,000 / mm3, erythrocyte sedimentation rate (ESR): 3 mm / h, procalcitonin: 0.089 ng / mL, renal and liver functions normal, serum sodium: 132 mg / dL, potassium: 3.9 mg / dL. Contrast-enhanced brain magnetic resonance imaging (MRI) revealed findings consistent with leptomeningeal involvement and pathological signal enhancement at the brainstem level (Figure 1). The patient was admitted to pediatric infection service with an initial diagnosis of meningitis, encephalitis, and a lumbar puncture was done. Lumbar puncture results were as follows: Cerebrospinal fluid (CSF) protein: 258 mg / dL, glucose: 37 mg / dL, concurrent blood glucose: 95 mg / dL, CSF pressure: 47 cmH2O. Treatment with ceftriaxone, vancomycin, and acyclovir was started in patients with abundant lymphocytes presenting direct examination on CSF. Ethiologic examinations included: Serum salmonella, brusella, measles, varicella, mumps, borrelia, chlamydia, mycoplasma, Ebstein-Barr virus, toxoplasmosis, cytomegalovirus serologies, which all came back negative; ANA, Anti-DNA and otoimmune panel were negative; complement C3, C4 immunoglobulin, and immunodeficiency panel were in normal range by age; antithyroglobulin antibodies and antimicrosomal antibodies were negative for Hashimoto’s encephalitis; thyroid function tests were normal; lactic acid and pyruvic acid for methabolic disease were normal; CSF was negative for tuberculosis PCR, ARB, MGIT, Herpes PCR and brucella; no growth was observed in blood, urine and CSF cultures. ARB and MGIT in the fasting stomach fluid were negative, tuberculin skin test was anergic, and Quantiferon assay was unspecified. The patient was transferred to our child intensive care unit on the 10th day of treatment with generalized tonic-clonic seizures, developed speech difficulty and neurologically worsening condition. Intravenous levetiracetam was loaded and continued with the maintenance dose. EEG showed no active epileptic activity, but a mild base arrhythmia was present. Patients physical examination results were; blood pressure: 100/70 mmHg, heart rate: 120/min, neurological examination results were; Glasgow coma scale: 10, deep tendon reflexes not present, muscle strength was 3/5 on the upper and lower extremities, bilateral papillae stasis and bilateral abducens paralysis was present and gag reflex was poor. There was no hemorrhage or edema in the immediate non-contrast brain tomography. Cerebral salt wasting was considered in the patient with a serum sodium of 120 mg / dL, urine sodium of 263 mg / dL, urine density of 1017, urine osmolarity of 600 mOsm / liter, serum osmolarity of 256 mOsm / liter and urine output of 8 mL/kg. The patient was supplemented with 3% hypertonic saline solution. When the response to the fluid treatment was not sufficient, fludrocortisone was added to the treatment. On the fourth day of intensive care unit admission, the patient was intubated, and invasive mechanical ventilation was performed with neurologically worsening condition with right central facial paralysis, 6th, 7th, 9th, and 10th cranial nerve involvement and gag, and airway reflexes were not present. In repeated contrast cranial MRI, supratentorial and infratentorial leptomeningeal contrast enhancement around the basal cistern, and a slight increase in the ventricular system width compared to the previous MRI were detected. Passive physical therapy exercises were started to the patient whose electromyographic examination revealed sensory nerve conduction to be normal, motor nerve conduction to be normal at the upper body half, a bilateral lower fibular nerve neuropathy and a drop foot. The patient regained consciousness but was quadri-paralysed and had ophthalmoplegia, lateral gaze palsy, areflexia and no gag reflex. The patient could not pass the spontaneous breathing trials and could not tolerate extubation. With the clinical and radiological findings, brain stem encephalitis was suspected in the patient. The patient was given 2 g / kg IVIG over four days. In the absence of clinical improvement, the patient underwent plasmapheresis. Plasmapheresis was performed in a pediatric intensive care unit with the Spectra Optia® (Terumo BCT, Lakewood, CO) apheresis device with a 12 Fr hemodialysis catheter placed in the internal jugular vein for five days in a row and 2 sessions on alternate days. The patient’s total blood volume was 3951 mL, total plasma volume was 2906 mL. Fresh frozen plasma was used as replica liquid in all treatments. Anticoagulation was achieved with ACD-A (Acid Citrate Dextrose-formulas) alone. A mean of 4219 mL (min:2270 mL–max:5109 mL) of blood was processed in the procedures, with an average of 2532 mL (min:1328 mL – max:3184 mL) replicates (Replacement per kilogram: average 42 mL / kg, min: 22 mL / kg-max: 52 mL / kg). The mean total blood flow rate was 45.2 mL / min (min:35 mL/minutes–max:50 mL/minutes). Processes lasted an average of 95.2 min (min: 54 min-max: 112 min). In all procedures, intravenous calcium replacement was performed at a dose appropriate to the patient’s body weight. In one procedure, the patient developed severe urticaria. The patient was administered antihistamines, but the procedure was terminated because there was no regression in the symptoms.
Control post-treatment cranial MRI showed leptomeningeal contrast enhancement and hydrocephalic regression. At the follow-up, the mechanical ventilator support was reduced, and the patient was excused. The patient was transferred to the clinic during the third week of intensive care. The patient was discharged on the 32nd day of hospitalization. There was a regression in the present findings in MRI taken at two months after treatment (Figure-2).
Discussion
Brainstem encephalitis is a rare clinical entity. Infection, autoimmune diseases, and paraneoplastic syndromes play a role in its etiology. With Listeria, enterovirus type 71, herpes simplex virus on top, trigger infections include; cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, measles virus, Brucella, salmonella, tuberculosis, aspergillosis, Borrelia, mycoplasma and Campylobacter jejuni. Neurobehçet’s disease, neurosarcoidosis, Bickerstaff’s encephalitis, Hashimoto’s encephalitis, Susac’s syndrome, Multiple sclerosis, systemic lupus erythematosus, and polychondritis are among autoimmune diseases associated with brain stem encephalitis [3]. In the case of Bickerstaff’s encephalitis, serum anti-GQ1b antibodies are generally positive, but negativity does not exclude the diagnosis [7]. In our case, the anti-GQ1b antibody level could not be studied. Another etiology, paraneoplastic syndromes, is frequently associated with anti-Yo, anti-Tr, anti-Hu, and anti-Ma antibodies. However, in most cases, no etiology can be detected as it is in our case [6].
In most cases, there is a respiratory or gastrointestinal system complaint about 7-10 days before the development of brainstem dysfunction [1]. In our case, a history of vomiting, complaints of diarrhea and treatment in an external center a week ago was present. Approximately 75% of patients have cranial nerve involvement. Cerebellar ataxia is more frequent in infectious and paraneoplastic etiologic brain stem encephalitis cases [8]. Ataxia was the presenting symptom in our case, and 6th, 7th, 9th and 10th cranial nerve involvement has developed in the follow-up.
For the etiologic diagnosis, MRI is very important. The most common MRI findings are increased signal in the pons, medulla oblongata and cerebellum on T2 weighted and FLAIR MRI sections. Although there are mainly infratentorial lesions in Listeria infection and Behçet’s disease, both infratentorial and supratentorial involvement are present in multiple sclerosis [6,9]. MRI is normal in cases of paraneoplastic etiologic brainstem encephalitis. There was both infratentorial and supratentorial involvement around the basal cistern at the time of MRI. With these radiological findings, autoimmune ground brainstem encephalitis was considered in our patient. In addition to diagnosis, MRI is also used for treatment response and clinical follow-up.
Serological and immunologic tests for infectious, autoimmune, and paraneoplastic causes, as well as brain biopsy, can be used for diagnosis [10]. Tan et al. in their study of 81 brainstem encephalitis patients between 1.5 and 72 years of age, 14 of the patients were diagnosed with brain biopsy. Biopsies were made of the brain stem, cerebellum, cerebellum, and thalamus. Only one patient developed dysarthria after brain biopsy, and no mortality associated with brain biopsy was reported [2]. We did not perform brain biopsy in our case.
The treatment is planned according to etiology. Appropriate antimicrobial therapy is used in the treatment of the infectious group. Because Listeria and herpes simplex virus are the most frequently treatable infectious agents, empirical treatment of ampicillin and acyclovir is generally initiated. In the autoimmune group, corticosteroids are used as first-line treatment. Plasmapheresis, intravenous immunoglobulin, cyclophosphamide, mycophenolate mofetil are used as second-line immunotherapies in patients with inadequate response to steroids [2,11]. Study of Tan et al. have shown that brainstem encephalitis with undetectable etiology is highly likely to have an autoimmune base and that this group has benefited strongly from immunosuppressive therapies. Empirically, immunotherapy is recommended in patients with brainstem encephalitis with undefined etiology and who have no spontaneous regression or progression with clinical and radiological progression [2]. Prytula et al. reported good clinical results in five patients with plasmapheresis in a series composed of 8 patients diagnosed with transverse myelitis, Bickerstaff brainstem encephalitis, paraneoplastic encephalitis, unidentified etiology encephalitis and neuromyelitis optica, age between 2-12, and the effectiveness of plasmapheresis has been noted in autoimmune-mediated central nervous system diseases [12]. Odaka et al. reported that they used steroids, IVIG and plasmapheresis alone or combined in treatment in a series of 62 Bickerstaff brachial encephalitis aged between 3 and 91 years [13]. In our case, IVIG treatment for four days with 2 gr/kg, followed by 7 sessions of plasmapheresis resulted in uneventful recovery. In our case, the etiology could not be determined, and the case which did not resolve with IVIG treatment was treated with plasmapheresis.
The cerebral salt loss is one of the most common causes of hypovolemic hyponatremia. It can be seen in the course of head trauma, intracranial infections, and masses. It is a transient phenomenon that generally improves within three weeks [13]. Proper fluid and fludrocortisone are used in treatment. Fludrocortisone acts directly on the renal tubules to reduce sodium excretion, thus avoiding negative salt balance [14]. In our case, the patient was admitted to pediatric intensive care unit, and hypertonic liquid and fludrocortisone treatment were applied, after hyponatremic convulsion due to cerebral salt loss. In our PubMed-based literature review, Vega et al. reported a 52-year-old woman with cerebral salt loss due to Listeria rhombencephalitis, but we could not find a case of brainstem encephalitis and cerebral salt loss associated with pediatric age group [15].
In conclusion, plasmapheresis therapy should be kept in mind in cases of pediatric patients with brain stem encephalitis which does not respond to current treatments.
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
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9. Wasenko JJ, Park BJ, Jubelt B, Lieberman KA, Swarnkar A, Joy SE, et al. Magnetic resonance imaging of mesenrhombencephalitis. J Clin Image. 2002; 26: 237–42.
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15. Vega J, Matamala G. Cerebral salt wasting syndrome associated with Listeria monocytogenes encephalitis. Report of one case. Rev Med Chil. 2013; 141(1): 104-8.
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Aslan N, Arslan D, Yıldızdaş D, Kocabaş E, Horoz ÖÖ, Hergüner Ö, Alabaz D, Gündeşlioğlu ÖÖ. A case of brainstem encephalitis treated with plasmapheresis. J Clin Anal Med 2018;9(3): 235-8.
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Bilateral cortical blindness after recurrent ischemic stroke
Murat Uysal 1, Serhat Karaman 2
1 Department of Anatomy, 2 Department of Emergency Medicine, Gaziosmanpasa University, Faculty of Medicine, Tokat, Turkey
DOI: 10.4328/JCAM.5516 Received: 18.12.2017 Accepted: 08.01.2018 Publihed Online: 10.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 239-41
Corresponding Author: Serhat Karaman, Department of Emergency Medicine, Gaziosmanpasa University, Tokat, Turkey. T.: +90 3562149444 F.: +90 3562133179 E-Mail: drserhatkaraman@hotmail.com
Cerebrovascular diseases, which are the third most common cause of death after cardiovascular diseases and cancer, represents an enormous public health burden. Visual loss caused by geniculocalcarine visual pathways are named cortical blindness. The causes of cortical blindness include head trauma, episodes of hypoglycemia or hypotension, cardiac arrest, stroke, tumor and occipital lobe epilepsy. We present a case of right occipital cortex with encephalomalacic change after a previous ischemic stroke and total cortical blindness with a newly developing ischemic stroke in the left occipital cortex.
Keywords: Cerebrovascular Disease; Bilateral Cortical Blindness; Stroke
Introduction
Acute bilateral blindness is a clinical condition which is rare and usually results from cortical causes. It is very difficult to put the diagnosis of the condition for a physician. Acute bilateral blindness can be an early sign of a disease that might be life-threatening [1]. Visual loss due to geniculocalcarine visual pathways is named cortical or cerebellar blindness. Total cortical blindness is observed much less than partial cortical blindness [2]. Acute bilateral blindness might manifest itself in life-threatening conditions such as pulmonary embolism, encephalitis, and methanol toxicity. Besides the rare occurrence of acute bilateral blindness, urgent diagnosis and treatment of the condition should be done in a short time [3]. We wanted to share the case applied to the emergency department with total bilateral blindness after the recurrent ischemic stroke involving occipital lobes only.
Case report
A 56-year-old female patient was admitted to our emergency department with a complaint of newly-emerging complete loss of vision. We have learned that the patient had an ischemic cerebrovascular disease a year ago. There was no symptom of lateralization on the physical examination. Blood pressure was 140/80 mmHg, and pulse was 86/min. There was atrial fibrillation observed on the electrocardiography (ECG). On the patient’s visual examination, it was seen that there was a complete loss of vision and the funduscopy was normal (Figure 1). Computed tomography (CT) of the patient revealed an encephalomalacia in the right occipital lobe and reduction in density that may suggest acute infarction in the left occipital lobe (Figure 2). On the other hand, in the diffusional magnetic resonance imaging (MRI), a diffusional restriction was seen in the medial segment of left occipital lobe compatible with acute infarction (Figure 3). Encephalomalacia was noticed in the right occipital lobe in the brain CT scan taken after the first ischemic stroke a year earlier found in the patient’s archival records (Figure 4). When the images were examined, it was found that total bilateral blindness developed because of the effect of the first ischemic stroke on the right visual field and the newly developed ischemic stroke on the left visual field. We have started antiaggregant and aspirin treatment and hospitalized the patient. Bilateral carotid Doppler ultrasonography (USG) was done one day after hospitalization showed millimetric calcific plaques that did not lead to internal carotid artery (ICA) flow velocity from the right common carotid artery (CCA) at the bifurcation level. Bilateral CCA, ICA and external carotid artery (ECA) flow patterns and velocities were monitored as normal. Bilateral vertebral arteries in vertebral artery Doppler USG examination were monitored as clear, and it has been found that the flow rates are decreasing on both sides, the decrease is even more on the left. The right flow volume was 70 ml/min, left was 40 ml/min, and the total was 110 ml/min, and they were observed to decrease.
Discussion
Systemic diseases, infections, syncope, arrhythmia, intoxications and cerebrovascular conditions should be carefully reviewed in the case of patients who had been referred to emergency services with similar complaints. We found related cases with cortical loss of vision, which occurred after few and different etiologies in the literature review. Khan et al. [4] reported bilateral visual loss resulted from systemic lupus erythematosus in a young female patient. In another case report, in an 84-year-old female patient with cardiomegaly and arrhythmia pulmonary embolism was detected. Her cranial imaging was interpreted as normal and acute bilateral blindness was detected in the case [1]. Also, there is a case of cortical visual loss in a 42-year-old female patient which is found to be due to reversible posterior leukoencephalopathy syndrome [5]. In the literature, cortical blindness and transient cortical blindness have also been reported which developed after coronary angiography intervention or cardiopulmonary resuscitation [6,7]. What distinguished our case from other cases is that the onset of the stroke affected the right visual field a year ago and newly developed stroke affected the left visual field which resulted in cortical bilateral total vision loss.
A detailed eye examination should be performed after reviewing the vital signs and stabilizing the conditions of patients referred with a visual loss [1]. If pupillary light responses and funduscopy are normal, ocular etiologies are effectively ruled out. Conversely, if pupillary reflexes and/or funduscopy are abnormal, an ocular-related cause of blindness is present [8]. Cranial imaging was requested when no pathology was detected other than the visual loss in our detailed eye examination. Emergency physicians should focus on the identification of life-threatening diseases by reviewing the ocular, psychogenic, and cortical etiologies in patients with vision loss. The distinction of ocular, cortical and functional causes of visual loss is of therapeutic importance. Early diagnosis and appropriate consultation will provide a good chance for the patient to see.
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
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7. Terlecki M, Wojciechowska W, Rajzer M, Jurczyszyn A, Bazan-Socha S, Bryniarski L, et al. Transient cortical blindness after coronary artery angiography. Postepy Kardiol Interwencyjnej. 2013; 9(1):105-8.
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Uysal M, Karaman S. Bilateral cortical blindness after recurrent ischemic stroke. J Clin Anal Med 2018;9(3): 239-41.
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Successful treatment with home care in a second-half twin pregnancy complicated with a too short cervix: a case report
Tahereh Zahedifard 1, Mohammad Zarei 2, Reza Nori 3
1 Department of Midwifery, Quchan Branch, Islamic Azad University, Quchan, 2 Nursing Department, Shirvan Center of Higher Health Education, North Khorasan University of Medical Sciences, Bojnurd, 3 Department of Nursing, Bojnurd Branch, Islamic Azad University, Bojnurd, Iran
DOI: 10.4328/JCAM.5634 Received: 22.12.2017 Accepted: 05.01.2018 Publihed Online: 07.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 242-4
Corresponding Author: Mohammad Zarei, Nursing Department, Shirvan Center of Higher Health Education, North Khorasan University of Medical Sciences, Bojnurd, Iran. GSM: +989151811304 T./F.: +985836248988 E-Mail: m.zarei@nkums.ac.ir
A 34-year-old primiparous female patient with twin pregnancy presented in the 26th week of pregnancy with a cervical length of 11 mm, with prolapse of membranes. The patient received a special kind of bed rest and supportive proceedings and the pregnancy completed successfully at 36 weeks and 5 days. In the second half of pregnancy, due to the risk of emergency cerclage, expectant management seems an appropriate and safe approach.
Keywords: Pregnancy; Cervix Disorders; Homecare
Introduction
Twin pregnancies have increased significantly in the past decade, mostly due to the use of assisted reproductive techniques. Twin pregnancies are associated with the risk of premature delivery. Almost half of those with a twin pregnancy give birth before 37 weeks of pregnancy. The rate is seven times greater than for single pregnancy delivery. The main cause of increased complications of preterm birth and neonatal mortality in twin pregnancies are the long-term morbidity associated with preterm delivery, respiratory distress, and infection in the neonatal period [1].
Incompetent cervix is a risk factor for preterm delivery that can be detected by dilatation of the cervix, with no pain, and prolapsed of membranes into the vagina in the second or third trimester of pregnancy. Cerclage is the surgical treatment of cervical insufficiency. Bleeding, uterine contractions, rupture of membranes and cervical dilatation of more than 4 cm are contraindications for cerclage. When the gestational age is greater, the possibility for surgery to trigger preterm labor is increased. Usually, after 23 weeks of pregnancy, cerclage should be avoided [2].
Skupski et al. (2014) suggest that cerclage treatment for incompetent cervix in the second half of pregnancy is inferior to bed rest, which allows a significant increase of the gestational age and reduces the risk of preterm birth and its complication [3]. Although it is believed that there is an association between maternal physical activity and risk of preterm labor, there is no evidence that bed rest is not useful for the patients. The purpose of this report is to present a case of second-half twin pregnancy with very short cervical pregnancy, which ended successfully with a particular kind of rest at home.
Case Report
A 34-year-old primiparous female referred to us for the first time after a positive pregnancy test. After the ultrasound at 9 weeks, it became clear that the current twin pregnancy was dizygotic. Due to the high risk of preterm delivery and inadequate cervical length, she was recommended to perform an ultrasound examination of cervical length in week 14 of pregnancy. Ultrasonography done at this time reported the pregnancy of 14 weeks and a cervical length 47 mm. At the next ultrasonography, at 22 weeks pregnancy, cervical length was 26 mm. The patient was advised to prevent preterm birth and perform cerclage. However, she refused the surgical procedure.
At the request of the patient, ultrasonography study of cervical length in the 26th week was conducted, which reported at the gestational age of 26 weeks and 3 days and the cervical length of 11 mm, with cervical herniation into the amniotic sac. According to the patient’s educational status, it was explained that cerclage, at this stage of pregnancy, should not be performed and should just relax at home.
We proposed her administration of heparin, to avoid the risks of thromboembolism, yet the patient refused. Therefore, the patient was trained about the effects and risks of thromboembolism. We advised to repeatedly massage her feet, hands, body, and rest in the Trendelenburg position and move in the crawling form (all-fours) inside the house. She could be in the standing position to go to the restroom only once a day. We also trained her to avoid constipation so that less pressure would be exerted on the cervix during a bowel movement. The patient’s weight and blood pressure were checked, and the fetal heart rate monitoring and uterine height were done at her home. To avoid depression and boredom and to have a good mood, the patient was given education about her companion and family in the neonatal period.
Two doses of intramuscular Betamethasone were given for assistance off lung maturity, at 24 hours interval, at 28 weeks of pregnancy. With this protocol of home rest, pregnancy progressed to 36 weeks and 4 days. Finally, the patient returned to the hospital with the rapture of the amniotic sac. On examination, it was reported a 4-cm dilation, and effacement of 70% with breech member presentation and the patient was prepared for a cesarean. Two baby boys with Apgar score of 9, were born healthy and without the need for neonatal intensive care. The mother and baby were discharged after a visit by a neonatologist to ensure their health. At follow up, both mother and baby were in good health and reported no problems.
Discussion
The cervical length reduction speed of twin pregnancies are greater than the singleton pregnancies. In our case, there was a higher rate of cervical length reduction, of about 3 mm per week, which arrived at 11mm at the end of the 26th week.
If a patient is diagnosed with uterine cervical incompetence and risk of preterm labor, there are two approaches available, like therapeutic cerclage and bed rest. Skupski et al. (2014), in their study, concluded that for very short cervix, in the second half of pregnancy, cerclage is better than bed rest [3]. Crowther et al. (2010) suggest that there is no sufficient evidence to say that bed rest, for prevention of preterm birth in twins, is effective. Although it does not reduce mortality and perinatal mortality, it canbe improve fetal growth [4]. In other studies, Galanaud et al. (2015) reported that the bed rest has long been associated with increased risk of thromboembolism [5]. However, in our patient, because the patient was advised every day in subsequence, for legs, hands and body massage, the risk was reduced. Also, considering that the patient was without uterine contractions, we advised her to go home and move on-all-fours position. This position is better than standing because according to the force of gravity, the weight of the uterus and its contents do not enter the cervix and the patient can move freely in the home. Therefore, several of the complications of bed rest, such as thromboembolism, fatigue, and muscular atrophy, are reduced [6]. This position can be used for patients who do not have contractions and only have an incompetent cervix.
Geoffrey et al. (1997) suggest that standing positions, in women with an insufficient cervix, cause dilatation of the cervix and prolapse of membranes further into the cervical canal. However, on women with a normal cervix, it had no effect [7]. Another issue they analyzed was that the patient was advised to rest on the ground, not on the bed, because the patient did not have to stand to move from the bed and, therefore, less pressure would be exerted on the cervix. Saccone et al. (2015) suggested that cerclage should not be performed very frequently in twin pregnancies with short cervical length in the second half, and any recommendation to do so requires more clinical trials [8].
Conclusion
Despite numerous studies on the management of cervical disease, there is still disagreement about the best treatment, based on the patient’s condition and physician order. However, in advanced stages of pregnancy, older age, according to emergency cerclage risks, including increasing the risk of infection and loss of pregnancy, it seems that expectant treatment including bed rest, keeping a Trendelenburg position at rest, moving around on all-fours, massage of foot and body, to reduce the risk of thromboembolism, and administration of corticosteroids for fetal lung maturity and antibiotics, if required, represents an appropriate and safe solution.
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. Yazdani SH, Zynalzade M, Bozari Z, Habibi S, Moradi M. The effect of cervical cerclage on prevention of preterm labor in twin pregnancy. Iran J Obstet Gynecol Infertil. 2013; 16(62): 6-10. Persian.
2. Cunningham, Leveno K, Bloom S. Williams Obstetrics. 24th ed. Newyork: Mc Graw Hill co; 2014.
3. Skupski DW, Lin SN, Reiss J, Eglinton GS. Extremely short cervix in the second trimester: bed rest or modified Shirodkar cerclage. J Perinat Med. 2014; 42(1): 55-9.
4. Crowther CA, Han S. Hospitalisation and bed rest for multiple pregnancy. Cochrane Database Syst Rev. 2010; 7(7): CD000110.
5. Drife J. Deep venous thrombosis and pulmonary embolism in obese women. Best Pract Res Clin Obstet Gynaecol. 2015; 29(3): 365-76.
6. Maloni JA. Antepartum bed rest for pregnancy complications: efficacy and safety for preventing preterm birth. Biol Res Nurs. 2010; 12(2): 106-24.
7. Wong G1, Levine D, Ludmir J. Maternal postural challenge as a functional test for cervical incompetence. J Ultrasound Med. 1997; 16(3): 169-75.
8. Saccone G, Rust O, Althuisius S, Roman A, Berghella V. Cerclage for short cervix in twin pregnancies: systematic review and meta-analysis of randomized trials using individual patient-level data. Acta Obstet Gynecol Scand. 2015; 94(4): 352-8.
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Zahedifard T, Zarei M, Nori R. Successful treatment with home care in a second-half twin pregnancy complicated with a too short cervix: a case report. J Clin Anal Med 2018;9(3): 242-4.
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A rare cause in the differential diagnosis of abdominal pain: stercoral colitis
Cihan Bedel 1, Ural Koç 2
1 Emergency Medicine Department, Antalya Training And Research Hospital, Antalya, 2 Radiology Department, Erzincan Mengücek Gazi Training and Research Hospital, Erzincan, Turkey
DOI: 10.4328/JCAM.5637 Received: 23.12.2017 Accepted: 10.01.2018 Publihed Online: 11.01.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 245-7
Corresponding Author: Cihan Bedel, Antalya Training and Research Hospital, 07100, Muratpaşa, Antalya,Turkey. GSM: +905075641254 E-Mail: cihanbedel@hotmail.com
Stercoral colitis is a rare and often fatal complication of constipation. Diagnosis of stercoral colitis is made in only 10% of patients before surgery. A 45-year-old female presented to the emergency department with abdominal pain and constipation. Computerized abdominal tomography was suitable with the diagnosis of stercoral colitis. Stercoral colitis complications are related to high mortality and morbidity. Early diagnosis and treatment should be started. We have presented a rare case of “stercoral colitis” and have observed the diagnosis and treatment methods in the light of literature information.
Keywords: Stercoral Colitis; Constipation; Abdominal Pain
Introduction
Constipation is common in psychiatric patients and can be due to a sedentary lifestyle, low-fiber diet, inadequate fluid intake, or anxiety around using the bathroom [1]. Up to 20% of patients who take antipsychotics develop constipation, and the anticholinergic effects of antipsychotics and antidepressants have been associated with fecal impaction, paralytic ileus, and bowel obstruction [2]. Diagnosis of constipation and its complications is often difficult in psychiatric patients. We present a case of a female patient with psychiatric illness who presented with constipation and abdominal pain and were found to have stercoral colitis. Stercoral colitis results from fecal impaction with secondary bowel ischemia. It is a rare occurrence overall, especially in young patients, and it is often misdiagnosed. In cases of stercoral colitis with perforation, mortality is as high as 60% [2]. We aimed to create awareness for stercoral colitis in patients with constipation and abdominal pain.
Case Report
A 45-year-old female with bipolar disorder presented to the emergency department with lower quadrant abdominal pain, nausea, and anorexia lasting for 2 days. She denied chronic constipation and had last bowel movement 5 days earlier. Physical examination revealed a moderately distended abdomen with tenderness in the lower quadrant and suprapubic region, with normal bowel sounds and no guarding or rebound tenderness. A hard stool was palpated in the rectal vault. Vital signs were normal, and laboratory studies were unremarkable. Past medications included olanzapine and lithium. A plain x-ray study of the abdomen revealed air-fluid level and fecal impaction (figure 1).
Contrast-enhanced computed tomography (CT) of the abdomen and pelvis was performed to rule out an obstruction (figure 2-3). CT scan demonstrated thickening of the colonic wall with a large volume of feces but no free air or mechanical obstruction or volvulus were identified. Wall thickness was over 3 mm in the rectosigmoid region. The colonic segment had increased cross-sectional diameter over 6 cm due to stool impaction. She was diagnosed with stercoral colitis without perforation. The patient was hospitalized in the general surgery clinic. She received i.v. fluids, oral laxatives, and water enemas. After numerous bowel movements, the patient’s pain and distention resolved. The patient was discharged on the 8th day of hospitalization with oral laxatives, enemas, and quetiapine.
Discussion
In the literature, more than 150 cases of stercoral colitis, with or without perforation, have been reported [3-4]. Stercoral colitis is an inflammatory colitis that is caused by increased intraluminal pressure from impacted fecal material in the colon [2]. It was the cause of 3.2% of colonic perforations in one series [5] and present in 0.04%-2.3% of randomly selected autopsy examinations [6]. Constipation is the most common risk factor, present in 81% of patients [5]. Medications including narcotics, non-steroidal anti-inflammatory agents, codeine tricyclic anti-depressants and tranquilizers, increase the risk of stercoral ulcer, most probably secondary to their tendency to cause constipation [2,7]. In our case constipation developed due to the anticholinergic effect of antipsychotic drugs.
Stercoral colitis with or without perforation takes place most commonly in the sigmoid colon because it is the narrowest portion of the colon, has the lowest blood supply, and is the area of maximal dehydration of feces [5]. The clinical presentation of stercoral colitis without perforation is changeable. Pain may be diffuse or localized, and patients may be misdiagnosed with diverticulitis or appendicitis [8]. On physical examination, most patients have peritonitis, but rarely a palpable abdominal mass or fecaloma in the rectum [5,9]. In our patient, there was abdominal distention, tenderness on palpation in the lower quadrant and suprapubic region. Plain x-ray study of the abdomen may demonstrate fecal loading, calcified fecaloma, or pneumo-mediastinum [5]. Free air on plain x-ray study is seen in only 70% of patients with perforated stercoral colitis [4-5,9]. Diagnosis of stercoral colitis is made in only 10% of patients before surgery, and many patients develop colonic perforation, peritonitis, septic shock, and death [10-12]. CT of the abdomen expedites diagnosis and treatment of stercoral colitis. CT findings of stercoral colitis include fecal impaction, pericolonic fat stranding, colon wall thickening > 3 mm, and proximal colonic dilatation [4,13]. In our patient’s tomography, wall thickness was over 3 mm in the rectosigmoid region. The colonic segment had increased cross-sectional diameter over 6 cm due to stool impaction. CT not only aids the diagnosis of stercoral colitis but also helps to guide treatment in patients with or without perforation. In stercoral colitis without perforation, 52% of patients can be treated non-operatively with a bowel regimen. The remainder deteriorates clinically and ultimately require surgery [13]. Methods to extract feces from the rectum, including digital disimpaction and enemas, do not improve abdominal discomfort [4]. In stercoral colitis with perforation, mortality is nearly 100% in patients treated nonoperatively, compared to 35-40% in patients treated operatively [9,11]. Stercoral colitis should be managed timely and adequately to avoid potentially life-threatening complications.
Conclusion
As a conclusion, emergency physicians should consider stercoral colitis in patients with constipation and abdominal pain. A high level of suspicion and early imaging are crucial to determine and cure this rare but potentially catastrophic disease.
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. De Hert M, Hudyana H, Dockx L, Bernagie C, Sweers K, Tack J, et al. Second-generation antipsychotics and constipation: a review of the literature. European Psychiatry. 2011; 26(1): 34-44.
2. Serpell J, Nicholls R. Stercoral perforation of the colon. British Journal of Surgery. 1990; 77(12): 1325-9.
3. J.Berry. Dilatation and rupture of sigmoid flexure short report. BMJ. 1894; 1(301): 4.
4. Wu CH, Wang LJ, Wong YC, Huang CC, Chen CC, Wang CJ, et al. Necrotic stercoral colitis: importance of computed tomography findings. World Journal of Gastroenterology: WJG. 2011; 17(3): 379.
5. Maurer CA, Renzulli P, Mazzucchelli L, Egger B, Seiler CA, Büchler MW. Use of accurate diagnostic criteria may increase incidence of stercoral perforation of the colon. Diseases of the colon & rectum. 2000; 43(7): 991-8.
6. Gekas P, Schuster MM. Stercoral perforation of the colon: case report and review of the literature. Gastroenterology. 1981; 80(5): 1054-8.
7. Dubinsky I. Stercoral perforation of the colon: case report and review of the literature. The Journal of emergency medicine. 1996; 14(3): 323-5.
8. Hsiao TF, Chou YH. Stercoral perforation of colon: a rare but important mimicker of acute appendicitis. The American journal of emergency medicine. 2010; 28(1): 112. e1-2.
9. Rozenblit A, Cohen-Schwartz D, Wolf E, Foxx M, Brenner S. Stercoral perforation of the sigmoid colon: computed tomography findings. Clinical radiology. 2000; 55(9): 727-9.
10. Heffernan C, Pachter HL, Megibow AJ, Macari M. Stercoral colitis leading to fatal peritonitis: CT findings. American Journal of Roentgenology. 2005; 184(4): 1189-93.
11. Bhatt VR, Murukutla S, DiPoce J, Gustafson S, Sarkany D, Mody K et al. Perforation in a patient with stercoral colitis and diverticulosis: who did it? Journal of community hospital internal medicine perspectives. 2014; 4(1): 22898.
12. Falidas E, Mathioulakis S, Vlachos K, Archontovasilis F, Villias C. Stercoral perforation of the sigmoid colon. A case report and brief review of the literature. Il giornale di chirurgia. 2011; 32(8-9): 368-71.
13. Wu CH, Huang CC, Wang LJ, Wong YC, Wang CJ, Lo WC, et al. Value of CT in the discrimination of fatal from non-fatal stercoral colitis. Korean journal of radiology. 2012; 13(3): 283-9.
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Bedel C, Koç U. A rare cause in the differential diagnosis of abdominal pain: Stercoral colitis. J Clin Anal Med 2018;9(3): 245-7.
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A very rare case of sphenoid lymphoma presenting as cavernous sinus syndrome
Taylan Gun 1, Aslan Guzel 2
1 ENT Department, Faculty of Medicine, Bahçeşehir University, Ankara Medical Park Hospital, Ankara, 2 Neurosurgery Department, Bahçeşehir University, Faculty of Medicine, Gaziantep Medical Park Hospital, Gaziantep, Turkey
DOI: 10.4328/JCAM.5669 Received: 23.01.2018 Accepted: 20.02.2018 Publihed Online: 22.02.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 248-50
Corresponding Author: Taylan Gun, Ankara Medical Park Hospital Kentkoop Mah. 1868 Sok. No:15, Batıkent, Ankara, Turkey. Tel: +90 3126668000 GSM: +905323435019 F.: +90 3126668666 E-Mail: taylangun@gmail.com
A 4-year-old boy admitted to our clinic with unilateral ophthalmoplegia, ptosis, and proptosis. He has been suffering the symptoms of a headache, nausea, dyspnea, fatigue, weakness, and loss of appetite for about three months. Complete blood count showed an increased white blood cell count with 77% blast cells, anemia, and thrombocytopenia. Magnetic resonance imaging (MRI) examination revealed the mass was obliterating the sphenoid and cavernous sinuses also causing osseous changes of the sinus walls. We performed endoscopic surgical decompression to relieve the symptoms of cavernous sinus syndrome also to obtain enough tissue samples for pathologic diagnosis. Pathologic examination revealed that the mass was diffuse B cell non-Hodgkin lymphoma and the patient was referred to pediatric oncology department for further treatment.
Keywords: Non-Hodgkin Lymphoma; Cavernous Sinus Syndrome; Ophthalmoplegia
Introduction
Cavernous sinus syndrome present with the symptoms related to the nerves passing through the cavernous sinus. Painful ophthalmoplegia (cranial nerves III, IV, and VI), proptosis, ocular or conjunctival congestion, Horner syndrome, trigeminal sensory loss, visual loss, and elevation of ocular pressure. Various combinations of these symptoms may be encountered. There are many reasons causing the situation such as infectious, inflammatory, vascular, traumatic, and neoplastic processes. Symptoms are typically unilateral but may be bilateral when there is a neoplastic process [1-3]. Besides, there are some specific situations causing cavernous sinus syndrome including carotid cavernous fistulas, carotid artery aneurysms, tumors, and Tolosa-Hunt syndrome [3].
In this report, we present a very rare case of B cell non-Hodgkin lymphoma which is obliterating the sphenoid sinus and causing cavernous sinus syndrome.
Case report
A 4-year-old child presenting with painful unilateral ophthalmoplegia, ptosis, and proptosis attended to our neurosurgical department. He has been suffering the symptoms of a headache, nausea, dyspnea, fatigue, weakness, and loss of appetite for about three months. He was referred to the radiology department for possible intracranial mass, and MRI examination was performed to rule out any intracranial masses. MRI investigation revealed the mass which was totally obliterating the sphenoid sinuses. T1 weighted images showed that the mass was contingent with ethmoid sinuses anteriorly, nasopharynx inferiorly and cerebral gyruses superiorly but not invading them. The mass consisted of hyperdense areas suggesting hemorrhage or calcification (Figure 1). The mass was hypodense on T2 weighed images consistent with MRI findings of lymphomas (Figure 2). Clivus, nasopharynx and sellar region were free of the disease. Vascular supply of the mass was weak on MRI angiography (Figure 3). The patient was referred to our clinic for evaluation of possible sphenoid mass etiologies. We performed ENT examination which was completely normal. On the third day, the patient developed sudden and complete visual loss. Despite conservative therapy with a high intravenous dose of methylprednisolone, we decided to operate the patient for absolute tissue diagnosis and surgical decompression. Under general anesthesia, the patient was operated endoscopically with 0°and 30° endoscopes. The mass was observed in left sphenoethmoid recess, and multiple punch biopsies were obtained for tissue diagnosis. Frozen section samples were reported as large round cell tumor which was non-specific. We decided to complete the decompression procedure. The tumor was discharged from sphenoid and cavernous sinuses (Figure 4). Patient’s symptoms relieved immediately after the surgery. The final histological diagnosis was diffuse large B‑cell type non-Hodgkin lymphoma. The patient was referred to the Medical Oncology department and received chemotherapy of cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone combined with 40 Gy radiotherapy.
Discussion
Sphenoid sinus tumors are very rare and seldom associated with symptoms such as nasal discharge and obstruction or epistaxis. A headache and cranial neuropathies are the most common presenting symptoms [4]. Because of the proximity, tumors of the sphenoid bone may invade many important skull base structures. Levine pointed out 13 critical structures that are at risk when there is a sphenoid disease: the dura, the internal carotid artery, the cavernous sinus, the optic nerve, the abducens nerve, the oculomotor nerve, the pituitary gland, the trochlear nerve, the ophthalmic nerve, the maxillary division of the trigeminal nerve, the sphenopalatine ganglion and artery, and the pterygoid canal and nerve [5].
Paranasal lymphomas are mostly affecting elderly patients, with a median age of 5 to 60 years [6]. However, there are a few reported non-Hodgkin lymphoma cases affecting children [3].
Also, there are several reported cases in adults in which cavernous sinus syndrome occurred as a manifestation of systemic non-Hodgkin lymphoma [7]. The literature on children is more scarce [8]. Diagnosis of paranasal lymphoma is usually delayed because the tumors in this area appear with a very few symptoms and are usually at an advanced stage at the time of diagnosis.
The cavernous sinuses are paired venous structures located on both sides of the sella turcica. Multiple important structures such as the carotid artery; its sympathetic plexus; cranial nerves III, IV, and VI; and the ophthalmic branch of cranial nerve V pass through the sinuses. Cavernous sinus syndrome caused by a tumor and acute or slowly progressive ophthalmoplegia is the dominant presentation, with diplopia the most common symptom. Cavernous sinus tumors are the predominant cause of cavernous sinus syndrome [8]. Tumors may be primary, locally spreading, or metastatic [9]. Meningiomas and neurofibromas are the most common primary tumors [9]. Locally spreading tumors are nasopharyngeal and pituitary originating tumors. Primary tumors are the most common neoplasms causing cavernous sinus syndrome. Akinci et al. reported a cavernous sinus syndrome as the initial presentation of childhood non-Hodgkin lymphoma [3].
This report indicates that cavernous sinus syndrome may occur as the initial presentation of non-Hodgkin lymphoma in children, and endoscopic tissue sampling and decompression surgery should be done immediately.
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. Huiping YE, Zhengpeng GONG, Wen YANG, Yubing DAI. Primary non-Hodgkin lymphoma of the sphenoid sinus with visual disturbance: A report of two cases. Oncol Lett. 2016;11(6):4252-4.
2. Roth DB, Siatkowski RM. Bilateral blindness as the initial presentation of lymphoma of the sphenoid sinus. Am J Ophthalmol. 2000;129(2):256-8.
3. Akinci A, Acaroglu G, Sayli TR, Demir B. Cavernous sinus syndrome as the initial presentation of childhood non-Hodgkin lymphoma. J Pediatr Ophthalmol Strabismus. 2009;46(4):232-4.
4. DeMonte F, Ginsberg LE, Clayman GL. Primary malignant tumors of the sphenoidal sinus. Neurosurgery. 2000;46(5):1084-91.
5. Levine H. The sphenoid sinus, the neglected nasal sinus. Arch Otolaryngol. 1978;104(10):585-7.
6. Wollner N, Mandell L, Filippa D, Exelby P, McGowan M, Lieberman P. Primary nasal– paranasal, oropharyngeal lymphoma in the pediatric age group. Cancer. 1990;65(6):1438-44.
7. Julien J, Ferrer X, Drouillard J, Philippe JC, Desbordes P. Cavernous sinus syndrome due to lymphoma. J Neurol Neurosurg Psychiatry. 1984;47(5):558-60.
8. Paysse EA, Coats UK, Ellis FD, Haidar JH, Sondhi N. Simultaneous cavernous sinus syndrome and facial lesion as presenting signs of Ki-1 positive anaplastic large cell lymphoma in a child. J Ped Ophthalmol Strabismus. 1997;34(5):313-5.
9. Thomas JF, Yoss RE. The parasellar syndrome: problems in determining etiology. Mayo Clin Proc. l970;45(9):617-23.
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Gun T, Guzel A. A very rare case of sphenoid lymphoma presenting as cavernous sınus syndrome. J Clin Anal Med 2018;9(3): 248-50.
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A case of Fahr’s disease presenting with seizures
Cihan Bedel 1, Göker Coşkun 2
1 Emergency Medicine Department, Antalya Training And Research Hospital, Antalya, 2 Medicine Department, Süleyman Demirel University Faculty of Medicine Emergency, Isparta, Turkey
DOI: 10.4328/JCAM.5687 Received: 14.01.2018 Accepted: 14.02.2018 Publihed Online: 16.02.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 251-3
Corresponding Author: Cihan Bedel, Acil Tıp ABD, Antalya Eğitim ve Araştırma Hastanesi, Antalya, Turkey. GSM: +905075641254 E-Mail: cihanbedel@hotmail.com
Fahr’s disease is a rare idiopathic bilateral and symmetrical calcification of the basal ganglia, thalami, subcortical hemispheric white matter and deep cerebellar nuclei. We report an unusual case of Fahr’s disease in a 53-year-old man who presented with generalized seizure in our emergency department. Based on clinical, radiological and endocrinological appearance, the patient was diagnosed with Fahr’s disease associated with hypoparathyroidism. Parenteral calcium and calcitriol supplementation were given in the emergency department. The clinical outcome was favorable after the treatment. Our case illustrates that Fahr’s disease, though rarely seen, has to be considered in a patient with convulsive state associated with calcifications of the basal ganglia.
Keywords: Fahr’s Disease; Hypoparathyroidism; Seizure
Introduction
Fahr’s disease (FD) is a rare entity characterized by symmetrical and bilateral calcifications over the basal ganglia, thalami, cerebellar dentate nucleus or white matter of the cerebral hemispheres [1]. The clinical manifestations of FD vary. General clinical features include movement disorders such as parkinsonism, speech disorders, psychiatric disorders, epileptic seizure, dementia, cerebellar or extrapyramidal dysfunction. Some cases with FD may present without neurological abnormalities [2-3]. It may be sporadic or familial as well as secondary to anoxia, irradiation, systemic disorders, toxins, and disorders of calcium metabolism [4-5]. We report a very rare case of FD due to idiopathic hypoparathyroidism in a 53-year-old man diagnosed by clinical and radiological evidence.
Case report
A 53-year-old male presented to our emergency department (ED) with sudden onset of a generalised tonic-clonic seizure. The oropharyngeal airway was inserted to maintain the unconscious patient’s airway. Diazepam was given as the first-line antiepileptic drug, and the seizure was responsive to the treatment. After the patient recuperated consciousness, a neurological examination was performed. Abnormal neurological signs including a mild degree of dysarthria, paresthesia and generalized neuromuscular irritability such as muscle cramps and tetany were found. Latent tetanic convulsions could also be displayed through the elicitation of Chvostek’s sign and Trousseau’s sign. The patient’s past medical history included convulsive episodes which were diagnosed as epilepsy. Laboratory studies including serum calcium 5.2 mg/dl (normal 8.8-10.6 mg/dl), phosphate 7.4 mg/dl (normal 2.5-4.5 mg/dl) and parathormone (PTH) level 3.2 pg/ml (normal 15-65 pg/ml) demonstrated idiopathic hypoparathyroidism. Additional diagnostic laboratory tests including thyroid hormones and vitamins were within normal range. His cranial computed tomography (CT) showed extensive symmetrical calcification of basal ganglia and cerebellum (Figure 1). In addition, bilateral and symmetrical calcifications were also detected over the lateral periventricular areas (Figure 2). A diagnosis of FD associated with idiopathic hypoparathyroidism was made on the basis of the clinical, laboratory and radiological findings. The patient was consulted by a neurologist for a probable seizure, and the patient was treated with an intravenous calcium infusion followed by per oral supplemental calcium and calcitriol, then referred to the endocrinology and neurology departments.
Discussion
FD is a rare inherited or sporadic neurological disorder characterized by the presence of bilateral intracranial calcifications with a predilection for the basal ganglia and dentate nuclei. It is commonly associated with endocrine disorders, particularly parathyroid and Vitamin D disturbances [6].
Clinical diagnosis is facilitated by the presence of bilateral and symmetrical calcifications in the basal ganglia in cranial CT. Detection of intracranial calcifications in CT scan is more sensitive compared to skull X-ray or magnetic resonance imaging. It was reported in the literature that in FD, there were symmetrical and extensive calcifications in the white matter of the cerebral or cerebellar hemispheres and basal ganglia [7-8]. As in the present case, the cranial CT findings were typical and consistent with those of FD.
Clinical presentations may be fairly variable. Neurological and psychiatric symptoms, if present at all, are highly variable and include progressive mental deterioration, convulsive seizures, parkinsonism, difficulty in speaking, ataxia, psychosis or affective disorders [1,9]. In the present case, there were no psychiatric symptoms. There were neurological signs such as dysarthria or those of hypoparathyroidism such as latent tetany and seizure.
Hypoparathyroidism has been reported as a cause of FD. It constitutes a very rare group of heterogeneous disorders characterized by hypocalcemia, hyperphosphatemia, normal or increased parathormone secretion, and target tissue resistance to the actions of PTH. Most reported cases of hypoparathyroidism are preceded by or simultaneously present with autoimmune disorders, such as Sjogren’s syndrome, Hashimoto’s thyroiditis, or Graves’ disease [10]. The pathophysiology of this condition is not well-defined, so there is no standard course of treatment. Treatment addresses symptoms on an individual basis [4-5]. Some reports of FD, correction of calcium and phosphate levels may lead to clinical improvement, in particular, the disappearance of epileptic seizures and abnormal movements. As in the present case, after treatment with parenteral calcium and calcitriol supplementation, there were clinical and laboratory improvements.
Conclusion
FD clinical manifestations can vary. It may begin at different ages and have a variety of presentations. The present case is important because it would appear that there is a few case in the literature of FD presenting with a generalized tonic-clonic seizure. The seizures in such patients may be due to calcium metabolism abnormities and/or dysfunction of cortico-basal connections.
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. Schmidt U, Mursch K, Halatsch M. Symmetrical intracerebral and intracerebellar calcification (“Fahr’s disease”). Functional Neurology. 2005;20(1):15.
2. Manyam BV, Walters AS, Narla KR. Bilateral striopallidodentate calcinosis: clinical characteristics of patients seen in a registry. Movement disorders. 2001;16(2):258-64.
3. Lam JS, Fong SY, Yiu G, Wing Y. Fahr’s disease: a differential diagnosis of frontal lobe syndrome. Hong Kong Medical Journal. 2007;13(1):75.
4. Verulashvili I, Glonti L, Miminoshvili D, Maniia M, Mdivani K. Basal ganglia calcification: clinical manifestations and diagnostic evaluation. Georgian medical news. 2006; 140:39-43.
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7. Benke T, Karner E, Seppi K, Delazer M, Marksteiner J, Donnemiller E. Subacute dementia, and imaging correlates in a case of Fahr’s disease. Journal of Neurology, Neurosurgery & Psychiatry. 2004;75(8):1163-5.
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10. Murakami T, Nambu T, Morimoto Y, Matsuda Y, Matsuo K, Yonemitsu S, et al. Pseudohypoparathyroidism type II in a woman with a history of thyroid surgery. Internal Medicine. 2014;53(7):743-7.
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Bedel C, Coşkun G. A case of Fahr’s disease presenting with seizures. J Clin Anal Med 2018;9(3): 251-3.
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Lneonatal meningitis due to streptoccocus dysgalactiae subspecies equisimilis: a case report and literature review
Nuriye Tarakci 1, Fatma Hilal Yılmaz 1, Nazlı Dilay Gültekin 1, Hüseyin Altunhan 1, Rahmi Örs 2
1 Department of Neonatology, Meram Medical Faculty, Necmettin Erbakan University, 2 Medova Hospital, Konya, Turkey
DOI: 10.4328/JCAM.5697 Received: 17.01.2018 Accepted: 14.02.2018 Publihed Online: 16.02.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 254-6
Corresponding Author: Nuriye Tarakci, Department of Neonatology, Meram Medical Faculty, Necmettin Erbakan University, Konya 42080, Turkey. T.: +90 3322236000 F.: +90 3322236585 E-Mail: nuriyetarakci@hotmail.com
Streptococcus dysgalactiae subsp. equisimilis (SDSE) was firstly reported as a toxon among human streptococcal pathogens in the year 1996. Diseases caused by SDSE may vary from milder skin involvements including wound infection, erysipelas, and cellulitis to life-threatening clinical pictures as streptococcal toxic shock syndrome and necrotizing fasciitis. We describe a case of SDSE sepsis and meningitis in a 2-day-old newborn. He was referred to our intensive care unit (ICU) with fever, respiratory distress, seizures, peripheral cyanosis, and somnolence. SDSE grew out of the CSF and blood cultures obtained on admission to the ICU. SDSE cases reported in the literature are frequently older patients with an underlying disease. Also, SDSE may cause serious neonatal infections.
Keywords: Streptococcus Dysgalactiae Subspecies Equisimilis; Neonate; Meningitis
Introduction
Neonatal sepsis is an informed serious disease, and Group B streptococci (GBS) is the most common cause of neonatal sepsis. The use of prophylactic antimicrobials has decreased the incidence of GBS-related disease [1]. SDSE was firstly reported as a human pathogen in 1996 [2]. This microorganism has Lancefield Group C or G antigens and rarely an antigen. This microorganism causes beta hemolysis and exerts streptokinetic activity on human plasminogen and proteolytic activity on human fibrin. SDSE can be found in the oropharynx, gastrointestinal tract, genitourinary tract and as normal skin flora. Diseases caused by SDSE vary from mild skin infections, such as wound infections, erysipelas, and cellulitis to life-threatening infections, such as streptococcal toxic shock syndrome and necrotizing fasciitis [3]. The most common cause of bacteremia is cellulitis [4]. Invasive SDSE infections are becoming increasingly more common worldwide [2]. The invasive form of SDSE infection is more common among older patients especially, in the presence of underlying disease and in cases where skin integrity is disrupted. We report here a case of neonatal sepsis and meningitis caused by SDSE occurring 2 days after birth. We also reviewed the literature on SDSE infections.
Case report
The neonate described here is a male delivered to a gravida 1 mother vaginally at 38-weeks gestation with a birth weight of 3800 gr. The woman had rupture of membranes 8 hours prior to delivery. The rupture of membranes was spontaneous. The Apgar scores at 1 and 5 minutes were 8 and 9, respectively. The neonate began vomiting, developed cyanosis, had moaning and feeding intolerance beginning on postnatal 16. hours. While he was treated (only with ampicillin) in another hospital with the diagnosis of early onset neonatal sepsis, his general health state deteriorated so much on the postnatal 3. day, and he was referred to our neonatal intensive care unit (NICU) with fever, respiratory distress, seizures, peripheral cyanosis, and somnolence. On admission to our NICU, he was treated with oxygen therapy, intravenous fluid and dobutamine (5 µg/kg/min) for hypotension (arterial blood pressure of 23/14 mm Hg). An arterial blood gas showed metabolic acidosis (pH: 7.28, HCO3: 17, pCO2: 38). A complete blood count showed leukopenia (300 cells/µL), mild thrombocytopenia (130,000/µL) and an elevated CRP level (35 mg/dl) and elevated procalcitonin level (36 ng/ml; normal range is <2 ng/dl) were detected. Renal and hepatic function test results (urea, creatinine, AST, ALT) and serum electrolyte levels were within normal limits. A lumbar puncture was performed, and analysis of CSF revealed the following values: WBC count 346 cells/mm3 (75% segmented neutrophils and 25% lymphocytes). The CSF protein level was elevated (650 mg/dl), and the CSF glucose level was decreased (21 mg/dl). Cultures of the blood, urine, spinal fluid, throat, external ear canal and rectum were obtained, and then antibiotic therapy was initiated (vancomycin, ampicillin, and amikacin). SDSE grew out of the CSF and blood cultures obtained on admission to the ICU. The microorganism was sensitive to penicillin G, cefotaxime, meropenem, linezolid and vancomycin and resistant to erythromycin, clindamycin, and levofloxacin (Minimal inhibitor concentration with E-test method=MIC values; penicillin G <0.12 mcg/mL, vancomycin 1mcg/mL). On the third day of therapy, a repeat lumbar puncture was performed. The CSF was clear, hypocellular, the protein was 120 mg/dl, and the CSF glucose/blood glucose ratio was 48/89. His mother did not allow us to obtain vaginal or anal swab specimens for antibiotic susceptibility testing. By 3rd weeks of treatment, the blood and CSF results were normal, and the child was clinically improved. The child’s immunity was evaluated and found to be normal. Six months later there were no residual neurological sequelae.
Discussion
SDSE is a microorganism with increasing clinical significance, which causes both invasive and non-invasive infections [5]. Invasive infection with SDSE is seen in older individuals with a suppressed immune system or disrupted skin integrity. Group C β-hemolytic streptococcus have been involved in several localized human infections including pharyngitis, pyodermitis, cellulitis, wound infections, abscesses, erysipelas and necrotizing fasciitis. Severe invasive infections often occur in predisposed hosts: in fact they are common in patients affected by underlying immunodeficiency predisposing diseases or conditions such as age (neonate or elderly), diabetes mellitus, HIV-1 disease, alcoholism and injection drug use, and also in patients with chronic cardiovascular diseases and those undergoing chemotherapy or affected by cancer [6]. We can say that our case is in the immunodeficiency category because it is a newborn. Yamaoka et al. reported a case of streptococcal toxic shock syndrome caused by SDSE in a 12-hour-old newborn without a previous history of premature rupture of membranes or meconium aspiration [2]. In the literature, two cases of early onset neonatal sepsis caused by group G streptococci were reported before identification of this microorganism. One of these cases had a history of meconium aspiration, and the other had prolonged rupture of membranes [7]. The demographic and clinical characteristics of a total of 3 cases cited in the literature are shown in Table 1. The reported neonates -including ours- were delivered vaginally and had no identifiable risk factors.
In the literature, screening of pregnant women was recommended as for the presence of GBS to prevent the development of early-onset neonatal sepsis [8]. In our case, the mother did not undergo screening during pregnancy.
Analysis of the emm gene for the amino acid sequence situated and the N-terminal end of the M-protein in patients with SDSE has been performed in epidemiological studies related to epidemics caused by invasive and non-invasive microorganisms [2]. The presence of the emm I gene in children is associated with invasive infection.
SDSE cases reported in the literature are frequently older patients with an underlying disease. Mortality rates have been high among patients with SDSE. In patients with bacteremia due to SDSE, mortality rates are reported to be 15-18% [4]. In addition to this reported case of SDSE in a neonate at our hospital, only 2 other cases among neonates have been reported to survive. The prognosis of neonates with SDSE infection is better than adults. This may be because neonates usually do not have any underlying disease but adults with SDSE often do, and neonates may be diagnosed earlier while they are still in the hospital at birth.
In conclusion, SDSE may cause serious neonatal infections.
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. Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. Pediatrics. 2005;115(5):1240-6.
2. Yamaoka S, Ogihara T, Yasui M, Hasegawa M, Hira S, Oue S, et al. Neonatal streptococcal toxic shock syndrome caused by Streptococcus dysgalactiae subsp. equisimilis. Pediatr Infect Dis J. 2010;29(10):979-81.
3. Takahashi T, Ubukata K, Watanabe H. Invasive infection caused by Streptococcus dysgalactiae subs. equisimilis: characteristics of strains and clinical features. J Infect Chemother. 2011;17(1):1-10.
4. Rantala S. Streptococcus dysgalactiae subsp. equisimilis bacteremia: an emerging infection. Eur J Clin Microbiol Infect Dis. 2014;33(8):1303-10.
5. Anantha RV, Kasper KJ, Patterson KG, Zeppa JJ, Delport J, McCormick JK. Fournier’s gangrene of the penis caused by Streptococcus dysgalactiae subspecies equisimilis: case report and incidence study in a tertiary-care hospital. BMC Infect Dis. 2013;20(13):381.
6. Milito C, Carello R, Fantauzzi A, Vullo V, Mezzaroma I. Streptococcus dysgalactiae subspecies equisimilis bacteremia in an HIV-1 patient with HBV/HCV co-infections: case report and literature review. Infez Med. 2014;22(3):241-6.
7. Carstensen H, Pers C, Pryds O. Group G streptococcal neonatal septicemia: two case reports and a brief review of literature. Scand J Infect Dis. 1988;20(4):407-10.
8. Verani JR, McGee L, Schrag SJ. Prevention of perinatal group B streptococcal disease revised guidelines from CDC. MMWR Recomm Rep. 2010;19(59):1-36.
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Tarakci N, Yılmaz FH, Gültekin ND, Altunhan H, Örs R. Lneonatal meningitis due to streptoccocus dysgalactiae subspecies equisimilis: a case report and literature review. J Clin Anal Med 2018;9(3): 254-6.
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If no suspection, then no diagnosis: A case report
Emin Kürşat Bulut 1, Ömer Faruk Ateş 2, Galip Beltir 1
1 Department of Orthopedics, Ankara Oncology Training and Research Hospital, 2 Department of Radiology, Ankara Atatürk Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/JCAM.5713 Received: 19.01.2018 Accepted: 20.02.2018 Publihed Online: 22.02.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 257-9
Corresponding Author: Galip Beltir, Ankara Oncology, Hospital, Ankara, Turkey. GSM: +905424045370 E-Mail: galipbeltir@hotmail.com
In this study, we examined the history and examination outcomes with differential diagnosis and further investigations of a 17-year old female patient with left wrist pain for about 3 years. It was reported the difficulty in diagnosis of a disease which can be presented in the wrist with atypical findings and that it must be considered in the differential diagnosis.
Keywords: Diagnosis; Wrist; Pain; Tumor
Introduction
In this study, a case of chronic wrist pain in a 17-year-old female patient was investigated. History of the patient and outcomes of the investigations were reported, and the readers were asked about the method they think for diagnosis and treatment in this case.
A case report either should provide new knowledge to the literature or attract attention to a new condition or disease, or report repeat of a condition or a case in order to demonstrate there are sufficient reasons to conduct further comprehensive studies [1-3]. In addition, the title and abstract should provoke the reader, providing the entire text to be read [4].
In this study, a definitive diagnosis was made in the further investigation and treatment was successfully achieved. The diagnosis for this localization is reported as case reports in recent years. In this study, we aimed to report repeat of this case, providing both further studies to be conducted on this issue and giving an idea to the readers about the approach method in such case.
Case Report
A 17-year-old female patient with pain in her left wrist over the last 3 years was seen in our orthopedics clinic. The patient reported no difference between the level of pain at night or during the day or exacerbation, and she reported occasional pain. During the examination, there was a mild soft tissue swelling and ulnar and volar deviation in the left wrist (Figure 1). The examination revealed that wrist of the patient could be brought to the neutral position by force, but the patient had severe pain during this maneuver. The joint motion range was full, but the radial deviation and hyperextension were severely painful.
The patient reported that she had used non-steroidal anti-inflammatory drugs by herself at first onset of the pain and these drugs fully resolved the pain, but later the drugs only somewhat decreased the pain and the specified deformity developed in her left wrist. In the anamnesis of the patient, there was no history of trauma or infection. It was noted that she had been referred to different hospitals and departments several times due to this complaint and underwent direct radiography, magnetic resonance imaging, electromyography in the upper extremity, hemogram biochemical parameters, rheumatologic blood tests, and left wrist Doppler examination, in addition, she had been examined for brucella and tuberculosis, but no significant findings had been found in all these investigations. It was reported that different treatment options were applied for the purpose of treatment including resting, static wristband, intraarticular injection and non-steroidal anti-inflammatory drugs, but the patient did not benefit from these. The patient reported that frequency and severity of the pain increased during the last year, causing her to have difficulties in daily activities.
Direct radiography revealed no significant finding except sclerosis in the middle one third at the joint surface of the distal radius suggesting early arthritic findings (Figure 2). On the MRI of the left wrist, there was edema appearance in the left distal radius metaphysis which was completely diffuse at distal. In addition, following intravenous contrast agent (IVCA) injection, there was a minimal contrast enhancement in the surrounding soft tissue (Figure 3).
In light of these information and images, what would be your presumed diagnosis and approach at the next step?
The patient was assessed in the Ankara Hospitals Tumor Council. It was decided by the council to perform wrist computed tomography (CT) examination for intraarticular pathologies. The CT revealed sclerosis in the nidus and surroundings near proximal of the radiocarpal joint in the distal radius. The patient was diagnosed with osteoid osteoma (Figure 4).
The patient underwent fluoroscopy guided nidus excision, showing maximum attention to protect the radius distal joint. The defective area was grafted (Figure 5). In the postoperative follow-ups, wrist pain of the patient was completely resolved, the joint motion range was full and pain-free. Postoperative month 6 controls were performed. The patient can sufficiently use her wrist, and she is satisfied with the outcome.
Discussion
Osteoid osteoma is a benign bone tumor which has been described for the first time by Jaffe in 1935. The tumor is most commonly seen in the 2nd and 3rd decades of life. Its etiology is unknown, and it has osteoblastic properties. It is often seen in the femur and the tibia, although it has been reported that this tumor may be seen in every bone [5-7].
The incidence of osteoid osteoma localized in the distal radius is reported to be less than 1%. However, recent case reports have presented an increasing number [7-10]. As in our case, intraarticular osteoid osteomas that may present with atypical symptoms and difficulties in the diagnosis may probably hide its real prevalence. In addition, posttraumatic or postoperative osteoid osteoma cases are reported in the distal radius [7,11].
Osteoid osteoma most frequently presents with pain which worsens at night. However, clinical presentations of these lesions at localizations surrounding the joint are not characteristics and may cause misdiagnosis [8]. Especially, the absence of accompanying nocturnal pain should not rule out osteoid osteoma in a patient presenting with chronic pain around the joint.
The differential diagnosis of wrist pain may include de Quervain tenosynovitis, osteomyelitis, carpal tunnel syndrome, stress fracture, avascular necrosis, malignant tumors such as Ewing’s sarcoma, inflammatory arthritis and Brodie abscess [8,10,12-16]. The differential diagnosis should be based on the detailed medical history of the patient, clinical examination, radiological and laboratory investigations [5,14].
Osteoid osteoma is usually characterized by a well-established nidus less than 1 cm and surrounding reactive bone formation on the CT imaging. In our study, we also observed pathognomonic nidus and reactive bone formation on the CT.
In conclusion, osteoid osteoma may present in an atypical localization like distal radius and with an atypical form, and herein we presented such a case. Osteoid osteoma should be kept in mind in the differential diagnosis of persistent pain in a joint following treatment.
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. Akgül S, Uzümcügil A, Bozkurt MF, Topçu M. Osteoid osteoma in a 16-year-old boy presenting with atrophy of the left thigh: diagnostic difficulties. Turk J Pediatr. 2008;50(4):373-6.
2. Green BN, Johnson CD. How to write a case report for publication. Journal of Chiropractic Medicine. 2006;5(2):72-82.
3. Ozturk R, Aydın M, Arıkan M, Toğral G, Aydın G, Güngör B. The report of tumor resection prosthesis infection due to Sphingomonas paucimobilis: A case report. Acta Oncol Tur. 2016; 49(1): 57-60.
4. Atik, OŞ. Are all case reports worth publishing? Eklem Hastalık Cerrahisi. 2016;27(2):61.
5. Ozturk R. Bone and soft tissue tumors. In: Atay T. Orthopaedics and sport medicine guide for researchers. 1.st ed. Ankara, Derman Tıbbi Yayıncılık. 2015;635-704.
6. Jaffe HL. Osteoid-osteoma. Proc R Soc Med. 1953;46:1007–12.
7. Deveci A, Fırat A, Bozkurt M, Hücümenoğlu S. A case of osteoid osteoma in the distal radius epiphysis with atypical onset. Acta Orthop Traumatol Turc. 2014;48(1):98-101.
8. Basran SS, Kumar S, Jameel J, Sajid I. Carpal tunnel syndrome: A rare manifestation of distal radius osteoid osteoma. J Clin Orthop Trauma. 2015;6(3):190-4.
9. Aktas B, Ozturan B, Kilic B, Demiroglu M, Ozkan K. A rare case of a medullary, multifocal lesion in the distal radius. JRSM Open. 2017;8(7):1-4.
10. Yiannakopoulos CK, Foufa K, Theocharakis S, Stamoulis E, Maniatis V. Osteoid osteoma of the radial styloid mimicking wrist arthritis: a case study. Hand Surg. 2012;17(2):225-8.
11. Adil A, Hoeffel C, Fikry T. Osteoid osteoma after a fracture of the distal radius. AJR Am J Roentgenol. 1996;167:145-6.
12. Fromm B, Martini A, Schmidt E. Osteoid osteoma of the radial styloid mimicking stenosing tenosynovitis. A case report. J Hand Surg Br. 1992;17:236-8.
13. Chloros GD, Themistocleous GS, Papagelopoulos PJ, Khaldi L, Efstathopoulos DG, Soucacos PN. Osteoid osteoma of the radial styloid mimicking de Quervain tenosynovitis. South Med J. 2007;100:1045-7.
14. Öztürk R, Arıkan ŞM, Şimşek MA, Özanlağan E, Güngör BŞ. Management of solitary fibrous tumors localized in extremity: case series and a review of the literature. Eklem Hastalik Cerrahisi. 2017;28(2):121-7.
15. Toğral G, Arıkan M, Aktaş E, Öztürk R, Güven O, Eksioğlu F. Surgical Management Of Bone Metastases From Urological Malignancies: An Analysis Of 70 Cases. Acta Orthop Traumatol Turc. 2015;49(6):634–40.
16. Ozturk R, Aydın M, Arıkan ŞM, Şimşek MA, Toptaş E, Güngör BŞ. Extremity soft tissue sarcomas of uncertain differentiation: Presentation, treatment, and outcomes in a clinical series of 59 patients. Bakırköy Tıp Dergisi (Ahead of print).
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Bulut EK, Ateş ÖF, Beltir G. If no suspection, then no diagnosis: A case report. J Clin Anal Med 2018;9(3): 257-9.
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A hidden etiology in a case of recurrent carpal tunnel syndrome: Giant cell tumor of the tendon sheath
Galip Beltir 1, Şefik Murat Arıkan 1, Ömer Faruk Ateş 2, Füsun Ardıç Yükrük 3, Sadettin Dolar 4
1 From Department of Orthopaedics and Traumatology, Ankara Oncology Training and Research Hospital, Ankara, 2 From Department of Radiology, Ankara Atatürk Training and Research Hospital, Ankara, 3 From Department of Pathology, Ankara Oncology Training and Research Hospital, Ankara, 4 From Department of Internal Medicine, İzmir Ege Üniversity Hospital, İzmir, Turkey
DOI: 10.4328/JCAM.5721 Received: 24.01.2018 Accepted:23.02.2018 Published Online: 25.02.2018 Printed: 01.05.2018 J Clin Anal Med 2018;9(3): 260-3
Corresponding Author: Galip Beltir, Ankara Oncology Hospital, Ankara, Turkey. GSM: +905424045370 E-Mail: galipbeltir@hotmail.com ORCID ID: 0000-0003-0452-4541
Giant cell tumors of the tendon sheath are the second most common neoplasms of hand and one of the rare reasons of carpal tunnel syndrome. Usually, the findings include swelling, tingling, pain, and loss of sense associated with the mass. A 54-year-old female patient with recurrent carpal tunnel syndrome had a massive lesion that was not detected on physical examination, but carpal tunnel compressed by the giant cell of the tendon sheath was detected through advanced investigations. Symptoms were resolved after surgical excision.
Keywords: Carpal Tunnel Syndrome; Hand; Wrist; Giant Cell Tumor
Introduction
Symptomatic median nerve compression in the carpal tunnel is called as the carpal tunnel syndrome. Symptoms are pain, weakness, and tingling throughout nerve extension [1].
Tenosynovial giant cell tumors are knowns as tendon sheath giant cell tumors and pigmented villonodular synovitis [2]. They are the second most common tumor of hand after simple ganglion cyst [3]. They are almost always benign tumors, but behave similar to some borderline tumors, because of their growth patterns, they have high local recurrence possibility [2,4].
Tenosynovial giant cell tumors are rarely reported as a reason of carpal tunnel syndrome and usually present with swelling at the volar location of the wrist besides carpal tunnel syndrome findings [5-9].
We reported a tenosynovial GCT case located in the carpal tunnel at a patient who has recurrent carpal tunnel syndrome without physical findings of a mass lesion.
Case report
A 54-year-old female patient presented with tingling and sensory loss in the left hand. Left-hand carpal tunnel syndrome was diagnosed, and CTS release operation was performed at our center. The patient referred to us for recurrence of his complaints 1 year later. There were symptoms as pain, feeling loss, tingling during finger flexion-extension movements. These symptoms were severe, especially at nights. Except for the old incision scar on the wrist, there was no swelling or obvious pathological finding. Bi-directional radiography was taken in terms of additional pathology that may cause these symptoms. No additional pathologic findings were found after the X-ray [Figure 1]. Electromyographic findings were compatible with carpal tunnel syndrome.CTS release surgery and advanced research for additional intraoperative pathologies were planned. The operation was performed under axillary block. A pneumatical tourniquet was placed around the arm, and inflation was maintained during the surgical procedure. During the operation, the median nerve was reached, and the nerve seemed thickened and edematous [Figure2]. Flexor tendons were reached in depth of the nerve.
Three different masses that suggest 3 different type of tumor were seen attached to the 2., 3. ve 4. flexor tendons. Tumors were attached to the tendons but had not invaded the tendon fascicles [Figure 3]. Affected tendons were dissected. All tumoral lesions were photographed together [Figure 4]. After excision and pernicious drain was applied, skin was repaired with non-absorbable sutures [Figure 5].
Postoperatively 1st-day Penrose drain was removed, and the patient went home with scar care every other day. Immobilization was not used. Complete healingwas occurred after 15 days.Histopathological examination revealed that the lesion was compatible with villonodular synovitis. Last clinical examination was performed at postoperative 24th month. The fingers had full range of motion and showed full recovery. Pain and other symptoms were improved. Local recurrence was not seen.
Discussion
Carpal tunnel syndrome caused by carpal tunnel compression due to benign tumors is well known [10,11]. Because of the absence of space in the hand compartments, tumor is starting to press to neurovascular endings with rapid growth, and this leads to an atypical clinical presentation imitating the carpal tunnel syndrome [7].
The most common tumors causing carpal tunnel syndrome are lipomas, vascular malformations and ganglions [9].
Giant cell tumors of the tendon sheath are the second most common neoplasms of hand, locatofed 8% at digits. Wrist located giant cell tumors of tendon sheath are the rare reasons of CTS [6, 11].
Soft tissue GCTs are separated into 2 parts according to their origin as tenosynovial and nontenosynovial. Nontenosinovial GCTs are rare, their behavior changes from borderline malignancy to complete malignancy [6].
Tenosynovial GCTs are known as Tendon Sheath GCT or PVNS. Almost all of them have benign behaviors; but they have high local recurrence possibility because of their growth patterns [2, 6].
In the literature, a malignant giant cell tumor-associated carpal tunnel syndrome case has also been reported [6].
First of all, a case report must be original like any scientific article. It must give a new message [12, 13]. In patients who have carpal tunnel syndrome because of a mass, there are findings as swelling at volar face of the wrist or pain during finger movements besides pain and weakness [5,9]. In our case, the pain provocation during finger movements of hand was uncertain. Also, there was no swelling that would suggest a mass lesion on physical examination.Direct radiography is useful in some soft tissue tumors and some soft tissue localized non-tumoral lesions [14]. In case of carpal tunnel syndrome due to mass lesion, standard x-ray evaluations usually do not help. It just may be seen as a homogenous opacity in the soft tissue [15]. In this case, direct radiographs did not contribute to reaching the diagnosis.Generally, MR imaging is recommended in patients who have atypical symptoms, sudden onset symptoms or clinical mass lesion or young patients [7]. MRI is useful in many tumors, especially helpful in evaluating malignancy development [16].
The current treatment method for simple carpal tunnel syndrome cases are open, mini-open or endoscopic carpal tunnel releasing [17]. In the case of carpal tunnel syndrome due to mass lesions, surgical resection of the mass leads to relaxation of the compressed nerve endings. In this study, the patient’s mass was resected by inserting the old incision line.
Conclusion
One of the rare causes of carpal tunnel syndrome is soft tissue mass. These lesions do not always provide significant clinical evidence to suggest mass. Especially in the patients who have recurrent carpal tunnel syndrome, we are recommending that physicians should be suspicious about mass lesion existence and we are also recommending examination by ultrasound or 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.
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Beltir G, Arıkan ŞM, Ateş ÖF, Yükrük FA, Dolar S. A hidden etiology in a case of recurrent carpal tunnel syndrome: Giant cell tumor of the tendon sheath. J Clin Anal Med 2018;9(3): 260-3.
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