April 2022
Investigation of metabolic disorders in the etiology of delirium in geriatric patients
Cigdem Dinckal 1, Pinar Tosun Tasar 2, Omer Karasahin 3, Sevnaz Sahin 4, Merve Gulsah Ulusoy 5, Nur Ozge Akcam 6, Ozan Fatih Sarikaya 1
Aysin Noyan 6, Fehmi Akcicek 4, Soner Duman 1
1 Department of Internal Medicine, Ege University Hospital, Izmir, 2 Department of Internal Medicine Division of Geriatrics, Ataturk University Hospital, Erzurum, 3 Infectious Diseases Clinic, Erzurum Regional Training and Research Hospital, Erzurum, 4 Department of Internal Medicine Division of Geriatrics, Ege University Hospital, Izmir, 5 Department of Biostatistics, Ege University, Izmir, 6 Department of Psychiatry, Division of Consultation Liaison Psychiatry, Ege University Hospital, Izmir, Turkey
DOI: 10.4328/ACAM.20732 Received: 2021-06-07 Accepted: 2021-09-01 Published Online: 2022-03-02 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):350-354
Corresponding Author: Pınar Tosun Tasar, Department of Internal Medicine Division of Geriatrics, Ataturk University Hospital, Erzurum, Turkey. E-mail: pinar.tosun@gmail.com P: +90 505 398 89 85 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7296-5536
Aim: The aim of this study was to examine metabolic parameters, which are among the factors that promote delirium, in geriatric patients pre-diagnosed with delirium by the Consultation-Liaison Psychiatry Unit of our medical school.
Material and Methods: The diagnosis and treatment records of 1435 patients over 65 years of age were retrospectively screened. For patients diagnosed with delirium, demographic data, mode of presentation, leukocyte count, and levels of hematocrit, sodium, potassium, albumin, C-reactive protein (CRP), urea, creatinine, glucose, vitamin B12, TSH, and T4 were recorded.
Results: Of the 1435 patients screened, 1147 patients with available survival and laboratory data were included in the study. Of these, 285 patients were diagnosed with delirium and 861 patients were not. In the delirium group, 63% of the patients had anemia, 33% had leukocytosis, 28% had hyponatremia, 47% had elevated serum creatinine, 90% had elevated CRP, 60% had hypoalbuminemia, and 53% had hyperglycemia.
Discussion: Our comparison of patients with and without delirium indicates that metabolic disorders such as hyponatremia, hypopotassemia, hypoalbuminemia, impaired renal function, hyperglycemia, presence of infection, and anemia are contributing factors in delirium. Delirium is a serious and common problem that increases morbidity and mortality in geriatric patients. Identifying metabolic markers of delirium can help diagnose delirium and predict mortality.
Keywords: Delirium, Geriatric, Mortality, Metabolic Disorder
Introduction
Delirium is a neuropsychiatric syndrome common among the elderly. It is serious and often fatal, involving severe cognitive impairment, changes in the sleep-wake cycle, and perceptual disturbances. Its diagnosis requires a cognitive assessment and a history of the onset of acute symptoms [1]. It is a clinical diagnosis, made with no laboratory measurements, imaging methods, or testing instruments. The diagnosis can only be made by careful clinical evaluation following thorough history-taking, behavioral observations, and assessment of cognitive functions [2]. Delirium is considered a warning sign that the patient’s medical condition may be leading to morbidity or mortality [3].
The prevalence of delirium in the elderly varies among different populations. It has been observed at rates of 10% in emergency rooms, 10-30% in hospitalized patients, and 40% in terminal patients, while it may be as high as 80% among intensive care patients [4].
Generally, delirium is the direct result of a physiological stressor. There are many possible causes of delirium and it is not always possible to identify the underlying cause. The main goal of treatment is to determine and eliminate the underlying cause; therefore, it is critical to identify factors that may be involved in the etiology.
In brief, whenever a patient is diagnosed with delirium, the underlying cause should be investigated. A diagnosis of delirium should be rapidly confirmed by further assessment and examination. Most patients with delirium require hospitalization. A diagnosis of delirium also leads to prolonged hospital stays and increased mortality.
In this study, we aimed to determine the metabolic disorders and precipitating factors that may be associated with delirium in patients over 65 years of age who were referred to the Consultation-Liaison Psychiatry (CLP) Unit of our hospital between 2005 and 2013, to determine the prevalence of these metabolic disorders, and to evaluate their relationships with mortality.
Material and Methods
The files of all patients who were evaluated and diagnosed with a psychological disorder (n=12962) in the CLP Unit between January 2005 and December 2013 were accessed. The records were reviewed by two physicians and patients aged 65 years or older (n=1435) were selected for the study. Patients with available survival data (n=1147) constituted the study sample.
These patients’ files were reviewed and they were divided into two groups: those who were diagnosed with delirium and those who were not. The study was approved by the Clinical Research Ethics Committee of Ege University (decision dated 03/04/2014, committee number 14-3.1/5). This retrospective evaluation was carried out in İzmir, the third largest city in Turkey.
The CLP records used in the diagnosis process comprised files structured as symptom checklists regarding cognitive disorders, mood disorders, psychotic disorders, anxiety disorders, and somatoform disorders according to the DSM-IV (Diagnostic Statistical Manual of Mental Disorders, Fourth Edition, Text Revision Criteria). Previous investigation of the reliability of these forms demonstrated high concordance of double-blind diagnoses based on file data.
After receiving the necessary permission, survival data were obtained from the Death Notification System of the Turkish Ministry of Health’s Public Health Agency using the patients’ citizenship numbers. Data regarding metabolic parameters were obtained from hospital records using hospital protocol numbers and the patients’ Turkish citizenship numbers. Laboratory results from the date on which CLP consultation was requested for the patients were also included in the study.
Statistical Analysis
The data were analyzed using SPSS 22 (IBM Corp., Armonk, NY, USA). Descriptive results pertaining to numerical variables were expressed as mean ± standard deviation and those of categorical variables were expressed as frequency and percentage. Chi-square analysis and pairwise comparisons (Student’s t-test, Mann-Whitney test) were performed in accordance with variable type.
Results
From the files of a total of 12962 patients who were evaluated and diagnosed with a psychological disorder by the CLP Unit between January 2005 and December 2013, the data of 1435 patients aged 65 years or older were obtained. Because survival data were not available for 288 of these patients, a total of 1147 patients constituted the study sample.
The prevalence of delirium among the 1435 elderly patients screened was 25.5%. The patients’ mean age was 74.18±6.2 years (range: 65-96 years), 53.4% were female and 46.6% were male, and most were young-old (65-74 years old, 56.3%) or middle-old (75-84 years old, 36.1%). The mean age of patients diagnosed with delirium was 73.53±5.91 years.
Laboratory results and survival data were available for a total of 1147 patients (285 patients with delirium and 861 without delirium). The most commonly evaluated biomarkers were creatinine, urea, sodium, potassium, and complete blood count variables, while thyroid function tests and vitamin B12 were least commonly requested by physicians on the date of consultation. Uric acid and complete urine analysis were not included in the study because they were not evaluated for many patients at the time of diagnosis. Table 1 presents the percentage distributions of laboratory variables requested for the patients on the date of consultation based on the presence of delirium.
In summary, metabolic evaluation of laboratory values in the delirium group revealed that 63% of the delirium patients had anemia, 33% had leukocytosis, 28% had hyponatremia, 47% had high serum creatinine, 90% had elevated CRP, 60% had hypoalbuminemia, 51% had hypocalcemia, and 53% had hyperglycemia.
In the logistic regression model created with laboratory variables statistically associated with the presence of delirium (Na, K, Ca, creatinine, urea, CRP, albumin, sedimentation rate, leukocyte count, hemoglobin, hematocrit), hypernatremia was found to be an independent risk factor increasing the likelihood of delirium by 31.45 times (p=0.032).
The survival data of 1114 (79%) patients were evaluated from their public records. While 209 (75%) of delirium cases resulted in death, 68 (25%) patients with delirium survived. The mortality rate was significantly higher among patients with delirium than those without (p<0.001).
In comparisons of the prevalence of metabolic disorders in patients with and without delirium, hypoalbuminemia, hyponatremia, hypernatremia, hypopotassemia, hyperpotassemia, hypocalcemia, elevated creatinine, hyperglycemia, CRP elevation, anemia, and leukocytosis were found to be significantly more common in patients with delirium (p<0.001). On the other hand, there was no significant difference in terms of vitamin B12 deficiency or hypothyroidism (Table 2).
Discussion
Delirium is one of the geriatric emergencies frequently encountered in old age. However, there are few studies conducted in the general elderly population evaluating mortality and metabolic conditions in older adults diagnosed with delirium based on psychiatric evaluation.
The most commonly used inflammatory marker in clinical practice is CRP. Therefore, we retrospectively evaluated patients’ CRP levels in the present study in order to investigate the relationship between delirium and inflammation. The difference between the two groups was statistically significant. In another study investigating the relationship between levels of CRP and insulin-like growth factor and rates of delirium in preoperative hip fracture patients, no relationship could be established between CRP values and the development of delirium. Postoperative CRP values were significantly higher in both the control group and the group of patients who developed delirium compared to preoperative values. Patients with delirium demonstrated a more marked change in CRP postoperatively than the control group. The lack of different CRP values in the delirium group compared to the control group makes it difficult to consider CRP as an independent risk factor in the development of delirium. On the other hand, the significant difference in the change in CRP in the delirium patients suggests that the inflammatory response has a role in the pathophysiology of delirium [5]. CRP is an important biomarker for the interpretation of these infectious and inflammatory processes [6].
Hyponatremia is the most common electrolyte imbalance, and advanced age is a risk factor for hyponatremia [7]. At 28%, the prevalence of hyponatremia among patients with delirium in the present study was found to be comparable to that seen among hospital inpatients. Although the prevalence of hyponatremia was higher in patients diagnosed with delirium compared to patients without delirium, the two groups had similar mean sodium values. The difference between hyponatremic patients with and without delirium in terms of increased risk of mortality was insignificant. This may be due to the fact that hyponatremia is itself a risk factor for mortality.
Hypernatremia is another common disorder in the elderly [8]. In the present study, the logistic regression model including laboratory variables statistically associated with delirium revealed hypernatremia to be an independent risk factor that increased the likelihood of delirium by 31.45 times. Older adults are also prone to hypokalemia and hyperkalemia [9].
In the present study, uremia and potassium imbalance significantly reduced survival time in the presence of delirium, while diabetes mellitus was not found to have a statistically significant effect on survival. However, hyperglycemia alone is regarded as a factor that precipitates delirium. It may also be associated with complications related to DM and increased mortality.
Hypo/hyperthyroidism is known to be one of the precipitating factors of delirium. Although thyroid hormones are responsible for regulating metabolism, a decrease in thyroid hormone levels also causes significant changes in the receptors of noradrenaline, serotonin, and GABAergic agents. However, the mechanism by which thyroid hormones lead to psychiatric disorders is not clear. Accordingly, in addition to variations of thyroid hormones, changes in the function of neurotransmitters can cause delirium [10]. We noted that thyroid hormone levels were generally overlooked when the current metabolic status of patients with a pre-diagnosis of delirium was evaluated on the date of consultation. When patients with and without delirium were compared, the difference between them was not significant, but this may be due to inadequate assessment during laboratory studies.
The prevalence of vitamin B12 deficiency in adults over 60 years of age is reported as 5-20%. The elderly are the group most at risk of vitamin B12 deficiency [11]. In a study of patients who underwent coronary artery bypass surgery, it was emphasized that cobalamin deficiency may be associated with an increased risk of delirium. In addition, preoperative cobalamin levels were found to be associated with delirium severity [12]. The relationship between vitamin B12 deficiency and delirium is usually presented in case reports; large-scale studies on the topic are extremely limited in number. Similarly, in the present study, we observed that analysis of vitamin B12 level was requested for very few patients during metabolic evaluations of patients on the date of consultation for a pre-diagnosis of delirium. Vitamin B12 was evaluated for a total of 205 patients, of whom only 3 had both delirium and vitamin B12 deficiency. Further studies evaluating the relationship between vitamin B12 and delirium in larger numbers of patients are needed.
The threshold hemoglobin level for identifying anemia in the elderly is controversial. The generally accepted practice is to use the same limit as in the young population. Older adults with hemoglobin concentrations below 11 g/dL were found to have poorer performance and higher mortality rates from myocardial infarction and heart failure [13]. Joosten et al. determined that anemia was an independent risk factor for delirium [14]. In the present study, anemia was detected in 63% of patients with delirium. The fact that cardiac disease was not a determinant of mortality due to delirium in our study may be attributed to the very high prevalence of anemia. However, further analyses are needed to elucidate this issue.
According to a recent meta-analysis, in addition to older age, diabetes, blood transfusion, preoperative albumin, postoperative albumin, preoperative hematocrit, postoperative hematocrit, preoperative hemoglobin, postoperative hemoglobin, preoperative sodium, postoperative sodium, and living in an institution were found to be significant in cases of delirium [15].
Delirium is common in elderly inpatients. A number of models have been proposed to calculate the risk of developing delirium during hospitalization. Inouye et al. stated that a simple predictive model based on four risk factors can be used at patient admission to identify the elderly individuals at greatest risk. The four main components in this predictive model are low vision, cognitive impairment, severe disease (evaluation by APACHE score), and high blood urea nitrogen/serum creatinine ratio (>18), each being worth 1 point [16]. Our aim in the present study was to contribute to the literature in terms of diagnosing delirium and predicting mortality by more comprehensively determining metabolic markers. We hope that more practical metabolic scales will be developed in future meta-analyses.
According to studies in the literature, inflammation and oxidative stress contribute to the pathophysiology of delirium. However, it remains unclear whether the neutrophil-to-lymphocyte ratio (NLR), an indicator of systemic inflammation, is associated with delirium. Results from multivariate logistic regression models showed that NLR was independently associated with delirium in elderly internal medicine patients and we think that future studies will show us the importance of NLR in predicting metabolic disorders [17].
In summary, delirium in elderly patients leads to higher mortality independently of all risk factors. Although metabolic disorders that lead to delirium have been investigated in different studies, not many of those studies had large patient samples. There is no standardization of laboratory tests to be requested for the diagnosis of delirium. We believe that a standardized laboratory testing pathway for determining metabolic status would reduce the likelihood of missing a delirium diagnosis and would facilitate early diagnosis and treatment. In this study, we identified many metabolic disorders in patients with delirium, but only potassium metabolism disorders and uremia were found to be associated with mortality. Due to inconsistent and insufficient laboratory testing of the patients, we may not have been able to detect all metabolic problems that influence mortality.
A limitation of the present study is that some laboratory data were missing and the type of delirium could not be determined due to the retrospective nature of the study. In addition, laboratory reference intervals specific to geriatric patients were not available and factors that may affect long-term mortality were not evaluated. The strengths of our study are that it identified metabolic problems that precipitate delirium in geriatric patients in a CLP Unit and investigated their associations with mortality. Moreover, this study can serve as a reference due to the high number of cases included in our analysis.
Conclusion
Delirium is a serious and common problem in geriatric patients that increases morbidity and mortality if not diagnosed and treated. The causes, diagnosis, and outcomes of delirium should be well known. Psychiatric consultation should be requested for all patients suspected of having delirium. All clinicians, and especially geriatricians and psychiatrists, should have a high awareness of delirium. Determining the metabolic markers of delirium may help diagnose delirium and predict mortality. Metabolic scales can be developed for this purpose.
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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Download attachments: 10.4328:ACAM.20732
Cigdem Dinckal, Pinar Tosun Tasar, Omer Karasahin, Sevnaz Sahin, Merve Gulsah Ulusoy, Nur Ozge Akcam, Ozan Fatih Sarikaya, Aysin Noyan, Fehmi Akcicek, Soner Duman. Investigation of metabolic disorders in the etiology of delirium in geriatric patients. Ann Clin Anal Med 2022;13(4):350-354
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Effect of isotretinoin use on hematological parameters and biochemical values
Yalçın Karagöz 1, Mustafa Tosun 2
1 Department of Health Management, Business Faculty, Düzce University, Düzce, 2 Department of Dermatology, Medicine Faculty, Sivas Cumhuriyet University, Sivas, Turkey
DOI: 10.4328/ACAM.20921 Received: 2021-10-26 Accepted: 2021-11-09 Published Online: 2021-11-15 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):355-359
Corresponding Author: Mustafa Tosun, Dermatology Department, School of Medicine, Sivas Cumhuriyet University, 58140, Sivas, Turkey. E-mail: mustafatosun@cumhuriyet.edu.tr P: +90 544 607 29 16 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6189-8016
Aim: The aim of this study was to investigate the general effects of oral isotretinoin on hematological parameters and biochemical values, and to identify whether these values vary according to age and gender.
Material and Methods: The study included 143 patients diagnosed with moderate or severe acne in the age range of 15-47 years. Patients were monitored retrospectively. Hematological parameters and biochemical values were recorded before treatment, then at the end of the first and third months of the treatment.
Results: The serum lipid levels, creatinine, cholesterol, triglyceride and AST values of liver enzymes, and renal function values were found to increase after the onset of treatment. Hematological parameters including LYM, HGB, HCT, RDW, MCV, PLT, MPV and PCT parameters were seen to increase after the onset of treatment, while the NEU parameter decreased. The values of other hematological parameters did not change.
Discussion: Although the use of oral isotretinoin has been shown to cause changes in hematological parameters and serum lipid levels, liver and renal function values, these changes usually remain within normal limits and continue with treatment.
Keywords: Isotretinoin, Acne, Hematological Parameters, Biochemical Values
Introduction
Acne vulgaris is a chronic inflammatory dermatological disease, which is more prevalent during adolescence and has a significant psychological effect on patients. It is a widespread condition during adolescence with a prevalence of approximately 85% [1]. Oral isotretinoin is a highly effective treatment method, which is widely used in acne treatment. Increased sebum production, altered keratinization, inflammation, and bacterial colonization are involved in the etiology of acne. Oral isotretinoin is the only drug that can affect these four pathogenic factors involved in the etiology of acne. It is known that oral isotretinoin reduces sebum secretion by decreasing sebocyte proliferation and differentiation and minimizing sebaceous gland size. It ameliorates follicular keratinisation and prevents follicular plug formation. It decreases the number of propionibacterium acnes and inflammation, thereby treating acne [2]. Oral isotretinoin is used in the treatment of acne that causes scarring and in the treatment of nodulocystic moderate to severe acne that does not respond to other systemic antibiotics and topical treatments.
Oral isotretinoin is a very effective treatment, although there are some side effects, including cheilitis, xerosis, conjunctivitis, xerophthalmia, nosebleeding, photosensitivity, elevated serum lipid levels (especially triglyceride and cholesterol), pancreatitis, hyperostosis, elevated liver enzyme levels, and teratogenicity [3].
The use of oral isotretinoin in the treatment of moderate to severe cystic acne was first approved by the Food and Drug Administration (FDA) in 1982. Serum lipid levels and liver enzymes of patients using oral isotretinoin are monitored by monthly blood testing, for which there is no generally accepted procedure. Moreover, there is no standard practice on how often these levels should be tested (weekly, monthly or bi-monthly), and which parameters (i.e. cholesterol, triglycerides, complete blood cell counts) should be considered [4]. This situation can lead to unnecessary financial expenses and cause unnecessary invasive procedures for patients. The aim of this study was to determine whether there is any significant difference in the specified parameters of patients before and during isotretinoin treatment. It was also aimed to determine the presence of a statistically significant difference in the parameters of the patients according to their age and gender.
Material and Methods
Before the study began, the necessary approval was received from the local ethics committee of our hospital dated 30/07/2018 and 2018-07/11 numbered decision, in accordance with the Patient Rights Regulation and ethical principles.
The study included 143 patients with moderate or severe acne vulgaris who were admitted to the Dermatology Clinic of Sivas Numune Hospital and started to receive oral isotretinoin treatment. Their medical records were retrospectively reviewed. Hematological parameters and biochemical values of the patients were compared before treatment, then at the end of the first and third months of treatment. These patients received 0.5-1 mg/kg of isotretinoin treatment. Patients with any liver disease, active infection, or hematological disease were not included in the study. The white blood cell (WBC), neutrophil (NEU), eosinophil (EOS), lymphocyte (LYM), basophil (BASO), monocyte (MONO), and red blood cell (RBC) counts, hemoglobin (HGB), hematocrit (HCT), aspartate aminotransferase (AST), red cell distribution width (RDW), mean corpuscular volume (MCV), platelet (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), creatinine, cholesterol, triglyceride, and alanine aminotransferase (ALT) levels, and the neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) values were evaluated.
The data obtained in the study were analyzed statistically using SPSS 23 software, licensed by Cumhuriyet University (Authorization Code: e56444b2255bd0030cf1). Parametric statistical tests were used since the data conformed to normal distribution. The Repeated- Measures ANOVA test was used to analyze the variables obtained from consecutive measurements made at three different time points. When the significance (p) value of Mauchly’s Test of Sphericity test was >0.05, the results of the Sphericity Assumed test were interpreted because the sphericity hypothesis was supported. When the significance (p) value of the Mauchly’s Test of Sphericity test was <0.05, the results of the Greenhouse-Geisser test were interpreted because the sphericity hypothesis was not supported.
Results
The study included a total of 143 patients (94 females, 49 males) with moderate or severe acne vulgaris, aged 15-47 years. From the analysis, it was examined whether there was a significant difference between the consecutive data obtained at three different time points and whether there were differences in terms of gender and age at these times. A significance level of 5% was considered to evaluate the results of the analysis.
According to the results of the Repeated Measures ANOVA test shown in Table 1, oral isotretinoin did not make a significant difference in WBC, EOS, BASO, PDV, NLR, PLR and ALT values. A statistically significant difference was determined in the hematological parameters of NEU, LYM, HGB, HCT, MCV, RDW, PLT, PCT and in the biochemical values of creatinine, cholesterol, triglyceride and AST.
The mean NEU values were found to be decreased compared to the baseline as the treatment procedure progressed. The mean values of LYM, HGB, HCT, creatinine and cholesterol were found to be increased compared to the baseline as the treatment procedure progressed. The mean MCV and RDW values were found to be decreased in the first month and increased in the third month compared to the baseline. The mean values of PLT, PCT, triglyceride and AST were found to be increased in the first and third months compared to the baseline, and decreased at 3 months compared to the first month.
According to the results of the Repeated Measures ANOVA test shown in Table 2, oral isotretinoin did not have a significant effect in terms of gender on the values of WBC, NEU, EOS, BASO, MONO, RBC, HGB, HCT, MCV, RDW, MPV, PDW, NLR, PLR, triglyceride, AST and ALT. A statistically significant difference was determined in the hematological parameters of LYM, PLT, PCT and biochemical values of creatinine and cholesterol.
When the mean values of LYM were evaluated, it was seen that the values in females increased compared to the baseline while those of males decreased. When the mean PLT and PCT values were examined, the values in females increased compared to the baseline, while the values of the males increased in the first month and decreased in the third month. The mean values of creatinine and cholesterol in both males and females increased in comparison to the baseline.
According to the results of the Repeated Measures ANOVA test shown in Table 3, with the exception of PCT, oral isotretinoin did not significantly affect all biochemical values and hematological parameters in terms of age.
The mean values of PCT in the age group ≤18 years old initially increased in the first and the third months compared to the baseline and decreased in the third month compared to the first month. The mean values of PCT in the age group 19-21 did not differ compared to the baseline. The mean values of PCT for the age group ≥22 years did not differ in the first month and increased in the third month compared to baseline.
Discussion
Systemic isotretinoin (13-cis retinoic acid), a vitamin A derivative, is an effective method in the treatment of moderate to severe acne, which does not respond to other treatments. It affects all the etiological factors of acne. It provides cell cyclus progression, cellular differentiation and apoptosis. It reduces sebum production and affects comedones. It reduces Propionibacterium acnes and has anti-inflammatory properties [5, 6].
However, oral isotretinoin may cause several side effects. The most critical side effect is teratogenicity. Other side-effects are dry lips, cheilitis, conjunctivitis, xerosis and biochemical changes (transaminase, triglyceride, cholesterol etc.), respectively [7]. The most commonly observed laboratory changes reported in the literature are high serum lipid and hepatic enzymes levels. In this study, cholesterol, triglyceride and AST values were found to be statistically significantly high in the third month of treatment compared to pre-treatment. There was also a statistically significant increase in creatinine values. The difference in cholesterol and creatinine values in females was found to be higher than in males. Similar results were reported by Ataseven et al. (2013) with high levels determined of cholesterol and triglyceride and no change observed in creatinine values [8]. In the current study, a significant increase in PCT values was also determined in the age groups under 18 years and over 22 years.
In a study by Alcalay et al. (2001), liver enzymes were not found to be high enough to cease treatment, only 1.5% of patients had high serum triglycerides, and no routine laboratory procedure was required in younger people [9]. In another study, it was suggested that laboratory values of patients with serum lipid levels and liver enzymes in the normal range before treatment should be monitored in the second month of the treatment, and if the values are normal, no further analysis is required [4]. In the current study, serum lipid and liver enzyme levels were found to be statistically significantly higher during the treatment than pre-treatment, but this situation did not require discontinuation of treatment.
When haematological parameters were evaluated, the PCT, PLT, RDW, MCV, HCT, HGB and LYM parameters were determined to be statistically significantly higher during treatment compared to the pre-treatment levels, while the NEU parameter was lower. When PLT, PCT and LYM parameters were evaluated in respect of gender, these parameters were significantly more varied in females than in males.
All Trans Retinoic Acid (ATRA) is a derivative of vitamin A. Since it allows the growth, differentiation and apoptosis of myeloid stem cells via CD34+ in bone marrow cells, it is used in the treatment of myelodysplastic syndrome [10]. Previous studies have demonstrated that ATRA increased the neutrophil and platelet counts and hemoglobin concentration [11]. Seçkin et al. (2016) also reported that they found HGB and PLT parameters to be statistically significantly higher considering the fact that isotretinoin is also a vitamin A derivative, which can increase bone marrow with similar effects [12].
In this study, the HGB, HCT and PLT parameters during treatment were found to be higher than pre-treatment. However, the NEU parameter was found to be lower than the pre-treatment value. A significant increase in the PLT parameter was also detected in the study conducted by Karadag et al. (2013), while no difference was found in the HGB, HCT and WBC parameters [13]. In another study, no significant difference in HGB, HCT and WBC parameters was found, whereas the PLT parameter was found to be significantly lower [14].
It is known that isotretinoin reduces TNF, IL-4, IL-17 and IFN- γ levels and is an anti-inflammatory and immunoregulatory drug [15]. In the current study, the effect of isotretinoin on inflammation was evaluated by examining inflammatory parameters (NLR, PLR, WBC, RDW and NEU). NLR and PLR are commonly used inflammatory markers that can be calculated from hematological parameters. NLR and PLR markers can be used to assess systemic inflammation in patients with psoriasis [16]. While there was no significant difference in NLR, PLR and WBC parameters in the current study, the RDW value increased and the NEU parameter decreased significantly. Seçkin et al. (2016) found that the WBC, NLR and PLR parameters did not change, while the RDW parameter was low [12]. In another study, it was revealed that PLT, PCT, WBC, NEU and MCV parameters differed during treatment and these changes appeared to fluctuate every month, but no significant difference was detected in other hematological parameters [17].
In the light of these findings, it can be said that a distinguishing feature of this study was that biochemical values and hematological parameters were extensively evaluated using more comprehensive data. Group comparisons were made according to gender and age variables, which have not been included in previous studies. In addition, the Repeated Measures ANOVA test was used in the statistical analysis.
Conclusion
Although some serum lipid and hepatic enzyme levels in this study varied during isotretinoin treatment, they generally remained within the normal range and did not lead to a condition that would require discontinuation of treatment. Hematological parameters varied in the same way. Some of the inflammatory parameters varied significantly (RDW ↑, NEU ↓), some did not change (WBC, NLR and PLR), and HGB, HCT and PLT parameters were found to be high. However, since the mean ± standard deviation values remained within normal limits, there was no need to discontinue treatment and no effect on the patient was seen. In light of all these findings, it can be said that oral isotretinoin treatment has a limited effect on hematological parameters, serum lipid levels, liver enzymes and renal functions. Therefore, it is recommended that patients should be checked for laboratory tests less frequently if there is no hepatic or haematologic disease prior to treatment. It is recommended that hematological parameters be monitored before treatment and not monitored during treatment unless an abnormal condition is present. This can be regarded as an important implication in terms of providing cost-effective healthcare services and preventing patients from undergoing unnecessary invasive procedures.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
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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5. Layton A. The use of isotretinoin in acne. Dermatoendocrinology. 2009; 1(3):162-9.
6. Nelson AM, Gilliland KL, Cong Z, Thiboutot D. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol. 2006; 126(10):2178-89.
7. Torzecka JD, Dziankowska-Bartkowiak B, Gerlicz-Kowalczuk Z, Wozniacka, A. The use of isotretinoin in low doses and unconventional treatment regimens in different types of acne: a literature review. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2017; 34(1):1.
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11. Ganser A, Seipelt G, Verbeek W, Ottmann OG, Maurer A, Kolbe K, et al. Effect of combination therapy with all-trans-retinoic acid and recombinant human granulocyte colony-stimulating factor in patients with myelodysplastic syndromes. Leukemia. 1994; 8(3):369-75.
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Yalçın Karagöz, Mustafa Tosun. Effect of isotretinoin use on hematological parameters and biochemical values. Ann Clin Anal Med 2022;13(4):355-359
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Platelet large cell ratio and immature granulocyte values in pelvic inflammatory disease
Nil Atakul, Berna Sermin Kılıc
Department of Gynecology and Obstetrics, Istanbul Training Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20926 Received: 2021-10-29 Accepted: 2021-11-14 Published Online: 2021-11-17 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):360-364
Corresponding Author: Nil Atakul, Department of Gynecology and Obstetrics, Istanbul Teaching and Research Hospital, 34093, Istanbul, Turkey. E-mail: nil_atakul@yahoo.com P: +90 532 241 31 52 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3874-8797
Aim: Pelvic inflammatory disease (PID) affects 4% of women of reproductive age and can lead to complications such as pelvic pain, ectopic pregnancy and infertility. Our study aimed to compare the Platelet Large Cell Ratio (PLCR) and percentage of immature granulocytes (%IG) results in PID and control groups and determine their significance for diagnosis, also to evaluate the association between early detection and severity of PID and parametric values such as length of hospital stay and duration of antibiotic treatment.
Material and Methods: In our retrospective case-control study, we retrospectively analyzed data of patients who presented to the Emergency Room of Gynecology and Obstetrics Department of Istanbul Teaching and Research Hospital with lower quadrant tenderness and/or fever and were admitted to the ward with a diagnosis of PID between January 2018 and January 2019. PID diagnosis was made using the criteria of “ Sexually Transmitted Diseases Treatment Guidelines, 2015”. PLCR and %IG values were calculated with semiconductor flow cytometry.
Results: A statistically significant difference was observed between groups in %IG, leukocyte count, CRP and blood sedimentation values (p <0.05). While a high correlation was found between %IG value and length of hospital stay, no correlation was found with the PLCR value. A cut-off value of 0.35 %IG showed a high sensitivity of 73% and specificity of 78% for PID diagnosis (AUC:0.81).
Discussion: Our study is one of the first to investigate PLCR and %IG value in patients with gynecological infections. Our study showed that the %IG value has a high differential diagnostic value, especially in PID patients, even in patients whose conventional infection markers were not elevated at the time of initial hospital admission.
Keywords: Pelvic Inflammatory Disease, PLCR, %IG
Introduction
Pelvic Inflammatory Disease (PID) is a sexually transmitted infection that affects 4% of women of reproductive age and causes complications such as pelvic pain, ectopic pregnancy and infertility [1-3].
Clinicians should use the diagnostic criteria for PID recommended by the Centers for Disease Control and Prevention (CDC) [2]. Barrier contraception methods appear to be protective [4,5], and their combination with first-line antibiotics has a high success rate [6]; in new studies, attempts are made to identify markers associated with conservative treatment failure to maximize timely treatment and avoid delays in surgical treatment [7]. Repeated episodes of PID have been found to increase morbidity and worsen fertility outcomes [8, 9].
Diagnostic biomarkers have been successfully used in various fields of medicine. However, timely diagnosis of bacterial infections remains a challenge. The earlier this treatment-delaying process is detected, the sooner additional preventive and potentially curative measures can be taken.
Platelet Large Cell Ratio (PLCR) reflects the proportion of platelets larger than 12 fL (the normal value for PLCR is 30% of the total platelet count). Large platelets are usually younger and contain more intracellular granules. Therefore, they have a higher thrombogenic potential [10, 11]. It is known that PLCR is mainly related to mean platelet volume (MPV), but is more sensitive to changes in platelet size. In support of this information, Babu et al. showed that PLCR value inversely correlates with platelet count and directly correlates with MPV and helps in the differential diagnosis of thrombocytopenia [12].
Despite the availability of immature granulocyte (IG) measurement, it is not yet used as a routine diagnostic tool in infected patients. Next-generation analyzers are now capable of automatically and very accurately determining the actual IG count and percentage in peripheral blood samples [13]. The performance of IG measurement remains uncertain compared with conventional infection markers such as white blood cell (WBC) count, absolute neutrophil count (ANC), and C-reactive protein (CRP).
Our study aimed to evaluate the results of PLCR and %IG in patients with pelvic infections such as tuba-ovarian abscess and endometritis in comparison between PID and control groups, to determine their significance in diagnosis and also to investigate whether they can be used as a cost-effective and rapid inflammatory marker to assess the relationship between early detection and severity of PID and parametric values such as length of hospital stay and duration of antibiotic treatment.
Material and Methods
In our retrospective case-control study, we retrospectively analyzed data of patients who presented to the Emergency Room of Gynecology and Obstetrics Department of Istanbul hospital with lower quadrant discomfort and/or fever and were admitted to the ward with a diagnosis of PID between January 2018 and January 2019. PID diagnosis, after exclusion of other diseases, was made using the ‘Sexually Transmitted Diseases Treatment Guidelines, 2015’ [2] diagnostic criteria in conjunction with one of the following major criteria and at least one of the minor criteria: Major criteria: Cervical motion tenderness on bimanual examination, tenderness over the uterus, tenderness of bilateral adnexa.
Minor criteria: Fever>38,3°C, abnormal cervical or vaginal discharge, elevated erythrocyte sedimentation rate (ESR), elevated C-reactive protein (CRP), laboratory findings of Neisseria gonorrhoeae and Chlamydia trachomatis infection of the cervix, increased leukocyte count on microscopic examination of the vaginal swab.
Exclusion criteria were defined as follows: severe trauma, infection immediately after surgery, cardiac shock, patients on immunotherapy, autoimmune disease, paraneoplastic syndrome, acute graft-versus-host disease.
A complete blood count (CBC) was requested when PID was suspected after taking a clinical history and administering physical therapy to patients presenting to the emergency room with complaints of acute abdominal pain and/or tenderness. Leukocyte count, neutrophil count, lymphocyte count, PLCR, and %IG were measured with an automated hematology analyzer (XN-1000; SysmexCorp.) from blood samples collected at the initial admission to the emergency room before hospitalization. Using data obtained from CBC analysis, PLCR and %IG values were calculated by semiconductor flow cytometry.
All patients who were submitted to our inpatient service received cefoxitin (2 g) parenterally every 6 hours and doxycycline (100 mg) parenterally twice a day for a minimal 48-hour admission, patients transitioned from parenteral to oral therapy after 48 hours of clinical improvement, followed by doxycycline (100 mg) orally twice a day for a total 14-day course.
The study patients were divided into two groups to compare the PLCR and %IG results: the PID group consisted of patients with PID diagnosis and the control group. The control group consisted of healthy women admitted to the Obstetric and Gynecological outpatient clinics of Istanbul Training and Research Hospital for routine gynecologic follow-up purposes, matched for age and BMI, and with no suspicion of PID and/or disease.
Our study was approved by the Ethics Committee of Istanbul hospital dated 07/02/2020 (Decision no: 2173). As our study is retrospective, informed consent could not be obtained from the patients.
Statistical Analysis
Continuous variables were expressed as mean ± standard deviation, and categorical data as numbers and percentages. For intergroup analysis of continuous variables, normality analyzes were performed using the Kolmogorov-Smirnov Goodness of Fit Test. Receiver Operator Characteristics Curve (ROC) analysis was performed to determine the success of the inflammatory marker %IG in predicting PID. Continuous variables were expressed as mean ± standard deviation, categorical data as numbers and percentages. Pearson correlation analysis was performed for correlation using length of hospital stay, CRP, duration of antibiotic use and s ESR as dependent variables and PLCR and %IG values as independent variables. Statistical significance was taken as <0.05 and SPSS 13 version was used for calculations.
Results
In Table 1, no statistically significant difference was found between age and BMI values in PID and control groups (p >0.05). A statistically significant difference was found between the groups in %IG, leukocyte values (p <0.05). The mean %IG value for PID patients was 0.53 and the mean PLCR value was 24.82. Although the PLCR value was lower than that of control patients, no statistical significance was reached.
In Figure 1, the ROC curve for PID and control groups showed a sensitivity of 73% and a specificity of 78% for PID diagnosis with a cut-off value of 0.35 for %IG (AUC:0.833). (Asymptotic 95% Confidence Interval, lower limit: 0.255, upper limit: 0.500).
In correlation analysis, although %IG values were positively correlated with length of hospital stay, CRP and leukocyte count (r=0.50), no correlation was found with prognostic factors such as duration of antibiotic use, leukocyte count, CRP values and PLCR values. A positive correlation was found between ESR and length of hospital stay and duration of antibiotic use (r=0.49, r=0.46) (Table 2).
Tubal-ovarian abscess (TOA) was found in 18 out of 42 PID patients (42%).
A complete blood count obtained during hospitalization showed leukocytosis (WBC 10.2 x 109/L) in 21 of 42 patients (50%).
Elevated CRP was found in 22 of 42 patients (50%) in the CBC taken during hospitalization (CRP >5 mg/L).
Blood culture results were positive in 8 of 42 PID patients (19%); E.coli grew in 4 patients, Streptococcus agalactia in 2 patients, and Staphylococcus epidermidis in 2 patients.
Discussion
The absence of the classic risk factors for PID and the triad of cervical, uterine or adnexal tenderness does not exclude the diagnosis of PID and TOA. Although PID is rare in perimenopausal women, it is critical to consider the diagnosis in differential diagnosis and to recognize it early. Clinical diagnosis of PID is often challenging, even for the most experienced clinicians.
The Centers for Disease Control and Preventation has highlighted this fact in its current guidelines; clinical diagnosis of PID has a positive predictive value between 65% and 90% [2]. This means that clinicians misdiagnose one in three patients. The reason for the low clinical diagnosis is that many adjacent organs (urinary tract, gastrointestinal tract, musculoskeletal system, etc.) have symptoms that mimic PID. No physical findings, imaging techniques, or serologic markers have high specificity and sensitivity for PID diagnosis.
The vast majority of women with tubal factor infertility do not have a history of PID, indicating the prevalence of subclinical, undiagnosed infection. Sweet estimates that approximately 60% of PID are subclinical, 36% are mild to moderate, and the remaining 4% are severe [14].
Despite all the advances in diagnostic and treatment methods, there are still cases of ruptured TOA, resulting in a mortality rate of 5 to 10% [15], if not diagnosed and treated in time, it can lead to bacteremia, septicemia, or septic shock.
The number of studies on PLCR is still limited. In a recent study consistent with our data, PLCR was detected to be statistically significantly lower (p <0.03) in patients with active periodontitis than in the control group [16]. We hypothesize that this is caused by large platelets that are destroyed during infection.
In our study, no correlation was found between PLCR values and length of hospital stay and duration of antibiotic use. Gao Y. et al. in their study, in contrast to our study, reported increased PLCR values with the severity of sepsis in patients with septic shock, but since there was no control group in their study, no correlation with the patient group was reported [17]. The fact that the patient population in their study was more critical than our patient group may explain the correlation with the severity of infection.
Our study is the first to report a %IG cutoff value for the diagnosis of PID. Some recent studies have investigated the role of percent IG measurement as a potential marker for predicting the severity of infection [18, 19]. However, these studies mainly focused on critically ill adult patients in intensive care units. Only one study examined % IG in a general outpatient setting that included all age groups, including pediatric, obstetric, and geriatric populations [19]. Nierhaus et al. found that the %IG value significantly distinguished infected patients from uninfected patients with a sensitivity of 89.2% and a specificity of 76.4%, especially in the first 48 hours after systemic inflammatory response syndrome (SIRS). The %IG value was more valuable than other clinical parameters such as CRP, lipopolysaccharide-binding protein, and interleukin 6. In their study, %IG showed a higher positive predictive value for SIRS than other parameters during the first five days of SIRS [18]. In another recent study conducted in the SIRS population, %IG at <2.0% value excluded the diagnosis of sepsis with a specificity of 90.9% [19].
Van der Geest et al. observed that WBC and CRP had comparable predictive power as %IG for microbial infections. However, they showed that %IG excluded infection at an early stage. In agreement with our study, it has been reported that %IG greater than 3% has a high sensitivity and is an indicator of sepsis risk [20]. In our study, only 50% of patients with PID had elevated CRP and WBC levels in the blood drawn at initial hospital admission. These results draw attention to the fact that %IG is a marker that increases in the early period, in line with previous studies [19,20].
Although blood culture is still considered the gold standard for diagnosing bacteremia and sepsis, only one-third of patients presenting with clinical features of sepsis have a positive blood culture, with a long incubation period for the detection of microorganisms [19]. In recent years, several publications have shown the association between blood culture results and %IG values [19, 21]. Both studies [20, 21] revealed the correlation of blood culture positivity with %IG value, and one study revealed that %IG value has equivalent utility to procalcitonin and CRP in distinguishing true bacteremia from contamination in culture-positive patients [21]. Similarly, in our study, only 19% of PID patients had positive blood culture results. The results of our two culture-positive patients were due to contamination. Due to the insufficient number of our culture-positive patients, statistical analysis with %IG values could not be performed.
No correlation was determined between duration of antibiotic use and %IG values in our study, but a high correlation was determined between the length of hospital stay and %IG values.
The duration of antibiotic use depends on the approach of different clinicians. There are very few publications on the association of %IG values with disease prognosis. In a single-center study conducted in 2015, an association with diffuse intravascular coagulation was found only for %IG value and lactate when distinguishing complicated from uncomplicated sepsis and in subgroup analyzes [22]. However, in the study by Park et al., elevated %IG was detected to be insufficient to differentiate between complicated and uncomplicated sepsis in their patients [23]. We hypothesize that the %IG value, which we found to be significant for the prognosis of PID patients, may contribute to the establishment of a standardized treatment model for these patients.
According to the results of our study, it was concluded that after %IG value, the ESR value also provided valuable data on PID prognosis according to conventional inflammatory markers. ESR is not recommended as a screening test in asymptomatic patients, but only as a supportive diagnostic test in symptomatic patients because it is influenced by several factors and has low sensitivity and specificity [24]. We think that the ESR value, a minor marker in PID diagnosis, together with %IG value may contribute to the duration and dose adjustment of antibiotic treatment.
Conclusions
Nowadays, the diagnosis of PID is based on conventional markers and culture-based pathogen detection, which are non-specific and have low sensitivity and specificity, especially in the early stages of the disease. This can lead to diagnostic uncertainty, delayed and/or overuse of antibiotics, and failure to identify women who might benefit from treatment, particularly those with subclinical infections. Our study is one of the first to investigate PLCR and %IG values in patients with gynecologic infections. We found that %IG value is an objective inflammatory marker that can be used for early diagnosis of PID, is simple and rapid, and does not waste time, especially in patients whose conventional infection markers are not yet elevated.
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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Download attachments: 10.4328:ACAM.20926
Nil Atakul, Berna Sermin Kılıc. Platelet large cell ratio and immature granulocyte values in pelvic inflammatory disease. Ann Clin Anal Med 2022;13(4):360-364
Citations in Google Scholar: Google Scholar
The comparison of radiologic measurements of the hip parameters between girls and boys
Elisa Calısgan 1, Betül Akyol 2, Resit Sevımlı 3, Caner Cengiz Turan 4
1 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Kahramanmaras Sutcu Imam University, Kahramanmaras, 2 Department of Physical Education and Sport, Faculty of Sport Sciences, Inonu University, Malatya, 3 Department of Orthopedics and Traumatology, Faculty of Medicine, Inonu University, Malatya, 4 Department of Orthopedics and Traumatology, Gözde Akademi Hospital, Malatya, Turkey
DOI: 10.4328/ACAM.20929 Received: 2021-10-31 Accepted: 2022-01-27 Published Online: 2022-02-04 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):365-369
Corresponding Author: Elisa Calisgan, Physiotherapy and Rehabilitation Department, Faculty of Health Sciences, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. E-mail: elisa.calisgan@inonu.edu.tr P: +90 534 246 24 71 Corresponding Author ORCID ID: https://orcid.org/0000 0003 4710 9540
Aim: This study aimed to compare the radiologic measurement of hip parameters between girls and boys aged 3,5 to 4 years.
Material and Methods: This retrospective study included 112 healthy children (n:57 girls, n: 55 boys) aged 3,5 to 4 years who required radiological images due to examination. Radiological images from Inonu University, Faculty of Medicine, Department of Orthopedia were used in the study. The measurements taken from the children were right and left femur head ossification, acetabular index and femur inclination angle.
Results: In girls, median right femur head ossification was 16.80 mm, median left femur head ossification was 15.30 mm, median right acetabular index was 24.100, median left acetabular index was 23.800, median right femur inclination angle was 147.400, median left femur inclination angle was 147.50°. In boys, median right femur head ossification was 18.40 mm, median left femur head ossification was 19.50 mm, the median right acetabular index was 17.40°, the median left acetabular index was 17.50°, median right femur inclination angle was 147.50°, and median left femur inclination angle was 148.70°.
Discussion: A statistically significant difference was found between girls and boys regarding right and left femur head ossification and acetabular index. This contributes to the determination of gender differentiation, gold standard values of hip parameters for diagnosis, evaluation and prognosis of hip diseases in children aged 3,5 to 4 years.
Keywords: Femur, Radiological, Hip, Parameters
Introduction
The largest bone in the human body is the femur, which has been researched in physical therapy, orthopedics and forensic anthropology for sex determination, diagnosis and prognosis of diseases [1-3]. A few anthropometric studies evaluated border parameters of the hip, which include distance between pubic tubercle, vertical and transverse acetabular diameter, anterior rim of acetabulum on dry hip bone using Vernier caliper [2]. Regarding age and gender, physical and forensic anthropology investigate using metric methods to determine the maxilla’s difference size, meatus aquatics externus, cervical bones, femur size, tibia and fibula size, and the width of the pelvis, fetal skeletal size [4]. Although femur bone and hip parameters are used to determine age and sex, and scientists research the stage of femur ossification, there is very little knowledge available about differences in hip parameters between girls and boys. Experts still do not know the differences between sexes and how to evaluate physically and virtually [5, 6]. Hip parameters, which are acetabular diameters, femur inclination angle, the ossification of femur head, acetabular index, are suitable for evaluating sexual dimorphizms, resulting from locomotion, differentiate width of pelvis between girls and boys. Femur inclination angle is evaluated with the meeting of the axis of the femur’ shaft and the femur neck axis and head [7, 8]. The femur head ossification was evaluated using the most superior, inferior, anterior and posterior points, and the distances between these points were calculated [9]. The acetabular angle is a radiological measurement used when evaluating the ossification of the epiphysis. Acetabular index, evaluation of acetabulum roof, is the standard method. In this measure, the lowest point of the cartilage Y is decided. Then the sclerotic part of the acetabulum point is determined. If the pelvic and the rear edge appear separately, both lines point where the acetabulum intersects. It should be taken with the line joining these two points, each line joining two ilium points (Hilgenreiner) is defined as the acetabular index. Average acetabular angle values should be less than 28° at birth. The angle becomes shallower progressively with age and should be less than 260 [10, 11].
Since, with the help of measurements taken from various anthropometric points on the femur and indices calculated from hip parameters, which have started to be used frequently in identification studies, the identification and determination of sexual differentiation in humans are commonly conducted from individuals and their radiographs, femur parameters are important to determine age and sex. Most of the studies used a device to measure portions of the femur, such as 3D models and radiography. Therefore, this study morphometrically evaluated hip parameters on radiographs [11]. There is, however, only a limited amount of data related to the parameters of the hip. To the best of our knowledge, there is no radiography study assessing the determination of sexual differentiation, the gold standard values for diagnosis and prognosis of hip diseases in children by using parameters of the hip. This study aimed to compare radiological measurements of the femur head ossification, acetabular index, and femur inclination angle (femur head/neck angle) between girls and boys aged 3,5 to 4 years.
Besides, this study’s purpose is the diseases such as DDH (Developmental Dysplasia of the Hip) diagnosed in boys and girls in the 3.5-4 age group, to evaluate objectively their symptoms, their effects on walking patterns, and observe their prognosis. For this purpose, the gold standard for femoral head ossification, femur inclination angle and acetabular index values were tried to be established. It was also aimed to contribute to the literature on age and gender determination in the field of anthropology, ethnology and determine the gold standard values for the diagnosis and prognosis of hip diseases.
Material and Methods
Study design
This retrospective study was performed in compliance with the principles of the Declaration of Helsinki. The study’s target population consisted of healthy children in June 2020 and July 2021 at the Department of Ortopedia, Faculty of Medicine, Inonu University. Individuals that met the inclusion criteria were selected from the target population using probable simple random sampling.
The required permission and consent were obtained from the Malatya Clinical Research Ethics Committee (approval number=2021/2324, approval date= 27/07/2021) for this study.
As part of the simple random sampling method, individuals were listed by number and those to be sampled were selected using a random number table.
The study included 112 healthy children aged 3.63 ± 1.07 years. Voluntary consent form was obtained from the participants’ families before the survey. Children who agreed to participate in the study and met the inclusion criteria were selected by a randomized sampling method in the relevant phase. Hip parameters of children aged 3,5 to 4 years are suitable for evaluating sexual dimorphizim. Age and locomotion have an effect on hip parameters; therefore, this study included paticipants who have the ability of locomotion. Also, femur head ossification was better observed in children with aged 3,5-4 years. The inclusion criteria were healthy Turkish children aged 3,5-4 years, adapting to the study.
Children were excluded from the study if they were outside the age range of 3,5-4 years, had an existing health problem such as developmental hip dysplasia, obesity, did not adapt to this study, or did not are approved by families.After applying these criteria, 20 children were excluded (four girls with hip subluxation, six boys with hydrocephalus, ten children’s families not willing to participate in the study).
Data collection
The demographic information and clinical characteristics of the children were recorded, including age and gender.
The femur head ossification size was evaluated using radiographs of both girls and boys aged 3,5-4 years (Figure 1). The most superior, inferior points and distances between these points were calculated. The radiographs are essential and recommended for evaluation because of high reliability [9, 11].
The acetabular index angle was evaluated in both girls and boys aged 3,5-4 years (Figure 2). Acetabular index was measured as the angle, which is a line connecting the lowest and lateral points of the iliac bone in the triradiate cartilage, the most supero-lateral point of the acetabulum and the Hilgenreiner line connecting the lowest end of iliac bones in both hips. Average values of the acetabular index angle should be less than 280 at birth. The grade becomes shallower progressively with age and should be less than 260 [12, 17].
Femur inclination angle was evaluated with the meeting of the axis of the femur’ shaft and the femur neck and head (Figure 3). There is an angle of 125-1300 between head and neck and femur body [13, 14].
Evaluation of femur head ossification, acetabular index angle and femur inclination was made using radiography.
Statistical analysis
Data obtained in the study were analyzed using IBM-SPSS Statistics 22.0 software. The Shapiro-Wilk test was used for evaluating normality. The Mann-Whitney U test was used to compare the significance of data that did not meet normality conditions. Results of the measured values were stated as median (min, max). In the power analysis performed, assuming that the difference between the acetabular index [14] (1 unit with α = 0.05 and 1-β (power) = 0.80, at least 25 patients (50 hips) were required for the sample. P<0.05 was accepted statistically significant [15].
Results
The evaluation of 112 healthy children (224 hips) was done, including 57 girls (114 hips; right: 57 hips, left: 57 hips) and 55 boys (110 hips; right: 55 hips, left: 55 hips) with a mean age of 3.63 ± 1.07. years (range: 3,5-4 years). It has been determined that the age variable does not affect the right and left femur head ossification, right and left acetabular index, right and femur inflation angle (p:0.397, p:0.237, p:0.521, p:0.659; p:0.675, p:0.857, respectively). No statistical differences were determined in respect of age between girls and boys (p:0.751).
In the intra-group analysis, statistically significant results were observed at all time intervals regarding right and left femur head ossification of girls and boys (p:0.05, p:0.003, respectively) (Table 1). Statistically significant differences were determined in respect of right and left acetabular indexes between girls and boys (p<0.001) (Table 1). There was no statistically significant difference in terms of right and left femur inclination angles between girls and boys (p>0.05) (Table 2).
Boys had higher points than girls with the significance of right and left femur ossification and lower points acetabular index than girls (Table 1).
Femur head ossification (right and left) is significant for determining the cut-off value of the difference between girls and boys (respectively; p:0.049, p:0.004) (Table 3).
The acetabular Index (right and left) is significantly essential to determine the cut-off value of the difference between girls and boys (p<0.001) (Table 3).
Femur Inclination Angle (right and left) is not significant for determining the cut-off value of the difference between girls and boys (respectively; p:0.112, p:0.672) (Table 3).
Discussion
This study investigated comparing radiological measurements of the femur head ossification, acetabular index and femur inclination angle between girls and boys aged 3,5 to 4 years. The results demonstrated that the right and left femur head ossification points, acetabular index in boys were higher than in girls. To the best of our knowledge, this is the first study to compare right and left femur head ossification, acetabular index and femur inclination angle between girls and boys aged 3,5-4 years.
According to previous studies, the size of femur head ossification was seen more prominent in boys aged 3,5-4 years because of a higher acetabulum score [15, 16]. In the current study, right and left femur head ossification and the acetabular index showed high score in boys aged 3,5-4 years. The conclusion of this study was similar to those of previous studies regarding the determination of gender differentiation from femur head ossification in children.
Previous studies have shown that there are differences between the genders in terms of the femur’s proximal and distal parts, according to studies of the proximal end of the femur used to determine sexual differentiation in humans. However, the distal femur part is not used to determine sexual differentiation [17, 18]. This conclusion was similar to the conclusion of the current study. This study also compared sex differentiation in children in terms of femur head ossification (distal femur part).
Kim et al. [19] compared the femur’s width and lateral condyles between girls and boys. They studied sex determination in 202 Koreans femur using the width of the lateral and medial femoral condyles. They found that the width of the medial and lateral condyles of the femur should help determine sex differentiation. This conclusion was similar to the conclusion of the current study regarding the determination of sex differentiation from femur head ossification in children.
Incesu et al. observed that acetabular index is measured higher in the left hip due to intrauterine positioning. It was suggested that the acetabular index should not used over eight years because of inconsistency in determining measurement points. In the case of radiographs, which were not evident in children, the risk of measurement differences was higher [20].
Nieves et al. investigated the differentiation of the femur neck size and total femur bone between girls (n:36) and boys (n:36). They found that boys have larger femur bone area, bone mineral density, and femur neck than girls. They concluded that femur bone parameters in males are higher than in females [21]. This conclusion was similar to the conclusion of the current in terms of femur bone parameters. Boys have larger femur head ossification than girls. However, this study did not evaluate the comparison of bone mineral density between girls and boys.
This study evaluated ossification of the femur head, acetabular index and femur inclination angle in children aged 3,5-4 years. Femur head ossification and acetabular index should be helpful for the determination of sexual differentiation. However, there was no statistically significant difference in terms of right and left femur inclination angles between girls and boys. In other words, right and left femur inclination angles should not help determine sex differentiation.
A limitation of the current study was that the width of acetabulum and femur density were not evaluated. Since radiographic imaging is harmful in healthy children due to radiation exposure, our study’s number is low. Therefore, the number of patients in the study may be higher. Also, the age group can be established in girls and boys.
Conclusion
In conclusion, this study demonstrated that femur head ossification and acetabular index should help determine sexual differentiation in children. This study provides further evidence on how radiological measurements taken from girls and boys aged 3,5 to 4 years differ in terms of femur head ossification, acetabular index, and femur inclination angle (femur head/neck angle). Also, it contributes to diseases such as DDH (Developmental Dysplasia of the Hip) diagnosed in boys and girls in the 3.5-4 age group to evaluate their symptoms, their effects on walking patterns objectively, and observe their prognosis. For this purpose, the gold standard of femoral head ossification, femur inclination angle and acetabular index values were established.
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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Elisa Calısgan, Betül Akyol, Resit Sevımlı, Caner Cengiz Turan. The comparison of radiologic measurements of the hip parameters between girls and boys. Ann Clin Anal Med 2022;13(4):365-369
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Evaluation of factors affecting mortality in cardiac arrest patients in the emergency department: A 5-year study
Nezih Kavak 1, Cemil Kavalcı 2
1 Department of Emergency, Dışkapı Yıldırım Beyazıt Training and Research Hospital, University of Health Sciences, Ankara, 2 Department of Emergency, Antalya Training and Research Hospital, Antalya, Turkey
DOI: 10.4328/ACAM.20931 Received: 2021-11-01 Accepted: 2021-12-06 Published Online: 2021-12-11 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):370-374
Corresponding Author: Nezih Kavak, Department of Emergency, Dışkapı Yıldırım Beyazıt Training and Research Hospital, University of Health Sciences, Altındağ, 06110, Ankara, Turkey. E-mail: nezih_kavak@hotmail.com P: +90 532 255 11 79 / +90 312 596 20 00 F: +90 312 318 66 90 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2751-0046
Aim: To evaluate factors affecting mortality from cardiac arrest (CA) in the emergency department (ED).
Material and Methods: Age groups, gender, location of CA, admission day, admission time, comorbidity, number of comorbidities, etiology, cardiac rhythm documented at the time of initiation of CPR (cardiopulmonary resuscitation), time interval from collapse to start of CPR, CPR duration, and mortality were evaluated.
Results: Of the 1932 patients, 1333 (69%) were male; 1582 (81.9%) patients died. Mortality in males was higher (p<0.05) and it was higher in patients aged 45 to 64 years and those aged 75 years (p<0.001). Mortality was higher in out-of-hospital CA (p<0.001). Mortality was high in patients who with comorbidities and those with more than 3 or 4 comorbidities (p<0.001). Mortality in non-cardiac CA was higher (p<0.001). Mortality was high in patients whose rhythms documented at the time of initiation of CPRs were pulseless electrical activity asystole and were not observed (p<0.001). Mortality was high in patients whose time interval from collapse to the start of CPR duration was longer than 0-5 minutes (p<0.001). Age, male gender, number of comorbidities, out-of-hospital CA, asystole and no observed rhythm documented at the time of initiation of CPR, time interval from collapse to start of CPR and CPR duration above 5 minutes (p<0.001 for all), and non-cardiac etiology (p=0.018) were determined as independent predictors for mortality in logistic regression analysis.
Discussion: Evaluation of the factors affecting mortality in CA is important for the survival of CA patients.
Keywords: Cardiac Arrest, Emergency Department, Mortality
Introduction
Cardiac arrest (CA), also known as cardiopulmonary arrest or circulatory arrest, is the cessation of adequate heart function and breathing [1]. CA is one of the most common causes of admission to the emergency department (ED), resulting in death if not immediately intervened and can occur in all age groups.
There are cardiac and non-cardiac causes in the etiology of CA [2]. Cardiac etiology of the CA accounts for approximately 2/3 of CA, where such patients often have underlying ischemic heart disease [3]. Non-cardiac etiology of CA causes include trauma, drug overdose, and sepsis, etc.
CA is evaluated in two groups: in-hospital CA (IHCA) and out-of-hospital CA (OHCA), depending on where the patient is located. ED is where IHCA cases mostly occur, and OHCA cases are also brought to ED for intervention. In general, OHCA is observed at a higher rate than IHCA, where approximately 200,000 IHCA and 350,000 OHCA cases occur annually in the United States [4].
Cardiopulmonary resuscitation (CPR) is the whole of applied methods to CA patients with the aim of returning to spontaneous circulation (ROSC).
Despite advances in CPR over the years, the mortality rate is still high in CA cases, and the survival rates are roughly 15-20% for IHCA and 5-10% for OHCA cases [3].
The present study aims to evaluate the factors contributing to mortality in CA cases in the ED.
Material and Methods
Patient population and study design
Following approval of the hospital’s local ethics committee, electronic hospital records of CA patients between January 1, 2015, and January 1, 2020 were retrospectively analyzed. Patients who developed cardiac arrest during follow-up after being admitted to ED and underwent CPR were accepted as IHCA. Patients with CA outside the hospital, who were brought to the ED by ambulance after first response (including CPR) by emergency health services teams and continued to be treated there, were considered OHCA. Patients under the age of 18, patients who were accepted as dead, and patients with missing hospital records were excluded from the study. In addition, only the initial CPRs of the patients were evaluated.
The patients included in the study were evaluated in terms of their age, gender, location of CA (in-hospital, out-of-hospital), admission day (weekdays [Monday to Friday] and weekends [Saturday and Sunday]), admission during the day (morning [8 am to 4 pm], evening [4-11 pm], night [11 pm to 8 am]), comorbidity, number of comorbidities, etiology of CA, cardiac rhythm documented at the time of initiation of CPR (shockable rhythms [pulseless ventricular tachycardia /ventricular fibrillation], pulseless electrical activity/asystole, no observed), the time interval from collapse to start of CPR, CPR duration (minute), and mortality. In this study, alive was referred to as the ROSC. The ROSC was considered as a return of pulse and its maintenance for longer than 20 minutes.
Statistical analysis
Statistical analysis was performed using Statistical Package for the Social Sciences 22.0 (SPSS Inc. Chicago, IL). Mean standard deviation, median, minimum and maximum values were given in descriptive statistics for continuous data, and number and percentage values were given in discrete data. The Shapiro-Wilk test was used to examine the conformity of continuous data to normal distribution. The Chi-square was used to compare categorical variables in patients with and without dying. The t-test and Mann-Whitney U test were used to compare continuous data of the living and the dead. The power of the CPR duration to distinguish the dead was evaluated by the area under the receiver operating characteristic (ROC) Curve (AUC). The best cut-off value was calculated using Youden’s index. Risk factors affecting mortality were analyzed using logistic regression analysis. P<0.05 was considered statistically significant.
Results
Gender analysis of the study group showed that out of 1932 patients, 1333 (69%) were male. The mean age of the patients was 50.15±16.20 years (range, min:18-max: 80). Seven hundred and thirty (37.8%) patients were 44 years of age or younger. The total number of patients who died in ED was 1582 (81.9%). Mortality was higher in males (p<0.05) and it was higher in the patients aged 45 to 64 years and those aged 75 years and over than in those aged 44 and below (p<0.001). CA occurred out-of-hospital in 1123 (58.1) patients. Mortality was higher in those with OHCA compared to IHCA (p<0.001) (Table1).
There was at least one comorbidity in 1260 (65.2%) of the CA patients, and the most common comorbidity was hypertension (HT) in 951 (49.2%) of the CA patients. Mortality was high in patients with diabetes mellitus (DM), ischemic heart disease, HT, chronic obstructive pulmonary disease, chronic kidney disease, chronic liver disease, malignancy, and other comorbidities, as well as patients with more than 3 or 4 comorbidities (p<0.001). Non-cardiac etiology was observed in 1257 (65%) of the CA patients, and mortality in non-cardiac CA was higher than those of cardiac CA (p<0.001). Sepsis, trauma, cancer, other and unknown etiologies were more common in deceased patients than in those who survived (p<0.001) (Table1).
Mortality was high in patients whose cardiac rhythm documented at the time of initiation of CPR was pulseless electrical activity asystole and was not observed (p<0.001).
Mortality was higher in patients whose time interval from collapse to start of CPR was more than 0-5 minutes (p<0.001) (Table 1).
The mean (mean± SD) age of the patients who died was 44.51±13.70 years, and the mean of age of the surviving patients was 51.40±16.45 (p<0.001). The mean (mean± SD) time of CPR was 12.40±6.06 and 31.98±7.16 for living and dead objects, respectively (p<0.001). The number of the comorbidities (mean± SD) was 0.52±0.86, and 1.99±1.68, respectively (p<0.001). AUC for CPR duration accounted for a significant proportion of variability in mortality (p<0.001), and the cut-off value was found as 17.5 minutes (Figure 1 and Table 2).
Age, gender (male), location (OHCA), number of comorbidities, cardiac rhythm documented at the time of initiation of CPR (pulseless electrical activity/asystole, no observed), time interval from collapse to start of CPR, and CPR duration above 5 minutes (p< 0.001 for all), and etiology (non-cardiac) (p=0.018) were determined as independent risk factors for predicting mortality in logistic regression analysis (Table 3).
After intensive care treatments, 41 (2.1%) patients were discharged from the hospital.
Discussion
CA is at the forefront of medical emergencies and is frequently observed in the ED. CA is a potentially reversible condition with successful CPR. The current mortality rate in CA remains critically high around the world, and it is therefore important to determine the factors affecting mortality.
In the current study, the mortality rate was 81.9%, and the survival rate to hospital discharge was 2.1%. The study by Sittichanbuncha et al. evaluated those who underwent CPR in ED, where 50.6% of patients died, and the survival rate at discharge was 11.1% [5]. In another study, the survival rate of patients to discharge from the hospital was 9.9% [6]. In the literature, the mean age of CA patients is approximately 56-75 years [3,7-10]. In the study by Alzahrani et al., three age groups were present and studied: under 45 years of age (22.8%), between 45-65 years of age (40.6%), and over 65 years of age (36.6%) [11]. The current study included patients aged 44 years and younger (37.8%), between 45-65 years (34.9%), 65 years and older (27.3%). Although the mean age of patients in the current study was 50.15, more than 1/3 of the patients were aged 44 years or younger.
It is known and expected that elderly patients have an increased risk of CA due to aging. However, our study showed that the incidence of CA increased towards the younger age group. Some studies suggest that age is not associated with survival, while one study suggests that advancing age is a poor prognostic factor [8,12-14]. The current study’s findings indicated that age is a contributing factor to mortality in CA patients. The results of our study suggest that age is a factor contributing to mortality in CA patients.
In the study by Pandian et al., there was no relationship between gender and mortality [6]. However, in our study, the mortality rate was higher in male patients (p<0.05). It is known that females have a lower incidence of CA than males due to various reasons, such as physiological differences between males and females and the protective effects of estrogen on the heart in females. This difference in mortality rate might be explained by the fact that most of the patients in the current study were males.
In this study, mortality was higher in OHCA than in IHCA. Contrary to OHCA, deterioration of physiological parameters in the majority of patients in IHCA can be a warning in terms of CA that may occur in these patients. Therefore, IHCA patients are relatively predictable and preventable.
In the study by Pandian et al., CA was observed more frequently during morning shift hours compared to evening and night hours [6], while there was no significant time difference in the study by Alzahraniet et al. [11]. In a large-scale multicenter study, an increase in OHCA was found between 8:00 and 10:59 in all age groups. They stated that this difference observed in the morning was caused by physiological changes, but was not significantly correlated with the mortality of admitted patients [15]. In this study, morning time admission was more common in CA; however, the results did not conclude a significant relationship between time of admission and mortality in CA patients.
Cardiovascular risks in mid-life cardiac CA, smoking, and antihypertensive treatment in non-cardiac CA are among the risk factors [3]. In the study by Pandian et al., 88.9% of patients had at least one comorbidity, and 29.1% had two or more comorbidities, with DM (34.3%) and HT (32.7%) being the most common comorbidities [6]. In a similar study conducted with CA in Turkey, the most common comorbidities identified in CA patients were HT (82%) and DM (67%) [9].
As the number of comorbidities increases in CA patients, the probability of survival of patients decreases. In a study, the survival rate for CA patients was 64% for patients with one or less comorbid disease and 9.6% for patients with two comorbidities, and all those with more than two comorbidities died [16]. In another study, a 20% survival rate was observed in those without comorbidity and 6% in those with more than two comorbidities [8]. Similarly, the survival rate decreased as the number of comorbidities increased in our study. In addition, all patients with three or more comorbidities could not be saved and died.
CA patients with cardiac etiology are most common among both in-hospital and out-of-hospital patients. In addition, survival in CA patients with cardiac etiology is higher than in non-cardiac etiology. As it is known, CA due to drug overdose in young adults has recently constituted an important part of OHCA [8]. CA due to drug overdose constitutes 11% of the overall CA in this study. Therefore, drug overdose should be considered in etiology, especially in young adult CA patients who are admitted to ED.
The survival rate in these patients ranges from 3% to 19% [17]. Traumatic CA accounted for 19.3% in our study, which might be due to the the fact that the hospital in which the study was held was a tertiary-level trauma center hospital in the region. The prognosis in traumatic CA is very poor and; some of these patients die before reaching the hospital. In the study by Xue et al., only 2.1% of traumatic CA patients survived within 24 hours, and none were discharged [18]. In the present study, there was a 0.9% survival rate in patients with traumatic CA. Furthermore, all patients with unknown etiology died in the ED, and all of these patients were considered as OHCA.
In the study by Ohlsson et al., 26.2%of the patients had ventricular fibrillation or ventricular tachycardia, 59.5% had asystole, and 14.3% had pulseless electrical activity, regardless of where CA occurred [3]. According to Pandian et al.’s study, 76% of CA patients had pulseless electrical activity/asystole, 8% had shockable rhythms, and 16% had no observed rhythm documented at the time of initiation of CPR [6]. Similar to these studies, the most common cardiac rhythm in this study was pulseless electrical activity/asystole (44%). Hence it can be concluded that the effect of rhythm documented at the time of initiation of CPR on mortality is significant in CA. The mortality rate in patients with cardiac rhythm documented at the time of initiation of CPR, ventricular fibrillation, and ventricular tachycardia is lower than those present with asystole and pulseless electrical activity [10].
CPR should be started as soon as possible after CA, in both IHCA and OHCA patients. The study of Vancini et al. found that the median CPR duration was 17 minutes, and the mortality was higher in those with longer, more prolonged CPR in ED [10]. It was reported in a study that CPR duration of 21 minutes or more was associated with increased mortality in IHCA [7]. In the large multicenter study conducted with IHCA, the median resuscitation time CPR duration was found to be 12 minutes in those with a return of spontaneous circulation, while it was 20 minutes in non-survivors [19]. In the current study, the median CPR duration was 10 minutes for those alive and 30 minutes for those who died.
Although this is a single-center study, the high number of patient populations is a valuable aspect. However, one of the main limitations of the current study is its retrospective design. In addition, the data on long-term follow-up of discharged patients were not available and not evaluated by this study.
Conclusion
CA patients are one of the most common conditions in ED. Our results showed that the mortality rate among CA patients was very high. The age, gender, localization of CA, comorbidity, number of comorbidities, etiology, cardiac rhythm documented at the initiation of CPR, the time interval from collapse to start of CPR, and CPR duration plays a role in mortality in CA cases.
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. Gul SS, Cohen SA, Avery KL, Balakrishnan MP, Balu R, Chowdhury MAB, et al. Interdisciplinary Cardiac Arrest Research Review ICARE group. Cardiac arrest: An interdisciplinary review of the literature from 2018. Resuscitation. 2020;148:66-82.
3. Ohlsson MA, Kennedy LMA, Juhlin T, Melander O. Midlife risk factor exposure and incidence of cardiac arrest depending on cardiac or non-cardiac origin. Int J Cardiol. 2017;240:398-402.
4. Lam V, Hsu CH. Updates in Cardiac Arrest Resuscitation. Emerg Med Clin North Am. 2020;38(4):755-69.
5. Sittichanbuncha Y, Prachanukool T, Sawanyawisuth K. A 6-year experience of CPR outcomes in an emergency department in Thailand. Ther Clin Risk Manag. 2013;9:377-81.
6. Pandian GR, Thampi SM, Chakraborty N, Kattula D, Kundavaram PP. Profile and outcome of sudden cardiac arrests in the emergency department of a tertiary care hospital in South India. J Emerg Trauma Shock. 2016;9(4):139-45.
7. Araç S, Zengin Y, İçer M, Gündüz E, Dursun R, Durgun H, et al. Acil Serviste Kardiyopulmoner Resüsitasyon Yapılan Hastaların Değerlendirilmesi; Retrospektif Çalışma (Evaluation of Cardiopulmonary Resuscitation Patients in the Emergency Department; Retrospective Study). Abant Tıp Dergisi/Abant Medical Journal. 2021; 10(1):140-51.
8. Moosajee US, Saleem SG, Iftikhar S, Samad L. Outcomes following cardiopulmonary resuscitation in an emergency department of a low- and middle-income country. Int J Emerg Med. 2018 1;11(1):40.
9. Geçmen Ç, Kahyaoğlu M, Kalaycı A, Naser A, Akgün Ö, Candan Ö et al. Üçüncü Basamak Bir Merkezden Kardiyak Arrest Serisi (Cardiac Arrest Series from a Tertiary Center). Koşuyolu Heart Journal. 2018; 21(1): 16-20.
10. Vancini-Campanharo CR, Vancini RL, de Lira CA, Andrade MD, Lopes MC, Okuno MF, et al. Characterization of cardiac arrest in the emergency department of a Brazilian University Reference Hospital: A prospective study. Indian J Med Res. 2016;144(4):552-9.
11. Alzahrani AH, Alnajjar MF, Alshamarni HM, Alshamrani HM, Bakhsh AA. Prevalence and Outcomes of Sudden Cardiac Arrest in a University Hospital in the Western Region, Saudi Arabia. Saudi J Med Med Sci. 2019;7(3):156-62.
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13. Johnson NJ, Salhi RA, Abella BS, Neumar RW, Gaieski DF, Carr BG. Emergency department factors associated with survival after sudden cardiac arrest. Resuscitation. 2013;84(3):292-7.
14. Parish DC, Dane FC, Montgomery M, Wynn LJ, Durham MD. Resuscitation in the hospital: differential relationships between age and survival across rhythms. Crit Care Med. 1999;27(10):2137-41.
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19. Goldberger ZD, Chan PS, Berg RA, Kronick SL, Cooke CR, Lu M, et al. American Heart Association Get With The Guidelines—Resuscitation (formerly National Registry of Cardiopulmonary Resuscitation) Investigators. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet. 2012;380(9852):1473-81.
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Nezih Kavak, Cemil Kavalcı. Evaluation of factors affecting mortality in cardiac arrest patients in the emergency department: A 5-year study. Ann Clin Anal Med 2022;13(4):370-374
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The effects of midazolam and fentanyl on neonates in elective cesarean section
Asiye Özdemir 1, Abdullah Özdemir 2, Ahmet Şen 3, Nesrin Erciyes 4
1 Department of Anesthesiology and Intensive Care, Ministry of Health Education and Research Hospital, Rize, 2 Department of Anesthesiology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, 3 Department of Anesthesiology, Faculty of Medicine, Kanuni Training and Research Hospital, Health Sciences University, Trabzon, 4 Deparpment of Anesthesiolog, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
DOI: 10.4328/ACAM.20934 Received: 2021-11-02 Accepted: 2021-12-02 Published Online: 2022-01-10 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):375-378
Corresponding Author: Abdullah Özdemir, Department of Anesthesiology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey. E-mail: Abdullah.1565@gmail.com P: +90 505 217 41 67 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4778-9622
Aim: As in all patients scheduled for surgery, obstetric patients may have both surgery and operating room fear, and secondary autonomic stress response may develop. To compare the effects of premedication with fentanyl or midazolam on maternal anxiety, tolerance of the birthing process, and central nervous system depression of the newborn.
Material and Methods: ASA II patients scheduled for elective cesarean section with spinal anesthesia who gave informed consent were randomized into two groups to receive either 0.025 mg/kg iv midazolam or 1 mcg/kg iv fentanyl. The APAIS score was recorded before and five minutes after premedication. Following the delivery of the newborn, the APGAR score was recorded at the first and fifth minutes, and the NACS score was recorded at the fifteenth minute. The primary outcome was a decrease in APAIS scores, the secondary outcomes were differences in APGAR and NACS scores.
Results: Data of 50 patients were analyzed. First-minute APAIS score was similar (19.3±5.3 vs 19.6±4.7, p=0.82), but the decrease at the fifth minute was more prominent in the midazolam group (10.8±3.8 vs 15.3±4.9, p=0.001). APGAR and NACS scores were similar (p=0.87, p=0.58, and p=0.65, respectively).
Discussion: This study found that midazolam was more effective in reducing anxiety in uncomplicated pregnant patients with no apparent postdelivery depression in the newborn.
Keywords: Preoperative Anxiety, Midazolam, Fentanyl, Cesarean Section, Newborn
Introduction
General and regional anesthesia can be applied in obstetric anesthesia. While choosing the anesthesia technique, ensuring the safety and comfort of both the mother and the baby to be delivered should be considered together.
In cesarean sections performed under general anesthesia, there is a risk of undesirable effects such as maternal aspiration of gastric contents, difficulty in intubation, fetal depression due to general anesthetics, low Apgar score and low NACS, fetal hypoxia and acidosis due to maternal hyperventilation, postpartum bleeding, postoperative pain, delayed mobilization, increased risk of thromboembolism, and delayed breastfeeding [1].
With the regional anesthetic approach, the mother can experience the moment of birth and breastfeed her baby early. In addition, the risks of intraoperative aspiration and difficulty in intubation are eliminated, and the depressant effect of anesthetic drugs in the newborn is avoided. While analgesia and early mobilization in the postoperative period are provided, the risk of thromboembolism and blood loss due to sympathetic blockage also decrease. At the same time, the neuroendocrine response to surgical stress is prevented, thus the need for anesthetics is reduced, making the work of the anesthesiologist easier [2]. Regional anesthesia has become an increasingly preferred method due to its high success rate [3].
Higher anxiety levels have been reported in patients who are young, female, who will undergo an operation for the first time, who have had previous bad anesthetic experience and have a fear of death [4].
With our study, we aimed to investigate at what doses midazolam and fentanyl can be used in premedication in order to relieve anxiety and pain caused by uterine contractions in the mother and to avoid negative effects on the baby.
Material and Methods
This study was conducted with the approval of the local ethics committee of Karadeniz Technical University Faculty of Medicine (registration number: 2007/49). Patients who were planned for elective cesarean section by the Gynecology and Obstetrics Clinic and had regional anesthesia indication were informed about the study in the preoperative period and their consent was obtained. Fifty patients, aged 21-38 years, ASA II, were included in the study and randomly divided into two groups of 25 each, and Amsterdam Preoperative Anxiety and Information Scale (APAIS) tests were applied to the patients before premedication in the preoperative waiting room (APAIS 1st minute). Then, one group was premedicated with midazolam 0.025 mg/kg iv (Group M), and the other group with fentanyl 1 µg/kg iv (Group F). After 5 minutes, the “APAIS” score was repeated (APAIS 5th minute). After this evaluation, the patients were taken to the operating table.
Non-invasive arterial pressure (NIAP), peak heart rate (HR) and pulse oximetry (SpO2) were measured. Crystalloid fluid replacement was applied to the patients before the operation. The patients were followed up in the intraoperative and postoperative periods for complications such as loss of consciousness, nausea, vomiting, tremor and agitation.
For spinal anesthesia, a 22 G spinal needle was used in the lateral decubitus position and 12.5 mg of levobupivacaine was administered intrathecally. The sensory block level was evaluated with cold-hot and pinprick tests. The operation was allowed to start when the sensory block was sufficient (thoracic 4 levels).
When the baby was delivered, the newborn was examined and APGAR scores were recorded at the 1st and 5th minutes. After basic neonatal care, and the umbilical cord was clamped and cut, “Neonatal Neurological and Adaptive Capacity Score (NACS)” was recorded at the 15th minute.
Statistical analysis:
The data obtained, demographic data, mean and standard deviation
were evaluated with t-test and Mann-Whitney U test. The relationship between APGAR, APAIS and NACS scores was analyzed with the Chi-square test. Interpreting the results of the analysis, p<0.05 was accepted as an indicator of the significant difference, and p>0.05 as the indicator that the difference was not significant.
Results
The pregnant women participating in the study were between the ages of 21-38. Midazolam was administered to one group (group M) and fentanyl to the other group (group F) for premedication. There was no statistically significant difference in terms of age and weight in demographic data of the groups. While there was no statistically significant difference in APAIS 1st minute score between the pregnant groups (p=0.82; p>0.05), there was a statistically significant difference between the APAIS 5th minute scores (p=0.001; p<0.05).
There was no statistically significant difference between the groups in terms of APGAR 1st and 5th minutes scores of the newborns (p=0.87; p>0.05). There was also no statistical difference between the groups in terms of NACS scores of the newborns (p=0.65; p>0.05). APAIS, APGAR and NACS scores of the groups were compared (Table 1).
Discussion
Anxiety, which is common in patients who will undergo an operation, reaches its highest level in the preoperative preparation room. The study by Won-Sung Kim et al. reported that there is a strong relationship between anxiety in patients and hemodynamic changes [5]. In several studies, it was reported that anxiety started a few days before the operation and reached its highest levels just before the operation and two days after it [6].
It has been reported that levels of anxiety are higher in patients who are young, women, who have had previous bad anesthetic experience, who will undergo surgery for the first time, and those who have a fear of death [4].
Anxiety of the patient increases the peroperative stress response due to anesthesia and surgery, and affects the peroperative hemodynamics by activating the sympathetic nervous system. Thus, tachycardia, hypertension, arrhythmia and increased pain in the postoperative period can occur. Reducing anxiety with sedation makes easier the work of the anesthesiologist during induction, reduces the need for anesthetic drugs, and helps stabilize hemodynamics [7].
Nowadays, sedation is routinely used in regional anesthesia applications. However, due to the fear of possible depressant effects on the newborn, it is not applied at all or rarely applied in cesarean operations. Cesarean section is a surgery in which the expectant mother experiences anxiety and perioperative stress. Therefore, sedation becomes more important in cesarean section patients compared to other surgical patients. This is because vasoconstriction develops in uterine arteries as a result of the mother’s stress and related autonomic response, and as a result, the risk of developing fetal distress increases.
There are many studies in the literature regarding the use of sedative drugs in regional anesthesia [8, 9]. However, there are a very limited number of studies on the use of midazolam and fentanyl in cesarean cases. Frölich et al. administered 1mcg/kg iv fentanyl and 0.02 mg/kg iv midazolam to expectant mothers during skin cleansing for spinal anesthesia. Their study reported that a significant sedation was achieved in the group receiving a combination of midazolam and fentanyl compared to the placebo group; also there was no difference between the newborn APGAR and NACS scores [9].
In our study, patients undergoing a cesarean section were given 0.025 mg/kg iv midazolam or 1 mcg/kg iv fentanyl prior to delivery to the operation room. Such a time was chosen in order to suppress the increased anxiety in pregnant women, a special patient group, and to reduce the pain that may occur during spinal block procedure. In the study by Frölich et al., fentanyl and midazolam were applied just before the spinal anesthesia procedure [9].
In the study by Senel AC et al., 0.02 mg/kg midazolam was given as a premedication in cesarean section patients with extremely intense affectivity before cesarean. Sedation levels of these mothers and mothers in the placebo group, and the APGAR and NACS scores of the newborns were compared. It was observed that adequate sedation was achieved in mothers who were premedicated with midazolam compared to the placebo group, and there was no significant difference between the newborns from the two groups in terms of APGAR and NACS scores [10]. We aimed to provide sedation with different drugs and doses.
There are many cases of low muscle tone in newborns of pregnant women given diazepam until a few decades ago [11]. For this reason, anesthesiologists do not prefer pharmacological premedication because of the possible depressant effects due to sedation in the newborn. However, midazolam has been discovered after diazepam and has a shorter effect. Its effects on the newborn are also minimal [10]. Therefore, we aimed to show that midazolam can be safely used for sedation in pregnant women who will undergo cesarean operation.
In a different study, it was observed that 90% of mothers fell asleep before the operation after administiration of iv midazolam for sedation in cesarean operations under spinal anesthesia. They reported that there was no difference between these operations and the control group in terms of neonatal APGAR scores and umbilical vein pH values [9].
Frölich et al., in order to overcome concerns such as the decrease in tonus due to midazolam and the potential respiratory depression due to fentanyl, administered a single dose of midazolam and fentanyl during cesarian section and observed the clinical outcome in the patient and the newborn. In this study, it was determined that 0.02 mg/kg midazolam and 1 mcg/kg fentanyl did not cause maternal depression, did not impair breathing, but were doses that had a clinical effect [9]. Therefore, in our study, we considered the possibility of preoperative use of 0.025 mg/kg of midazolam, which is close to this dose and effective in our clinical practice, and 1 mcg/kg fentanyl due to its sedo-analgesia effect.
One of the reasons why deep sedation is not preferred in cesarean section operations performed under regional anesthesia is that the mother wants to see the baby born and remember that moment. The drug doses we determined were chosen as doses that would not cause amnesia in the mother, and the mother was not prevented from seeing her baby.
In order to ensure standardization in the study, all APGAR, NACS and APAIS scores were made by the same anesthesiologist. When the difference between the groups that received premedication with midazolam and fentanyl in the preoperative waiting room was evaluated, there was a statistically significant difference between APAIS scores. A statistically significant level of sedation was achieved in the mother in both the midazolam group and the fentanyl groups. Furthermore, higher levels of sedation were observed in the midazolam group There was no statistically significant difference between the groups in our study in terms of APGAR (1st and 5th minutes) and NACS values of newborns.
As a limitation in our study, since some surgeons and patients did not want to participate in the study, the number of patients included in the study was low.
Conclusion:
The dosage and timing of the drugs we used provided a decrease in the anxiety of mothers, and we believe that it does not have any negative effect on newborns. We believe that there is a need for studies with more cases on this subject.
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. Morgan GE Jr, Mikhail MS, Murray MJ, Larson CP. 3rd ed. Clinical Anesthesiology. New York: McGraw Hill; 2004. p. 830-1.
2. Papadopoulou E. Maternal stress-response during emergency cesarean section with general and spinal anesthesia. Reg Anesth Pain Med 2005(1); 30:72 DOI: 10.1136/rapm-00115550-200509001-00134
3. Kayacan N, Arıcı G, Akar M, Karslı B, Zorlu G. The Comparison of Different Regional Anesthetic Tecniques on Hemodynamic Effect and Postoperative Analgesic Requirement for Caesarean Section T. Klin.J. Gynecol Obs. 2004; 14: 200-6.
4. Klopfenstein CE, Forster A, Gessel EV. Anesthetic assessment in an outpatient consultation clinic reduces preoperative anxiety. Can J Anesth. 2000; 47(6): 511-15.
5. Won-Sung Kim, Gyeong-Jo Byeon, Bong-Jae Song, Hyeon Jeong Lee. Availability of preoperative anxiety scale as a predictive factor for hemodynamic changes during induction of anesthesia. Korean J Anesthesiol. 2010; 58(4): 328–33.
6. Miller Ronald D. Psychological preparation and preoperative medication in anesthesia; 4th ed. Philadelphia, PA: Churchill Livingstone; 1994. p.1015.
7. Rama-Maceiras P, Gomar C, Criado A, Arizaga A, Rodriguez A, Marenco ML. Sedation in surgical procedures using regional anesthesia in adult patients: results of a survey of Spanish anesthesiologists Rev Esp Anestesiol Reanim. 2008; 55(4):217-26.
8. Ahmed A, Khan FA, Hussain A. Comparison of two sedation techniques in patients undergoing surgical procedures under regional anaesthesia. J Pak Med Assoc. 2007; 57(11):548-52.
9. Frölich MA, Burchfield DJ, Euliano TY, Caton D. A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neonatal effects. Can J Anaesth. 2006; 53(1):79-85.
10. Senel AC, Mergan F. Premedication with midazolam prior to caesarean section has no neonatal adverse effects. Rev Bras Anestesiol. 2013; 64(1):16-21.
11. Haram K. “Floppy infant syndrome” and maternal diazepam (Letter). Lancet 1977;2: 612–3.
Download attachments: 10.4328:ACAM.20934
Asiye Özdemir, Abdullah Özdemir, Ahmet Şen, Nesrin Erciyes. The effects of midazolam and fentanyl on neonates in elective cesarean section. Ann Clin Anal Med 2022;13(4):375-378
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Effects of melatonin and N-acetylcysteine on lung ischemia reperfusion injury
Atilla Durkan 1, Muharrem Cakmak 2, Refik Ulku 3, Selver Ozekıncı 4, Ebru Kale 5
1 Thoracic Surgery Clinic, Gazi Yasargil Education and Research Hospital, Diyarbakir, 2 Department of Thoracic Surgery, Fırat University Faculty of Medicine, Elazig, 3 Department of Thoracic Surgery, Faculty of Medicine, Dicle University, Diyarbakir, 4 Department of Pathology, Faculty of Medicine, Dicle University, Diyarbakir, 5 Department of Biochemistry, Hamidiye Faculty of Medicine, Health Sciences University, Istanbul, Turkey
DOI: 10.4328/ACAM.20935 Received: 2021-11-03 Accepted: 2022-02-02 Published Online: 2022-02-04 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):379-383
Corresponding Author: Muharrem Cakmak, Fırat University Faculty of Medicine, Department of Thoracic Surgery, Elazig, Turkey. E-mail: drcakmak@gmail.com F: +90 424 233 35 55 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9504-2689
Aim: In our study, we aimed to determine the effects of using melatonin, N-acetyl cysteine, and low potassium dextran solution (LPDS) as a preservative solution on ischemia/reperfusion injury.
Material and Methods: A total of 48 male Sprague-Downey rats were used. Rats were divided into 8 groups: group 1: ischemia, group 2: ischemia+melatonin, group 3: ischemia + N-acetylcysteine, group 4: ischemia+melatonin + N-acetylcysteine, group 5: ischemia + reperfusion, group 6: ischemia + reperfusion + melatonin, group 7; ischemia + reperfusion + N-acetyl cysteine, and group 8; ischemia+reperfusion+melatonin+N-acetyl cysteine. Total antioxidant capacity (TAOC), malondialdehyde (MDA) and neutrophil values of each group were determined. The TAOC was obtained by spectrophotometric measurement of the absorption level of the color formed by the hydroxylion formed by the Fenton reaction with orthodianisidine. The MDA value was obtained spectrophotometrically using the thiobarbituric acid method, and the Neutrophil count was obtained as cell count using Papanicolau Stain stain.
Results: While the highest TAOC values were in groups 4, 2, 3, 1, the lowest TAOC values were in groups 5,7,6,8. The highest MDA values were in groups 5, 7, 6, 1, 8, whereas the lowest MDA were in groups 4, 2, 3 (p<0.05). Neutrophil in bronchoalveolar lavage increased in groups 5,7,6,3,2,8,4.
Discussion: In lung ischemia reperfusion, the use of melatonin and/or N-acetyl cysteine, and LPDS decreases plasma MDA levels and increases TAOC values. Additionally, the use of these antioxidants and preservation solutions decreases cell damage immunohistochemically, the cytokines mediating inflammation, the PMNL, and the inflammatory response associated with them.
Keywords: Ischemia; Melatonin, N-acetylcysteine, Reperfusion
Introduction
Many cells, mediators, receptors, and free oxygen radicals are responsible for ischemia- reperfusion damage to tissues and organs [1, 2]. Neutrophils, complement and other polymorphous leukocytes are effective in endothelial damage, and free oxygen radicals play a role in ischemia reperfusion injury, especially during the reperfusion phase [3, 4]. The main preservation solutions used in lung transplantations are low potassium dextran solution (LPDS), euro-collins (E-C), and wisconsin solution (W-S) (5).
Melatonin is an effective molecule preventing the toxic effects of free radicals. Having antioxidant properties, this molecule can protect the lung against ischemia reperfusion injury [6, 7]. N-acetyl cysteine, a potent antioxidant and anti-inflammatory, has mucolytic properties and protects the lung against ischemia reperfusion injury [8]. LPDS is one of the modified lung preservation solutions and is used in many lung transplant programs [5].
In our study, we aimed to report the results of the use of melatonin, known to protect the lung from ischemia and has antioxidant activity, N-acetyl cysteine, having mucolytic properties, and LPDS, a preservation solution. Additionally, we tried to determine the total antioxidant capacity (TAOC) and serum Malondialdehyde (MDA) levels, indicators in the evaluation of ischemia reperfusion injury.
Material and Methods
After the approval of Dicle University Ethics Committee (approval date/no: 12.03.2008/18), a total of 48 Spraque-Downey male rats were used in the study. All rats were divided into 8 groups.
Group 1 was the ischemia-only group, group 2 was ischemia+melatonin, group 3 was ischemia+N-acetylcysteine, group 4 was ischemia+melatonin+N-acetylcysteine, group 5 was ischemia+reperfusion, group 6 was ischemia+reperfusion+melatonin, group 7 was ischemia+reperfusion+N-acetylcysteine, and group 8 was ischemia+reperfusion+melatonin+N-acetylcysteine group.
Procedures
After sedation with Sodium-Pentobarbital, a 2 cm collar incision was made in the cervical region. A 0.5 cm incision was made in the trachea, and a 5F tracheostomy cannula was inserted and connected to a ventilator.
The incision line was extended from the cervical region below the xiphoid and total sternotomy was performed. By revealing the left hilum of the lung, the left pulmonary artery was cannulated with a 24G angiocath and heparinized. The atraumatic clamp was placed to the left lung hilum to create ischemia.
Group 1 rats were exposed to ischemia for 2 hours by placing an atraumatic clamp on the left lung hilum. Group 2 rats were administered melatonin 3mg/kg i.p. with LPDS (15 min, 15-20cc) 15 minutes before ischemia, and then the hilus was exposed to ischemia for 2 hours. Group 3 rats were given N-acetylcysteine 150mg/kg i.p. with LPDS 15 minutes before ischemia and and then were exposed to ischemia for 2 hours. Group 4 rats were administered melatonin and N-acetylcysteine i.p. with LPDS 15 minutes before ischemia and were exposed to ischemia for 2 hours. Group 5 rats were exposed to ischemia for 2 hours and then reperfused for 2 hours. Group 6 rats were exposed to ischemia for 2 hours, and just before reperfusion, they were given melatonin i.p. with LPDS and were exposed to reperfusion for 2 hours. Group 7 rats were exposed to ischemia for 2 hours, and then N-acetylcysteine i.p. with LPDS was given just before reperfusion, and they were exposed to reperfusion for 2 hours. After being exposed to ischemia for 2 hours, group 8 were given melatonin and N-acetylcysteine i.p. with LPDS just before reperfusion, and the rats were exposed to reperfusion for 2 hours.
At the end of the experiment, approximately 5cc of blood was taken by cardiac puncture for TAOC capacity measurement. Plasma and serum parts were separated, and serum part was kept in deep freezer at -80 C°, and then antioxidant capacity levels were measured in an autoanalyzer (Abbott Aeroroset, USA) with the antioxidant capacity kit developed by Erel. Afterwards, the absorption level of the color formed by the hydroxyl ion formed by the Fenton reaction with orthodianisidine was measured spectrophotometrically in the autoanalyzer. The intensity of the color was evaluated according to the antioxidant capacity, and the test results were calculated as mmol/lt.
At the end of the experiment, the upper lobe of the lung was taken from the rats and washed with isotonic solution. MDA analysis was performed using the thiobarbituric acid method. 0.5gr tissue taken from lung tissue was homogenized with 4.5 ml 5.5% Trichloroacetic acid and kept for 10 minutes at 100°C, then 1ml of thiobarbituric acid was added to the samples that were kept at +4°C for 30 minutes and cooled, and measured spectrophotometrically (Shimadzu, 1800 series, Japan) at 532 nanometers (nmo/gr).
Approximately 1cc of saline was given to the main bronchus of the left lung with 24G Angiocut and aspirated, and the samples were spread on the preparation. The samples were then stained with Papanicolau stain. BAL evaluation was performed at 40 magnification, by counting 50 cells in 2 distant regions where cellularity is most intense. Lymphocytes, Macrophages, PMNL and Resp. Epithelial numbers were recorded. Those with no cells were evaluated as zero. The number of neutrophils was estimated in %.
Tissue samples weighing 1g were taken from the lower lobe of the left lung and sent for pathological examination. Then, all rats were sacrificed by heart puncture.
Statistics
IBM SPSS Statistics 22.0 was used for data analysis. Continuous variables were expressed as mean ± standard deviation, while categorical variables as number-ratio. Homogeneity analysis of variances was done with Levene’s test (p>0.05). The Shapiro-Wilk test was used to evaluate the normal distribution (p>0.05). Results were evaluated with the Kruskal-Wallis test, analysis of variance and the Mann-Whitney-U test. Some results were evaluated by giving different scores to each group among themselves.
Lung alveolar hemorrhage values and parenchymal damage were expressed as scoring. The absence of hemorrhage was scored 0 (grade 0), a single red cell in the alveoli was scored as 1 (grade 1), erythrocyte populations that did not completely fill the alveoli were 2 (grade 2), and erythrocyte populations that completely filled the alveoli were scored as 3 points (grade 3).
In the lung parenchymal injuries, the absence of damage was scored as 0 (normal), focal inflammation as 1 (very mild damage), perivascular, peribronchial edema, vascular congestion and inflammation as 2 (moderate damage), and severe vascular congestion and thrombosis with intrapulmonary-interstitial edema as 3 points (severe damage).
Results
All rats were at the same age, weighing 250-300 grams. The decrease in group 1 TAOC value was found to be statistically significant compared to groups 2, 3, 4 (p<0.05), and the decrease in TAOC values in groups 5, 6, 7, 8 was statistically significant compared to groups 1, 2, 3, 4 (p<0.05). The increase in group 8 TAOC value was statistically significant compared to groups 6 and 7 (p<0.05) (Table 1).
The decrease in MDA value in group 1 was statistically significant compared to groups 2, 3, 4, 5, 6, 7. There was a statistically significant decrease in group 2 MDA value compared to groups 1, 5, 6, 7, 8. The decrease in group 3 MDA value was statistically significant compared to groups 1, 4, 5, 6, 7, 8. The decrease in group 4 MDA value was statistically significant compared to groups 1, 3, 5, 6, 7, 8. On the other hand, the increase in group 5 MDA value was statistically significant compared to all groups. There was a statistically significant increase in group 6 MDA value compared to groups 1, 2, 3, 4, 5. The increase in group 7 MDA value was statistically significant compared to groups 1, 2, 3, 4, 5, 8. Finally, the increase in group 8 MDA value was statistically significant compared to groups 2, 3, 4, 5, 6, 7 (p<0.05). While the decrease in MDA values in groups 2, 3, and 4 was found to be statistically significant compared to groups 5, 6, 7, 8, the increase in MDA values in group 5 was statistically significant compared to groups 6, 7, 8. The decrease in MDA values in group 8 was statistically significant compared to group 6, 7 (p<0.05) (Table 2). When the TAOC and MDA values of the groups were compared, the increase in the MDA values of groups 5, 6, 7, 8 and the decrease in the TAOC values of the same groups were found to be statistically significant (p<0.05). There was a contrast between MDA and TAOC.
According to BAL results, the increase in lavage neutrophil ratio in group 1 was significant compared to groups 2, 3, 4 (p<0.05). The neutrophil count of group 1 and 5, which did not receive pharmacological agents, was higher than in the other groups. Considering the groups receiving pharmacological agents, the lowest neutrophil count was in group 8 (Table 3).
When the MDA, TAOC and neutrophil ratios of the groups were evaluated, neutrophil counts of group 8 were statistically low (p<0.05). In groups 1 and 5, neutrophil counts in BAL were statistically high, and MDA levels were also statistically high in these groups. On the other hand, TAOC values were found to be low (p<0.05) (Figure 1).
When the groups were evaluated in terms of alveolar hemorrhage, all in group 1 were grade 3, one in group 2 was grade 0, 5 in group 2 were grade 1, one in group 3 was grade 0, 4 in group 3 were grade 1, one in group 3 was grade 2, two in group 4 were grade 0, 4 were grade 1, all in group 5 were grade 3, 5 in group 6 were grade 2, one was grade 3, 4 in group 7 were grade 2, 2 were grade 3, 5 in group 8 were grade 2, and one was grade 3 (Figure 2).
When the groups were evaluated in terms of parenchymal damage, all in group 1 had severe, 4 in group 2 had normal, 2 had mild, two in group 3 had normal, 4 had mild, 5 in group 4 had normal, one had mild, all in group 5 had severe, two in group 6 had mild, 4 had moderate, one in group 7 had mild, 5 had moderate, two in group 8 had mild, and 4 had moderate damage (Figure 3).
Discussion
Lung transplantation is the most appropriate treatment method in terminal lung disease. However, graft dysfunction plays an important role in early morbidity and mortality. Graft dysfunction is caused by pathological changes due to ischemia-reperfusion injury, especially in the early period. The most important factor responsible for ischemia reperfusion injury is free oxygen radicals. Melatonin and N-acetylcysteine are also among the most important antioxidants [6-8].
Melatonin is a hormone secreted from the pineal gland with antioxidant and anti-inflammatory effects. N-acetylcysteine is a thiol compound and scavenges free radicals by both nonenzymatic and conjugation and reduction mechanisms. In the initial stage of lung damage due to free radicals, they both penetrate the cell rapidly and act as a scavenger of free radicals [8, 9]. In our study, the effects were evaluated by administering melatonin and N-acetyl cysteine to the subjects, which underwent ischemia/reperfusion. As a result, the antioxidative effects of both melatonin and N-acetylcysteine were shown in accordance with the literature.
Free oxygen radicals are very difficult to show in serum due to their very short lifespan. Therefore, the effectiveness of free oxygen radicals in serum can be evaluated by measuring the serum level of MDA resulting from lipid peroxidation. In many experimental studies, Melatonin has been shown to produce low levels of MDA [7, 10]. In our study, we studied serum levels of MDA to evaluate the effect of free oxygen radicals and detected low MDA levels in the groups given melatonin and N-acetyl cysteine (p<0.05).
There are many anti-oxidant molecules available against oxidative damage in the organism. However, their half-life is very short. Therefore, measurement of TAOC is more important. TAOC is the parameter that contributes most to this defense level [11]. In our study, we used Melatonin and/or N-acetyl cysteine to show the efficacy of protecting the lung from ischemia reperfusion injury. The decrease in group 1 TAOC value was found to be statistically significant compared to groups 2, 3, 4 (p<0.05). The decrease in TAOC values in groups 5, 6, 7, 8 was statistically significant compared to groups 1, 2, 3, 4 (p<0.05). The increase in group 8 TAOC value was statistically significant compared to groups 6, 7 (p<0.05).
In their rat studies, Sener et al. found that the antioxidant activity of melatonin and/or N-acetyl cysteine was significantly effective on TAOC and MDA levels [12]. Topal et al. reported in their study that the use of hyperbaric oxygen increased oxidative stress and negatively affected the antioxidant activity in the groups given melatonin [13]. In our study, there was a contrast between MDA and TAOC .
Bronchoalveolar lavage is a method that allows the analysis of proteins, cellular elements and cellular products in the distal air spaces of the lung. In their study, Inci et al. found that BAL nitrite levels were low in the group given melatonin. In another ischemia reperfusion study, BAL neutrophil ratios were low in groups exposed to ischemia and used alpha-2 antagonists, and BAL neutrophil ratios increased in cases with low antioxidant levels [14, 15]. In our study, the increase in lavage neutrophil ratio in group 1 was significant compared to groups 2, 3, 4 (p<0.05). The neutrophil count in groups 1 and 5, which did not receive pharmacological agents, was significantly higher. Considering the groups receiving pharmacological agents, the lowest neutrophil count was in group 8.
In lung transplantations, pharmacological preservation solutions and pharmacological drugs are used to prevent ischemia-reperfusion injury. These are mostly solutions such as E-C, LPDS, W-S. The superiority of LPDS protection solution has been reported in many studies [16, 17].
Kelly et al. investigated whether the preservation solutions changed the membrane potential. In the study, the membrane potential changed in the W-S and E-C given group, the membrane potential did not change in the LPDS given group, LPDS inhibited free reactive oxygen production, and thus prevented organ failure due to primary lung transplantation [18].
Conclusion
The use of melatonin and/or N-acetyl cysteine as well as LPDS as a preservation solution in lung ischemia reperfusion reduces plasma MDA levels and increases TAOC levels. Additionally, the use of these antioxidants and preservation solutions decreases cell damage immunohistochemically, the cytokines that mediate inflammation, the PMNL, and the inflammatory response associated with them. The use of melatonin, N-acetyl cysteine, and LPDS as a preservation solution can be considered a correct choice in ischemia reperfusion situations.
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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3. Panday A, Sahoo M, Osorio D, Batra S. NADPH oxidases: An overview from structure to innate immunity-associated pathologies. Cell Mol Immunol. 2015; 12(1):5-23.
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5. Latchana N, Peck JR, Whitson B, Black SM. Preservation solutions for cardiac and pulmonary donor grafts: A review of the current literature. J Thorac Dis. 2014;6(8): 1143–9.
6. Turkyilmaz Z, Hatipoglu A, Yuksel M, Aydogdu N, Hüseyinova G. Comparison of effects of melatonin, pentoxifylline and dimethyl sulfoxide in experimental liver ischemia-reperfusion injury by three different methods. The European Research Journal. 2019;5(1):148-58.
7. Panah F, Ghorbanihaghjo A, Argani H, Haiaty S, Rashtchizadeh N, Hosseini L, at al. The effect of oral melatonin on renal ischemia–reperfusion injury in transplant patients: A double-blind, randomized controlled trial. Transplant Immunol. 2019;57:1012-41.
8. Shafiei E, Bahtoei M, Raj P, Ostovar A, Iranpour D, Akbarzadeh S, at al. Effects of N-acetyl cysteine and melatonin on early reperfusion injury in patients undergoing coronary artery bypass grafting: A randomized, open-labeled, placebo-controlled trial. Medicine. 2018; 97(30): e11383.
9. Cipolla-Neto J, Amaral FGD. Melatonin as a Hormone: New Physiological and Clinical Insights. Endocr Rev. 2018;39(6):990-1028.
10. Ko SF, Chen YL, Sung PH, Chiang JY, Chu YC, Huang CC, et al. Hepatic 31P-magnetic resonance spectroscopy identified the impact of melatonin-pretreated mitochondria in acute liver ischaemia-reperfusion injury. J Cell Mol Med. 2020;24:10088-99.
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12. Wang ML, Wei CH, Wang WD, Wang JS, Zhang J, Wang JJ. Melatonin attenuates lung ischaemia–reperfusion injury via inhibition of oxidative stress and inflammation. Interact CardioVasc Thorac Surg. 2018;26(5):761–7.
13. Goc Z, Szaroma W, Kapusta E, Dziubek K. Protective effects of melatonin on the activity of SOD, CAT, GSH-Px and GSH content in organs of mice after administration of SNP. Chin J Physiol. 2017;60(1):1–10.
14. Czigany Z, Craigie EC, Lurje G, Song S, Yonezawa K, Yamamoto Y. Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation. Int J Mol Sci. 2020; 21(18): 6747.
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Atilla Durkan, Muharrem Cakmak, Refik Ulku, Selver Ozekıncı, Ebru Kale. Effects of melatonin and N-acetylcysteine on lung ischemia reperfusion injury. Ann Clin Anal Med 2022;13(4):379-383
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Periostin expression upregulated in leiomyosarcoma
Sefik Gokce 1, Dilsad Herkiloglu 1, Ecmel Işık Kaygusuz 2, Ozge Cevik 3
1 Department of Obstetric and Gynecology, Yeni Yuzyıl University, Gaziosmanpasa Hospital, Istanbul, 2 Department of Pathology, Zeynep Kamil Training and Research Hospital, Istanbul, 3 Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
DOI: 10.4328/ACAM.20937 Received: 2021-11-03 Accepted: 2021-12-15 Published Online: 2021-12-18 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):384-388
Corresponding Author: Şefik Gökçe, Department of Obstetrics and Gynecology, Yeni Yüzyıl University, Private Gaziosmanpaşa Hospital, Gaziosmanpasa, Istanbul, Turkey. E-mail: sefgokce@gmail.com P: +90 545 875 10 50 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0939-4539
Aim: Uterine leiomyosarcomas (LMSs) are rare tumors of the uterus and constitute 1-2% of uterine malignancies. Due to metastases, high recurrence rate and poor prognosis of these tumors, the search for new biomarkers for early diagnosis has increased. In our study, we aimed to show the gene expression and protein level of periostin in leiomyosarcoma as a new biomarker in order to predict prognosis and treatment, together with early diagnosis in leiomyosarcoma.
Material and Methods: Between 2010 and 2020, 12 patients diagnosed with “leiomyosarcoma” and 13 patients diagnosed with “myoma” in our tertiary care hospital, after histopathological examination of clinical samples, were included in the study. Tumor cell necrosis, cellularity, atypia and mitotic index findings of each patient diagnosed with LMS were examined, and staging was performed using the 2009 International Federation of Gynecology and Obstetrics (FIGO) classification system. The tumor preparations of the cases were taken from the pathology archive and re-evaluated, and the gene expression and protein level of periostin were studied in appropriate blocks using ELISA and PCR methods.
Results: According to the FIGO classification, four patients were Stage 1a, six patients were Stage 1b, one patient was Stage 2a, and one patient was Stage 2b. It was determined that the periostin protein was mainly localized in the cytoplasm of leiomyosarcoma cells, and the expression of the periostin gene was increased in cancer tissues compared to myoma tissues, but the difference was not significant (2.16±1.79 vs. 4.01±2.84; p=0.062). Although the mean protein level in periostin tissues was higher in leiomyosarcoma cases, the difference was not significant (LMS: 1.69±1.52; Myoma: 0.88±0.93; p=0.115).
Discussion: Our study is the first to examine the relationship between periostin and leiomyosarcoma. The findings of our study show that periostin can be used as a biomarker for leiomyosarcoma.
Keywords: Leiomyosarcoma, Periostin, Myoma.
Introduction
Uterine leiomyosarcomas (uLMSs) are rare tumors of the uterus and constitute 1-2% of uterine malignancies [1]. Since these tumors are associated with metastases, high recurrence rate, and poor prognosis, mitotic index, patient age, lymphovascular space invasion (LVSI), and tumor size are evaluated as prognostic biomarkers in high-grade uLMS [2]. Although uLMS is the most common uterine sarcoma, it is difficult to distinguish these tumors from benign leiomyomatous diseases with myometrial localization and preoperative imaging. It is thought that MR and newly developed tissue analysis methods will be more important in the diagnosis with preoperative imaging and in distinguishing the benign or malignant degeneration border of putative fibroids [3]. The gold standard treatment for uLMS is surgical excision with negative margins. If the specimen sent during operation is known to be malignant as a result of the frozen examination, total hysterectomy is preferred. However, mostly, uLMS is diagnosed post-operatively after surgical excision, assuming benign leiomyomatous disease [4]. In studies and follow-ups, adjuvant treatments have not been shown to be beneficial in survival in uLMS, and biomarkers of early diagnosis and response to treatment have not yet been determined [5].
Periostin (POSTN), also known as osteoblast-specific factor 2, first identified in murine osteoblast-like cells in 1993, is a member of the fasciclin protein family [6]. Periostin has been found to be expressed at different levels in multiple solid tumor-associated malignancies. Studies show that periostin can induce tumor angiogenesis, invasion, and metastasis, thus leading to the emergence and progression of malignancies [7]. Yang et al. showed in their meta-analysis that patients with high levels of periostin expression had a worse prognosis than those with no or low levels of expression [8]. Particularly, it was observed that the expression of periostin in tumor tissues was significantly overexpressed compared to precancerous or normal tissues, and a correlation was observed between high periostin levels and undifferentiated tumor differentiation, microvascular invasion, and lymph node metastases [8].
In our study, we aimed to show the gene level and protein expression of periostin in uLMS as a new biomarker to predict prognosis and treatment, together with early diagnosis.
Material and Methods
Patients
The study included 12 patients whose clinical samples were diagnosed with “leiomyosarcoma” after histopathological examination and 13 patients diagnosed with “myoma” in our tertiary care hospital between 2010 and 2020. Detailed pathology reports and clinical information of the cases were obtained by scanning the archive. As a result of the information obtained, it was seen that the patients underwent either myomectomy or hysterectomy and bilateral salpingo-oophorectomy, as well as pelvic and/or paraaortic lymphadenectomy operations, for example, according to the results of the frozen examination. Tumor cell necrosis, cellularity, atypia and mitotic index findings of each patient diagnosed with LMS were examined and staging was performed using the 2009 International Federation of Gynecology and Obstetrics (FIGO) classification system [9]. The tumor preparations of the cases were taken from the pathology archive and re-evaluated, and the gene expression and protein level of periostin were studied in appropriate blocks using ELISA and PCR methods.
Ethics
The study was approved by the Ethics Committee of Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital. All patients consented to treatment according to institutional guidelines, with informed consent. All patients consented to anonymous evaluation and analysis of data and treatment outcomes. This study was carried out in accordance with the Declaration of Helsinki and the guidelines of Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital Ethics Committee.
Gene expression of Periostin by qRT-PCR
From each paraffin block, 5 tissue sections (each 10-μm thick) were collected into 1.5-ml microfuge tubes. Extraction of total RNA from paraffin-embedded tissues was determined in duplicate using FFPE RNA isolation kit (Invitrogen; Catalogue number K156002) according to the manufacturer’s recommendation. One µg RNA was reverse transcribed to cDNA with the High Capacity cDNA Reverse Transcription Kit (Applied Biosystem) according to the manufacturer’s instructions. Amplification was performed with an ABI StepOne Plus detection system using a SYBRGreen PCR Master Mix (Applied Biosystem). The reaction conditions were as follows: 95°C for 10 min, then 40 cycles of 95 °C for 15 sec, 60°C for 1 min. The results were analyzed using StepOne Software v2.3 (Applied Biosystems, Foster City, CA), and normalized by GAPDH as an internal control. Data were expressed as fold induction relative to the control.
Protein Levels of Periostin by ELISA
Formalin-fixed paraffin-embedded 4 tissue sections (each 10−15-μm thick) were collected into a 1.5 ml centrifuge tube. Samples were incubated in 250 μl buffer (pH 7.5, 0.05 M Tris, 1 mM EDTA, and 0.5% Tween 20). Protein extraction of all samples was performed as described previously [10]. Protein concentrations were measured with the Bradford method [11]. Periostin levels were measured with the sandwich enzyme-linked immunosorbent assay (ELISA) in accordance with the manufacturer’s protocols (Fine Test; Catalogue number EH0255) with inter-assay cv: <12% and intra-assay cv: <10%, respectively. The mean minimum detectable quantity of human Periostin was 0.094ng/ml. Periostin values were presented as gn/μg protein. All ELISA measurement was performed using a microplate reader was used (BioTek Epoch, Winooski, VT, USA). Results were given as milliliter per milligram of protein.
Histopathological evaluation
After fixation, samples were embedded in paraffin blocks and cut into 5 μm thick sections using a Leica RM2125RTS microtome device (Leica Biosystems, Nussloch, Germany). Selected paraffin sections were stained with hematoxylin-eosin (H&E) staining for morphological evaluation, and the remaining sections were used for immunohistochemistry. All slides were examined under a light microscope (Olympus BX-51, Olympus, Tokyo, Japan).
Statistical analysis
Data are shown as the mean±standard error from at least three independent experiments. One-way ANOVA was applied to evaluate differences among the multiple groups. Student’s t-test was used to perform the statistical comparisons between the two groups. If the variances were homogeneous, the two groups were compared using the least significance difference (LSD) method. Otherwise, Dunnett’s T3 method was included to analyze nonhomogeneous variances between the two groups. All statistical tests were two-sided, and P<0.05 (*) and P<0.01 (**) were considered statistically significant. All analyses were performed using SPSS version 18.0 (IBM, Chicago, IL).
Results
According to the FIGO classification, four patients diagnosed with LMS were Stage 1a, six patients were Stage 1b, one patient was Stage 2a, and one patient was Stage 2b.
Although the mean POSTN gene expression level was higher in the patient group, the difference was not significant (2.16±1.79 vs. 4.01±2.84; p=0.062). Although the mean POSTN protein expression levels were higher in the patient group, the difference was also not significant (1.69±1.52 vs. 0.88±0.93 ng/μg protein; p=0.115) (Table 1) (Figure 1).
In the correlation analysis, it was determined that there was a positive correlation between POSTN protein expression and POSTN gene expression (r=0.879; p<0.001).
In the correlation analyzes performed, no significant correlation was found between POSTN protein expression and hematological parameters (p>0.05 for each). However, there was a positive correlation between the POSTN gene expression and red cell distribution width (r=0.414; p=0.020) and the mean platelet volume (r=0.364; p=0.037), and there were no significant correlations between POST gene expression and other hematological parameters (p>0.05 for each) (Table 2).
A positive correlation was found between POSTN protein expression and mitotic index (r=0.338; p=0.049). Likewise, the same positive correlation was found between POSTN gene expression and mitotic index (r=0.478; p=0.008). A positive correlation was found between POSTN gene expression and tumor diameter (r=0.463; p=0.010) and necrosis (r=0.390; p=0.027). There were no significant correlations between POSTN protein and gene expression levels and other parameters (p>0.05 for each) (Table 3).
Discussion
Uterine leiomyosarcoma, which constitutes approximately 65% of uterine sarcoma cases, is the most common uterine sarcoma [12]. In most uLMS cases, pathological diagnosis based on smooth muscle cell phenotype, cellular atypia, high mitotic index and coagulative necrosis expression is made after tumor resection [13]. uLMS is a malignant tumor with a poor prognosis with a 5-year survival rate of less than 15% in advanced stages, with a recurrence rate of 50-70% after resection [14]. Adjuvant treatments such as chemotherapy, radiotherapy, and hormone receptor blockade are still controversial to reduce relapses and improve survival rates. As a result of our study conducted in uLMS with such a poor prognosis, POSTN protein (2.16±1.79 vs. 4.01±2.84) and gene (1.69±1.52 vs. 0.88±0, 93 ng/μg protein) expression was increased compared to myoma tissue. Our findings show that it can be a marker for early diagnosis of uLMS with rapid progression and metastasis. With this result, our study is the first to examine the relationship between POSTN and uLMS.
It has been found that POSTN is expressed in various normal tissue types such as pancreas, lung, liver, thyroid, stomach, ovary, breast and connective tissue [15]. POSTN, a component of the extracellular matrix (ECM) produced and secreted by fibroblasts, has been shown in studies to interact with various integrin receptors and their signals for differentiation, adhesion and migration regulated by multiple cytokines [16]. Studies have shown that POSTN, whose role is shown in the physiological process, may also be associated with asthma, myocardial damage and cancer, which are pathological processes, with different levels of expression [17]. Tumor invasion and high metastasis capacity are among the most important causes of poor prognosis and decreased survival. Overexpression of POSTN expression has been found to be closely associated with tumor angiogenesis in esophageal squamous cell carcinoma [18]. Siriwardena et al. showed that POSTN protein can increase the formation of tumor local capillaries [19-21]. It is predicted that POSTN interacts with integrin-αvβ3 in malignancy-associated endothelial cells and stimulates the FAK pathway, thereby inducing tumor angiogenesis by regulating VEGR receptor Flk-1/KDR [22]. Some studies have supported the hypothesis that POSTN is involved in lymphatic metastasis and distant metastases of breast cancer [21]. A study on oral squamous cell carcinoma showed that cancer cells expressing high levels of POSTN were more likely to metastasize to the lymph nodes and lungs [22]. In our study, we showed that the gene expression and protein level of POSTN, which are highly expressed in other malignant tumors and are associated with poor prognosis, are increased in malignant tumors with a high local recurrence and metastasis rate such as uLMS [23,24].
Jamaluddin et al. revealed the proteomic profile of uterine fibroids to analyze the ECM protein expression pattern. Using genetic sequencing and isobaric labeled quantitative mass spectrometry (iTRAQ), they analyzed samples in two main groups: MED12 positive and negative mutation (one of the most common anomalies in fibroids). These researchers concluded that POSTN was significantly up-regulated in fibroids regardless of MED12 status [25].
Conclusion
Our study is the first to examine the relationship between POSTN and uLMS. Our results show that POSTN can be used as a biomarker in uLMS. Further and comprehensive studies are needed to fully elucidate the clinical value and prognostic impact of POSTN.
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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Evaluation of knowledge, attitudes and behaviors about COVID-19 among cancer patients
Seher N. Kazaz, Atila Yıldırım
Department of Medical Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
DOI: 10.4328/ACAM.20940 Received: 2021-11-06 Accepted: 2021-12-06 Published Online: 2021-12-14 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):389-393
Corresponding Author: Atila Yildirim, Department of Medical Oncology, Faculty of Medicine, Karadeniz Technical University, 61080, Trabzon, Turkey. E-mail: dr_atila_yildirim@hotmail.com P: +90 543 477 33 42 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6067-5646
Aim: COVID-19 pandemic is experienced intensely with variants in our country, as in other countries. The presence of cancer in patients is associated with morbidity and mortality in the course of COVID-19 disease. In this study, we aimed to evaluate the level of knowledge, attitude and behavior regarding coronavirus disease in cancer patients.
Material and Methods: The questionnaire, consisting of three sections and 25 questions measuring knowledge, attitudes and behaviors of cancer patients about COVID-19, was filled face-to-face by each patient in July 2020.
Results: Most of the cancer patients were aware of the symptoms related to COVID-19 and applied the protection methods such as wearing masks, hand washing, and social distance. Participants with higher levels of education had significantly higher knowledge levels. Although half of the patients were worried about continuing cancer treatment during the pandemic process, 70 % of the patients did not think of delaying the treatment; 48.7 % of the patients were informed by the oncologists about COVID-19 infection. The majority of patients expressed that they did not receive supportive products during the COVID-19 outbreak.
Discussion: In general, cancer patients were conscious of the pandemic, but nevertheless, during this period, they showed a high compliance with their doctors.
Keywords: Attitudes, Behaviors, Cancer, COVID-19, Knowledge
Introduction
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the pandemic of COVID-19 (Coronavirus disease-2019), started in December 2019 in Wuhan city, China, affecting the whole world, causing the death of thousands of people [1]. This pandemic was recognized by the World Health Organization on January 30, 2020 [available at: http://www.euro.who.int/en/health-topics/emergencies/pages/news/news/2020/01/2019-ncov-outbreak-is-an-emergency-of-international-concern]. The first identified COVID-19 case in Turkey was announced by the Ministry of Health on March 11, 2020.
This virus causes deadly pneumonia leading to acute respiratory failure syndrome [2]. Elderly people and patients with comorbidity are more likely to become infected. In addition, serious complications such as acute respiratory distress syndrome (ARDS) are observed more frequently in these individuals [3]. Cancer patients have lower immunity than other people due to both cancer and immunosuppressive therapy, making them more susceptible to infections [4]. Accordingly, we can say that cancer patients infected with SARS-CoV-2 coronavirus are more risky than other populations. In this context, cancer care was immediately established as a health priority by the National Medical Council and the Ministry of Health.
In one study, the disease was more severe in cancer patients than in non-cancer patients [5]. Another study found that cancer patients diagnosed with COVID-19 had a 2.3 times higher risk of death, a 2.8 times higher risk of needing intensive care, and a 2.8 times higher risk of developing at least one serious symptom than those without cancer. However, utilization of invasive mechanical ventilation was determined higher in patients with cancer [6]. Recently, many vaccines against coronavirus have been developed and social vaccination programs have been initiated in many countries. However, strong infection control measures still need to be implemented [7].
The European Society of Medical Oncology (ESMO) guidelines for the management of cancer patients during the COVID-19 outbreak should prioritize adjuvant therapies in patients with resected high-risk diseases that are expected to achieve a significant absolute survival benefit. Similarly, the benefits and risks of palliative treatments during pandemic should be discussed. “Treatment holidays”, “Stop and Go”, if available, maintenance and transition to oral medications should be considered [available at: https://www.who.int/news-room/q-a-detail/q-a-coronaviruses].
There is very limited data in the literature regarding the knowledge levels, thoughts, behaviors and attitudes of cancer patients towards COVID-19. Knowledge about COVID-19 is ever-expanding and changing as the virus mutates. In addition, there is a lot of information pollution on this subject in the written and visual media. Thus, patients should be informed accurately by their oncologists about the risks associated with the pandemic process and cancer treatment so that they can better comply with pandemic measures as well as cancer treatment. In this study, we aimed to evaluate the knowledge, attitudes and behaviors of cancer patients about COVID-19 who applied to our clinic during the rapidly rising pandemic. This study also can provide useful data to plan health education programs about COVID-19 among cancer patients.
Material and Methods
A cross-sectional prospective single-center study was executed using a survey to evaluate the level of knowledge, attitude and behaviors of cancer patients in response to coronavirus disease. This study was approved by Karadeniz Technical University Medical Faculty, Medical Oncology Outpatient Clinic in July and August, 2020.
The survey, consisting of 25 questions in total, was outlined into 3 sections. In the first section, patients were asked general information about COVID-19. In the second section, questions were raised about their thoughts on prevention methods. In the third part, questions were asked about the COVID-19 outbreak and cancer. For simplicity and clarity, the majority of options were created as “yes, no or not sure”. Questions were given one point for correct response and zero points for incorrect or unsure answers.
A preliminary phase was made to evaluate the validity and reliability of the questionnaire prior to its use. The survey was pre-tested on 15 participants who were excluded from the study sample. The patients were requested to fill the questionnaire twice one week apart. Internal consistency reliability was evaluated using Cronbach’s alpha. Cronbach’s alpha value of the pilot study was 0.90 and the intra-class correlation coefficient was 0.83. In other words, the results showed sufficient internal consistency reliability.
The sample size was calculated using the open.Epi (Open source epidemiologic Statistics for Public Health) software. At a 95% confidence interval, the calculated sample size was 197 contributors, and we included 220 participants in the study.
Patients who were over 18 years of age, who had normal intelligence levels as clinical observation and who did not have organic brain syndrome, who were not in the terminal period of cancer, and who agreed to the study were included in the study. Individuals with brain metastasis or primary brain tumors were not included in the study site and subjects.
Statistical Analysis
The SPSS program was used for the analysis of the data. Descriptive statistical analysis was applied for identifying the items included in the questionnaire. While applying the analyses, we presented continuous numeric variables with normal distribution as mean ± standard deviation. Also, those without normal distribution as median, minimum, and maximum values, and percentages were used to describe categorical data. The suitability of the data for a normal distribution was analyzed using the Kolmogorov-Smirnov test. Comparison of numerical variables between independent groups was analyzed using the Mann-Whitney U test and the Kruskal-Wallis test because the normal distribution condition was not met. The Bonferroni test from the posthoc test statistics was used to determine the source of the significant difference between the groups. P- values <0.05 were considered statistically significant.
Ethical Considerations
The study was approved by the Ethics Board Committee of Karadeniz Technical University Medical Faculty (Ref No: 24237859-455 Date: 03.07.2020), and ethical principles laid down in the Declaration of Helsinki have been followed.
Results
Participant characteristics
A total of 220 patients participated in the survey. One hundred and eight of the patients (49.1%) were female and 112 (50.9%) were male. Most of the patients were married (90.5%). The majority of the patients involved in the study lived in the family home (98.2%), and 56% of the patients had education less than a high school degree. About half of the patients had a history of one or more chronic diseases (48.6%). Most of the diagnoses the patients had were gastrointestinal cancers (33.2%) and breast cancer (26.8%). Additionally, 41% of these patients were metastatic; 59% were nonmetastatic. The ECOG performance scores of 87% of patients were 0 and 1; the rest were 2 and 3 (Table 1).
Results of the Questions Related to Attitudes and General information of cancer patients about COVID-19
The majority of patients (72.7%) claimed that they had never heard the word “pandemic” before. The most commonly used information sources were written and visual media (TV, newspaper etc.) (89%). Almost all the participants answered the question about where the outbreak first appeared correctly. The majority of the patients (87.3%) knew the route of transmission of the virus; 90% of patients reported fever, cough and fatigue as main symptoms; 90% of the patients thought that most patients could overcome this infection with early treatment. The majority (85.9%) stated that the COVID-19 disease would be more severe in those with chronic disease. While 85% of the patients who participated in the survey thought it is beneficial to wear a mask to prevent the transmission of the virus, 10% reported that it was not useful; 68.6% of the patients answered the question of whether people with COVID-19 can transmit the virus to others when they have no fever and cough, and 14.5% said it cannot be transmitted; 86.4% of the patients stated it was wrong that the children and young adults do not need protection because they are not affected by COVID-19. The majority of patients (99.1%) responded correctly to the question that hands should be washed at least 20 seconds to prevent contamination (Table 2).
Knowledge Score about the COVID-19 of cancer patients
As a result of participants’ responses, we calculated the knowledge score according to questions 3-13 in the survey. When calculating this score, only correct answers were accepted from the three options. The total knowledge score varied between 3 to 11, with a mean of 9.88 ± 1.55. The relation between socio-demographic characteristics and knowledge scores about COVID-19 is demonstrated in Table 1. Nearly similar knowledge mean scores were observed for male and female participants (9.93 ± 1.54 vs 9.88 ± 1.56, respectively) with no statistically significant difference. Also there were no statistically significant differences in information scores according to age groups (p>0.05) and marital status (p= 0.06). As expected, knowledge mean scores were significantly correlated with education level (p<0.001). Contributors in the survey with university or higher education had significantly higher knowledge mean scores compared to those with lower levels of education (Table 1).
Results of the Questions Related to Cancer and COVID-19 Outbreak
In the third part of the survey, questions were asked about the COVID-19 outbreak and cancer. Due to the data showing that COVID-19 disease will progress more seriously in cancer patients, the participants were asked about this, and 87.7% stated that they thought so. During the COVID-19 pandemic period, 38.6% of the patients stated that their examinations should be done on time, despite the risk of transmission, and the remaining patients wanted to postpone. Half of the cancer patients thought that the COVID-19 outbreak did not prevent cancer patients from continuing their treatment, however, 27.3% thought it was an obstacle. Half of the patients were concerned about the continuation of cancer treatment during the pandemic. Most of those who were concerned expressed that they were more afraid of the COVID-19 transmission than disruption of their cancer treatments.
All of the patients said they wore masks when they left the house during the outbreak; 72.7% of the patients stated that they came to the hospital with one relative, and the majority of patients stated they were paying attention to social distance with other people; 82.7% of the patients thought that they implemented the general measures adequately to protect against the disease. The majority of patients expressed that they did not receive supportive products because of cancer during the period of the COVID-19 outbreak (Table 3).
Discussion
We aimed to learn knowledge levels, attitudes, behaviors and concerns of our cancer patients about COVID-19. As a result of the questions, the knowledge level of the patients was generally high, and this situation was even higher, especially in patients with high educational levels. In similar studies in the literature, the knowledge levels of the people about COVID-19 were found to be related to their education levels [8,9]. Likewise, the knowledge levels of the patients about the methods of protection from COVID-19 were also found to be high in our study.
However, while the majority of patients stated that they had not heard the word ‘’pandemic’’ before, they mostly received information about COVID-19 from visual and print media such as TV and newspapers. It was determined that they received much less information from the internet. Unlike our study, in a study conducted with a healthy population in Egypt, the most frequently referenced sources of information about COVID-19 were social media platforms and the internet [10]. This may be related to the fact that more than half of our patients have a low education level and are not able to use the internet effectively. Although the COVID-19 outbreak affects the entire population, it has also been shown by a study conducted in China that this disease can be more serious in cancer patients and that the mortality due to COVID-19 disease is approximately 3 times higher in cancer patients [7]. In this study, we tried to observe how the COVID-19 pandemic affected cancer patients, their concerns, their opinions about follow-up and treatments. Half of the patients had concerns about the continuation of cancer treatments during this period. The vast majority of concerned patients stated that the COVID-19 transmission made them more anxious than the disruption of cancer treatment. Despite this, it was seen that 70% of the patients did not think of delaying treatment. In light of these data in this study, it was observed that the cancer patients adapted to the treatment at a high rate during the pandemic process. Another finding indicating patient-doctor compliance was that only about 11% of the patients under follow-up wanted to postpone their follow-up visits, and half of the patients wanted to their follow-up programs to be in line with the recommendations of their doctors. We think these are very important data for oncologists. Interestingly, less than half of the patients stated that their oncologist informed them about COVID-19. The reason for this may be that there were no clear guidelines for follow-up and treatment of cancer at that time. Especially during this epidemic period, there is increasing information pollution regarding the use of additional supplements for protection from COVID-19 on television, social media and the internet. Based on our question, the majority of our patients (60.9%) stated that they did not take any additional protective or supportive products. In a similar study on cancer patients in our country, more than half of the patients (52.3%) were taking additional nutritional supplements [9]. Such supportive treatments should be evaluated individually and applied by professionals.
Our study has several limitations. The survey was conducted rapidly on 220 patients in a one-month period, because there was no data on this subject when this study was designed, but it was completed late because of the pandemic conditions. The other limitation of this study is related to questionnaire because we want to learn our patients’ opinions about COVID-19 with cancer disease, so some of the questions we write for patients to choose have two choices and some of them have three choices. This caused some difficulties in calculating the knowledge score. We had to exclude some interpretative questions from the knowledge score.
Conclusion
In general, cancer patients were conscious of the pandemic in this study. Despite patients’ fears about the pandemic, it was observed that the treatment compliance of cancer patients was high. As the pandemic continues spreading especially for our country, more multicenter studies in a special population such as cancer are needed. This study can provide useful data to plan health education programs about COVID-19 among cancer patients individually.
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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Seher N. Kazaz, Atila Yıldırım. Evaluation of knowledge, attitudes and behaviors about COVID-19 among cancer patients. Ann Clin Anal Med 2022;13(4):389-393
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Anxiety and depression in coronary artery bypass surgery patients: A prospective clinical study
Nihan Yeşilkaya, Çağrı Kandemir, Hasan İner, Börteçin Eygi, Orhan Gökalp, Yüksel Beşir, Levent Yılık, Ali Gürbüz
Department of Cardiovascular Surgery, Faculty of Medicine, Izmir Katip Celebi University, İzmir, Turkey
DOI: 10.4328/ACAM.20941 Received: 2021-11-08 Accepted: 2021-12-12 Published Online: 2021-21-18 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):394-398
Corresponding Author: Nihan Yeşilkaya, Clinic of Cardiovascular Surgery, İzmir Katip Çelebi University, Atatürk Training and Research Hospital, Basın Sitesi Mah., Karabağlar, 35650, İzmir, Turkey. E-mail: nihankarakas@gmail.com P: +90 539 643 46 47 F: +90 232 244 44 44 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1756-0402
Aim: A prospective view on the incidence of depression and anxiety in coronary artery bypass graft (CABG) surgery may reveal the importance of psychological support as a part of cardiac rehabilitation. This study aims to determine depression and anxiety levels of CABG patients in the preoperative and postoperative periods, and their correlation with demographic data and length of hospital stay.
Material and Methods: Ninety-eight patients undergoing elective first CABG surgery were assessed in terms of depression and anxiety using Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) on day before, 3 days after, 7 days after and 30 days after surgery. Age, gender, length of hospital stay, and profession were also evaluated to see whether they affect depression and anxiety.
Results: In patients, (60 males, 38 females, mean age 46±6.54, range of 43-76 years) the levels of depression and anxiety symptoms were higher on the postoperative 3rd and 7th days than in the preoperative period (p<0.001).
Discussion: Depression and anxiety affect postoperative outcomes and recovery after cardiac surgery. Psychological preventive counseling and a detailed explanation of cardiac surgery may reduce patients’ emotional stress, medical and economic costs.
Keywords: Anxiety, Cardiac Surgery, Depression
Introduction
Since the relation between psychosomatic medicine and coronary artery disease was first described in 1979 [1], the effects of depression and anxiety on coronary artery disease have been defined in many studies [2–4]. Fewer studies are devoted to depression and anxiety in CABG patients in the pre-and postoperative period [5,6]. Tested quality of life after successful CABG remains low in nearly 25-40% of patients [7]. Low levels of depression and anxiety before surgery are associated with the absence of cardiac symptoms for 6 months after CABG [8]. Unsatisfactory results after CABG as a result of depression and/or anxiety revealed the necessity of more studies in this field.
In studies that examined depression and anxiety in CABG patients, age, gender, occupation, and length of hospital stay were found to be the most related factors, but to our knowledge, there is no study examining all these factors in the pre-and postoperative period in CABG patients. Our study is aimed, in particular, at raising awareness of stress by determining the levels of depression and anxiety in the pre-, peri- and postoperative periods in CABG patients, and their relation with age, gender, occupation, and length of hospital stay.
Material and Methods
Design and Sample
The study population consisted of patients who were hospitalized for preoperative evaluation for first-time, elective isolated on-pump CABG. All patients fulfilled the following criteria: native Turkish speaker, ability to read and write, no psychiatric history/medications, no neurological deficit, no dementia, no emergency CABG surgery, and written consent to participate. Patients with additional procedures (valve surgery, aortic surgery, carotid artery endarterectomy, etc.) or off-pump CABG were excluded in order to have a homogeneous population.
In our study, it was planned to include 125 patients. Fifteen patients declined to participate, 9 patients were excluded in the preoperative period, one patient died on the postoperative second day, and the questionnaire data of 2 patients were missing (Figure 1).
As a result, the study was conducted with 98 patients (mean age: 59.46±6.54 years, ranging between 43 and 76 years, 38.8% females), who underwent CABG surgery at our institution from September 2019 to February 2020.
Measurement
Depression and anxiety were measured with Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI).
The BDI and the BAI were developed by Beck et al. to measure behavioral signs of depression in adolescents and adults, and for rating anxiety. In BDI, scores were summed, scores with a range of 0 to 63 indicate levels of depression (a score from 0 to 9 indicates no depression, 10-16 mild depression, 17-29 moderate depression, and 30-63 severe depression). The BAI consists of 21 questions, scores ranging from 0 to 63 indicate levels of anxiety (a score from 0 to 7 indicates no anxiety, 8-15 mild anxiety, 16-25 moderate anxiety, and scores≥ 26 indicate severe anxiety).
Procedure
All patients were operated by the cardiovascular team of our clinic, on-pump CABG. The proximal anastomosis was performed under either cross-clamp or side-clamp regarding aortic calcification.
After obtaining informed consent, patients completed two questionnaires sequentially four times: the day before, on the 3rd, 7th, and 30th days after the surgery. They were taken to a quiet room and completed the tests alone. Preoperative, postoperative assessments on days 3 and 7t were done with in-hospital patients, while the tests were performed at an out-patient visit on postoperative 30th day. For patients who were discharged before the postoperative 7th day, the tests were completed by telephone questionnaire.
Ethical Statement
The study was approved by the Institutional Review Board of Izmir Katip Celebi University and each patient gave written informed consent to participate. The study was planned and performed in accordance with the World Medical Association Declaration of Helsinki.
Data analysis
The power analysis for this study was based on the paper by Acıkel and colleagues [9]. In the Wilcoxon signed-rank test, calculated for 57 people, it is enough to determine the differences between the scales at a significance level of 0.05 (α) with a 95% power. The calculation was made with G * Power 3.1.9.7 package program.
We used the Shapiro-Wilk test to analyze the homogeneity of the variables. The Wilcoxon Signed-Rank test was used for the analysis of anxiety and depression differences before and after the operation. Between-group differences according to gender were analyzed using the Mann-Whitney U test. Spearman’s correlation tests were used for the assessment of correlation. The Kruskal-Wallis test and Friedman’s analysis were also used. Data analysis was performed using SPSS 24.0, and p-values <0.05 were considered statistically significant.
Results
Ninety-eight patients completed the tests and their full medical records were available at the data collection system of our hospital. Sixty of them were males, and 38 were females. Their average age was 46±6.54 years, ranging between 43 and 76 years. Nineteen of the patients were housewives, 29 were retired, 24 were self-employed and 26 had other professions. The average preoperative hospital stay was 4.92±2.71 days, and the average postoperative stay was 7.39±1.9 days.
Depression and anxiety scores are analyzed statistically. Average BAI was 5.91±4.7 preoperatively, which increased to 15.12±5.04 on the postoperative 3rd day. Average BDI was 3.9±3.58 preoperatively, which increased to 10.89±4.08 on the postoperative 3rd day. Statistical analysis of both BDI and BAI tests is summarized in Table 1. We found that the level of depression and anxiety symptoms was higher in the postoperative period than in the preoperative period (p<0.001).
We found that the symptoms of depression and anxiety levels were lower in the preoperative period than in the postoperative days 3 and 7 (p<0.001). However, there were no statistical differences in depression and anxiety levels between the preoperative period and postoperative 30th days. The average BAI scores were 5.91±4.7 and 5.68±3.78 on preoperative and postoperative 30th days, respectively. The average BDI scores were 3.9±3.58 and 3.64±3.32 on preoperative and postoperative 30th days, respectively.
Anxiety and depression scores were analyzed and classified as cut-off scores. The percentage of scores are shown in Table 2.
Correlations between preoperative stay, postoperative stay, age and anxiety, depression scores were analyzed with the Spearman correlation test. Positive correlations were found between preoperative stay and preoperative anxiety scores, postoperative 30th-day anxiety, preoperative depression scores, postoperative 30th-day depression scores. There were positive correlations between postoperative stay and postoperative 30th-day depression scores. There was also a positive correlation between age and postoperative 3rd-day anxiety scores. The results of correlations are shown in Table 3.
There was no statistical difference regarding depression and anxiety scores between the genders. In a similar fashion, there was no correlation between profession and Beck’s depression and Beck’s anxiety test scores.
Discussion
Depression and anxiety, before and during the recovery period, are as important as physical morbidities in determining outcomes such as the ability to function [10]. Many studies have shown depression prior to CABG to be a significant predictor of morbidity and mortality in the months and years following surgery [5,11], and similar effects have also been found for anxiety [12,13]. On the other hand, postoperative depression is a potential risk for cardiac events in the first year and 6-8 years after CABG [14]. Patients experience elevated feelings of anxiety both in the early and late postoperative period, between 10% and 20% of them show clinical levels of postoperative anxiety leading to disturbances in the healing period [15]. This study aims to define the course of depression and anxiety before and after CABG, and its relationship with demographic data and length of hospital stay in a sample of patients undergoing first-time, elective CABG.
In our study, both depression and anxiety scores have been found higher in the postoperative period than preoperative period (p<0,001). In other studies with high preoperative depression scores have a long preoperative hospital stay, and unfamiliar hospital environment may cause fear and stress [16,17]. We have the shortest mean preoperative hospital stay with 4.92±2.71 among the studies dealing with the length of hospital stay and depression. We assume that this is the main reason for the low baseline depression scores.
There is a significant increase in depression levels on the postoperative 3rd day, which reflects mild depression symptoms. This is consistent with recent papers [9,15,18]. The higher rate of depressed patients a few days after CABG is not surprising, as the depression scale contains items assessing somatic complaints such as sleep disturbances, loss of appetite, energy, and sexual drive [19]. Moreover, after the surgery, patients wake up in the intensive care unit, with no one familiar, separated from their families. In these circumstances, depression is thought as an understandable and inevitable reaction to CABG, and, as a result, is not treated most of the time [20]. Following that, in our study, the scores tend to decrease on the postoperative 7th day, and reach baseline levels on the postoperative 30th day. These findings corroborated other research that indicates about 20% of CABG patients were depressed postoperatively [19,21].
We found normal levels of anxiety preoperatively, and this may be explained by two main reasons. First, surgeons provide detailed information about perioperative outcomes to patients and their relatives in our clinic. A more certain knowledge about probable outcomes relieves anxiety. As a second reason, similar to depression, anxiety is high in CABG patients while they are on the waiting list with an unknown surgery date [22]. Short hospital stay in our clinic explains low anxiety scores in the study. In the same trend with depression, anxiety peaks on postoperative 3rd day, slightly decreases on postoperative 7th day, and returns to baseline levels at postoperative 30th day. Most of the previous studies have revealed a prominent decrease in the postoperative period [6,15,19]. Our results reflect the unsteady status of patients because of the “unknown” healing process. They do not know what to eat, how often to walk, when their incisions will heal, all of these are sources of anxiety in the very first part of the postoperative period. These differences from other studies may be explained by the performance of other scales, which do not include questions reflecting somatic disturbances.
In our study, there is a significant positive correlation between age and anxiety on postoperative 3rd day. There is no correlation between the preoperative test scores. In contrast, Krannich et al. showed that the younger the patients, the more the decrease in pre-post surgery depression and anxiety scores [6]. The authors speculate that younger patients might imagine a much greater loss while waiting for open-heart surgery. On contrary, Perski et al. showed that older patients more often suffered from depression than younger ones [22]. We think that the postoperative increase of anxiety in older patients in our study can be explained by the difficulties related to physiological changes in aging. Older patients more often tend to think that they would have no one to look after the operation, when younger people think they can handle it on their own.
Several studies have studied the association between hospital stay and depression/anxiety levels in cardiac surgery patients. Our findings are consistent with the study of Poole et al, which includes only the length of post-CABG stay [23]. We found that a longer postoperative stay leads to higher depression levels on the postoperative 30th day. In a study that aggregated length of stay data between 2007-2009 across 28 hospitals in the United Kingdom, the mean stay for the 19522 CABG patients was 12.48 days (SD=10.94) [23]. Our mean length of stay is 7.39, which can be explained by the fact that we recruited only first-time, elective patients. Likewise, we also have a short preoperative hospital stay, and our results reveal that the longer the preoperative stay, the higher the depression and anxiety scores, for both the day before surgery and postoperative 30th day.
As Acıkel et al. revealed in their results [9], no significant correlation was found between gender and profession separately and BDI-BAI scores in our study. Koivula et al. found no difference in the prevalence of depression by gender or employment status, as well [24]. In the study by McCrone et al., although no statistical difference was seen in terms of depression between the genders, postoperative anxiety scores were higher in women [10]. They interpret their findings with a small number of women in the sample, typical of other recent studies as well. Korbmacher et al. declared higher depression and anxiety results in the postoperative period for women, and likewise, they explained this by the fact that less than 27% of patients were females in their sample [25]. Our study with 38.8% of female patients is above the other ones, and power analysis showed that our numbers are more than enough to have reliable results. Unfortunately, we did not analyze age, profession, or length of stay regarding different genders, and this should be a topic for future research to enlighten the effect of gender on depression and anxiety with CABG patients. Study Limitations
There are some strengths as well as weak points in our study. In terms of strengths, our study examined patients undergoing CABG in a single hospital and therefore removes the influence of inter-hospital variation in patient care. Moreover, both our sample size and the percentage of women are more than enough for reliable results, according to the power analysis, which was performed prior to the study.
The BDI and BAI tests have been widely used in CABG patients so far. Both tests have questions that seek answers reflecting somatic and cognitive symptoms. Many of these somatic symptoms are characteristic of CABG patients in the postoperative period. This may be counted as a weak point of our study.
Conclusion
Between 30% and 40% of CABG patients experience depression and anxiety at rates significantly higher than prevalent in community samples [12]. Both depression and anxiety seem to confer greater morbidity and mortality, though behavioral and biological mechanisms are poorly understood. We believe that accurate diagnosis and intervention among CABG patients may impact distress levels, and surgeons are encouraged to establish referral and treatment pathways in collaboration with mental health professionals.
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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6. Krannich JHA, Weyers P, Lueger S, Herzog M, Bohrer T, Elert O. Presence of depression and anxiety before and after coronary artery bypass graft surgery and their relationship to age. BMC Psychiatry. 2007;7:1–6.
7. Rymaszewska J, Kiejna A, Hadryś T. Depression and anxiety in coronary artery bypass grafting patients. Eur Psychiatry. 2003;18(4):155–60.
8. Of anxiety, depression and stress in CABG candidate patients and factors affecting it at Farshchian Cardiovascular Hospital in Hamadan. Iran J Heal Educ Heal Promot. 2021;9(2):212–25.
9. Açıkel MET. Evaluation of depression and anxiety in coronary artery bypass surgery patients: A prospective clinical study. Brazilian J Cardiovasc Surg. 2019;34(4):389–95.
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13. Tully PJ, Winefield HR, Baker RA, Denollet J, Pedersen SS, Wittert GA, et al. Depression, anxiety and major adverse cardiovascular and cerebrovascular events in patients following coronary artery bypass graft surgery: A five year longitudinal cohort study. Biopsychosoc Med. 2015;9(1):1–10.
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16. Aburuz ME. Pre-operative depression predicted longer hospital length of stay among patients undergoing coronary artery bypass graft surgery. Risk Manag Healthc Policy. 2019;12:75–83.
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Download attachments: 10.4328:ACAM.20941
Nihan Yeşilkaya, Çağrı Kandemir, Hasan İner, Börteçin Eygi, Orhan Gökalp, Yüksel Beşir, Levent Yılık, Ali Gürbüz. Anxiety and depression in coronary artery bypass surgery patients: A prospective clinical study. Ann Clin Anal Med 2022;13(4):394-398
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Is there a relationship between childhood traumatic experiences, somatoform dissociation, and subjective tinnitus?
Eser Sagaltici 1, Hasan Belli 1, Seyda Belli 2, Erman Senturk 1, Onur Okan Demirci 3
1 Department of Psychiatry, University of Health Sciences, Bagcilar Training and Research Hospital, 2 Department of Otorhinolaryngology, University of Health Sciences, Bagcilar Training and Research Hospital, 3 Deparment of Psychology, Istanbul Gelisim University, Istanbul, Turkey
DOI: 10.4328/ACAM.20942 Received: 2021-11-09 Accepted: 2021-12-12 Published Online: 2021-12-15 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):399-403
Corresponding Author: Eser Sagaltici, Mustafa Yaşar Caddesi Gençosman Mahallesi, Bagcilar Training and Research Hospital, 34165, İstanbul, Turkey. E-mail: dresersagaltici@yahoo.com P: +90 506 496 49 26 / +90 212 440 40 00 F: +90 212 562 69 22 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4217-2658
Aim: This study aimed to reveal the existence of childhood traumatic experiences representing the symptoms of somatoform dissociation in patients with subjective tinnitus.
Material and Methods: One hundred forty patients with cases of tinnitus for more than six months and 118 healthy volunteers between the ages of 18 and 35 were admitted. Researchers employed the Childhood Trauma Questionnaire (CTQ), Somatoform Dissociation Questionnaire (SDQ), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) in cases with tinnitus and control subjects, and Tinnitus Handicap Inventory (THI) solely in the tinnitus group.
Results: We found very high levels of emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect, SDQ, BDI, and BAI in patients with subjective tinnitus. However, there was a statistically significant positive correlation between SDQ and THI. When patients with tinnitus were separated using the SDQ cutoff score, very high levels of emotional abuse, physical abuse, emotional neglect, and physical neglect were found in patients with SDQ ≥ 35 scores. We also found the high-level THI predicted the SDQ.
Discussion: We have determined that tinnitus is associated with a strong effect to integrate childhood traumatic experiences and somatoform dissociation. Trauma-oriented psychotherapies may be useful for patients with subjective tinnitus to manage trauma-related symptoms.
Keywords: Tinnitus, Psychological Trauma, Dissociative Disorders, Psychosomatic
Introduction
Many people report noticing certain sounds without any external stimuli, defined as tinnitus. Clinicians can list tinnitus as subjective or objective. Vascular irregularities or myoclonus of palatal muscles may cause objective tinnitus. Objective tinnitus is a rare clinical condition. In subjective or idiopathic tinnitus, patients perceive many sounds in their head and/or in one or both ears. Data suggest that subjective tinnitus may occur specifically in adults [1]. Tinnitus is a frequent symptom, and it is estimated that in about 15% to 20% of the adult community may exist briefly or enduringly [2]. Persistent tinnitus (more than six months) is regularly associated with emotional disorders, damaged sleep quality, and social recession [3]. There are speculative comments about the etiopathogenesis of these complaints in subjective or idiopathic tinnitus.
Many studies have been published examining the relationship between tinnitus and psychiatric disorders and symptoms. In one of these, the authors demonstrated a strong relationship between subjective tinnitus and psychiatric comorbidity and symptoms. In this study, 26.70% of patients with tinnitus had at least one psychiatric diagnosis. The authors also found that anxiety disorders and somatoform disorders were significantly higher in tinnitus patients than in normal subjects [4]. Research in the field of tinnitus is expanding. There have been some controversial findings of whether psychiatric symptoms are causal or consequential seen in patients with tinnitus. If a relationship between childhood trauma and tinnitus can be demonstrated, a causal relationship can also be designed.
Extensive research has advanced our knowledge of the relationships between childhood traumatic experiences and psychological problems later in life. After checking for other psychosocial risk determinants, childhood trauma has been associated with the evolution of most mental health difficulties, including mood and anxiety disorders, eating disorders, personality disorders, dissociative disorders, substance addiction, and psychosis [5]. Furthermore, childhood trauma is associated with an array of further problems in those serving mental health settings, including somatoform symptoms, and interpersonal problems [6]. In addition, interestingly, a study suggested that, in patients receiving the subjective tinnitus diagnosis, childhood traumatic experiences were a factor that impacted the severity of clinical status. In this study, high rates of emotional abuse, emotional neglect, and physical neglect were found, in addition to high rates of physical abuse and sexual abuse [7].
The relationship between tinnitus and stress can also include a link between inner ear sensitivity and neuroendocrinological, immune, and toxic alterations connected to stress activation [8]. In another study, authors suggested that somatization and stress could be considered as a determinant influencing injury and dysfunction of the auditory device. They also suggested that the vulnerability to neurotic disorders and lack of coping abilities could perform a crucial function in the clinical records of patients affected by severe tinnitus [3]. If childhood traumatic experiences are a risk factor in the precipitation of tinnitus, somatoform dissociative symptoms may exist that identify a vulnerable traumatic stress in patients with tinnitus.
The answers to these questions are important for understanding the role of the childhood traumatic experiences in programming tinnitus after adverse early life events, because this may have important implications for understanding the pathogenesis of subjective tinnitus. We hypothesized that there may be childhood traumatic experiences that represent symptoms of somatoform dissociation in patients with subjective tinnitus.
Material and Methods
Participants and study design
Researchers designed the study prospectively. The study example consisted of patients who presented to the Otorhinolaryngology clinic, between November 2019 and July 2021. The researchers added one hundred forty patients who had complaints of tinnitus for more than six months and one hundred eighteen healthy volunteers between the ages of 18 and 35. Patients underwent a complete ear-nose-throat, internal medical, and neuropsychiatric examination. The researchers offered audiometry, whole blood tests, and biochemical analysis. Hence, they eliminated the possible diseases.
The researchers recruited control subjects in part from their social environment. Control subjects were not from the same family. The researchers specifically excluded those with current and past history of tinnitus complaints. The researchers also excluded all individuals with significant medical and/or psychiatric pathologies such as schizophrenia, manic-depressive psychosis, and behavioral disorders with social withdrawal or suicidal risk. Especially young adults were included in the study. Thus, organic diseases were tried to be excluded as much as possible.
Researchers employed the Childhood Trauma Questionnaire (CTQ), Somatoform Dissociation Questionnaire (SDQ), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) in cases with tinnitus and control subjects. The researchers also conducted the Tinnitus Handicap Inventory (THI) solely in the tinnitus group because researchers did not add the individuals with symptoms of tinnitus to the control group.
Written informed consent was obtained from each subject after a full description of the study’s goals and protocol. The research contract was carried out following the ethical policies declared in the Helsinki Declaration and signed by the Ethics Board of Bagcilar Training and Research Hospital, Istanbul (Document no: 2020.07.2.15.116). Informed consent was obtained from all members who joined the study.
Measurements
Tinnitus and psychiatric evaluations were based on:
The Turkish version of the Tinnitus Handicap Inventory (THI), which is is a highly reliable questionnaire for examining reproductions; it is not influenced by age, sex, and hearing loss, provides clear outcomes, simple to practice, and offers more psychometric measures. Each of the 25 questions in this questionnaire has three answer options: Yes, Sometimes, and No, and the numbers are measured using 4, 2, and 0 respectively. In this way, the results were evaluated with the lowest being 0 and the highest 100 points [9].
The Childhood Trauma Questionnaire (CTQ) is a 28-item self-report instrument. Bernstein et al developed this scale. It assesses emotional, physical, and sexual abuse, as well as physical and emotional neglect in childhood [10]. The sum of the scores obtained from each type of trauma gives a total score ranging from 25 to 125. Some researchers practiced the Turkish variant of the scale in many studies [11].
The Somatoform Dissociation Questionnaire (SDQ) is a 20-item self-report tool that assesses the severity of somatoform dissociation. Nijenhuis et al developed this scale [12]. Sar et al. modified the Turkish version of the scale [13].
The Beck Depression Inventory (BDI) was revealed by Beck et al. [14] to evaluate signs of depression. Rates range from 0 to 63, with higher scores indicating more severe depression. The Turkish account of the scale was modified by Hisli [15].
The Beck Anxiety Inventory (BAI) was produced by Beck et al. [16] to evaluate symptoms of anxiety. The numbers range from 0 to 63, with higher scores showing more severe anxiety. The Turkish translation of the scale was adapted by Ulusoy et al. [17].
Statistical Analysis
Descriptive statistics were presented as median values and interquartile ranges (IQR) (25% to 75%) or mean, and standard deviation for quantitative variables, and frequencies and percentages for categorical variables. The Chi-square test or Fisher Exact test were used to determine possible differences between groups in terms of categorical variables. Normality tests were carried out using one-sample Kolmogorov–Smirnov and Shapiro-Wilk tests and through histogram graphs. Student’s t-test was used for comparisons of variables when parametric assumptions were met. The Mann–Whitney U test was utilized for comparing continuous variables between the two groups. Multiple linear regression models were used to investigate potentially predictive factors for the SDQ in the tinnitus patients. The variables evaluated were determined as significant variables derived from our results and literature review, in accordance with clinical experience. The tests for assumptions-linearity, homoscedasticity, and multicollinearity were carried out by the authors (the assumptions met). All the analyses were two-sided with alpha of 0.05, and were performed with SPSS statistical software (IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.).
Results
The analyzes in the study were conducted with a total of 258 participants, 140 of whom were tinnitus patients and 118 were healthy controls. Eighty (57.1%) of 140 patients were female and the mean age was 27.13 (SD=6.03) years. Sixty-one (51.7%) of the 118 controls were female and the mean age was 26.92 (SD=5.85) years. Seventy-five (53.6%) of the patients in the patient group and 65 (55.1%) in the control group were married. In the patient group, 36 (25.7%) were primary school graduates, 71 (50.7%) were high school graduates, 33 (23.6%) were university graduates or higher. Twenty-five (21.2%) primary school graduates, 65 (55.1%) high school graduates, 28 (23.7%) university and higher graduates made up the control group. Sixty (42.9%) people were employed and 80 (57.1%) were unemployed in the patient group. Sixty (50.8%) people were employed and 58 (49.2%) people were unemployed in the control group. There was no statistically significant difference between patients and controls in terms of age, gender, marital status, education level, and employment status (for all p>0.05). According to tinnitus lateralization, 94 (67.1%) unilateral and 46 (32.9%) bilateral tinnitus were described. The mean THI total score of the patients was 58.97 (SD=12.12), the mean age of disease onset (years) was 26.15(SD=6.18), and the mean disease duration (months) was 13.25(SD=16.90).
When the researchers compared CTQ scores of the patients with tinnitus group and control subjects, they found the patients with the tinnitus group’s CTQ averages on emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect score to be significantly higher than in the control subjects (p<0.001 for all). When they also compared the the SDQ, BDI, and BAI scores of the patients with tinnitus group and control subjects, they found the patients in the tinnitus group had significantly higher SDQ, BDI, and BAI scores than the control subjects (p<0.001 for all). These data are summarized in Table 1.
Tinnitus patients were divided into two groups according to the cut-off score of the SDQ. When the CTQ scores of the SDQ ≥ 35 group and SDQ < 35 groups in tinnitus patients were compared, the SDQ ≥ 35 group’s CTQ averages on emotional abuse, physical abuse, emotional neglect, and physical neglect score were found to be significantly higher than those of the control subjects (p<0.001 for all). When the THI, BDI, and BAI scores of the SDQ ≥ 35 group and SDQ < 35 groups were compared, the patients with the SDQ ≥ 35 group’s THI, BDI, and BAI scores were found to be significantly higher than those of the SDQ < 35 groups (p<0.001 for all). These data are summarized in Table 2.
Multiple linear regressions were calculated to predict SDQ, based on age, gender, THI, tinnitus duration, and tinnitus laterality (Table 3). A significant regression equation was found [F (5, 133) = 4.934, p=.000] with an R2 of .156 for SDQ. As a result of entering method evaluation, it was detected that SDQ was significantly predicted by the high THI level (p<0.001).
Discussion
In our paper, we first argue that childhood traumatic experiences are an attribution or causal explanation for events, deriving from a search for meaning that reflects an interaction between somatoform dissociation and subjective tinnitus. Many researchers noted the importance of psychiatric comorbidity, and they examined psychiatric comorbidity, they often found the possibly linked to the experience of depression and anxiety. They did not examine the causative importance of childhood traumatic experience for whether it was effective in the emergence of tinnitus. For this goal, researchers included young adults to study, because it might not be simple to eliminate organic causes in older patients. We found very high levels of emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect, SDQ, BDI, and BAI in patients with subjective tinnitus. However, there was a statistically significant positive correlation between SDQ and THI. When the researchers divided the patients into two groups according to the cut-off score of the SDQ, they found very high levels of emotional abuse, physical abuse, emotional neglect, and physical neglect in patients with the SDQ ≥ 35 score. Indeed, the relationship between SDQ and childhood traumatic experiences is well-known, it is a classic fact. Interestingly, we also found the high-level THI predicted the SDQ.
A study of a specific effect of childhood traumatic experiences on subjective tinnitus has been proposed in a recent study by Belli et al. [7], which emphasizes the importance of THI severity, physical abuse, emotional abuse, physical neglect, and emotional neglect. They have also emphasized that childhood traumatic experiences may affect the pathological process and may predispose to developing tinnitus, depression, and anxiety. Considering this study, based on our study, which argues that subjective tinnitus is associated with a strong effect to integrate childhood traumatic experiences and somatoform dissociation, we can suggest that subjective tinnitus may be a form of trauma-based memory and its related somatization. High levels of childhood traumatic experiences, particularly in the triggering of the pathological process and the formation of the somatization stage, may be common in persons who go on to develop subjective tinnitus. An important study reported that anxiety, depression, somatization, and other psychiatric symptoms increased during subjective tinnitus [4]. It could be argued that tinnitus may serve to bind or contain overwhelming childhood traumatic experiences.
Many authors describe somatoform dissociation as somatic symptoms that cannot be explained by a medical condition. As for the source of dissociation, many studies have marked that it is significantly connected with traumatic experiences, particularly when they are severe, persistent, connected to interpersonal trauma, and happen in childhood [18, 19]. Yet, other researchers have identified the relationship between traumatic experiences and somatoform dissociation [20,21]. Interestingly, in our study, we found that high levels of THI predicted SDQ. However, we detected significant childhood traumas and SDQ levels in the group with objective tinnitus. We can construct a causal explanation based on these findings. We are also aware that these explanations are insufficient. Studies with a larger sample are needed to strengthen the discussion.
Dissociation questions the individual’s perception of being in control, which is associated with self-esteem and a feeling of identity. The extent of self-esteem was found to be a predictor of the action of the hypothalamic-pituitary-adrenal axis [22]. Reports from two investigations confirm that dissociative disorder is associated with raised circulating cortisol levels after a certain traumatic event [23,24]. The relationship between tinnitus and stress may also include the link between inner ear sensitivity and stress-related neuroendocrinological, immune, and toxic variations [8]. Two authors suggested the role of psychosomatic and stress reactions in the development of tinnitus, supported by the neurophysiological model. According to this model, tinnitus becomes chronic and decompensated as a result of faulty circuits in a complex neural network that includes sensory, limbic, and autonomic components [25]. These findings and discussions may be related to the hypothalamic-pituitary-adrenal axis and cortisol secretion in programming the brain after adverse early life events, because this may make important contributions to understanding the pathogenesis of subjective tinnitus.
Childhood adverse experiences may be thought to sensitize some medical pathologies during adult life. Some psychotherapy approaches such as trauma-oriented psychotherapies and clinical practice may offer a different perspective for the understanding of some symptoms that have been defined as tinnitus. Those approaches reprocessing of adverse or traumatic experiences and even directly targeting tinnitus symptoms may reduce the level of pathology. Trauma-oriented psychotherapies may be useful for patients with tinnitus to process trauma memories, manage trauma-related symptoms, and deal with depression and anxiety symptoms. While the debate over the relevance of childhood traumatic experiences and somatoform dissociation in the development of subjective tinnitus is conceptually important, exploring the effectiveness of trauma-oriented psychotherapies in treatment outcome studies in patients with subjective tinnitus may help address more clinically relevant questions.
Our study was restricted to a comparatively small example and cross-sectional procedure, and larger studies involving more patients and better-structured researches are required. In addition, the study method is quite selective. It is known that tinnitus is often accompanied by other psychiatric disorders and symptoms, but these comorbidities have not been diagnosed. This may be a weakness. Only depression and anxiety symptoms have been screened in the study.
Conclusion
We have determined that tinnitus is associated with a strong effect to integrate childhood traumatic experiences and somatoform dissociation. Trauma-oriented psychotherapies may be useful for patients with subjective tinnitus to manage trauma-related symptoms.
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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Eser Sagaltici, Hasan Belli, Seyda Belli, Erman Senturk, Onur Okan Demirci. Is there a relationship between childhood traumatic experiences, somatoform dissociation, and subjective tinnitus? Ann Clin Anal Med 2022;13(4):399-403
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Safety of interventional bronchoscopy in elderly patients
Melahat Uzel Şener, Ayperi Öztürk, Aydın Yılmaz
Department of Interventional Pulmonology, University of Health Sciences, Ankara Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20947 Received: 2021-11-12 Accepted: 2022-01-11 Published Online: 2022-01-13 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):404-409
Corresponding Author: Melahat Uzel Şener, Department of Interventional Pulmonology, University of Health Sciences, Ankara Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey. E-mail: melahatuzeldr@yahoo.com.tr P: +90 505 649 74 38 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8309-9517
Aim: Interventional bronchoscopy (IB) is a frequently used method in the diagnosis and /or treatment of malignant or benign airway stenosis. The gradual increase in the elderly population appears as difficulties in the diagnosis and treatment process. In this regard, in this cohort over 65 years old who underwent endobronchial treatment, comorbidities, complications, procedural mortality were evaluated.
Material and Methods: The study has a retrospective and observational design. Patients who underwent rigid bronchoscopy in the interventional pulmonology unit between March 2019 and March 2021 were included in the study. Differences were evaluated in terms of comorbidity and complications in the groups <65, 65-74 and ≥75 years of age.
Results: In the study, 317 IBs were performed in 268 patients. Among the age groups, the rates of hypertension, diabetes mellitus, coronary artery disease, and chronic renal failure were found to be significantly higher in the ≥75 age group (p<0.05). It was observed that complications did not differ between age groups (p>0.05).
Discussion: Although there is an increase in comorbidity rates in elderly patients, according to this study, there is no age-related contraindication for the procedure. Endobronchial treatment decision should not be made primarily according to age.
Keywords: Endobronchial Treatment, Rigid Bronchoscopy, Geriatric; Mortality, Complication
Introduction
The elderly population is increasing day by day all over the world. This situation occurs with an increasing disease burden. In elderly patients, fragility, the presence of comorbidities, the use of multiple drugs, and the need for social support appear as factors that complicate the diagnosis and treatment process [1,2]. Interventional bronchoscopy (IB) is a commonly used method for the diagnosis and/or treatment of malignant or benign airway stenosis. Lung cancer can present with malignant airway obstruction (MAO) in 10% of cases at admission [3]. Since the incidence of lung cancer increases with age, the rate of elderly (> 70) patients requiring interventional procedures is gradually increasing [4]. IB is an effective and safe method in malignant airway obstruction. It can be used as bridging therapy before systemic therapy and for safe diagnosis in critically ill patients [5,6].
IB improves the quality of life and respiratory functions, and can provide weaning. Benign airway stenosis includes post-intubation, post-tracheostomy, infection-related stenosis, and transplant airway disease. Hemoptysis, foreign body aspiration, stent placement are rigid bronchoscopy (RB) indications [7]. RB is the gold standard method for airway obstruction. Ventilation, airway management, suction, direct intervention to bleeding, tumor removal and wide diameter enabling stent placement are the greatest advantages of this procedure [8]. It is applied with an acceptable rate of complications and mortality after appropriate patient selection [9].
General anesthesia (GA) with total intravenous anesthesia (TIVA) or sedation during RB is another cause of difficulty in selecting elderly patients [10]. The American Society of Anesthesiology (ASA) scores are generally high in elderly patients who undergo this procedure [11]. According to various reasons, the need for endobronchial diagnosis or treatment with RB is increasing in elderly patients [12]. In this study, we aimed to contribute to treatment planning with RB in elder population. For this reason, we present in this context, we investigated the comorbidities, complications and procedural mortality in patients over 65 years of age who underwent endobronchial treatment with RB.
Material and Methods
Patients who underwent endobronchial diagnosis and treatment with IB between March 2019 and March 2021 were included in our study. After obtaining approval from the local ethics committee of our hospital, the data were collected retrospectively (Local Ethics Committee No: 710/ 21.01.2021). All patients were treated in the interventional pulmonology unit by the same team of three interventional pulmonologists.
Patients’ age, gender, accompanying comorbidities, pre-procedure diagnoses and indications, pre- and post-procedure pathological diagnoses were recorded. Patients were divided into groups as <65 years, 65-74 years, and ≥75 years. The difference between the three groups was evaluated for these parameters.
The drugs used for various indications before the procedure and causing bleeding tendency were grouped as acetylsalicylic acid, anti-platelet agents -clopidogrel- and anticoagulants -low molecular weight heparin (LMWH), warfarin, non-vitamin K antagonist oral anticoagulants (NOACs).
Preliminary diagnoses before the procedure were grouped as malignant pathologies and benign pathologies. In endobronchial treatments, first of all, lesion localization was recorded. Patients with a pre-procedural diagnosis were grouped as lung cancer, extra-thoracic malignancy, post-intubation tracheal stenosis (PITS), post-tracheostomy tracheal stenosis (PTTS), and benign tumor. Patients with no known diagnosis before the procedure were grouped as “none”.
Mortality in the first week after the procedure was evaluated as procedural mortality.
Interventional procedures
All procedures were performed under GA with TIVA. The ASA [13] classification performed in the pre-procedure evaluation was recorded. ASA scores are grouped as non-life-threatening (ASA-1,2,3) and life-threatening (ASA-4,5). Electrocardiogram, invasive arterial blood pressure, oxygen saturation, and arterial blood gas monitoring were routinely performed in each patient throughout the procedure. Jet ventilation was performed with a system integrated into the rigid bronchoscope.
The patients were intubated with RB in the operating room (Efer-Dumon, 11 mm-diameter, 43 cm length, Efer Endoscopy, Marseille, France). Treatment procedures were argon plasma coagulation (APC) (ERBE ICC 200/APC 300 electrosurgical unit, rigid APC probe, 50 cm length, 2.3 mm diameter), mechanical tumor resection (MTR), cryoextraction, cryotherapy (ERBOKRYO® CA unit, rigid cryoprobe 3 mm diameter, 53 cm length; ERBE, Medizintechnik, GmbH, Tübingen, German), dilatation, stent placement, stent revision and combinations of these procedures. Procedure indications were classified as PITS, PTTS, malignant airway stenosis, tracheoesophageal fistula, foreign body, hemoptysis, and benign airway stenosis.
Complications were grouped as bleeding, respiratory failure, unstable hemodynamics and arrhythmia. Bleeding was graded as “Grade 0- No bleeding or minimal bleeding that stopped on its own; Grade1- Mild bleeding that could be stopped with cold 0.9% NaCl solution or epinephrine solution (1 mg / 100 ml saline water); Grade 2- Moderate bleeding that required argon plasma coagulation or bronchial balloon blockage; Grade 3- Severe bleeding that resulted in transfusion of blood products, vasopressor support, rescue operation or death” [14].
Age groups of <65, 65-74 and ≥75 years were compared in terms of complications and procedural mortality.
Statistical analysis
SPSS 16.0 for Windows package program was used for the statistical analysis. Normality analyzes of the continuous data were performed using the Shapiro-Wilk Test. Firstly, descriptive statistics were expressed. Normally distributed data were expressed as mean ± standard deviation, and non-normally distributed data were expressed as median and interquartile range. Pearson’s Chi-Square and Fisher’s Exact tests were used for comparisons of categorical data; categorical data were expressed as the counts and percentages. The p <0.05 level was used for the statistical significance.
Results
Two hundred sixty-eight patients (M / F: 222/46) who underwent IB were included in the study. Recurrent endobronchial therapy was performed in 33 patients. Seventeen of 33 patients had lung cancer, 3 patients had extra-thoracic malignancy, 3 patients had airway obstruction due to benign tumors, and 10 patients had PITS / PTTS. A total of 268 patients underwent interventional procedures with 317 RB at different visits.
The mean age was 61 ± 12 years; 152 patients (56.7%) were <65 years old, 116 were ≥65 years old. Comorbidity distributions in patients are given in Table 1. Thirty-one patients classified as other comorbidities had atrial fibrillation, papillomatosis, valvular heart disease, hypothyroidism, hyperlipidemia, rheumatoid arthritis, bronchiectasis, and psychosis. When the comorbidities were evaluated, statistically significant differences were found between the age groups in terms of hypertension (HT), diabetes mellitus (DM), coronary artery disease (CAD), chronic renal failure (CKD) and lung cancer (LC) (p <0.05). The lung cancer rate was significantly higher in the <65 years of age group, the others were higher in the ≥75 years of age group (p <0.05; Table-1).
Although the ASA score was higher in patients over the age of 65 years, this difference was not statistically significant (p = 0.052).
Indications for procedures, pre-diagnoses and post-procedural pathological diagnoses according to age groups are shown in Table 2. There was no difference between <65 and ≥65 years of age groups in terms of pre-diagnoses and indications (p> 0.05).
Procedure localizations were as follows: 102 tracheae, 8 main carina involvement, 83 right main bronchi, 33 right intermediary bronchi, 79 left main bronchi and 12 left lower lobes. The endobronchial procedures applied are given in Figure-1.
The use of drugs that may cause bleeding in age groups was examined, and it was observed that there was a significant increase in the use of acetylsalicylic acid, LMWH, and warfarin in advanced age (p <0.05; Table-1). Before the procedure, the use of these drugs was discontinued at the appropriate time and the procedures were applied. However, in 7 cases, due to the high risk of ischemia, procedures were performed without discontinuation of these drugs. Grade 2 bleeding was observed in only one patient among these procedures.
No complications occurred in 257 (81.1%) of all procedures (Table 1). It was observed that there was no difference between the age groups in bleeding, respiratory failure, hemodynamic instability, and severity of bleeding (p> 0.05). Mortality due to Grade 3 bleeding during the procedure occurred in 1 patient. No procedural mortality was observed except for this patient.
Discussion
In daily practice, we encounter elderly patients more frequently and we apply more invasive procedures as life expectancy increases. Nowadays, in interventional pulmonology, endobronchial procedures are being used more frequently, and awareness of this issue is increasing, especially in lung cancer treatment approaches. Central airway stenosis is seen in 20-30% of the follow-up of primary or metastatic lung cancers [15]. As far as we can see in the literature, there are very few studies evaluating the approach, comorbidity, procedure risk, safety and mortality in elderly patients in rigid bronchoscopy. Therefore, we wanted to discuss elderly patients from this perspective according to our two-year experience. In the study of Özgül et al, it was seen that 47.2% of 2029 interventional procedures were performed due to malignant airway stenosis in 10-year experience [16]. In our study, this rate was 76%. There was no significant difference between patients < 65 and ≥ 65 years of age.
In Davoudi et al’s study evaluating 18 patients over the age of 80, the most common comorbidities were hypertension, arrhythmia, and coronary artery disease, and they reported that there were controllable complications (hypotension, arrhythmia, hypoxia, and bleeding) in procedures and there was no need for intubation [17]. In another study evaluating fiberoptic bronchoscopy, two groups were compared retrospectively, and mortality and side effects were found more frequently in octogenarians (> 80 years of age); additionally, it was reported that comorbidities were more common in these patients, but no relationship was established [18].
Ernst et al reported in their study on 554 patients, in which all age groups were evaluated, that the complication rate due to the interventional procedure was 19.8% [19]. In another study, Valipour et al found that the life-threatening hemoptysis rate was 5-15% [20].
In our study, it was found that HT, DM, CAD, and CRF were significantly more common in advanced age. The complication rate was 18%. Although there was an increase in comorbidities with advanced age, there was no difference in terms of complications according to age groups. The use of acetylsalicylic acid and anticoagulants was found to be higher in the patient group aged 75 years and over, but there was no difference in terms of bleeding. In addition, patients with respiratory failure, hemodynamic instability and uncontrolled bleeding were all <65 years of age, contrary to expectations. The nature, localization, vascular neighborhood or invasion of the lesions are other important risk factors for bleeding complication independent of age.
In studies on safety and efficacy of fiberoptic bronchoscopy, no difference was found between the age groups in terms of complications, and it was found to be safe in the elderly [21,22]. However, sedation was used in the procedures in these studies. Complications in rigid bronchoscopy can be thought to be related to the total intravenous GA. According to Pathak et al’s study on cardiovascular complications, hypercarbia and hypoxia can be associated with general anesthesia [10]. Grendelmeier et al evaluated the use of propofol in flexible bronchoscopy and rigid bronchoscopy and found that there was no significant difference in complications, but there was more hypotension and carbon dioxide retention in elderly patients [23]. In our study, the ASA score was higher in the elderly group, but there was no difference in complications. In Murgu et al study, ASA 3 and 4 were detected in 90% of the patients, and it was found to be unrelated to mortality [11]. There was no significant increase in mortality rates with age in our study.
According to the McLaughlin et al’s study, in which 73 patients over the age of 85 were evaluated for fiberoptic bronchoscopy, the difference in comorbidity load should be considered when deciding whether to perform invasive procedures, but age alone should not be considered a contraindication [21].
Retrospective and single-center design were the main limitations of this study. In addition, the quality of life was not evaluated after the procedure. Studies evaluating the performance status before and after the procedure can guide the management of elderly patients.
Conclusion
Elderly patient admissions are increasing day by day; this leads to an increased need for endobronchial treatment. In these patients, the burden of comorbidity is higher than the younger patient group. Poor ASA score and comorbidities are important in deciding whether to perform the procedure, but there is no scientific evidence to show that these factors are contraindications. In this study, comorbidities were found more frequently in elderly patients, but there was no difference in procedural complications and mortality. The decision to perform the procedure should be made with the patient according to the indication, considering the risks and benefits.
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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Melahat Uzel Şener, Ayperi Öztürk, Aydın Yılmaz. Safety of interventional bronchoscopy in elderly patients. Ann Clin Anal Med 2022;13(4):404-409
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Single center experiences in merkel cell carcinoma and unprecedented presentation
Kayhan Ozdemir 1, Baris Mantoglu 2, Fatih Altintoprak 3, Enes Bas 2, Necattin Firat 3, Ebru Kayra 4, Emre Gonullu 2, Ali Muhtaroglu 5, Erhan Eroz 6
1 Department of General Surgery, Urgup State Hospital, Nevsehir, 2 Department of General Surgery, Sakarya University Training and Research Hospital, Sakarya, 3 Department of General Surgery, Faculty of Medicine, Sakarya University, Sakarya, 4 Department of Pathology, Sakarya University Training and Research Hospital, Sakarya, 5 Department of General Surgery, Igdir State Hospital, Igdir, 6 Department of General Surgery, Toyota State Hospital, Sakarya, Turkey
DOI: 10.4328/ACAM.20950 Received: 2021-11-15 Accepted: 2021-12-31 Published Online: 2022-01-03 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):410-414
Corresponding Author: Kayhan Ozdemir, Department of General Surgery, Urgup State Hospital, Nevsehir, Turkey. E-mail: drkayhan1@gmail.com P: +90 553 380 02 89 F: +90 264 888 40 01 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8041-198X
Aim: Merkel cell carcinoma (MCC) is a rare skin tumor with an aggressive course. If there is no distant metastasis in its treatment, excision with negative surgical margins is the primary method. Since it is usually detected in incidental postoperative pathology reports, negative surgical margins must be observed during the removal of lesions on the skin.
Material and Methods: In our study, we analyzed eleven patients diagnosed with MCC in our hospital between January 2010 and January 2020. Patients with perineural or vascular invasion, borderline microscopic positive findings, residual disease, and/or regional lymph node involvement among patients with tumors larger than 1.5 cm in pathology reports were referred to adjuvant treatment.
Results: The tumors were most frequently located in the thigh (25%), head-neck (25%), forearm (16.6%), inguinal (16.6%), and gluteal region (16.6%), respectively. The patients were followed up for an average of 38 months postoperatively (11-62 months). Complete cure was achieved in five (45.4%) of the cases. The average survival duration was 36 months (11-62 months). Recurrence was observed in two of our cases. Despite metastases occurring at different times in different abdominal organs abdomen, the surveillance was longer than expected, with an excellent response to multidisciplinary treatments.
Discussion: The features of the lesion should be carefully examined in the preoperative period. If in doubt, a sentinel biopsy should be performed during surgery by performing systemic screening. A multidisciplinary approach should be preferred in metastatic lesions. If intra-abdominal metastases are resectable, surgical treatment may prolong the surveillance.
Keywords: Merkel Cell Carcinoma, Metastasis, Surgical Treatment
Introduction
Merkel cell carcinomas (MCC) are aggressive neuroendocrine tumors with the risk of local invasion, lymph node metastasis, and distant metastasis. It is approximately twice as mortal as malignant melanoma, a skin tumor with a poor prognosis. The 5-year survival has been reported to range between 0 and 18% for advanced-stage MCC [1]. Although its incidence according to geographical regions and races, it is common in the Caucasians and male gender in the age range of 70-80 [2,3]. Based on surveillance and epidemiology data in the United States, its current incidence was reported as 0.79 per 100,000. Caucasians account for 94.9% of these cases 1.0% are black, and 4.1% are other races (Asia-Pacific Islander, Native American, or other). These reports show that Merkel cell carcinoma is sporadic in patients of Asian descent [4].
For many years, the dissection of the primary tumor and regional lymph nodes with negative surgical margins subsequently adjuvant chemoradiotherapy (CRT) is the current treatment method for the treatment of MCC [5]. In our article, we evaluated 11 patients who were diagnosed with MCC between 2010 and 2020, who underwent surgical treatment solely, or received adjuvant chemoradiotherapy after surgical treatment. In one of our cases, which has not been encountered in the literature yet, gastric, testicular, and pancreatic metastases were encountered at different times during the course of the disease. Survival was prolonged with orchiectomy and pancreatectomy. This is the one and the only Merkel cell carcinoma case in the literature to have both pancreatic and gastric metastasis during the course of the disease. The demographic characteristics of the patients, tumor localization, treatment method, the existence of lymph node metastasis or distant metastasis, recurrences, and survivals were analyzed (Table 1). Our aim was to evaluate treatment modalities that can prolong survival in Merkel cell carcinoma.
Material and Methods
In our study, we analyzed 11 patients who were found to have Merkel cell carcinoma after 1862 surgical procedures performed under local anesthesia in our outpatient clinic conditions between January 2010 and January 2020. In these cases, the localization of the mass, its diameter, surgical margins, presence of re-excision, presence of distant metastases, presence of lymphatic dissection and survival were detailed. This study was approved by the Faculty of Medicine, Sakarya University Ethics Committee (No. 71522473/050.01.04/425; date: 27.07.2020). The National Comprehensive Cancer Network (NCCN) current guideline was used to determine the appropriate treatment method. Patients with perineural or vascular invasion, borderline microscopic positive findings, residual disease, and/or regional lymph node involvement among patients with tumors larger than 1.5 cm in pathology reports were referred to adjuvant treatment.
Descriptive analyses were performed to provide information on general characteristics of the study population. The Kolmogorov-Smirnov test was used to evaluate the normal distributions of numerical variables. Accordingly, the Mann-Whitney U test was used to compare the numeric variables between groups. The numeric variables were presented as mean ± standard deviation. Categorical variables were compared using the Chi-Square test. Categorical variables were presented as a count and percentage. A p-value <0.05 was considered significant. Analyses were performed using SPSS statistical software (IBM SPSS Statistics, Version 25.0. Armonk, NY: IBM Corp.)
Results
Seven of the twelve patients were male, five were female, and the average age was 73 years (50-88). The solitary lesion was detected in all patients. Tumors were most frequently located in the thigh (25%), head-neck (25%), forearm (16.6%), inguinal (16.6%), and gluteal region (16.6%), respectively. The patients were followed up for an average of 38 months postoperatively (11-62 months). Complete cure was achieved in five (45.4%) of the cases. Re-excision was performed in two patients due to positive surgical margins. Sentinel lymph node biopsy (SLNB) was performed in four patients. Lymph node dissection was performed due to detected lymph node metastasis in three of these patients. Distant metastases mainly were to bone and lung. The average survival duration was calculated 36 months (11-62 months). Recurrence was observed in two of our cases. Surgical treatment was applied to the 2.5 cm mass localized in the right gluteal area in a patient. Merkel cell carcinoma was revealed on the histological examination of the specimen, and surgical margins were clear (Figure 1A,1B, 1C). Right orchiectomy was performed when recurrence was detected in the right testicle on abdominal computed tomography (Figure 2A, 2B) of the patient who presented with complaint of testicular enlargement in the 12th month (Figure 1D, 1E). The patient received three cycles of cisplatin etoposide treatment. Distal pancreatectomy and splenectomy procedures were subsequently performed due to detected solitary metastasis in the distal pancreas on the abdominal tomography taken at 16 months (Figure 2C). Merkel cell carcinoma was revealed on the histological examination of the pancreas and spleen, and surgical margins were clear (Figure 1F). The patient, whose oncological treatment was continuing, was followed up in remission for 12 months. Merkel cell carcinoma metastasis was detected in biopsies taken from the mass found in the fundus and corpus of the stomach (Figure 3A, 3B) in the endoscopy performed upon the presence of epigastric pain at the 28th month of follow up (Figure 1G, 1H). The patient, who had widespread metastasis on control positron emission tomography (PET-CT) (Figure 2D), died in the 38th month of follow-up.
Despite metastases occurring at different times in different abdominal organs , the surveillance was longer than expected, with an excellent response to multidisciplinary treatments. Another feature of the case that has not yet been reported in the literature is the presence of gastric, pancreatic, and testicular metastases at different times.
Discussion
Although the clinical features of early-stage MCC are unclear, they may occur in erythematous, papillary, and nodular forms. It is usually diagnosed on the basis of histological and immunohistochemical findings. Most MCCs are seen in the head and neck site or extremities [6]. In our cases, tumors were frequently located in these sites. As a standard treatment option in early-stage MCC, local excision is performed considering the surgical margins [7]. In the case of suspicion, lymph node dissection may be considered if positive lymph nodes are detected on lymph node evaluation using Sentinel Lymph Node Biopsy (SLNB). In this case, the tumor stage is defined as stage 3. Adjuvant radiotherapy (RT) or re-excision may be considered if there are concerns about the surgical resection margin’s adequacy for the primary tumor or the nodal staging process is missing [8]. According to the current NCCN guidelines, Stage II MCC standard treatment options include local excision with negative margins, followed by the SLNB procedure and adjuvant RT. Chemotherapy may be considered for patients with stage IV MCC, but there is insufficient evidence that chemotherapy results in permanent disease control or regional palliation [9] .
According to recent NCCN guidelines, when clinically possible, local excision with a 1 or 2 cm intact margin should be performed in all primary MCC tumors [10]. However, different excision margins have not yet been compared in any controlled clinical study [11]. In a large population study of primary MCC tumors by Perez et al, there was no significant association between the risk of local recurrence at the margin of 1 cm surgical resection and no significant effect in overall survival and disease-specific survival [12]. In our study, surgical resection with a 1 cm clear margin was performed in patients considered to have MCC before the surgical procedure. Male gender, advanced age, increased tumor size, and immunodeficiency have been associated with a poor prognosis in MCC [13]. However, lymph node involvement is the most important prognostic feature of clinically localized MCC [14, 15]. SLNB was performed in four patients who were thought to have lymph node involvement. Extended lymph node dissection was performed due to lymph node involvement detected in three of them. When the MCC patients presented to hospitals, their state was in 65% local disease, %26 regional lymph node metastasis, and distant metastasis in 8% [16]. MCC metastasizes most often to lymph nodes and then another skin area (9% -30%). These are followed by the lungs (10-23%), the central nervous system (18%), bone (10-15%), and the liver (13%). Lung and bone metastases were more common in our metastatic cases than in others. It is also possible to perform SLNB in patients with clinically negative lymph nodes, as roughly 20% to 30% of clinically negative MCC patients have positive SLN histology findings [17]. Since MCC is highly sensitive to radiation, adjuvant RT is an important component of MCC therapy. Even though Allen et al. [6] reported in a retrospective study that adjuvant RT could not provide significant local control, most of the other clinical studies showed that postoperative adjuvant RT improved local control to a greater extent [18,19]. Adjuvant RT is recommended for patients with a tumor larger than 1.5 cm who have vascular invasion, perineal invasion, positive microscopic margins on histopathological examination, residual disease, and/or regional lymph node involvement. According to NCCN guidelines, adjuvant nodal RT is routinely recommended when SLNB cannot be performed or when a patient presents clinically positive regional lymph node findings [10]. However, a more specific consensus is required on adjuvant RT indications. We applied postoperative radiotherapy to six patients with distant metastases. We also provided a complete cure with re-surgery for our patient who relapsed after four years in the same site. In a patient that suchlike a case has not existed in literature yet; We demonstrated that survival could be prolonged if synchronous resectable intra-abdominal and testicular metastases were surgically removed. MCC is a rare, aggressive skin cancer. Rapid diagnosis and active treatment are essential for the treatment of this disease. We recommend resection and subsequently postoperative RT in eligible patients with isolated intra-abdominal metastases, without peritonitis carcinomatosis. Further studies are needed with a high number of patients to conclude an accurate treatment strategy.
Conclusion
We demonstrated that survival could be prolonged if synchronous resectable intra-abdominal and testicular metastases were surgically removed. MCC is a rare, aggressive skin cancer. Rapid diagnosis and active treatment are essential for the treatment of this disease. We recommend resection and subsequently postoperative RT in eligible patients with isolated intra-abdominal metastases, without peritonitis carcinomatosis. Further studies with a high number of patients are needed to conclude an accurate treatment strategy.
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. Harms PW, Harms KL, Moore PS, DeCaprio JA, Nghiem P, Wong MKK, et al. The biology and treatment of Merkel cell carcinoma: current understanding and research priorities. Nat Rev Clin Oncol. 2018;15(12):763-76.
2. Agbai ON, Buster K, Sanchez M, Hernandez C, Kundu RV, Chiu M, et al. Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. J Am Acad Dermatol. 2014;70(4):748-62.
3. Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE. Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol. 2010;37(1):20-7.
4. Fitzgerald TL, Dennis S, Kachare SD, Vohra NA, Wong JH, Zervos EE. Dramatic Increase in the Incidence and Mortality from Merkel Cell Carcinoma in the United States. Am Surg. 2015;81(8):802-6.
5. Cassler NM, Merrill D, Bichakjian CK, Brownell I. Merkel Cell Carcinoma Therapeutic Update. Curr Treat Options Oncol. 2016;17(7):36.
6. Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23(10):2300-9.
7. Singh B, Qureshi MM, Truong MT, Sahni D. Demographics and outcomes of stage I and II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Database. J Am Acad Dermatol. 2018;79(1):126-134.e3.
8. Fiedler E, Vordermark D. Outcome of Combined Treatment of Surgery and Adjuvant Radiotherapy in Merkel Cell Carcinoma. Acta Derm Venereol. 2018;98(7):699-703.
9. Bhatia S, Storer BE, Iyer JG, Moshiri A, Parvathaneni U, Byrd D, et al. Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base. J Natl Cancer Inst. 2016;108(9):djw042.
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14. Tarantola TI, Vallow LA, Halyard MY, Weenig RH, Warschaw KE, Grotz TE, et al. Prognostic factors in Merkel cell carcinoma: analysis of 240 cases. Tarantola TI, Vallow LA, Halyard MY, et al. Prognostic factors in Merkel cell carcinoma: analysis of 240 cases. J Am Acad Dermatol. 2013;68(3):425-32.
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Kayhan Ozdemir, Baris Mantoglu, Fatih Altintoprak, Enes Bas, Necattin Firat, Ebru Kayra, Emre Gonullu, Ali Muhtaroglu, Erhan Eroz. Single center experiences in merkel cell carcinoma and unprecedented presentation. Ann Clin Anal Med 2022;13(4):410-414
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Comparison of psychological status, physical activity level, and birth results of adolescent and adult pregnant women
Berrin Aktan 1, Salim Erkaya 2, Türkan Akbayrak 3
1 Departmant of Physical Therapy, Etlik Zübeyde Hanım Gynecology Training and Research Hospital, 2 Departmant of Perinatology, Etlik Zübeyde Hanım Gynecology Training and Research Hospital, 3 Department of , Faculty of Physical Therapy and Rehabilitation, Hacettepe University, Ankara, Turkey
DOI: 10.4328/ACAM.20951 Received: 2021-11-15 Accepted: 2022-03-09 Published Online: 2022-03-24 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):415-418
Corresponding Author: Berrin Aktan, Etlik Zübeyde Hanım Gnecology Training and Research Hospital, Ankara, Turkey. E-mail: berrin_ay@yahoo.com P: +90 532 551 07 31 / +90 312 565 60 54 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4840-5720
Aim: The aim of this study was to investigate the differences between adolescent and adult pregnant women in terms of psychological status, physical activity level, and birth outcomes.
Material and Methods: This study was conducted on pregnant women who admitted to the Pregnancy Polyclinic of Etlik Zübeyde Hanım, Gynecology Training and Research Hospital. The study included 38 adolescent pregnant women and 38 adult pregnant women. While adolescent pregnant women were named as Group 1, adult pregnant women were named as Group 2. The International Physical Activity Questionnaire-Short Form (IPAQ-SF) and the Edinburgh Postpartum Depression Scale (EPDS) were used in the study.
Results: The mean body weight before delivery was 76.50±11.25 kg in Group 1 and 75.16±10.80 kg in Group 2. It was found that the mean weight gain during pregnancy was 18.4±6.20 kg in Group 1 and 14.76±4.77 kg in Group 2 (p<0.05). The mean weight gain was significantly higher in Group 1. It was found that there was no statistically significant difference between the groups in terms of 3rd trimester EPDS scores (p>0.05). However, it was found that postpartum EPDS scores were significantly higher in Group 1 compared to Group 2 (p<0.05).
Discussion: The results of our study show that adolescent pregnant women tend to gain excessive weight during pregnancy. Postpartum depression symptoms were found to be higher in adolescent pregnant women. Adolescent women who get pregnant during a sensitive development period should be provided with prenatal care and social support.
Keywords: Adolescent Pregnancy, Physical Activity, Neonatal Outcomes, Postpartum Depression
Introduction
The World Health Organization (WHO) defines 10-19 age range as the adolescent period, 20-24 age range as the youth period, and defines individuals between the ages of 10 and 24 as young people. It is estimated that 17.5% of the world population is in the 15-24 age group [1].
Pregnancy of younger women who have not reached physical, psychological and social maturity is an important public health problem in all countries of the world. Pregnancy in this period negatively affects the health of both mother and baby. Pregnancy in adolescence is considered a high risk [2]. Postural adaptations occur during pregnancy to accommodate abdominal growth and change in the center of gravity [3]. The most common complications in adolescent pregnancy include bleeding, preeclampsia, urinary tract infection, preterm birth, premature birth, cephalopelvic incompatibility, fetal distress, fetal anomaly, and presentation anomaly [4]. Neonatal complications have been reported to be significantly higher in babies of adolescent women compared to babies of adult women. The most commonly seen neonatal complications of babies of adolescent pregnant women are low birth weight (LBW) and delayed intrauterine growth, while neonatal mortality was defined in 6.9% of the cases [5]. Although many studies on adolescent pregnancy have been conducted in our country, it has been observed that comparative physical activity, psychosocial factors and their birth outcomes have not been studied together.
The aim of this study was to investigate differences between adolescent and adult pregnant women in terms of psychological status, physical activity level, and birth outcomes.
Material and Methods
This study was conducted on pregnant women who admitted to the Pregnancy Polyclinic of the Etlik Zübeyde Hanım, Gynecology Training and Research Hospital. Our study was designed as a prospective study. Pregnant women with gestational diabetes and those with participation barriers and complications including Type 1 diabetes, persistent bleeding, membrane rupture, history of growth retardation, chronic systemic vascular disease, and preeclampsia were excluded from the study. Inclusion criteria for the study were as follows: nulliparity, pregnant women with BMI <30, being a citizen of the Republic of Turkey, adolescent pregnant women (15-18 years old). Ethical approval for the study was obtained from the Ethics Committee for Non-Interventional Clinical Research of Hacettepe University with the decision number 2019/12-11.
The population of the study consisted of pregnant women who applied to our hospital between January 2020 and March 2020. Sample calculation was not made in the study, and adolescent pregnant women admitted during the study period and adult pregnant women with similar characteristics formed the sample of the study. The study included 38 adolescent pregnant women and 38 adult pregnant women with similar anthropometric characteristics and gestational age between 29-36 weeks of gestation. Adolescent pregnant group was named as the 1st group, and the adult pregnant group was named as the 2nd group.
Detailed obstetric and medical histories and demographic information of the pregnant women were recorded. All evaluations regarding pregnancy were performed twice in both groups in the 3rd trimester (between 29th and 36th weeks) and in the 2nd month after delivery. Both groups of pregnant women were compared in terms of postpartum gestational age and birth weights of their babies.
The International Physical Activity Questionnaire-Short Form (IPAQ-SF) was applied to pregnant women (Group 1 and Group 2) to determine the level of physical activity. In addition, the Edinburgh Postpartum Depression Scale (EPDS) was used to evaluate the depression level of pregnant women during pregnancy and postpartum period.
The IPAQ and IPAQ-SF were developed by the International Consensus Group in Geneva in 1998 to evaluate the physical activity levels of individuals according to standards. The Turkish version of the questionnaire was made by Sağlam M. et al. in 2010 [6].
Edinburgh Postpartum Depression Scale:
The EPDS was developed by Cox in 1987 to screen for depression in postpartum women in England. The scale is a self-report scale. The scale is a screening scale for determining the risk of postpartum depression and is also used during pregnancy [7]. The Turkish version of the questionnaire was made by Aydın N. et al. in 2004 [8].
Statistical analysis
Statistical analyses were performed using SPSS version 20 software (SPSS Inc., Chicago, IL., USA). The descriptive statistics of categorical variables were given by numbers and percentages, and continuous variables were given by mean ± standard deviation. In the evaluation of the study data, Student’s t-test was used for the two-group comparison of the variables that have a normal distribution. A p-value <0,05 was accepted statistically significant.
Results
The mean age of the 38 adolescent pregnant women (Group 1) was 17.86±0.57 years, and the mean age of the 38 adult pregnant women (Group 2) was 26.34±4.34 years. The mean height was 161.71±7.13 cm in Group 1 and 161.31±5.18 cm in Group 2. There was no significant difference between the groups in terms of average height (p>0.05) (Table 1).
The mean body weight before pregnancy was 58.07±10.21 kg in Group 1 and 60.39±10.99 kg in Group 2. There was no significant difference in the mean body weight pre-pregnancy between Group 1 and Group 2 (p>0.05) (Table 1). The mean body weight before delivery was 76.50±11.25 kg in Group 1 and 75.16±10.80 kg in Group 2. There was no significant difference between the groups in terms of the mean body weight before delivery (p>0.05) (Table 1). It was found that the mean weight gain during pregnancy was 18.4±6.20 kg in Group 1 and 14.76±4.77 kg in Group 2 (p<0,05). The mean weight gain was significantly higher in Group 1. The physical characteristics of the pregnant women participating in the study are summarized in Table 1.
The mean duration of marriage was 9.97±5.08 months in Group 1 and 25.31±21.22 months in Group 2.
It was found that there was no statistically significant difference between the groups in terms of the 3rd trimester EPDS scores (p>0.05) (Table 2). However, it was found that postpartum EPDS scores were significantly higher in Group 1 compared to Group 2 (p<0.05). The mean EPDS scores of the pregnant women according to the groups are shown in Table 2.
It was found that there was no statistically significant difference between the groups in terms of the mean 3rd trimester and postpartum IPAQ-SF scores of the pregnant women (p>0.05). The comparison of the mean 3rd trimester and postpartum IPAQ-SF scores of the pregnant women according to the groups are shown in Table 3.
Discussion
In this study, we compared differences between adolescent pregnant women and adult pregnant women in terms of socio-psychological status, physical activity level and birth outcomes. According to the results of the study, it was determined that the demographic characteristics of pregnant women in both groups were similar, and adolescent pregnant women gained more weight during their pregnancy. Adolescent pregnant women may have special problems due to poor pre-pregnancy nutritional status, nutritionally poor diets during pregnancy, early weight gain adequacy and body image concerns. However, it is not known for sure whether these problems are related to irregular weight gain patterns during adolescent pregnancy [9]. Similar to our study, in the study conducted by D. Howie et al. in the USA, the weight gain of adolescent pregnant women (≤19 years of age) and adult pregnant women (≥20 years of age) during pregnancy were compared and it was found that more than 27% of adolescent women and approximately 18% of adult pregnant women gained excessive weight during pregnancy [10]. In a prospective study conducted on 150 adolescent pregnant women, it was determined that adolescent pregnant women had inadequate antenatal care that could lead to adverse maternal and birth outcomes [11].
In our study, it was determined that the depression status of adolescent and adult pregnant women was similar in the third trimester, while the depression level of the adolescent pregnant women was higher in the second month postpartum. In another study comparing depression levels of adolescent and adult pregnant women in the 3rd trimester and in the 3rd month postpartum, it was found that the depression levels of adolescent pregnant women were higher during both pregnancy and postpartum period compared to adult pregnant women [12]. In another study, a prospective research questionnaire was applied to 212 adolescent pregnant women during pregnancy and 6 weeks after the delivery and it was reported that poor social adjustment was found to be associated with perceived maternal stress, less social support, and less positive view of pregnancy [13]. In another study, evaluating the depression levels of 396 adolescent pregnant women and 286 adult pregnant women, it was found that adolescent mothers exhibited higher depression rates before and at 6 months postpartum compared to adult mothers [14]. In a study in which prenatal care and support were provided to adolescent pregnant women, it was stated that a significant number of adolescent pregnant women were affected by depression. They suggested that there is a need for comprehensive interventions involving partners and families and that address the challenges that adolescent mothers face [15].
In our study, when the physical activity levels of adult and adolescent pregnant women were compared in the 3rd trimester and in the 2nd month after delivery, it was found that there was no difference between the groups in terms of the duration of labor in pregnant women, and there was no difference between the baby weights. In the literature, there is little information about the physical activity levels of adolescent pregnant women. In a cohort study conducted by Steinl et al., physical activity levels of 157 adolescent pregnant women (13-18 years) were investigated and physical activity level of the adolescent women was low during pregnancy [16]. In our study, when adolescent and adult pregnant women were compared in terms of physical activity level, it was found that both groups were inactive. We think that this lack of adequate activity was due to the social indications experienced during the COVID-19 pandemic.
When we evaluate our study results in terms of birth results, it was found that there were no significant differences between the groups in terms of the birth weight of the babies. In the literature, results regarding adolescent pregnancies and birth outcomes are variable. In a study similar to our study, it was found that early pregnancy was not associated with low birth weight alone [17]. In a study examining adolescent pregnant women, it was shown that low birth weight and young maternal age (>17 years) were significantly associated [18]. Again, it has been shown in several studies that infants of adolescent mothers, especially those who were the babies of mothers younger than 20 years of age are much more likely to have low birth weight [19, 20]. One of the reasons for this has been suggested to be due to the fact that nutritional supply for the adolescent mother and her baby is problematic during this period when adolescent mothers are still developing and not fully matured [21]. Studies have suggested additional support and prenatal care to minimize the risk of adverse outcomes in adolescent pregnancies [22, 23]. In our study, we detected no significant difference between the groups in terms of postpartum results; this may be due to the developments in maternal health policies and antenatal care services in our country.
Limitations
Since our study was conducted during the COVID-19 period, a limited number of pregnant women could be reached. In addition, the physical activities, nutritional habits, and psychological states of pregnant women may have been affected by the COVID-19 pandemic. To support our results, there is a need for studies with a higher sample size. In addition, there is a need for comparative studies evaluating adolescent pregnancies by including other COVID-19-related parameters.
Conclusion:
The results of our study show that adolescent pregnant women tend to gain excessive weight during pregnancy. In addition, postpartum depression symptoms were found to be higher in adolescent pregnant women. Adolescent women who get pregnant during a sensitive development period should be provided with prenatal care and social support, including recommendations for physical activity during pregnancy and proper nutrition. In addition, we suggest that psychological support should be provided to prevent postpartum depression.
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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Download attachments: 10.4328:ACAM.20951
Berrin Aktan, Salim Erkaya, Türkan Akbayrak. Comparison of psychological status, physical activity level, and birth results of adolescent and adult pregnant women. Ann Clin Anal Med 2022;13(4):415-418
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Venous port catheter implantation for chemotherapy: Our experience in pediatric cases
Nevin Aydın 1, Gülseren Yılmaz 1, Osman Esen 2, Hayrünisa Kahraman Esen 3
1 Department of Anesthesiology and Reanimation, University of Health Sciences, Kanuni Sultan SüleymanTraining and Research Hospital, 2 Department of Anesthesiology and Reanimation, Vocational School of Health, İstinye University, 3 Department of Pediatric Surgery, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.20958 Received: 2021-11-19 Accepted: 2021-12-07 Published Online: 2021-12-18 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):419-422
Corresponding Author: Hayrünisa Kahraman Esen, Zümrütevler Mah., Handegül Sokak, No:98/16, Maltepe, İstanbul, Turkey. E-mail: nisakahraman@hotmail.com P: +90 505 713 68 23 Fax: +90 216 457 38 00 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3541-6546
Aim: The use of central venous access devices and especially venous port catheters is increasing day by day due to frequent venous interventions and long-term and painful treatment in chemotherapy treatment of cancer patients. In this study, we aimed to evaluate the applications of chemotherapy port-catheters in pediatric patients.
Material and Methods: Between 2014 and 2017, 76 pediatric cancer patients who were inserted venous port catheters for chemotherapy treatment in our hospital were evaluated retrospectively. Demographic data, diagnoses, port implantation site, and complications observed during and after the procedure were examined. The ports were placed under general anesthesia. Fluoroscopy was used during port placement, but not ultrasound.
Results: The mean age of the patients was 6.88 ± 4.79 (1-16) years and consisted of 31 (40.8%) female and 45 (59.2%) male patients. A chemotherapy port-catheter was inserted through the right subclavian vein in 48 patients, the left subclavian vein in 27 patients, and the right internal jugular vein in 1 patient. Five French (n=46; 60.5%), 6Fr (n=18; 23.7%) and 7Fr (n=12; 15.8%) port catheters were used for the number of patients involved. Arterial puncture was seen in 17 patients. Infection developed in 12 patients who received antibiotic therapy. Resorbed pneumothorax developed in one (1.3%) patient. No malposition was observed during the procedure.
Discussion: Despite some complications that may occur during chemotherapy port-catheter implantation in patients who will receive chemotherapy, it is a preferred method in terms of patient comfort. It is recommended to use imaging methods during and after the procedure to reduce complications.
Keywords: Child, Port catheters, Fluoroscopy, Vascular access, Ultrasound imaging
Introduction
Intravenous administration of chemotherapeutic agents in oncology and hematology patients, their long-term parenteral alimentation, blood transfusions, providing comfort for these patients, and facilitation of the maintenance of home-therapies make chemotherapy port-catheter implantation an important issue. Venous port applications relieve children and their parents from the stress of searching for an appropriate venous route, increase the quality of life, confidence in medical care, and adherence to treatment [1-3]. Its application can be achieved under local or general anesthesia. The use of central venous access devices and especially venous port catheters in chemotherapy treatment in cancer patients is increasing day by day.
Implantation of a chemotherapy port catheter has become a common interest of anesthetists, general surgeons, chest surgeons, radiologists, cardiovascular surgeons. In our study, we aimed to evaluate the pediatric applications of chemotherapy port-catheters performed in our clinic.
Material and Methods
The study was approved by the ethics committee (KAEK/ 2015.14.5) and was conducted in accordance with the Helsinki Declaration. This study was performed with patients registered in our database who had been referred to the clinic of pediatric hematology and oncology of our hospital for chemotherapy port-catheter implantation. In our study, a total of 76 patients who were referred to our clinic between 2014, and 2017 for implantation of chemotherapy port-catheter were evaluated.
Before the procedure, the patients were evaluated for their general health status, the presence of bleeding diathesis, and vascular access site to be used for intervention. The relatives of the patients were told before the procedure about the the upcoming procedure, its potential complications, and the purpose of the procedure; then they completed a procedural consent form. Peripheral vascular access was opened, the sterile drape was placed, and under general anesthesia, priorly subclavian vein because of easy of application, and secondly internal jugular veins were preferred. Reservoirs were placed on the midclavicular line, and on the pectoral muscle creating a port pocket, and the catheter was implanted. Ultrasound was not used during the procedure, but fluoroscopy was used. After the procedure, the port catheter was irrigated with physiologic saline, and the reservoir was filled with diluted heparin (2500 U standard heparin in 10 cc physiologic saline). After the procedure, control chest radiograms were obtained within the first two hours, and 24 hours later. The location of chemotherapy port-catheter was evaluated as for hemothorax, and pneumothorax. After implantation, when wound healing was achieved, chemotherapy sessions were initiated.
Statistical analysis
Analysis of data was carried out using SPSS 21 program (Chicago, IL, USA). Data were expressed as numbers and percentages. The Chi-square test was utilized to compare groups. Logistic regression analysis was performed to assess the impact of variables on the occurrence of arterial puncture. A p-value less than 0.05 was considered statistically significant.
Results
Port catheters were implanted in 76 patients in our clinic. The mean age of the patients was 6.88 ± 4.79 (range, 1 to 16) years, the study population consisted of 31 (40.8%) female, and 45 (59.2%) male patients. Chemotherapy port-catheter was implanted with the indications of acute lymphoblastic leukemia (ALL) (n=60; 79.0%), acute myeloid leukemia (AML) (n=8; 10.5%), non-Hodgkin lymphoma (NHL) (n=3; 2.6%), neuroblastoma (n=2; 2.6%), and malignant neoplasm of soft tissue (n=1; 1.3%). Five French (n=46; 60.5%), 6Fr (n=18; 23.7%), and 7Fr (n=12; 15.8%) port catheters were used for respective number of patients. An overview of baseline descriptives is presented in Table 1. The relationship between the studied variables and occurrence of complications such as pneumothorax, arterial puncture and port infection is demonstrated in Table 2. Accordingly, arterial puncture was more often encountered in patients receiving procedure on the left side (p=0.013) and who undergo more than 1 intervention (p<0.001).
Arterial puncture was observed in 17 (22.4%) patients. Infection developed in 12 (15.8%) patients who were treated with antibiotherapy. Pneumothorax developed in one (1.3%) patient and resorbed. Complications such as wound site hematoma and inappropriate orientation of the port catheter were not observed in any patient. More than one procedure for vascular access was associated with 13.827 times increased risk for arterial puncture (p=0.027).
Discussion
Many chemotherapeutic agents damage the vein wall and occlude venous route. If the administered drug extravasates, it may cause cellulitis, phlebitis, and tissue necrosis. Chemotherapy port-catheters ensure a long-term and reliable venous route, and play an active role in the treatment of oncology, and hematology patients [4].
Early and late-term complications may be seen related to the implantation of chemotherapy port-catheters. Early-term complications include pneumo-hemothorax, malposition, malfunction of the catheter, arrhythmia, cardiac perforation, port pocket site infection, arteriovenous fistula, left thoracic duct lesion, and phrenic or brachial plexus lesion. Late-term complications include skin necrosis, broken catheter, catheter embolus, infection, catheter occlusion, and disconnection, difficulty in both localization of the port site, and aspiration of blood, and extravasation of fluids [4,5].
In recent years, any difference has not been observed in the techniques of port implantations performed by surgeons, and radiologists in many centers. The use of fluoroscopy and ultrasound in radiology confers an advantage. In our study, during punctures, Doppler ultrasound was not used because of technical inadequacies. These technical inadequacies naturally constitute disadvantages. Arterial puncture, which is the most frequently observed complication is a result of this condition. However, this disadvantage did not prevent us from carrying out this procedure, which should be performed within the facilities of our hospital. Not all clinics in Turkey and in the world implant port catheters under ultrasonographic guidance. The greatest advantage of ultrasound is to decrease the risk of arterial punction. Port-catheter implantation under radiological guidance decreases procedure-related complications like pneumothorax, hemothorax, and catheter malposition [6]. Subclavian vein was generally preferred for our port applications, and in only one case, jugular vein was preferred because of difficulty in subclavian access. In the literature, the incidence of pneumothorax varies between 0.1, and 3.2% [6]. In one of our patients (1.3%) pneumothorax was seen. The incidence of pneumothorax was in compliance with the data reported in the literature. We noted that repeated procedures and interventions on the left side were associated with a higher rate of complications.
During implantation of chemotherapy ports through the subclavian vein, catheter may be caught, and then breaks between the clavicle, and the first rib, leading to the emergence of pinch-off syndrome [5]. In our patients, pinch-off syndrome did not develop. The tendency to hypercoagulation and deep vein thrombosis may develop secondary to infusion of chemotherapeutic agents and catheterization in cancer patients. Deep vein thrombosis did not develop in our patients. Catheter-related thrombosis and infection are the most frequently encountered serious complications of vascular ports, with reported incidence rates ranging between 0-7.7% and 1.5-13%, respectively [7,8]. Catheter-related thrombosis did not develop in our patients. Diluted heparin delivered into the reservoir during the procedure decreases formation of thrombosis. Chemotherapeutic drugs given during treatment mostly depress immune system of cancer patients, and these patients are more prone to infection [9]. Though the definition of port catheter- related infections differs in different studies, and among many authors, conditions characterized by the presence of bacteria on the surface of catheter without clinical findings of bacteremia or inflammation, signs of local infection at the access site of catheter not accompanied by systemic infection, detection of the growth of the same microorganism in blood cultures of peripheral blood specimens, and catheter, presence of septic thrombophlebitis, hyperemia, purulent discharge, and tenderness elicited by palpation on the tunnel or port pocket site are termed as port catheter infection [10]. As reported in the literature, the incidence of chemotherapy-related port-catheter infection ranges between 2.6, and 9 percent [11]. In the literature, the incidence of port pocket site infection has been reported between 0.3, and 4.4 percent [8]. In our series, catheter-related infection was observed in 12 (15.8%) patients. Frequently, staphylococcus epidermidis, staphylococcus aureus and candida spp. Are held responsible for catheter-related infection [12-14]. According to the literature, removal of the port is not advised for every patient carrying signs of infection. In the presence of persistent sepsis/bacteremia, infection refractory to antibiotherapy or signs of port tunnel infection, systemic complications (septic thrombosis/embolism, osteomyelitis, abscess formation or endocarditis), certain microorganisms as S. aureus or Candida spp. and in unstable patients (those with port infection, and hypotension), port catheter should be removed [15]. In our study, port catheter was withdrawn because of a catheter-related infection. The risk of port infection increases in patients whose wound healing is delayed because of the use of chemotherapeutic agents, state of disability, and sickness.
Conclusion
Despite some complications that may occur during chemotherapy port-catheter implantation in patients who will receive chemotherapy, it is a preferred method in terms of patient comfort. In our study, more than one procedure and intervention on the left side was associated with a higher complication rate. It is recommended to use imaging methods during and after the procedure to reduce complications.
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. Viana Taveira MR, Lima LS, de Araújo CC, de Mello MJ. Risk factors for central line-associated bloodstream infection in pediatric oncology patients with a totally implantable venous access port: A cohort study. Pediatr Blood Cancer. 2017;64(2):336-42
3. Simon A, Furtwängler R, Graf N, Laws HJ, Voigt S, Piening B, et al. Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on? GMS Hyg Infect Control. 2016; 12:11
4. Kim J, Turner MC, Sun Z, Rialon KL, Sinyard RD 3rd, Schooler GR, et al. Vascular complications in pediatric port removal. Am Surg. 2017;83(4):143-5.
5. Cil BE, Canyiğit M, Peynircioğlu B, Hazirolan T, Carkaci S, Cekirge S, et al. Subcutaneous venous port implantation in adult patients: a single center experience. Diagn Interv Radiol. 2006;12(2):93-8.
6. Bodner LJ, Nosher JL, Patel KM, Siegel RL, Biswal R, Gribbin CE, et al. Peripheral venous access ports: outcomes analysis in 109 patients. Cardiovasc Intervent Radiol. 2000;23(3):187-93.
7. Ballarini C, Intra M, Pisani Ceretti A, Cordovana A, Pagani M, Farina G, et al. Complications of subcutaneous infusion port in the general oncology population. Oncology. 1999;56(2):97-102.
8. Schwarz RE, Groeger JS, Coit DG. Subcutaneously implanted central venous access devices in cancer patients: a prospective analysis. Cancer. 1997;79(8):1635-40.
9. Groeger JS, Lucas AB, Thaler HT, Friedlander-Klar H, Brown AE, Kiehn TE, et al. Infectious morbidity associated with long-term use of venous access devices in patients with cancer. Ann Intern Med. 1993;119(12):1168-74.
10. Vescia S, Baumgärtner AK, Jacobs VR, Kiechle-Bahat M, Rody A, Loibl S, et al. Management of venous port systems in oncology: a review of current evidence. Ann Oncol. 2008;19(1):9-15.
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12. Yildizeli B, Laçin T, Batirel HF, Yüksel M. Complications and management of long-term central venous access catheters and ports. J Vasc Access. 2004;5(4):174-8.
13. Fätkenheur G, Buchheidt D, Cornely OA, Fuhr HG, Karthaus M, Kisro J, et al. Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO): Central Venous Catheter (CVC)-related infections in neutropenic patients. Ann Hematol. 2003; 82(Suppl. 2):S149-57.
14. Hengartner H, Berger C, Nadal D, Niggli FK, Grotzer MA. Port-A-Cath infections in children with cancer. Eur J Cancer. 2004;40(16):2452-8.
15. O’Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control. 2011;39(4Suppl. 1):S1-34.
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Nevin Aydın, Gülseren Yılmaz, Osman Esen, Hayrünisa Kahraman Esen. Venous port catheter implantation for chemotherapy: Our experience in pediatric cases.Ann Clin Anal Med 2022;13(4):419-422
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The effect of prolonged immobilization on elbow range of motion in supracondylar humerus fractures treated with closed reduction and percutaneous pinning
Erdem Sahin 1, Ali İhsan Tuğrul 2, Musa Ergin 3, Fatih Durgut 4
1 Department of Orthopaedics and Traumatology, University of Health Sciences, Erzurum Regional Training and Research Hospital, Erzurum, 2 Department of Orthopaedics and Traumatology, Konya Beyhekim Training and Research Hospital, Konya, 3 Department of Orthopaedics and Traumatology, Selcuk University, Konya, 4 Department of Orthopaedics and Traumatology, Dicle University, Diyarbakır, Turkey
DOI: 10.4328/ACAM.20960 Received: 2021-11-20 Accepted: 2021-12-07 Published Online: 2021-12-25 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):423-425
Corresponding Author: Erdem Sahin, University of Health Sciences, Erzurum Regional Training and Research Hospital, 25240, Yakutiye, Erzurum, Turkey. E-mail: dr.erdemsahin@gmail.com P: +90 544 392 17 11 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8333-0803
Aim: The purpose of this study was to evaluate the effect of prolonged immobilization on elbow range of motion in Gartland type III supracondylar humerus fractures treated with closed reduction and percutaneous pinning.
Material and Methods: In this retrospectively designed study, patients whose k-wires and cast were removed after sufficient callus tissue was visible were classified as Group A, and patients who had k-wires removed and arm casts used for more than 2 weeks prolonged were classified as Group B. All patients had Gartland type III supracondylar humerus fracture. Clinical outcomes of two patient groups were analyzed and compared.
Results: The final analysis included 72 patients. Group A consisted of 37 patients. Group B consisted of 35 patients. Group B had a significantly lower ROM than Group A in the second month (p< 0.001). Group B had a significantly lower ROM than Group A in the third month (p=0.004). There was no significant difference in ROM between Group A and Group B in the sixth (p=0.48) and twelfth months (p=0.54).
Discussion: In this study, there was no significant difference in ROM between patients who used long-arm casts for two weeks after their pins were removed and those who started mobilization early. Some patients may have to use long arm casts for a more extended period of time. However, it should be kept in mind that early rehabilitation reduces elbow contracture.
Keywords: Supracondylar, Humerus Fracture, Gartland Type 3, Prolonged immobilization
Introduction
Supracondylar humerus fractures (SHF) are the most common elbow fractures in children. They are more common in children aged 5-8 years, with an annual incidence of 177.3 per 100.000 cases. (1) Supracondylar humerus fractures are more common in boys than in girls. (2) Falls are the most common cause of supracondylar humerus fractures because falling on an outstretched hand with an extended arm leads to hyperextension of the elbow, resulting in a supracondylar humerus fracture.
The Gartland classification system is used to choose the ideal treatment for SHF. (3) Surgery is one of the first methods of choice to treat displaced SHF (Gartland type II-IV and flexion type). The goal of surgery is to restore the normal elbow range of motion (ROM) and the carrying angle. (4)
Closed reduction and percutaneous pinning are standard treatments of SHF for three reasons. It protects soft tissues from trauma, causes few complications, and yields positive health outcomes. (5) There is no standard time to remove the pins. They are removed after 3-6 weeks after the callus tissue becomes visible. However, removal of pins in patients with prolonged immobilization takes 5-8 weeks, depending on patient factors (pain, anxiety, or nonadherence to post casting instructions). (6)
Elbow contracture is a common post-SHF complication. (7) There is a correlation between post-SHF elbow contracture and prolonged postsurgical casting. (8) This study compared the clinical outcomes of two patient groups. The sample consisted of patients treated with closed reduction and percutaneous pinning for SHF. The first group consisted of patients who used casts for two weeks after pin removal. The second group consisted of patients who did not use casts after pin removal. The research hypothesis was as follows: “ROM is more limited in patients with prolonged immobilization in long arm casts.”
Material and Methods
The study was approved by the institutional review board. The study retrospectively analyzed the clinical outcomes of patients treated with closed reduction and percutaneous pinning (divergent-lateral pins) between 2018 and 2020 for SHF (Gartland type III). The exclusion criteria were (1) Gartland-type II and flexion-type fractures, (2) early reoperation due to complications, (3) pathological fractures, (4) metabolic bone disease, and (5) other percutaneous pinning methods, such as cross pinning.
The same surgical team operated on all patients between 2018 and 2020. All patients underwent closed reduction and divergent lateral pinning. The sample was divided into two groups: (1) patients who started ROM rehabilitation after their pins were removed after the callus tissue became visible (Group A) and (2) patients who used long arm casts for two weeks after their pins were removed (Group B). The pins were removed in the outpatient clinic. All patients were followed up for 12 months. Their Month 2, Month 3, Month 6, and Month 12 elbow ROM grades and Flynn class ROM (12th month) were compared. Complications were recorded. Table 1 shows Flynn’s criteria (9) for outcomes.
The elbow carrying angle, extension and flexion, lower arm rotation, and shoulder external rotation on both arms were recorded. The carrying angle is the angle between the upper and lower arm when the elbow is entirely straight. The carrying angle was measured using a goniometer. The lower arm rotation was measured as degrees of supination and pronation from the neutral position when the elbow flexed at 90 degrees. Maximum external rotation in the shoulder was measured when the glenohumeral joint was in the neutral position in the sagittal and frontal plane and the elbow flexed at 90 degrees.
Data analysis
Data were analyzed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, v. 15.0) at a significance level of 0.05. All patients admitted to the hospital between 2018 and 2020 were included in the sample. Mean and standard deviation was used for descriptive statistics. The Mann–Whitney U test was used to compare the two groups.
Results
The sample consisted of 72 patients with Gartland type III SHF. Group A consisted of 22 boys (59.4%) and 15 girls (40.6%) with a mean age of 6.54 years (min: 2 and max: 12). Group B group consisted of 20 boys (57.1%) and 15 girls (42.9%) with a median age of 6.17 (min: 2 and max: 11). The two groups were homogenous in terms of age and gender (Table-2).
In Group A, the pins were removed between days 21 and 36 (median: 26). In Group B, the pins were removed between days 30 and 33 (median: 28). There was no significant difference in pin removal times between the groups (p=0.61).
Group B had a significantly lower ROM [80 (45°-145°)] than Group A [110° (65°-150°)] in the second month (p< 0.001). Group B had a significantly lower ROM [110° (80°-150°)] than Group A [120° (95°-150°)] in the third month (p=0.004). There was no significant difference in ROM between Group A [145° (110°-150°)] and Group B [120° (100°-150°)] in the sixth month (p=0.48) There was no significant difference in ROM between Group A [150° (120°-150°)] and Group B [150° (120°-150°)] in the twelfth month (p=0.54). There was no significant difference in outcomes between the type of treatment groups about four categorical groups according to Flynn’s classification for the cosmetic outcome (carrying angle) (p=0.22). There was no significant difference in the outcome between the groups (p=0.22) and the functional outcome (ROM) (p=0.34).
Discussion
Supracondylar humerus fractures (SHF) are the most common elbow fractures in children, accounting for about 12-17% of all pediatric fractures. (10) SHF are associated with a high risk of short- and long-term complications due to injury and treatment.
Medial and lateral crossed pinning and lateral pinning (using two pins) are the two most common fixation techniques for treating SHF. Although numerous researchers have compared the surgical outcomes of those two techniques, (11) their results have been inconclusive. Therefore, surgeons prefer either one or the other, depending on their experience and skill levels. Lee et al. found that four in ten pediatric orthopedic surgeons preferred the lateral pinning technique. (12) We also prefer to use lateral pinning to treat SHF in our clinic.
When we observed enough callus tissue on the radiograph, we removed the pins between the third and fifth weeks in accordance with the literature. (13) In our clinic, we remove pins as early as possible because post-SHF infections are associated with the pin tract. (14) We removed all pins in the polyclinic because it is a safe procedure that does not cause too much pain. (15,16)
In the case of pain, low cognitive activity and parental anxiety, patients used long arm casts for two more weeks. When we analyzed the data retrospectively, we observed that about half the patients underwent prolonged immobilization in long arm casts.
Patients with early elbow mobilization (active-assisted or passive) are likely to have better articular homeostasis and ROM and a lower prevalence of edema and hematoma. (17)
Patients who start post-immobilization rehabilitation early are more likely to get their elbow function back to normal. Therefore, starting rehabilitation too late may have adverse effects, such as loss of ROM, strength, and function. Full recovery of elbow injuries depends on early physical therapy intervention. (18)
Group B had more limited early joint movements than Group A. However, there was no significant difference in joint movements between the two groups in the sixth and twelfth months. This result shows that some patients should use long arm casts longer for a full recovery.
The groups had similar complication rates. There is no research indicating a negative correlation between prolonged use of long arm casts and complications.
This study had three limitations. This study was retrospective that might have been subject to selection and information bias. Second, the sample size was relatively small. Third, patients were followed up for a short period. The last two limitations might have prevented us from detecting axial and sagittal plane deformities.
Conclusion
In conclusion, our results did not show a significant difference in ROM between patients who used long arm casts for two weeks after their pins were removed and those who started mobilization early. Some patients may have to use long arm casts for a more extended period of time. However, it should be kept in mind that early rehabilitation reduces elbow contracture.
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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16. Symons S, Persad R, Paterson M. The removal of percutaneous Kirschner wires used in the stabilisation of fractures in children. Acta Orthop Belg. 2005;71(1):88-90.
17. Fusaro I, Orsini S, Stignani Kantar S, Sforza T, Benedetti MG, Bettelli G, et al. Elbow rehabilitation in traumatic pathology. Musculoskelet Surg. 2014;98 (Suppl. 1):95-102.
18. Murtezani A, Pustina A, Bytyçi C, Hundozi H. Rehabilitation of children after elbow injuries. Niger J Med. 2007;16(2):138-42.
Download attachments: 10.4328:ACAM.20960
Erdem Sahin, Ali İhsan Tuğrul, Musa Ergin, Fatih Durgut. The effect of prolonged immobilization on elbow range of motion in supracondylar humerus fractures treated with closed reduction and percutaneous pinning. Ann Clin Anal Med 2022;13(4):423-425
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Hyperuricemia in psoriasis and psoriatic arthritis
Jinan Q. Mohammed 1, Abdulsatar J. Mathkhor 2
1 Department of Dermatology, 2 Department of Rheumatology, Basrah Teaching Hospital, Basrah, Iraq
DOI: 10.4328/ACAM.20965 Received: 2021-11-22 Accepted: 2021-12-23 Published Online: 2021-12-27 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):426-429
Corresponding Author: Jinan Q. Mohammed, Department of Dermatology, Basrah Teaching Hospital, Basrah, Iraq. E-mail: jinanbubsari@yahoo.com P: +964 780 111 70 39 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9031-4975
Aim: Psoriasis is a common, chronic, disfiguring, inflammatory, non-infectious skin disorder associated with cardiovascular diseases, obesity, diabetes mellitus, hypertension, and hyperlipidemia. The association between psoriasis and hyperuricemia was also reported. Therefore, we aimed to evaluate serum uric acid levels in psoriasis and psoriatic arthritis (PsA) patients.
Material and Methods: The study involved one hundred twenty (64 males and 56 females) patients, including 88 with psoriasis vulgaris and 32 with PsA, matched for age and sex with 120 healthy controls. Disease activity scores using Psoriasis Area Severity Index (PASI) score and Disease Activity Score using 28 joints (DAS28) were estimated for all patients. In addition, serum uric acid levels were measured for all the study participants.
Results: Serum uric acid levels were 6.2±2.5 mg/dl and 4.1±1.2 mg/dl for psoriatic patients and controls, respectively. High serum uric acid levels were associated with high PASI scores and high DAS28 in psoriatic and PsA patients, respectively.
Discussion: Psoriasis and PsA are significantly associated with hyperuricemia. Hyperuricemia is correlated to high PASI and high DAS28.
Keywords: Hyperuricemia, Psoriasis, Psoriatic Arthritis, Serum Uric Acid
Introduction
Psoriasis is a chronic, non-contagious skin disorder characterized by chronic inflammation and hyperproliferation of skin cells, leading to the formation of erythematous, well-defined plaques with silvery-white dry loose scales, usually over extensor aspects of the body.[1] The estimated prevalence ranges between 1% and 3%, making this disorder a serious health problem, which can occur at any age and is mostly affects the age group of 50-69.[2] Psoriatic arthritis, which is inflammatory arthritis, develops in 30% of patients with Psoriasis. Psoriasis and PsA affect women and men equally.[3] PsA may involve both the axial skeleton (spondylitis and/or sacroiliitis) and the peripheral joints. It also affects skin, nails, and enthuses.[3] Psoriasis is known to be associated with hypertension, cardiovascular diseases, diabetes mellitus, hyperlipidemia, obesity, and metabolic syndrome. It is a proliferative disease with a rapid and high turnover of skin cells, 10 times faster than normal, and increased serum uric acid levels.[4] Studies conducted in Russia and Germany revealed higher serum uric acid levels in patients with Psoriasis [5,6]. In addition, high serum uric acid levels are also associated with the components of metabolic syndrome like obesity, hypertension, and cardiovascular diseases [7]. In patients with psoriasis, hyperuricemia is associated with metabolic abnormalities. Therefore, it may cause several health-related comorbidities. These comorbidities can further decrease the quality of life of psoriatic patients who are already upset from the unsightly chronic disfiguring skin lesion [8]. Therefore routine screening of serum uric acid levels should be carried out for patients with Psoriasis. Presently, there is no work being done in Iraq that assessed the association between hyperuricemia and Psoriasis. Therefore, we conducted this study to determine this association.
Material and Methods
This case-control study was carried out in Dermatology and Rheumatology outpatient departments in Basrah Teaching Hospital from April 2020 to April 2021. A sample of 120 (64 males and 56 females) patients was divided into two subgroups: 88 patients with Psoriasis, diagnosed by a dermatologist in the dermatology outpatient, and 32 patients with PsA, who fulfilled the classification criteria of PsA [9]. In addition, this study included 120 (60 males and 60 females), age- and sex-matched controls, recruited from the general population. Data collection was done through an interview with the patients using a special questionnaire developed by the researchers. The questionnaire included information about age, sex, disease duration, and drug history. Psoriatic and PsA patients were investigated for complete blood cell count and erythrocyte sedimentation rate (ESR). Serum uric acid levels were measured for both the patient group and controls. Psoriasis area and severity index (PASI) [10] were calculated for each patient with Psoriasis. For each of four anatomic areas (head, upper limb, trunk, and lower limbs), the severity of erythema, induration, and scaling and the percentage of surface area involvements were assessed. PASI scores can range from a lower value of 0, corresponding to no signs of Psoriasis, up to a 72.0 as maximum. Disease activity score using 28 joints (DAS28) and ESR [11] was measured for all patients with PsA. Postmenopausal, pregnant and lactating women, elderly patients, patients with endocrine, metabolic, renal problems, and patients using systemic steroids or any drugs that are known to affect serum uric acid level were excluded from the study. The local ethics committee approved the study design. Verbal consent was obtained from all participants before their involvement.
Statistical analyses
SPSS software version 25.0 was used for data analysis. Percentages and mean were used to present the data in tables. In addition, a comparison of study groups was carried out using the Chi-square test for categorical data and Student’s t-test for continuous data. P <0.05 was considered statistically significant.
Results
Of the total sample of 120 patients (88 with Psoriasis and 32 with PsA), 64 (53.34%) patients were males, and 56 (46.66%) were females, with the mean age of 41±3.5 and disease duration of 10±5.3. There were 120 (60 males and 60 females) individuals in the control group with a mean age of 43±2.5 years. Serum uric acid levels were 6.2±2.5 mg/dl and 4.1±1.2 mg/dl for patients and controls, respectively; the difference was statistically significant (p=0.002), as shown in Table 1. Serum uric acid level was 6.2±2.4 mg/dl in patients with Psoriasis, which was slightly higher than that of patients with PsA, but the difference was not statistically significant (>0.05), as shown in Table 1. Table 2 shows the correlation between serum uric acid levels and disease duration, which were 24.8±4.8 ng/ml in patients with disease duration <10 years, and 14.4±6.5 ng/ml in patients with disease duration equal and more than 10 years, the difference was statistically significant (p<0.05). Serum uric acid levels in patients with Psoriasis were 6.9±4.2 ng/ml and 5.5±2.2 ng/ml for high PASI and low PASI; respectively, the difference was statistically significant (p<0.05). Serum uric acid levels in patients with PsA were 7.0±3.6 ng/ml and 5.4±2.3 ng/ml for high DAS28 and low DAS28, respectively; accordingly, the difference was statistically significant (p<0.05) as shown in Table 3.
Discussion
Psoriasis is characterized by hyper-proliferation of keratinocytes which requires an increased rate of DNA formation. Consequently, DNA degradation also occurs at a higher rate. This increased cell turnover leads to an increased rate of purine formation and metabolism as purines are a fundamental part of DNA. Uric acid is endogenously formed as a product of the metabolic breakdown of purines. Increased degradation of purines may be reflected as higher levels of serum uric acid in psoriasis patients. Elevated serum uric acid levels may further be a risk factor for hypertension, renal disease, gout, and cardiovascular diseases [12, 13]. In this study, there were 64 (53.34%) male and 56 (46.66%) female patients with a male to female ratio of 2:1.75. A similar male predominance among psoriatic patients has been reported by Gisondi et al., Haider et al., and Ejaz et al. [14–16], and was in accordance with a study done in Japan by Takahashi et al. where the ratio was 1.98:1 done [17]. In this study, serum uric acid levels were observed to be higher among patients (mean serum uric acid =7.1±1.5 mg/dl) as compared to controls (mean serum uric acid =4.2±1.2 mg/dl). This was in accordance with the studies conducted by Gisondi et al., Khan et al., Yilmaz et al. [7,14,18]. The higher serum uric acid levels among patients with psoriasis can be explained by an increased rate of purine metabolism due to the rapid epidermal turnover, leading to accumulation of uric acid, which is the end product of purine degradation. Contrasting results were reported by Nicolae et al. and Agravatt et al., who found no correlation between serum uric acid level and psoriasis [19,20]. This study showed no difference in serum uric acid levels among patients with psoriasis and psoriatic arthritis. In this study, a higher serum uric acid level was found to be associated with a long disease duration, which is in accordance with a study done by Maryam Ghiasi et al. [21] who found that serum uric acid levels were in the normal range but the value was significantly higher in patients with a more severe form of psoriasis, and uric acid level was exacerbated by an increases in the severity and duration of psoriasis. The association between hyperuricemia and the extent of body surface area (BSA) involvement reflected by the PASI score has been evaluated in some earlier studies. In 2011, Kwon et al. [22] reported the relationship between the extent of BSA involvement and serum uric acid level was statistically highly significant. Gisondi et al. found that serum uric acid levels were significantly higher in patients with PASI scores of >10 when compared to those with PASI scores of <10 [14]. These findings agree with our result; we found a significant correlation between high serum uric acid levels and high PASI scores. In contrast to our result, Collazo et al. [23] reported that this relation was not statistically significant. A study by Bruce IN et al. on hyperuricemia in psoriatic arthritis found that there was no association between PASI score and hyperuricemia [24]. A study by Brenner W et al. on serum uric acid levels in PUVA-treated and untreated patients with psoriasis showed no relationship between the serum uric acid level and the extent of psoriatic skin involvement, indicating that increased epidermal turnover may not play a role in psoriatic hyperuricemia. They also mentioned that the elevated uric acid levels in psoriasis may be explained by a combination of genetic predisposition and hyperalimentation [25]. In this study, hyperuricemia was associated with higher disease activity in patients with PsA. No similar finding was reported in the literature for comparison.
Conclusion
Psoriasis and PsA are significantly associated with hyperuricemia. In addition, hyperuricemia is correlated to high disease activity in both psoriasis and PsA.
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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2. Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T. Psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J Investig Dermatology Symp Proc. 2004;9(2):136–9.
3. Sankowski AJ, Łebkowska UM, Ćwikła J, Walecka I, Walecki J. Psoriatic arthritis. Polish J Radiol. 2013;78(1):7–17.
4. Asim SA, Hameed A, Niaz F, Sarwat A. To assess the frequency of raised serum uric acid level in patients with psoriasis and compare it with healthy controls in outpatient of a tertiary care hospital. Int J Adv Res 2016; 4(6): 2124-32.
5. Gerkowicz A, Pietrzak A, Szepietowski JC, Radej S, Chodorowska G. Biochemical markers of psoriasis as a metabolic disease. Folia Histochem Cytobiol. 2012;50(2):155–70.
6. Kanbay M, Yilmaz MI, Apetrii M, Saglam M, Yaman H, Unal HU, et al. Relationship between serum magnesium levels and cardiovascular events in chronic kidney disease patients. Am J Nephrol. 2012;36(3):228–37.
7. Yilmaz E, Tamer E, Artüz F, Külcü Çakmak S, Köktürk F. Evaluation of serum uric acid levels in psoriasis vulgaris. Turkish J Med Sci. 2017;47(2):531–4.
8. Augustin M, Radtke MA. Quality of life in psoriasis patients. Expert Rev Pharmacoeconomics Outcomes Res. 2014;14(4):559–68.
9. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: Development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665–73.
10. Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Ann Rheum Dis. 2005;64(Suppl. 2):65–8.
11. Salaffi F, Ciapetti A, Carotti M, Gasparini S, Gutierrez M. Disease activity in psoriatic arthritis: Comparison of the discriminative capacity and construct validity of six composite indices in a real world. Biomed Res Int. 2014;2014.
12. Forman JP, Choi H, Curhan GC. Plasma uric acid level and risk for incident hypertension among men. J Am Soc Nephrol. 2007;18(1):287–92.
13. Ali N, Mahmood S, Islam F, Rahman S, Haque T, Islam S, et al. Relationship between serum uric acid and hypertension: a cross-sectional study in Bangladeshi adults. Sci Rep. 2019;9(1):1–7.
14. Gisondi P, Targher G, Cagalli A, Girolomoni G. Hyperuricemia in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2014;70(1):127–30.
15. Haider S, Wahid Z, Najam-us-Saher, Riaz F. Efficacy of Methotrexate in patients with plaque type psoriasis. Pakistan J Med Sci. 2014;30(5):1050–3.
16. Ejaz A, Suhail M, Iftikhar A. Psoriasis in pakistani population: Associations, comorbidities, and hematological profile. J Pakistan Assoc Dermatologists. 2013;23(1):42–6.
17. Takahashi H, Takahashi I, Tsuji H, Ibe M, Kinouchi M, Hashimoto Y, et al. Analysis of psoriatic patients registered in Asahikawa Medical College Hospital from 1983 to 2007. J Dermatol. 2009;36(12):632–7.
18. Khan S, Agrawal S, Baral N, Lamsal M. Evaluation of ADA activity as a potential marker of disease severity in psoriasis patients. Psoriasis Targets Ther. 2018; 8:59–63.
19. Nicolae I, Tampa M, Ene CD, Mitran CI, Mitran MI, Sarbu MI, et al. Correlations between related-purine derivatives and renal disorders in patients with psoriasis vulgaris. Exp Ther Med. 2019;17(2):1012–9.
20. Agravatt AM, Sirajwala HB. Original article a study of serum uric acid level in patients with psoriasis. Int J Res Med. 2014;2(3):13–6.
21. Maryam Ghiasi ,Amir Houshang Ehsani ,Arash Dahande ,Mona Abdoreza .Serum uric acid levels in patients with psoriasis. Tehran University Medical Journal. 2012; 70(1): 58-63.
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MicroRNA 7 downregulates alpha-synuclein expression: An in vivo study of an early intervention strategy
Fatma Y. Elnozahy 1, Hala M.Abouheif 1, Doaa Abdelmonsif 2,3, Seham Zakaria Nassar 1, Eman El Eter 1
1 Department of Medical Physiology, Faculty of Medicine, 2 Department of Medical Biochemistry, Faculty of Medicine, 3 Center of Excellence for Research In Regenerative Medicine And Application (CERRMA), Alexandria University, Alexandria, Egypt
DOI: 10.4328/ACAM.20975 Received: 2021-11-28 Accepted: 2021-12-29 Published Online: 2022-01-01 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):430-434
Corresponding Author: Fatma Yosry El Nozahy, Department of Physiology, Faculty Of Medicine, Dr. Fahmy Abdel Meguid Street, Mowssat Building El Shatby, Alexandria, 2156, Egypt. E-mail: fatma.yosry@ymail.com P: +20 100 207 08 80 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8924-8376
Aim: In this study, we aimed to investigate in vivo the modulation of striatal alpha-synuclein (α-SYN ) in the rotenone model of PD as an early intervention strategy using miRNA (miR-7) before the establishment of pathology.
Material and Methods: Parkinson’s disease was induced in male Wistar rats by subcutaneous injection of rotenone (2.5mg/kg) daily for 5 weeks. Rats received a single bilateral striatal injection of miR-7 mimic 2h before injection of rotenone. The expression of striatal miR7, α-SYN mRNA, α-SYN protein were assessed.
Results: Early intervention by miR-7 mimic succeeded to elevate the striatal level of miR7and to decrease α-SYN overexpression in vivo.
Discussion: The early intervention with miR-7 mimic could reverse pathology and downregulates α SYN overexpression in rotenone-induced rat model at the transcriptional and post- transcriptional levels.
Keywords: Parkinson’s Disease, α-SYN Gene Overexpression, Chitosan Nanoparticles, miRNA7 Mimic
Introduction
Parkinson’s disease (PD) is a neurodegenerative disease affecting 1% of those over the age of 60 [1]. Clinically, PD is characterized by motor symptoms of rest tremor, bradykinesia (or akinesia), and postural instability, and non-motor symptoms such as olfactory dysfunction, constipation, and cognitive impairment [1,2]. The association of aging with PD is well detailed, and aging is documented to be the most important risk factor for the development of PD [1]. The prevalence of PD and the burden of sick people will increase in future due to an increase in the elderly population [3]. One of the main mechanisms of Parkinson’s disease pathophysiology is the overexpression of the α-synuclein (α-SYN) protein and the subsequent formation of Lewy bodies, which are small acidic protein enriched in the presynaptic terminals of neurons [4]. The fact that α-SYN protein overexpression is implicated in cognitive and motor impairments in PD has attracted many researchers as a new potential therapy for PD [5]. The miRNAs are capable of modulating several signaling pathways in several diseases such as Parkinson’s disease, making them potent modulators of gene expression [6]. Based on previous studies, normal level of miR-7 permits normal neurogenesis in the central nervous system, also keeps α-SYN protein expression at the physiological level [7]. Furthermore, the role of miR-7 on α-SYN protein downregulation, at both the transcript and protein level was documented by Doxakis and colleagues [8]. Herein, we use miR-7 mimic in vivo to investigate its role as an early intervention strategy for PD. Chitosan nanoparticles were chosen as a delivery system for our treatments, whereas many studies documented its unique ability for cell transfection in vivo and in vitro [9]. To date, the implication of miR-7 in vivo as an early intervention in parkinsonism remains unclear.
Material and Methods
1. Preparation of nanoparticles
1.1 Preparation of chitosan nanoparticles
Chitosan nanoparticles were prepared by the ionic gelation method following Zhao and Wu method [10]. The formation of chitosan nanoparticles was shown by the turbidity of the solution. Next, the nanoparticles were collected by centrifugation, freeze-dried (Buchi, Lyovapor L-200, Switzerland) and stored at 4 ºC for characterizations.
Concerning FITC-labeled chitosan nanoparticles, 5-10 mg of the FITC dye was dissolved in TPP solution and added dropwise to the chitosan solution under magnetic stirring at room temperature in the dark. FITC-labeled chitosan nanoparticles were centrifugated and washed with DIH2O till the free FITC could not be detected in the supernatant.
1.2. Preparation of chitosan/miRNA nanoplexes
CS/miR-7 mimic nanoplexes were prepared via the ionic gelation method. Accordingly, lyophilized miRNA 7 (Qiagen. Cat. No. 219600) was dissolved in RNAase- free buffer solution and was added by pipetting to chitosan solution (20µg /ml). The mixture was then vortexed and incubated for 45 min with vigorous shaking for 30 min at room temperature till the formation of nanoplexes [11].
1.3. Nanoparticles Characterization
Particle size, surface charge of freshly prepared CS NPs and chitosan /miRNA samples were measured using a Zetasizer Nano ZS (Malvern Instruments, UK), based on Photon Correlation Spectroscopy (PCS) techniques. No dilutions were performed during the analysis. The measurements were made at 25oC [12].
1.4. Morphological Analysis
Morphological characterization of unloaded CS NPs, miR-7 loaded CS NPs was carried out using JEM-1400 series 120 kv transmission electron microscopy (TEM), USA [12].
1.5. The loading efficiency of miRNA
Onto chitosan NPs was obtained by measuring the total miRNA concentration added, compared with supernatant free miRNA concentration after loading to CS NPs [13].
2. In vivo study
2.1 Laboratory animals
Adult male albino rats (300-350 g, 14 weeks) were obtained from the Physiology Department Animal House, Alexandria Faculty of Medicine, Egypt. They were maintained on standard conditions (natural dark/light cycle, controlled room temperature (25±2oC), with free access to water and food. The ethical guidelines of Alexandria University on laboratory animals and the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 80-23, revised 1978) were adopted. Further, the Ethics Committee of Alexandria
Faculty of Medicine approved this study.
2.2 Study design
The study was conducted on 33 rats divided into 3 groups:
– Control group (11 rats) received a bilateral striatal injection of a single dose (1µl) of phosphate-buffered saline (PBS) using a stereotaxis technique 2 hours before S.C injection of DMSO, daily for 5 weeks (negative control group). Disease group (11 rats): received a bilateral striatal injection of a single dose (1 µl) of PBS using stereotaxis technique 2 hours before s.c injection of 1ml of Rotenone (2.5mg/kg) [14], dissolved in DMSO) daily for 5 weeks (positive control group). Treated group (11 rats): received bilateral striatal injection of a single dose (1µl) of chitosan (Sigma Aldrich, USA) nanoparticles incorporated with miR-7 mimic (50 pmole/μl/site of injection) [15] using stereotaxis technique 2 hours before s.c injection of 1ml of Rotenone dissolved in DMSO (2.5mg/kg) daily for 5 weeks as illustrated in Figure 1.
3. Animals sacrifice and Striatal tissue sampling
The animals were sacrificed using ether anesthesia after the end of 5 weeks. Then whole brains were removed, rinsed with ice-cold saline and each striatum was immediately dissected and stored at -80oC for biochemical analysis.
3.3. Quantitative reverse transcription PCR (qRT PCR) for miRNA 7
Striatal total RNA, including miRNA, was extracted following the manufacturer’s protocol of miRNeasy Mini Kit (Qiagen, Hilden, Germany). Then, TaqMan miRNA reverse transcription was carried out with specific miRNA 7 primers (Applied Biosystems, USA) . The TaqMan microRNA assay system was then used for quantification of miRNA 7 using the TaqMan® Universal PCR Master Mix II (Applied Biosystems, USA). The amplification reaction was run in StepOne real-time PCR system (Applied Biosystems, USA) and StepOne™ Software v2.3 was used for data analysis using the 2-ΔΔCt method for calculation of gene expression relative to the housekeeping U6 snRNA [16].
3.4. Quantitative reverse transcription PCR (qRT PCR) for α-SYN
Reverse transcription was done following the protocol of reverse transcriptase (RT) Superscript II kit (Invitrogen, USA). The amplification of α-syn cDNA was performed in StepOne real-time PCR system (Applied Biosystems, USA). Then, the expression of α-syn mRNA was calculated using the comparative CT method relative to the housekeeping gene GAPDH.[16]
3.5 Western Blot analysis of α-SYN protein
Striatal tissue samples were homogenized in radioimmunoprecipitation (RIPA) buffer Next, BCA protein assay was adopted to measure the lysate total protein concentration. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and blotting to nitrocellulose membranes (Bio-Rad, Mississauga-Canada) were done. The membranes were then incubated with the specific primary antibodies and corresponding secondary antibody and protein bands were visualized using 3,3’,5,5’-tetramethylbenzidine (TMB) stain. Quantification of protein bands was done using Quantity One software (Bio-Rad Laboratories-USA), where protein expression was normalized to the control group and β-actin protein [17]
Statistical analysis
Data were expressed as median and interquartile range. Statistical analysis was performed with IBM SPSS statistics, version 21.0 (IBM Inc.). The results were analyzed using the Kruskal-Wallis test, Pairwise comparison between each 2 groups was done using the Post Hoc Test (Dunn’s for multiple comparisons test). P-value ≤0.05 was defined to be statistically significant
Results
1. Zeta size and Zeta potential of nanoplexes
Zeta sizer’s results documented that the miRNA 7 loaded nanoparticles measured about 200 nm. The PDI value of chitosan nanoparticles was miRNA 7 loaded chitosan nanoparticles was 0.62, thus indicating a narrow and acceptable particle size distribution (PDI <0.7) (Figure 2 A). Zeta potential of miRNA-loaded chitosan nanoparticles revealed the positivity of nanoplexes, which is favorable for good cellular uptake (Figure 2 B). These results showed that the fabricated nanoplexes are of good size and potential.
2. Morphology
Chitosan nanoparticles and chitosan-loaded miRNA 7 mimic nanoparticles morphology was analyzed by TEM. In the present study, TEM images revealed that chitosan nanoparticles have a nearly spherical shape, regular surface, and different sizes ranging from 120 to 200 nm on scale bar 200 nm, while the chitosan loaded miRNA 7 nanoparticles show semi- spherical shape, irregular and rough surface with a size range from 120 to 200 nm. These results showed (Figure 2 C&D) a slight change in size between the chitosan nanoparticles and the loaded nanoplexes. In addition, surface irregularity of the nanoplexes may be explained by the success of miRNA loading.
3. The loading efficiency of miRNA
The efficiency of miRNA encapsulation inside chitosan nanoparticles was measured using a UV spectrophotometer. Data analysis via nanometer revealed 95% loading efficiency
of miRNA incorporated inside chitosan nanoparticles.
4. Expression of striatal miR-7
There was a statistically significant decrease in the Striatal miR-7 expression level of the rotenone group (PD group) as related to the control group. The miR-7 mimic treatment succeeded to increase striatal miRNA 7level, which was almost near to the control group (Figure 3A).
5. Effect of miR-7 administration on striatal α-SYN mRNA expression
There was a statistically significant increase in the Striatal level α-SYNC mRNA expression in the rotenone group (PD) as related to the control group. Treatment with miR-7 mimic succeeded to decrease striatal α-SYNC mRNA expression levels significantly in relation to the rotenone group but still, there was significant difference with the control group (Figure 3B).
6. Effect of miR-7 administration on striatal α-SYN protein expression
The present study showed that there was a statistically significant increased striatal α-SYNC protein expression in the rotenone group (PD) versus the control group. Early intervention with miR-7 mimic succeeded to decrease protein expression compared to the rotenone group, while failed to normalize it (Figure 3C&D).
Discussion
To date, this is the first research that investigated miRNA 7 as early intervention strategy in vivo for Parkinson’s disease and studied its potential role in different aspects of the disease. A variety of nanoparticles have been fabricated for the delivery of miRNA therapies. In the current study, we selected chitosan as miRNA delivery platform. It is well known that chitosan is a Cationic polymer, which can form complexes with negatively charged materials due to its abundant amine groups thus chitosan is a promising delivery system [18]. The obtained particle morphology and size are in line with previous studies [12]. Concerning the success of miRNA loading , the present study reported 95% of loading efficacy, which is in parallel to previous reports, which have documented a high loading efficacy between chitosan nanoparticles and negatively charged materials as miRNAs [13, 18].
miR-7 is expressed in different areas of the brain and binds selectively to the 3’UTR of the α- SYN gene, which significantly decreases the synthesis of α-SYN and inhibits its aggregation [19]. Time of intervention is a cornerstone in stopping the progression of the disease [20], thus we investigated its early administration. Initially, we found that miR-7 was down expressed in PD rats, and its expression, following the treatment strongly, restored its normal level, loss of dopaminergic neurons and downregulated the overexpression of α-SYN protein in PD rats. Taken together, these results confirm that miR-7 could target α-SYN overexpression to attenuate its pathological sequence in PD when injected early. It is well known that dopamine depletion and α-SYN accumulation are the major diagnostic features of PD [21]. Previous study has shown loss of normal striatal level of miR-7 as pathological features of PD [22]. In accordance with these previous results, our study revealed reduced level of miR-7 in striatal tissues in rotenone-induced PD rats. Early intervention with miR-7 mimic succeeded to increase its striatal expression and restored its level to normal. Similarly, Zhou et al reported the restoration of miRNA 7 in the MPTP mice model upon administration of the miRNA 7 mimic [23]. Interestingly, peripheral administration of rotenone-induced α-synuclein aggregation with the formation of Lewy bodies, similar to those observed in PD [14]. The same observations were detected in the current study, as we reported an increase in α- synuclein mRNA relative expression and α- synuclein protein expression in striatal tissues of rotenone induced PD rats. In the present study, α-synuclein mRNA and protein expression was efficiently modulated by early intrastriatal miR-7 mimic injection. The direct effect of miR-7 on α-synuclein expression was first documented, in vitro, by Junn et al who demonstrated that transfection with 40 nM of miR-7 in HEK293T cells resulted in a decline of α-synuclein expression both at protein and mRNA levels [7]. mTOR pathway and autophagy are among the mechanisms that mediate the regulation of α- synuclein expression by miR-7 as reported in vitro [24]. Furthermore, a pervious study declared that miR-7 downregulates α-SYN expression by targeting mRNA, causing prevention of α-synuclein protein expression [25]. Consequently, these promising results particularly in relation with early intervention strategy before establishing pathology augments the neuroprotective role of miR-7 as an effective modifying strategy in PD
Conclusion
In conclusion, the results of our study offer insights into early intervention with miR-7 in rats with PD; upregulation of miR 7 expression prevented α- SYN aggregation Moreover, these data give clue to therapeutic potential for miR7 early in the treatment of PD, which requires a broadening of the therapeutic perspective through the usage of frequent doses and different duration of treatment.
Acknowledgment
Thanks are hereby extended to Alexandria Faculty of Medicine, the Experimental Animal Facility (managed by the Medical Physiology department), for housing of the experimental animals, and the Center of Excellence for Research in Regenerative Medicine and its application (CERRMA), for providing all the needed equipment.
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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Does the angle and position of the syndesmosis screw in the axial plan affect the reduction of syndesmosis?
Bekir Karagoz 1, Rıdvan Mete Oral 2, Hasan Bombacı 3
1 Department of Orthopaedics and Traumatology, Adiyaman University Training And Research Hospital, Adıyaman, 2 Department of Orthopaedics and Traumatology, Health Science University, Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, 3 Department of Orthopaedics and Traumatology, Health Science University, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20977 Received: 2021-12-01 Accepted: 2022-01-03 Published Online: 2022-01-03 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):435-439
Corresponding Author: Bekir Karagoz, Altınsehir Mahallesi, 3017 Sokak, No:27, Daire No:7, Merkez, Adıyaman, Turkey. E-mail: drbkr71@gmail.com P: +90 545 646 89 14 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7447-452X
Aim: In this study, it was aimed to evaluate the reduction quality in surgically treated syndesmosis injuries and to determine the importance of the insertion position of the syndesmosis screw for the reduction quality.
Material and Methods: Sixty patients treated for syndesmotic injury were included in the study. To determine the reduction quality of the syndesmosis, both ankles were scanned with computed tomography. The distance between the medial fibula and the tibial incisura 1 cm above the joint level was measured at the most anterior (a) and the most posterior (b) edges. Rotation; The angle between the line tangent to the anterior and posterior tibial tubercles and the line passing through the anterior and posterior fibular tubercles was measured by (q1). The direction and position of the syndesmosis screw were evaluated according to the line tangent to the tibial tubercles (Vq).
Results: When the mean a, b distance and q1 angle were compared with normal ankle values, the difference between all values was found to be statistically significant (p <0.05). A significant relationship was found when analyzing the relationship between screw position and reduction quality (p = 0.008).
Discussion: It has been found that placing the screw closer to the posterior provides better reduction compared to placing it closer to the anterior. A significant correlation was found between the screw insertion point on the fibula and the reduction of syndesmosis. No correlation was found between the angle of screw insertion in the axial plane and the malreduction of the syndesmotic joint.
Keywords: Ankle fracture, Syndesmosis, Malreduction, Malleolus
Introduction
Ankle fractures are among the most common lower extremity injuries that often require surgical treatment. In order to minimize the risk of post-traumatic arthritis in displaced fractures, anatomical restoration of the joint surfaces should be provided [1]. In addition to treating the fracture itself, it is also important to achieve reduction of syndesmosis. In many studies, anatomical reduction of syndesmosis after ankle injuries has been associated with better clinical outcomes [2,3].
Syndesmotic injury has been the subject of many studies due to the difficulty in diagnosis, treatment type and surgical reduction. Diastasis resulting from the complete disruption of this complex structure can usually manifest itself on flat anterior-posterior ankle and mortise radiographs [4]. However, conventional radiographic measurements to evaluate the integrity of the tibiofibular relationship may yield inaccurate or inadequate results [5]. In recent studies, it has been advocated that computed tomography is the method of choice for evaluating syndesmosis reduction [6]. Many studies in the literature have reported the difficulty of obtaining an accurate reduction in syndesmosis after surgical fixation [7,8].
Although there are studies in the literature suggesting that misplacement of the syndesmosis screw causes anteroposterior translation of the fibula on the tibia incisura, there are not enough studies on clear reference points independent of anatomical variations for correct syndesmotic screw placement [9,10].
The aim of this study is to evaluate the reduction quality in operatively treated syndesmotic injuries and to determine the importance of screw insertion position on reduction quality, which is one of the intraoperative factors affecting syndesmosis reduction.
Material and Methods
Approval for this retrospective study was obtained from the ethics committee of our institution (No: 2020/214-3179). The records of patients who were operated on for ankle fracture accompanied by syndesmosis injury in our hospital between January 2019 and December 2019 were examined, and patients who met the inclusion criteria were determined. Inclusion criteria were (1) patients with ankle fracture, accompanied by syndesmosis injury and operated on, (2) those in the age range of 18-65, (3) having a follow-up period of at least 6 months and regular follow-up visits, (4) patients with postoperative computed tomography (CT) of both ankles. Exclusion criteria were (1) additional injury other than ankle fracture, accompanied by syndesmosis injury in the same extremity, (2) patients under followed up due to pre-operative chronic syndesmosis injury. Patients meeting these criteria were excluded. Among the 98 ankle fractures detected as a result of screening, 60 patients who were operated on who were found to meet the inclusion criteria were included in the study. Thirty-seven (61.7%) of these patients were male and 23 (38.3%) were female. The average age was 43.95 years (range; 18-64 years).
Surgical Technique
Fibula fixation consisted of fixation by using interfragmentary screw and a neutralization plate for spiral and oblique fracture patterns after anatomic reduction or as a bridge plating for partial fracture patterns. The Cotton test which is one of the intraoperative maneuvers, was used to detect syndesmotic damage during surgery, based on the principle of pulling the fibula laterally with a hook or clamp after internal fixation was applied to the fibula. The test was accepted as positive if there was a lateral movement of the fibula more than 2 mm [11]. Syndesmosis was reduced indirectly using a pointed reduction clamp with the ankle in the neutral dorsiflexion position. The clamp was placed approximately 1.5-2 cm proximal to the mortise level, just distal to the level where the fixation screw would be placed. Detection of decreased tibiofibular opening in fluoroscopic mortise image was interpreted as reduction. Syndesmotic fixation was achieved by sending a 3.5 mm transsindesmotic tricortical position screw parallel to the joint surface, aiming at an angle of approximately 30º from the posterolateral to the anteromedial of the tibia.
Radiological Evaluation
A CT scan of both ankles (Aquilion Lightning™, Canon Medical Systems) was performed on the postoperative 2nd day to evaluate the reduction quality of the syndesmosis, the position of the syndesmosis screw and to compare it with the normal healthy side. In order to clearly define syndesmosis, axial CT scans for both ankles were considered, allowing better visualization of the transverse relationship between the fibula and the incisura fibularis in the tibia. To avoid any discrepancy in axial scanning, the legs were standardized by placing them on the scanner at bilateral neutral adduction and 20 degrees of internal rotation. The thickness of the CT slices was planned as 2 mm. Evaluation of the CT scans was performed by an orthopedic and traumatology specialist. In order to obtain results consistent with the studies in the literature, the syndesmosis tibiotalar joint was evaluated in parallel axial scans, 1 cm proximal to the midpoint of the tibial plafond [5,12]. Two previously reported measurement methods were used to evaluate the syndesmotic reduction quality. In the first method, the amount of translation was evaluated comparatively by measuring the distance between the medial fibula 1 cm above the joint level and the incisura fibularis in the tibia at the front edge (a) and the rearmost edge (b) (Figure 1a). This method has been used in several studies with acceptable reliability [5,13]. As a result of the measurements, the difference between the anterior and posterior measurements for the operated and normal sides was calculated. A difference of more than 2 mm between these measurements was considered a poor reduction [5]. In the second method, it was aimed to measure the isolated rotation of the fibula with respect to the tibia. For this purpose, the angle (q1) between the line tangent to the anterior and posterior tibial tubercles and the line passing through the anterior-posterior fibular tubercles was measured (Figure 1b) [13,14]. The direction and position of the screw used to fix the syndesmosis were evaluated according to the line (Vq) tangent to the tibial tubercles (Figure 1c). The intersection point of the Vq with the syndesmosis screw was determined. Then the distance (Va) between this point and the anterior tubercle of the tibia and the distance (Vp) between the posterior tubercle of the tibia were measured and recorded. In the case of Va> Vp, the screw was considered to be anteriorly located, if Va <Vp, the screw was considered to be posterior. In addition, the angle (α) between the syndesmosis screw and Vq was calculated and the statistical analysis of the relationship between the angle α and the anterior or posterior orientation of the existing screw was performed. However, a statistical analysis of the relationship between α angle and reduction quality was performed (Figure 1d). The correlations between the quality of syndesmosis reduction obtained as a result of the analyzes and dislocation, fracture type, screw joint distances and screw insertion angles were examined.
Statistical Evaluation
In this study, statistical data analysis was performed with IBM SPSS version 23. Basic statistics such as frequencies, percentages, averages, maximum and minimum values and confidence intervals of the appropriate variables were found. Correlation coefficients were calculated to determine the relationships between variables. The nonparametric Mann-Whitney Test was used to understand the mean order differences of two independent groups with non-normal dependent variables. The level of significance was set as p <0.05 for all statistical analyzes.
Results
Thirty-six (60%) of the lateral malleolus fractures were type C, 24 (40%) were type B according to the Weber classification. When we look at the fracture types, 26 (43.3%) trimalleolar fractures, 19 (31.7%) isolated lateral malleolus, 10 (16.7%) bimalleolar fractures, 5 (8.3%) lateral and posterior malleolar fractures were evaluated. While 12 (20%) of the patients had dislocation together with ankle fracture, 48 (80%) patients had isolated ankle fractures. The distance of the syndesmosis screw to the insertion distance was 10 mm or less in 5 (8%) patients, between 11-20 mm in 33 patients (55%), and 21 mm and above in 22 patients (37%). When we look at the reduction quality, syndesmosis malreduction was detected in 24 (40%) of the total 60 cases in the postoperative CT scan (Figure 2). When the 24 cases with malreduction were evaluated separately, the distance ‘a’ in 11 (46%) patients, distance ‘b’ in 5 (21%) patients, and both ‘a’ and ‘b’ distance in 8 (33%) patients were more than 2 mm from the normal side (Table 1). The average value of the q1 angle on the operated side was 13.76 ± 6.39, while the average value on the normal side was 10.86 ± 0.23. When malreduction cases were examined separately, the mean value of the operated side q1 angle was 15.91 ± 6.1, and the mean value of the normal side q1 angle was 10.37 ± 1.88 (Table 1).
Mean values of a, b and a/b of the operated side were statistically significantly higher than the mean values of the normal side (Table 1). There was a significant difference between the mean q1 of the normal and operated sides (p <0.05). The values of q1 on the operated side are significantly greater than on the normal side. When the malreduction cases were examined separately, it was found that the mean q1 angle of the operated side was statistically significantly higher than the mean q1 angle of the normal sides (p <0.05). No statistically significant correlation was found in the Spearman correlation analysis of reduction quality with dislocation and fracture type (p> 0.05). When the relationship between reduction quality and screw joint distance was examined, in the analysis performed by dividing the screw joint distances of 10 mm and below, between 11-20 mm and over 21 mm on the operated side, no statistically significant relationship was found between the reduction quality and screw joint distance (p> 0.05). As shown in Table 2, in the analysis of the relationship between screw position and reduction quality, a significant relationship was found by calculating the p-value as 0.008 (p <0.05). In addition, no statistically significant correlation was found between the screw insertion angle less or more than 90 degrees and the reduction quality (p> 0.05).
Discussion
The results we obtained in this study are consistent with previous studies in the literature, according to which CT scans are a sensitive indicator that can be used to determine the quality of syndesmosis reduction [15-17]. In addition, a significant relationship was found between the postoperative syndesmosis malposition and the position of the screw in the anteroposterior axis in the axial plane in ankle fractures with syndesmosis injury.
Recently, new imaging and evaluation techniques that provide highly accurate information about syndesmosis damage and syndesmosis malreduction have raised interest in this topic [5,18]. Various methods have been proposed to measure the reduction quality of syndesmosis in axial CT scans, as well as different techniques to optimize operative syndesmotic reduction [12-14].
In studies in the literature investigating postoperative syndesmosis malreduction, its prevalence was reported to be between 16% and 52% [5,18]. In our study, the incidence of malreduction was found to be somewhat higher, although it had similar results with previously published studies. We attribute this high rate to the increased sensitivity of CT, which allows imaging of both rotational and sagittal translation of the fibula, and our use of the indirect syndesmosis reduction technique in all patients during surgery.
Previous clinical studies analyzing postoperative CT scans of syndesmotic screw fixation have suggested that misplacement of the syndesmotic screw in the axial plane causes anteroposterior translation of the fibula over the tibia incisura [9,10]. Lee et al. concluded that for optimal syndesmosis screw fixation, the screw should be parallel to the ground, while the tibial tubercle is perpendicular to the ground [19]. The findings in this study show that the angular relationship of the screw with the line passing through the tibial tubercles is not significantly related to the quality of the reduction, considering the axis that makes a 90° angle to the line that is tangent to the anterior and posterior tubercles.
One of the important issues in the treatment of syndesmosis injury is the restoration of fibular rotation. Thordarson et al. reported that rotational excess of more than 5° causes non-physiological loading in the ankle joint [20]. A prospective study by Vasarhelyi et al showed rotational asymmetry of more than 10° in 25% of cases [21]. In our study, the q1 value was measured to detect the presence of rotational asymmetry. According to the data we obtained, in the patients we included in the study, it was found that the average of the operated side was 2.9° higher than the average of the healthy side. When patients with malreduction were evaluated in isolation, this difference was determined as 5.5. We believe that the reason why the difference of 2.9° between the operated side and the healthy side averages in the patients we included in the study increased to 5.5° only in patients with malreduction is related to the location of the screw. In cases with malreduction, the increase in the frequency of anterior (Va) localization causes the fibula to roll in the incisura as a result of the compression of the screw placed in the anterior. This situation suggests that the q1 angle increases by causing internal rotation of the fibula.
Some of the limitations of this study are the lack of clinical and long-term radiological follow-up. The strength of the study is that it has a sufficient number of cases to provide a “power factor”.
Conclusion
CT detects significantly more syndesmotic malreduction postoperatively than standard radiographic measurements. In addition, our results support that the most determining factor in the reduction of the fibula in syndesmosis damage is the correct reduction of the syndesmotic joint just before fixation during surgery, as well as the proper anteroposterior positioning of the screw used for fixation in the axial plane.
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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Bekir Karagoz, Rıdvan Mete Oral, Hasan Bombacı. Does the angle and position of the syndesmosis screw in the axial plan affect the reduction of syndesmosis? Ann Clin Anal Med 2022;13(4):435-439
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Evaluation of the effectiveness of different hemostatics and bioactive materials on the success of vital pulp therapy
Ayşegül Göze Saygın 1, Murat Ünal 2, Merve Candan 2, Pınar Demir 3, Levent Akıncı 4, Ömer Fahrettin Göze 5
1 Department of Pediatric Dentistry, Faculty of Dentistry, Sivas Cumhuriyet University, Sivas, 2 Department of Prosthodontics, Faculty of Dentistry, Sivas Cumhuriyet University, Sivas, 3 Department of Pediatric Dentistry, Faculty of Dentistry, İnönü University, Malatya, 4 Department of Endodontics, Faculty of Dentistry, İnönü University, Malatya, 5 Department of Pathology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
DOI: 10.4328/ACAM.20979 Received: 2021-12-02 Accepted: 2022-01-03 Published Online: 2022-03-15 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):440-445
Corresponding Author: Ayşegül Göze Saygin, Department of Prosthodontics, Sivas Cumhuriyet University, 58140, Sivas, Turkey. E-mail: aysegulgoze@hotmail.com P: +90 0507 706 97 60 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2826-5011
Aim: The aim of this study was to evaluate the response of the pulp in combination of hemostatic agents with pulp capping materials (PCMs).
Material and Methods: A total of 96 rats were used. Two molar teeth of each rat were included and all groups were created of 4 animals. In the occlusal cavities of the teeth, pulp perforations were performed for direct pulp capping. Thereafter, three different agents, which were forming the main groups [Group1: Sterile saline, Group2: Sodium hypochlorite, Group3 :Mecsina Hemostopper] at different periods of time used on pulp perforations and according to PCMs coated on the exposed pulp area, were divided into subgroups (Dycal, Biodentine, Theracal, and MTA Repair HP). Subsequently, all groups were left for two different waiting periods of 7 and 28 days. Half of the rats were sacrificed on the 7th and the remaining half were sacrificed on the 28th day, followed by micro-CT and histological analyzes.
Results: When the results of the study were examined, a statistical difference was observed between groups in terms of dentine bridge (DB) formation on the 7th and 28th days, while there was no statistical difference between inflammatory cell response and DB quality. Micro-CT images showed no formation of DB on the 7th day, while DB formation was observed on the 28th day on specimens.
Discussion: The combination of MHS and NaOCl may be preferable in order to provide pulp bleeding control in dental applications.
Keywords: Bioactive Materials, Direct Pulp Capping, Hemostatic agents, Histology, Micro-CT
Introduction
Direct pulp capping (DPC) is a process of direct covering of the pulp tissue with a tissue-friendly material that stimulates the repair of dentine and maintains the viability of the pulp. After the perforation, bleeding occurs in the capillaries under the pulp tissue. The amount of hemorrhage is proportional to the number of damaged vessels and the size of the wound surface opened [1]. It has been argued that after waiting for hemostasis, the most frequently applied treatment method, in which accumulated blood is removed with SS, may cause problems such as dislocation of the clot and reactivation of hemorrhage, and may also stimulate pulp inflammation [2].
The use of a hemostatic agent (HA) is recommended to promote the formation of the blood clot during hemorrhage control in the pulp for treatment of the vital pulp [3]. For the control of pulp hemorrhage, some solutions such as sodium hypochlorite (NaOCl) solution, sterile saline (SS) 2% chlorhexidine, hydrogen peroxide and electro-surgery etc. were used in many studies [4]. In addition, are the main reasons for the preference of this HA are the following: it has a good solvent effect against organic wastes, it is an antiseptic, it has low surface tension, it is easy to find and cheap [5].
Mecsina hemostopper (MHS) as a herbal agent includes 46% vitis vinifera extract, 16% hypericum perforatum extract, 12% glycyrrhiza glabra extract, 8% urtica angustifolia extract, 6% mentha arvensis juice, 5% alpinia officinarum extract, 4% syzygium aromaticum extract, and 3% thymus serpyllum extract. It can be used in liquid form in dentistry.
Although many biocompatible materials were developed for use in the DPC procedure, Ca(OH)2 is still considered the gold standard for comparing and evaluating the success of these newly produced products [6]. Theracal, Biodentine and MTA Repair HP are known as bioactive endodontic, and tricalcium silicate-based materials have been used as DPC materials in the present study. It is stated that an ideal bioactive endodontic material (BEM) in dentistry should be bactericidal, bacteriostatic, biocompatible, stimulating hard tissue formation and preserving
pulp vitality. It is also reported that a BEM should prevent tissue inflammation and tissue degeneration and stimulate the healing process [7]. A new bioactive material, MTA Repair HP, is manufactured in the form of a high-plasticity bioceramic material, which aims to preserve the biological properties of traditional ProRoot MTA as well as improve its chemical and physical properties.
The aim of this study is to investigate the pulpal response to 3 different HAs with 3 different pulp capping materials using micro-CT and histological imaging. The null hypothesis of the present study is that the pulpal response did not differ in the application of the HAs with different capping materials.
Material and Methods
This research was approved by the Ethics Commission of the University Animal experiments (ID: 65202830-050.04.04-188). A total of 96 Wistar male albino rats (200-220 gr) were used in the study. All experiments were conducted in compliance with the National Institute of Health’s Guidelines for the Care and Use of Laboratory Animals and in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Subjects were kept in standard test cages at 22-24 °C, 55-70% humidity, 1 atm pressure for 12 hours in a light/dark room and their health status was checked.
Animals
The animals have been anesthetized with ketamine HCL (25 mg/kg) and xylazine (10 mg/kg). After anesthesia, the mouths of the animals were cleaned from food residues and existing extraneous attachments, and the working place was disinfected with the batticon. A total of 192 molar teeth of the 96 rats, including the upper jaw right and left first molars of each rat.
Pulp Capping Procedure
Main groups were formed according to the type of hemostatic agents (HAs):
*Group 1: 0.9% Sterile saline (SS)
**Group 2: 5% NaOCl (group 2)
***Group 3: Mecsina Hemostopper (MHS)
Class 1 cavities were formed from the occlusal surface with diamond round burs to the first molar teeth of the rats. After cavity preparation, the pulp perforations were performed with sharp dental explorers. The hemostatics impregnated cottons were applied to the pulp perforated area. The groups were then divided into 1 week and 4 weeks (n = 8) according to type DPC material.
In Groups 1, 2 and 3, following the application of the HAs, application procedures of DPC materials (Dycal(a), Biodentine(b), Theracal(c), MTA Repair HP(d)) were performed according to the manufacturers’ recommendation (Table 1).
After 7 and 28 days of periods, the sacrification procedures were performed. In order to observe the formation of dentine bridge (DB) in the pulp, the teeth were imaged with micro– computed tomography (Micro-CT). After micro-CT imaging, histological hematoxylin- eosin examinations were performed to examine the inflammation cell response, DB formation in the pulp and the quality of the hard tissue formation. The histological evaluation criteria are shown in Table 2.
Micro-Computed Tomography
The fixed block sections were scanned using a micro-CT machine (SkyScan1172 version 1.5; Bruker Micro-CT, Kontich, Belgium). Each section was mounted in the middle of the specimen platform and scanned at 80 kV and 124 μA with a resolution of 13.68 μm, frame averaging 3, rotational step of 0.6°, and 180° rotation using 0.5-mm aluminum filters and 54% beam hardening reduction average scan time was 45 min. Raw data were reconstructed with NRecon Software version 1.6.4.8 (Bruker Micro-CT) to obtain rough measurements of the newly formed DB. Because of the contribute a precise and certain images of each sample and allowed measurements of the DBs, Data Viewer software version 1.4.4 was used to obtain 3 distinct views (coronal, sagittal, and transaxial) of each image in 2-dimensional form. Raw data were analyzed with CT analyzer (CTan) Software version 1.11.10. Two-dimensional slices were acquired in the axial plane to determine the first and last images in the coronal-to-apical direction from which newly formed DB could be assigned from the pulp.
Histological Analysis
For the histological analysis, the samples were decalcified in 10% formic acid after being fixed in 10% formalin solution and embedded in paraffin blocks. Five micron sections were obtained from samples embedded in paraffin blocks and each section was stained with hematoxylin- eosin. Histological preparations were examined by a pathologist (F.G) under a light microscope (Eclipse E 600, Nikon, Tokyo, Japan) at 100X magnification.
Statistical Analysis
The data were analyzed using SPSS 22.0. Kruskal-Wallis and Mann-Whitney U tests were used for the statistical analysis of the data. A p-value <0.05 was accepted statistically significant.
Results
Micro-CT Analysis
Four samples were randomly selected from each group for micro-CT analysis. Micro-CT images, reconstructed in the sagittal plane, showed DB formation 28 days after pulpotomy (Figure 1).
The highest and lowest average volumes of DBs were recorded in Group 3b (10,7×10-3mm3) and Group 1a (2,1 x 10-3 mm3), respectively (Table 3). While the highest DB volume was seen in MHS group (7,8×10-3mm3), the lowest bridge formation volume was shown in Group 1 (2,9×10-3mm3).
Hard tissue formation
When the values of the 1st and 4th weeks were evaluated in terms of DB formation among all groups, the scores were found to be statistically significant (p<0.05). No hard tissue formation was observed in some samples of the SS and NaOCl groups (1A-D; 2A,B) at week 1 (Figure 2A-F). When the histological images
of the 1st week were evaluated, incomplete dentine bridge and irregular hard tissue formation were observed in NaOCl and MHS groups (2C, D; 3A-D) in Figure1 (G-L). However, in all groups at 1 week, the statistical difference was insignificant (p> 0.05).
While incomplete DB appearance was shown in the Dycal group at the 4th week, , regular DB formation was observed in many of the samples treated with NaOCl and MHS (Groups 1a-d, 2a-d, 3a) in Figures 2a-i. At 28 days, the best scores according to DB scoring were seen in MHS+Biodentine, MHS+Theracal and MHS+MTA HP groups (Figures 2B, C, D). However, in all groups, the difference obtained on the histological images of the 4th week in terms of DB formation was not statistically significant (p>0.05). When DB formation was evaluated at week 4, regular tubular structure was observed, but this formation was not found to be statistically significant between all groups (p> 0.05) (Figure 3a).
Inflammatory Cell Response
When the 1st-week values were evaluated, the highest inflammation scores were seen in SS+Dycal, NaOCl+Dycal and NaOCl+Theracal (1,63) groups, while the lowest inflammation scores were found in MM and BM (1.25) groups, and the statistical difference between the groups was insignificant (p> 0.05). When the inflammation values of the 4th week were examined, although there was a decrease in the inflammation scores in all the groups, the statistical difference between the groups was insignificant (p> 0.05). When the inflammation scores at the 1st and 4th weeks were compared, the difference has been found to be statistically insignificant (p> 0.05) (Figure 3a).
Quality of dentine formation in dentine bridge
When the quality of DB in the 4th week was evaluated between the groups, no statistical difference was observed between the groups. The difference between the groups was found to be statistically significant (p <0.05) in terms of DB formation between the 1st week and 4th week, but the difference in inflammation cell response was found to be statistically insignificant (p> 0.05) (Figure 3b).
Discussion
The 30-day life cycle of rats has been shown to be equal to the 30-month life cycle of human beings, and it has been reported that the response of pulpal injury in rat molar teeth is observed on the fifth day after injury [8]. However, as the highest level of pulpal response has occurred on days 5 and 6 and as the formation of tertiary dentine, depending on the severity of the injury, has actualized on days 7-35, we preferred the observation intervals of the 7th and 28th days in present study [9].
Sterile saline (SS) is known to be the most conventional hemostatic material used in clinical practice to provide bleeding control in DPC. However, its long waiting period in clinical applications, the difficulty experienced in patient cooperation and difficulty in providing isolation have led clinicians to use alternative hemostatic agents. In the present study, NaOCl, which has a shorter clinical application time (20 sec), and MHS, which is a newly-introduced herbal material were applied during the pulpal treatment.
Long et al. have used different pulp capping materials in the treatment of rats [10]. They have examined the pulp inflammation cell response, hard tissue formation, and dentin bridge quality in the 1st and 4th weeks. They reported that there was no statistically significant difference between the 1st and 4th weeks in terms of inflammatory cell response and dentin bridge quality, but there was a significant difference between the 1st and 4th weeks in terms of hard tissue formation. These results were found to be similar to those we obtained in the present study.
Sodium hypochlorite (NaOCl) is used in the treatment of pulp at different concentrations (3-5%) and durations (30-80 sec) as a hemostatic agent [11,12]. In the present research, NaOCl was applied at a concentration of 5% for 20 seconds to control pulpal hemorrhage. The mechanism of action of herbal-based MHS, another hemostatic agent we use in the study, is to provide the formation of erythrocyte aggregation through encapsulated protein network formation [14,15]. MHS is limited in studies when the literature review is made. MHS provides its hemostatic activity by increasing the amount of vascularization by clot formation from erythrocytes.
Ankaferd blood stopper (ABS) containing herbs similar to MHS, used in present study, reduces the prevalence of inflammation [16]. This research has shown similar results for the inflammation criteria compared with the present study.
In clinical pratice, Dycal is an ideal pulp capping material, it has been criticized and controversial for tunnel defects in the bridge it forms [19,20]. In addition, the unstable physical properties of the calcium hydroxide allow particles of this material to migrate to the pulp, which can lead to necrosis [19]. TheraCal LC, which was the other material used in the study, was similar to Biodentine and MTA HP because it contains tricalcium silicate, but its hardening with light provides an advantage in terms of ease of use. Biodentine is highly preferred in children and adults due to its good physical and mechanical properties such as high tightness and stimulation of tertiary dentin production.
MTA Repair HP, an agent within MTA group, exhibited high plasticity and ease of manipulation, and these properties have been effective in choosing this material because of the advantage of a permanent restoration in one session, and also because there is no study available on dental pulp in the literature. Benetti et al. have concluded that histologically compared traditional MTA and MTA Repair HP materials are biocompatible and trigger biomineralization. They also have reported that the inflammatory response was moderate and
low at 7 and 30 days [20]. In the present study, inflammatory responses have been found to be similarly low in the groups treated with MTA Repair HP.
Histological images are often used to evaluate the healing process in many pulp capping studies. It has been emphasized that quantitative evaluations of thin sections are not very reliable due to the idea that histological sections may cause non-objective interpretations [24]. Okamoto et al. have stated that there is a significant increase in the density of tertiary dentine in the 4th week in their study in which they have used ProRoot MTA and iRoot BP materials and evaluated with micro-CT [21]. There was a significant increase in dentine density between the groups in the 1st and 4th weeks, similar to the present study. Micro-CT imaging method is a non-invasive procedure and has recently been used in pulp studies for morphological evaluation [22]. We have chosen to use both histological and micro-CT imaging methods in this study.
Studies on human and animal models have shown that MTA is more effective than the other materials in the formation of tertiary dentine [23]. In the groups where the pulp hemostasis is controlled with NaOCl and with especially MHS, dentine bridge formation with an irregular tubule structure has been observed on histological image samples after 1 week. Regardless of the differences in DPC materials, in the histological sections, tubular structure was found to be more regular in the MHS-treated group in terms of hard tissue formation scoring. Since MHS and MTA Hp materials have been used on pulp in-vivo for the first time in literature, we believe that this study will guide and contribute to new clinical studies. Thereafter, clinical studies on human pulp are needed.
The present study showed that bleeding control could be safely achieved in a short period of 20 sec by using NaOCl and herbal-based material MHS. We also think that the combined use of these NaOCl and MHS with newly developed bioactive endodontic materials will increase the success of direct pulp capping. We believe that the use of hemostatic agents
(NaOCl and MHS) that provide hemorrhage control in such a short period of time, especially in pediatric patients, will help pediatric dentists in the clinic.
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: This study was supported by Sivas Cumhuriyet University Scientific Research with Diş-220 project number.
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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Download attachments: 10.4328:ACAM.20979
Ayşegül Göze Saygın, Murat Ünal, Merve Candan, Pınar Demir, Levent Akıncı, Ömer Fahrettin Göze. Evaluation of the effectiveness of different hemostatics and bioactive materials on the success of vital pulp therapy. Ann Clin Anal Med 2022;13(4):440-445
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Turkish adaptation of the post-intensive care syndrome questionnaire: A validity and reliability study
Özlem İbrahimoğlu 1, Sevinç Mersin 2, Eda Polat 3
1 Department of Nursing, Faculty of Health Sciences, İstanbul Medeniyet University, İstanbul, 2 Department of Nursing, Faculty of Health Sciences, Bilecik Seyh Edebali University, Bilecik, 3 Department of Nursing, Faculty of Health Sciences, İstanbul Medeniyet University, İstanbul, Turkey
DOI: 10.4328/ACAM.20980 Received: 2021-12-02 Accepted: 2022-01-19 Published Online: 2022-01-20 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):446-450
Corresponding Author: Özlem İbrahimoğlu, Sağlık Bilimleri Fakültesi, İstanbul Medeniyet Üniversitesi, Cevizli Yerleşkesi, 34685, İstanbul, Turkey. E-mail: oogutlu@gmail.com P: +90 0216 280 41 62 F: +90 228 214 13 82 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0925-0378
Aim: In this study, we aimed to adapt and determine the psychometric properties of the Turkish version of the Post-Intensive Care Syndrome Questionnaire.
Material and Methods: This methodological study was conducted with 120 patients discharged from different intensive care units in Turkey between May 2020 and June 2021. Data were collected using a Socio-Demographic Form, Post-Intensive Care Syndrome Questionnaire, the General Health Poll, and the Pittsburgh Sleep Quality Index. Language and content validity were studied to adapt the scale. The construct validity was analyzed using confirmatory factor analysis. Reliability was evaluated with Cronbach’s alpha coefficient, item-total score correlation, and similar measurement tools.
Results: As a result of confirmatory factor analysis, the 10-item and 3-factor structure of the scale was determined. The factor loads of the items were between 0.60 and 0.90. Cronbach’s alpha was determined as 0.94. There was a strong positive correlation between scales.
Discussion: The Turkish version of the Post-Intensive Care Syndrome Questionnaire is a valid and reliable instrument for the Turkish population.
Keywords: Intensive Care, Psychometrics, Reliability, Validity
Introduction
Intensive care units (ICU) reduce mortality rates by increasing the chance of survival of patients with technological developments and advances in medicine [1]. This especially contributes to the controlled recovery of patients suffering from uncontrolled infections and sepsis, catabolic state, major surgical interventions, traumas, multiple organ failures, SIRS, and prolonged mechanical ventilation [2]. Therefore, it often provides a sense of security and control for patients and their families. Although ICU has an important place in the survival of patients, it has been determined that patients who experience intensive care have memory, attention, emotion and insomnia problems [3-5]. These problems have been termed “post-intensive care syndrome” (PICS) by the Society of Critical Care Medicine [6]. PICS is a cognitive, physical, and mental disorder that occurs during ICU stay or after discharge from an ICU and involves the long-term prognosis of ICU patients and its effects on the patient’s family [7]. These problems create serious obstacles both to discharge from the hospital to the home environment and to adapting to daily life after returning home [3].
Prolonged stay of patients in the ICU causes an increased risk of long-term physical, cognitive and mental complications. Risk factors for PICS include advanced age, delirium, acute brain dysfunction, hypoxia, hypotension, glucose dysregulation, sepsis, sedation, mechanical ventilation, and premorbid mental and physical comorbidity [8,9].
Post-ICU patients may suffer from physical problems like weakness, dysphagia, wasting syndrome, dyspnea, pain, sexual dysfunction, etc., as well as mental health problems like depression, anxiety, panic disorder, or posttraumatic stress disorder (PTSD) [4,8]. Torres et al. [9] identified depression, anxiety, PTSD, weakness, and movement disorder in patients with intensive care experience. In the study of Chung et al. [10], it was stated that the patients who remained on mechanical ventilation for a long time in the ICU experienced nightmares, panic disorder, anxiety, difficulty in breathing and the feeling/fear of suffocation. In addition, Colbenson et al. [1] reported that most of the patients staying in the ICU experienced cognitive problems for a long period of their lives. They stated that the physical effects of the intensive care experience also impair the patient’s quality of life and as a result, they may have difficulty in continuing their daily lives. They also reported that frequent re-admission to the ICU may lead to trauma in patients and their families.
Many assessment tools are used to evaluate the cognitive, physical, and mental difficulties experienced by patients with intensive care experience in Turkey [11-13]. However, there is no scale where these difficulties of patients were evaluated with a single scale. Therefore, the aim of this study is to evaluate the psychometric analysis of the Post-Intensive Care Syndrome Questionnaire.
Material and Methods
Participants and Setting
This study was conducted between May 2020 and June 2021 with 120 patients (considering the number of scale items for the 18-item scale) in the ICU of an education and research hospital in Turkey. The literature recommends that the sample size should be 5-10 people for each scale item in validity and reliability studies [14,15]. The criteria for inclusion were age over 18 years, experience of staying in the ICU for at least 2 nights, at least 1 month and not more than 1 year after leaving the ICU, and voluntary participation in the study. The list of patients discharged from the ICU was accessed through the hospital’s automation system. Data were collected via telephone. Before the study began, patients were contacted by phone to inform them about the purpose and process of the study.
Instruments
Socio-demographic Form: It was used to collect socio-demographic information of the patients.
Post-Intensive Care Syndrome Questionnaire (PICSQ): It was developed by Jeong and Kang [16]. The 4-point Likert-type (0=Never, 1=Sometimes, 2=Most often, 3=Always) scale consists of 18 items and three sub-dimensions. These are cognitive (1st, 2nd, 3rd, 4th, 5th, 6th items), physical (7th, 8th, 9th, 10th, 11th, 12th items), and mental (13th, 14th, 15th, 16th 17th, 18th items) sub-dimensions. The total score of PICSQ is between 0 and 54, or the mean is between 0 and 3. High scores show that the level of PICS is high. The Cronbach’s alpha for the PICSQ was 0.94 and its sub-dimensions were between 0.87 and 0.95 in this study.
General Health Poll (GHP): It was developed by Goldberg [17] and adapted in Turkish by Kılıç [18]. It consists of 20 items on a 4-point Likert-type scale. The minimum and maximum scores of the scale are 0 and 36. High scores indicate that the incidence of mental problems (anxiety and depression) increases. Cronbach’s alpha for the GHP was 0.75 for this study.
Pittsburgh Sleep Quality Index (PSQI): It was developed by Buysse et al. [19] and tested for the Turkish language by Ağargün et al. [20] to evaluate the sleep quality in the last month. The index includes 24 questions, nineteen of these are self-report questions and answered by the patient, five questions are answered by a spouse or roommate. These five questions are not included in the scoring and are therefore used for clinical information only. The last of the self-report questions (question 19) is about the availability of a roommate or spouse and is not used in scoring. The total score is between 0-21. A total score higher than five indicates poor sleep quality. In this study, the Cronbach’s alpha for the PSQI was 0.69.
Ethical Consideration
Permission was obtained from the corresponding author of the original PICSQ [16] and from the University Ethics Committee. The study was conducted according to the Declaration of Helsinki and consent was obtained from the patients who volunteered to participate in the study.
Statistical Analysis
For the analysis of the data, SPSS 21.0 and AMOS 22.0 statistical programs were used. Number, percentage, mean and standard deviation were calculated for descriptive statistics. Language and content validity were studied during the adaptation process. Confirmatory factor analysis (CFA) was used within the scope of the validity, and item-total correlation, Cronbach’s alpha coefficient, and equivalent form analyses were used within the scope of the reliability of the study. CFA evaluates whether a previously defined and constrained construct has been validated as a model. CFA is one of the structural equation models, and in structural equation models, the model fit must be ensured first. In the evaluation of model fit, “Chi-square statistics to the degree of freedom ratio” (X2/df), “statistical significance of individual parameter estimates” (t value), “standardized root-mean-square residual” (SRMR), “goodness-of-fit index” (GFI), “non-normed fit index” (NNFI), “comparative fit index” (CFI) and “root mean square error of approximation (RMSEA)” were used. Structural Equation Modelling was also applied. Pearson correlation analysis was applied to determine the relationship between the scales. For statistical significance, p<0.05 was accepted.
Results
Of the patients, 60.8% (n=73) were females, their mean age was 53.68±13.68 years, 66.7% (n=80) were hospitalized in the surgical ICU, 57.5% (n=69) were admitted electively, and 23.3% (n=28) received mechanical ventilation. The mean length of stay in the ICU was 3.33±2.33 days, and the mean time after discharge was 5.64±3.47 months, and 13.3% (n=16) were re-hospitalised.
Validity
The findings obtained in the CFA performed with the 18 items and 3-sub-dimensional structure of the PICSQ are given in Table 1. According to the results of the CFA, it was determined that the item factor loads were quite high, but the values of the model fit indices were not in the appropriate ranges. When the suggested covariance connections were examined, it was determined that the items had a high correlation with the items in the other factors, despite the high factor loading in the factor they belonged to. This indicates that the scale has a low level of discrimination and, accordingly, the model fit indices cannot reach a sufficient level. On the other hand, it was determined that there was no significant improvement in the fit indices, although the suggested covariance connections were made for the other items in the factor to which the items belonged. For the stated reasons, the items with high correlation with the items in other factors were gradually removed from the scale (primarily with the highest covariance correlation value), and the model fit indices were tried to be improved. After the remaining 10 items and three covariance connections in the scale (item3-item5, item9-item11, item16-item18), it was determined that the model fit indices reached good and very good levels, and the factor loads remained within the appropriate ranges (Table 1).
The results of the validity analysis, consisting of factor load and t values, are shown in Table 2. As a result of the CFA, it was determined that the factor loads of the remaining 10 items in the scale were higher than 0.40, and the t values of the items were significant (p<0.01). It was also determined that the total scale had 84.52% of the total variance. According to the results obtained, it was determined that the PICSQ is a valid scale with 10 items and 3 sub-dimensional structures. The verified model’s CFA diagram is shown in Figure 1.
Reliability
Cronbach’s alpha was evaluated to determine the internal consistency of the scale. Cronbach’s alpha was 0.94 for the scale, and it was between 0.87 and 0.95 for sub-dimensions. It was determined that the item-total correlation for all items ranged from 0.64 to 0.82 (Table 2).
The minimum and maximum scores of the PICSQ are 0 and 30, and the mean score was determined as 14.86±5.65. The minimum and maximum scores of the cognitive, physical, and mental sub-dimensions of the PICSQ are 0-12, 0-9, and 0-9, respectively. The mean scores of the cognitive, physical, and mental sub-dimensions of the PICSQ were 5.12±2.44, 5.32±2.20, and 4.41±1.78, respectively. The minimum and maximum scores of the GHP are 0 and 36, and the mean score was 13.21±4.97. The minimum and maximum scores of the PSQI are 0 and 21, and the mean score was 11.95±1.71 (Table 3).
For the scale’s equivalent form reliability analysis, the correlation results between PICSQ, GHP, and PSQI are given in Table 3. Correlation values of the relationship between PICSQ total scores and GHP were determined as 0.38; correlation values of the relationships between the sub-dimensions of PICSQ and GHP were determined between 0.27 and 0.38 (p<0.01). When the correlations between PICSQ and PSQI were examined, the correlation between the total scores was 0.42, and the correlations of the sub-dimensions were between 0.25 and 0.42 (p<0.01). These correlation results show the consistency of the PICSQ.
Discussion
The Turkish validity and reliability of the PICSQ were evaluated in this study since there is no comprehensive tool that can be used in Turkey to evaluate the PICS in patients with intensive care experience. This study was conducted with 120 patients. The literature recommends that the sample size should not be less than 5-10 times the number of scale items in order to perform factor analysis in scale studies [14,15]. For this reason, at least 5 participant rules were provided for each item of the 18 items used in the assessment.
Validity
In this study, the construct validity of the PICSQ was determined by factor loads, and it was determined that although the factor loads were quite high, the values of the model fit indices were not in the appropriate ranges. For this reason, the proposed covariance connections were examined and 8 items (1, 2, 8, 10, 12, 13, 15, 17) that had a high correlation with the items in the other factors, despite the high factor load in the factor they belonged to, were gradually removed from the scale. As a result of CFA, the model fit indexes of the remaining 10 items in the scale were determined as x2/df=0.196; SRMR=0.039; GFI=0.906; NFI=0.950; CFI=0.968; and RMSEA=0.100 (Table 1). The results of this study meet the perfect fit criteria specified in the model fit index results in the literature [21,22]. In the study, it was determined that the scale covered 84.52% of the total variance. In addition, in this study, the factor loads of the items were between 0.60 and 0.90, and a 3 sub-dimensional structure was determined (Table 2). This result meets the recommendation in the literature that factor loads should be greater than 0.40 and explain at least 30% of the variance [14]. In addition, it was determined that the 3 sub-dimensional structure of the scale was similar to the original scale [16].
Reliability
Cronbach’s alpha coefficient used to evaluate the internal consistency of this scale was calculated as 0.94 (Table 2). In scale validity and reliability studies, it is recommended to calculate Cronbach’s alpha coefficient to determine the reliability of the Likert-type scale [23]. Cronbach’s alpha coefficient of the original scale was reported as 0.93 [16]. It is stated that the scale is not reliable if Cronbach’s alpha is 0.00<α<0.40, it is low reliable if 0.40<α<0.60, it is reliable if 0.60<α<0.80, and it is quite reliable if 0.80<α<1.00 [14]. Since the Cronbach alpha value was determined to be higher than 0.70 in the Turkish version of the PICSQ, it can be said that the scale is a very reliable instrument.
Another test used to assess internal consistency is item-total score correlation. It is stated that the total score correlation of an item should be at least 0.30 statistically [24]. In this study, each of the item-total correlations of the scale was determined above the recommended minimum level (0.64-0.82). Therefore, it can be said that the internal consistency of the scale and all its items is high (Table 2).
It is recommended to either re-test the scale or use equivalent tests to determine the invariance of the scale over time [14,24]. In this study, a re-test was not performed because of the PICS instability in the patients after discharge from the ICU. This problem was solved using similar scales. In this study, GHP and PSQI were used as equivalent tests to determine the invariance of the scale over time. In the correlation analyses performed between the scales, the correlation values between PICSQ total and GHP and PSQI were found to be 0.38 and 0.42 and statistically significant (p<0.01) (Table 3). When correlation values are evaluated as 0-0.2=very weak, 0.2-0.4=weak, 0.4-0.6=moderate, 0.6-0.8=strong, and 0.8-1.0=very strong [23], it can be said that there is a strong and significant positive correlation between the scales.
Limitations
This study was conducted via telephone, but not face-to-face. Therefore, a formal environment could not be created. This study was conducted with patients discharged from different ICUs of a single hospital. In addition, other cognitive, physical, and mental factors affecting patients could not be controlled.
Conclusions
When the validity and reliability analyses were evaluated together, it was determined that the Turkish version of the PICSQ was a reliable and valid scale with 10 items and a 3-dimensional structure. PICSQ can be accepted as a valid and reliable tool to evaluate PICS in adults with intensive care experience in Turkey. It can be recommended to apply the scale to different and wider populations in Turkey.
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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Download attachments: 10.4328:ACAM.20980
Özlem İbrahimoğlu, Sevinç Mersin, Eda Polat. Turkish adaptation of the post-intensive care syndrome questionnaire: A validity and reliability study. Ann Clin Anal Med 2022;13(4):446-450
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Knowledge and clinical experiences of pediatric dentists and endodontists regarding regenerative endodontic procedures
Pınar Demir 1, Beril Demircan 1, Elçin Tekin Bulut 2, Neslihan Şimşek 2
1 Department of Pediatric Dentistry, 2 Department of Endodontics, Faculty of Dentistry, Inonu University, Malatya, Turkey
DOI: 10.4328/ACAM.20983 Received: 2021-12-03 Accepted: 2022-01-11 Published Online: 2022-01-17 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):451-456
Corresponding Author: Beril Demircan, Department of Pediatric Dentistry, Faculty of Dentistry, Inonu University, Malatya Elazığ Highway, 13. Km, 44280, Malatya, Turkey. E-mail: berildmrcn@gmail.com P: +90 422 341 01 06 / +90 530 874 22 14 F: +90 0422 341 11 07 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2865-7843
Aim: Pediatric dentists and endodontists perform regenerative endodontic procedures (REPs) on immature permanent teeth with necrotic pulp. The aim of this survey was to gather information about the knowledge and clinical experiences of pediatric dentists and endodontists regarding REPs.
Material and Methods: A 23-question survey was formed and a participation link was sent via e-mail. The questions were prepared based on AAE guide. The survey consisted of various types of questions to obtain information about the physicians’ age, gender, education information, previous regenerative endodontic therapy (RET) experiences and preferred REPs clinical protocols.
Results: A total of 207 volunteers, 101 pediatric dentists and 106 endodontists participated in the study. RET was chosen by 68.1% of participants as their first choice in incisors, 50.2% in premolars and 40% in molars. The most important criterion is the stage of root development (44.8%) to decide between RET or apexification; 53.5% of the participants learned about REPs during residency training; 70.5% of the participants had applied REPs before (pediatric dentists (77.2%), endodontics (64.1%)). Most of the physicians stated that a candidate suitable for RET in the future would encourage them to practice.
Discussion: The majority of pediatric dentists and endodontists do not adequately follow published standard clinical protocols. However, conducting studies under standard conditions is very important in evaluating the results of clinical protocols. This is very thought-provoking that even specialist physicians who can treat patients in this regard are confused. Therefore, physicians should be informed about this issue and a common protocol should be adopted in treatments.
Keywords: Endodontics, Pediatric Dentistry, Regenerative Endodontics, Surveys, Questionnaires
Introduction
Regenerative endodontic treatment is a method that has become popular in recent years and can replace traditional endodontic treatment. REPs primarily aim to eliminate the signs/symptoms of the infection, prevent re-infection and provide periapical bone healing [1]. However, unlike traditional endodontic therapy, REPs also aim to get increased root wall thickness and/or increased root length and a positive response to vitality testing. Although, these desirable goals and outcomes have increased the popularity of REPs in recent years (Clinical Considerations for a Regenerative Procedure. Available at: https://www.aae.org/specialty/publications-research/research/regenerative-database/) [2], the pertinent literature still includes “many knowledge gaps” [3]. Top cited articles in the literature revealed that researchers are in search for successful protocols to be used for regenerative endodontics [4]. The analysis of clinical procedures for REPs showed that these procedures vary greatly [5]. Also, a systematic analysis of the failed cases remarked the variability of REP protocols despite the American Association of Endodontics (AAE) clinical considerations for a regenerative procedure [6].
A detailed, time and effort-intensive survey is a useful research method to gather information about an individual’s perspective and experiences on a particular issue or topic [7, 8]. Although few surveys pointed out that practitioners generally have positive thoughts, regenerative endodontic therapy is a challenging and confusing issue with its clinical protocols and outcomes [9-12]. From this perspective, the aim of this web-based survey was to gather information about the knowledge and clinical experiences of pediatric dentists and endodontists towards REPs.
Material and Methods
The study was approved by the Inonu University Health Sciences Non-Interventional Clinical Research Ethics Committee (Decision No: 2019/340). A 23-question survey (appendix) was formed using google forms. Forms were sent via e-mail, which contained informative text and a participation link. The questions were prepared based on the AAE guide updated on 4/1/2018 (Clinical Considerations for a Regenerative Procedure. Available at: https://www.aae.org/specialty/publications-research/research/regenerative-database/) by two endodontists, a pediatric dentist and a pediatric dentistry resident, and also checked by a biostatistics professor. The first part of the survey gathered information about the age, gender, education and experience of the participants. The second (questions 1 to 10) and third (question 11 to 23) parts of the survey were intended to collect information about previous REPs experiences and the preferred REPs application, respectively. Participants, who did not perform REPs before, skipped questions between 7 and 12. The results were analyzed and presented as percentages [12].
Results
A total of 207 volunteers, 101 pediatric dentists (48.7%) and 106 (51.2%) endodontists, participated in this study. Men accounted for 20% of the participants, 80% of the participants were women, with an average age of 30.80±5.52 years. The distribution of experience period in pediatric dentists according to the type of specialization was more than 5 years in 32.67% of dentists, 1-5 years in 33.66 % of dentists, less than a year in 11.88%, 21,78% were still residents. Among endodontists, 18.44% had more than 5 years of experience, 26.21% had 1-5 years, 7.76% had less than a year, 47.57% were still residents. “What is your routine treatment approach for immature permanent teeth with necrotic pulp and open apex?” was the first question about the experience (Table 1).
The physicians stated that the most important criterion is the development stage of the root (44.8%), when it is necessary to decide between RET or apexification. These data were 53% for pediatric dentists and 37.1% for endodontists. Also, the second most important criterion for endodontists closest to the first choice was the patient’s cooperation (31.4%). Besides, uncooperative patients (63.1%), cases, which require post-core restorations (41.2%) and poor oral hygiene (33.9%) were criteria that discouraged physicians to apply REPs (Table 2).
When asked “What do you think is the most important factor in REP’s success?” using a scaffold was the most preferred answer for both pediatric dentists (32.6%) and endodontists (46.2%). In addition, the percentages of all participants’ answers were as follows: using a scaffold (39.6%), sterile working conditions (26%), the quality of the restoration (9.1%), provide bleeding (7.7%), the size of the apical diameter (7.2%), using intracanal medicaments (IC) (4.8%), age of the patients (2.4%), minimal or no instrumentation of dentinal walls (1.9%) and systemic condition of the patient (0.9%). Also, most of the pediatric dentists (75.7%) and endodontists (79.6%) think that there is no age limit to apply REP.
When we asked the doctors’ methods of obtaining information about REP, 30.61% of pediatric dentists chose “my research and studies”, 9.18% chose “AAE guideline”, 52.4% chose “during my residency”, 4.08% “courses and seminars about REPs”, 4.08% “other” chose option; 20% of endodontists chose “research and studies”, 14.28% “AAE guideline”, 55.23% chose “courses and seminars about REPs”, 5.71% “during my residency”, 4.76% chose “other” option.
Participants who stated that they had applied REPs before accounted for 70.5% (77.2% of pediatric dentists and 64.1% of endodontics). In addition, answers of the participants about to which teeth that they had previously applied REPs are shown in Table 2. Another data on the previous experiences of physicians were the number of teeth they had applied REPs in a year. The majority of the participants (59.8%) stated that they applied REPs to 1-3 teeth in a year, 26.5% of them applied REPs to 4-10 teeth, 7.4% applied REPs to 11-20 teeth and 6.1% applied to more than 20 teeth in a year. The percentages of age groups of patients undergoing REPs were 70% for ages between 6-15, 25.8% for ages between 15-18, and 24.4% of patients were older than 18.
The most preferred irrigation solutions used at the first appointment to pediatric dentists were sterile saline (59.7%), 2.5% NaOCl (55.1%), 17% EDTA (40.2%), 1.5% NaOCl (39%) and chlorhexidine (14.9%). The most preferred irrigation solutions for endodontist were 2.5% NaOCl (50.6%), 17% EDTA (48.1%), sterile saline (40.5%), 1.5% NaOCl (40.5%) and chlorhexidine (16.4%). In addition, none of the pediatric dentists marked MTAD, and none of the endodontists marked the hydrogen peroxide.
The rubber dam was definitely used by 87.1% of pediatric dentists and 94.3% of endodontists; 38.8% of the participants (55% of pediatric dentists/23.5% endodontists) stated that no instrumentation should be done, 57.2% (44% of pediatric dentists/69.8% endodontists) required minimal instrumentation and 3.8% (1% of pediatric dentists/6.6% endodontists) reported that it should be done as in routine root canal treatment.
The details of the answers given to the question of IC (intracanal) medicament selection are given in Table 2; 43.2% of the physicians declared that they call patients for a second appointment after two weeks, 26.2% after three weeks, 18.9% after one week, 11.1% after four weeks, and 0.4% after five or more weeks. The approaches of the participants when they detect persistent signs of infection are given in Table 3.
The choice of local anaesthesia in the scaffold formation appointment was important for 67.3% of pediatric dentists and 55.1% of endodontists (Table 3). Physicians preferred to use 17% EDTA (64.7%), sterile saline (50%) and 2.5% NaOCl (31.3%) to remove IC medicament. All answers to this (18th) question are explained in detail in Figure 1. Physicians’ answers given to the question of scaffold selection are given in detail in Table 3. If it is not achieved to induce bleeding, 48.4% of the pediatric dentists and 38.6% of the endodontists stated that they would terminate REPs.
The answers regarding the choice of coronary barrier material are given in Table 3. Factors that encourage REP application are given in Figure 2. When asked about the treatment option of a case, the responses were variable. All answers to this (23rd) question are explained in detail in Figure 3. All questions and options are attached in the appendix.
Discussion
Necrotic immature teeth are difficult to treat due to thin dentinal walls and open apex. RET as an alternative to apexification has promising clinical and radiographic outcomes such as continued root development, formation of new vascularized tissue [13]. Still, in the literature, the problem caused by the variability of the clinical protocols of RET is emphasized [2-5]. There is an up-to-date guideline in the published literature called “AAE Clinical Considerations for a Regenerative Procedure”, we designed the survey based on this study. Analysis of this survey results indicated that most of the pediatric dentists and endodontists do not follow or pay attention not only to this protocol and any other protocols, but also up-to-date literature of REPs after residency training. Some survey studies on REP showed that 50.6-56.4% of the physicians who participate the surveys had received training before [9-12] and 88-93.5% of them volunteered to receive training on RET [10].
Based on Cvek’s classification of root development, stage 1, 2 or 3 (short root, thin canal walls and wide-open apex) is proper for RET, and stage 4 may treat with RET or apexification with MTA as an apical plug [2]. When most of the pediatric dentists (53%) evaluate the root development stage, endodontists evaluate the root development stage (37.4%) and the cooperation of the patient (31.4%) to choose between REP and apexification according to this study results.
The age limit for patients to perform REP is another controversial issue. When Lee et al. asked participants whether there was an age limit for REP, there was a balance between yes (49.8%) and no (49.8%) [12]. In our study, the majority of the participants (78.2%) think that the age of the patient is not an obstacle for RET. Besides, it was stated that the treatment of a middle-aged patient’s permanent teeth with open apex with REP was successful [14]. When we asked physicians about the patients’ characteristics for who absolutely did not want to apply RET, the most popular answer was uncooperative patients (63%).
REP experiences of physicians were also investigated in different survey studies. The rate of participants who stated that they had applied any type of REP before, varied between 24.5 and 60% [9-12, 15]. According to our results, 77.2% of pediatric dentists and 64.1% of endodontists have previously applied REP. Most of them (59.8%) declared that they applied REP to 1-3 teeth per year. This result is less than the rate (76.9%/ 1-3 teeth per year) of Lee et al. stated in their study [12]. Additionally, in our study, the rate of physicians who applied RET patients ≤5 in the last five years is 51.3%, which is consistent with the rate reported by Tong et al (59.5%) [15].
A survey showed that 19.4% of the physicians preferred pulpal regeneration as an optimal treatment for necrotic immature teeth [10]. In this study, the rates were 68.1%, 50.2% and 40% for immature incisors, premolars and molars, respectively. Although, long-term follow-up studies, which evaluate the success of RET did not reveal a difference between tooth groups, there are more case reports of RET success in the literature and the fact that anterior teeth are affected more by traumatic dental injuries [16,17] may cause more application of REP to the central and lateral teeth.
It is aimed to introduce stem cells, a blood clot scaffold, and bioactive growth factors by providing periapical bleeding [18]. In 2018, it is reported that 75% of pediatric dental specialists and trainees, and 94.3% of endodontists use blood clots as a scaffold [11,12]. In our study, most (85%) of the participants choose blood clots as a scaffold. Additionally, other preferences were PRP (64%) and PRF (68.9%). Besides, the result that 32.6% of pediatric dentists and 46.2% of endodontists think that the success of REP depends on the use of a scaffold may be interpreted as physicians’ interest and care to scaffold formation. In accordance with this information, 43.4% of the participants thought to terminate the treatment if there was no bleeding. Another issue in terms of bleeding is the choice of local anesthetic solution. AAE recommends 3% mepivacaine without vasoconstrictor as a local anesthetic solution to induce bleeding (Clinical Considerations for a Regenerative Procedure. Available at: https://www.aae.org/specialty/publications-research/research/regenerative-database/). Petrino’s study also supports this [19]. The majority of the participants (61.1%) preferred local anesthetic solutions without vasoconstrictor and pediatric dentists (67.3%) paid more attention the choice than endodontists (55.1%).
Our study also tried to make a connection between the success of the RET and isolation of the tooth with a rubber dam. Pediatric dentists (87.1%) and endodontists (94.3%) agreed about the importance of the rubber dam isolation. Besides, 26% of the all participants remarked sterile working conditions as the most important factor for the success of REP. Lin et al. emphasized that a sterile microenvironment is necessary for tissue regeneration [20].
The various methods of irrigation, the use of IC and TAP (triple antibiotic paste) studied for disinfection, these methods have no superiority over each other in terms of treatment outcomes. Since, pertinent literature revealed that the level of disinfection determines treatment outcomes, recommendations about instrumentation of dentin walls in RET should be reviewed [21]. The use of 1.5% NaOCl followed by 17% EDTA can be beneficial and can prevent the negative effect of high concentrations of NaOCl on “survival and differentiation of stem cells of apical papilla” [22]. In this survey, endodontists preferred to use 2.5% NaOCl (50.6%), 17% EDTA (48.1%), and sterile saline (40.5%), while pediatric dentists preferred sterile saline (59.7%), 2.5% NaOCl (55.1%) and 17% EDTA (40.2%). Regarding instrumentation of the dentin walls, while the majority of pediatric dentists (55%) preferred no to apply instrumentation, most of the endodontists (69.8%) preferred minimal instrumentation. However, the findings of a previous study reported that 70.2% of endodontists did not instrument the dentinal walls [12].
A review about antimicrobial therapeutics in RET indicated that TAP continues to maintain its value in terms of its effectiveness in eliminating microorganisms [23]. Besides, Ca(OH)2 is recommended as an intracanal medication in RET because of its antimicrobial property [2]. In this study, the most preferred IC was Ca(OH)2 (60.3% of the physicians). However, Lee et al reported a lower percentage (52.2%) for Ca(OH)2. Systematic analysis notified that the persistent infection is responsible for 79% of failed RET cases [6]. In the presence of persistent infection, 16.9% of the participants declared that they would terminate RET, while the majority (55.5%) would apply a different IC and follow-up.
In this study, MTA and Biodentin are frequently preferred due to their advantages in treatments [24]. MTA was the most preferred material (93.6%) while Biodentine was the second best (62.6%) for pediatric dentists and endodontists as a coronal barrier.
Participants in different fields of expertise specified RET as a better treatment option when compared to implant application with ratios ranging between 50 and 87.1%. Also, 84.5-96.8% of them volunteered to protect teeth and surrounding tissues [9,10]. In the case question directed to the participants, the majority preferred regenerative and endodontic procedures for tooth preservation instead of extraction (Figure 3). These preventive approaches of physicians are promising for the future of regenerative therapy. Physicians express their needs as more conclusive evidence (63.1%) and having a suitable patient (71.3%) to be encouraged for future REP applications.
Conclusion
Although the literature on REP indicates successful treatment outcomes, pediatric dentists and endodontists are not sufficiently encouraged to prefer regenerative endodontic procedures as the first option for the treatment of immature permanent teeth with necrotic pulp. Therefore, physicians should be given training on REP and the results of the studies should be reported with success and failure, and the literature should be supported.
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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Pınar Demir, Beril Demircan, Elçin Tekin Bulut, Neslihan Şimşek. Knowledge and clinical experiences of pediatric dentists and endodontists regarding regenerative endodontic procedures. Ann Clin Anal Med 2022;13(4):451-456
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Clinical effect of monocyte/high-density lipoprotein ratio on the prediction of bone metastases in patients with prostate cancer
Utku Dönem Gündoğdu 1, Fuzuli Tuğrul 2, Funda Karabağ Çoban 3
1 Department of Medical Oncology, Afyonkarahisar Park Hayat Private Hostipal, Afyonkarahisar, 2 Department of Radiation Oncology, Eskişehir City Hospital, Eskişehir, 3 Department of Molecular Biology and Genetics, Faculty of Science and Literature, Uşak University, Usak, Turkey
DOI: 10.4328/ACAM.20985 Received: 2021-12-03 Accepted: 2022-01-12 Published Online: 2022-01-19 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):457-460
Corresponding Author: Utku Dönem Gündoğdu, Department of Oncology, Private Parkhayat Hospital, 03200, Afyonkarahisar, Turkey. E-mail: dr.utkudonem@gmail.com P: +90 506 505 70 76 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3881-5075
Aim: This study aimed to determine the predictability of bone metastasis with a Monocyte/HDL-cholesterol ratio in prostate cancer patients.
Material and Methods: A comparison of monocyte/high-density lipoprotein in patients with and without prostate cancer was planned. Patients with hematological diseases and lipid metabolism disorders and those who were using lipid-lowering drugs were excluded from the study. Out of 95 patients, 54.7 % of the patients participating in the study were metastasized, while 45.3 % did not. Inflammatory markers with neutrophile-lymphocyte ratio (NLR) and thrombocyte-lymphocyte ratio (TLR) were found to be high in patients with bone metastases.
Results: Statistically significant difference was found between the patients’ presence or absence of metastasis and NLR t (93) = 2.089; p = 0.040; p <0.05). Another statistically significant difference was observed between the non-metastasized patients and TLR (t (93) = 2.586; p =0.012; p <0.05).
Discussion: In the current study, there was no relationship found between the monocyte-HDL ratio (MHR), Gleason Score (GS) level, and bone metastasis. The relationship between monocyte metastasis and HDL-C metastasis cancer is controversial in the literature.
Keywords: Bone Metastasis, Prostate Cancer, Monocyte, Lipoprotein, HDL-Cholesterol
Introduction
The development of atherosclerotic plaque, the biology of tumor formation and metastasis are linked to angiogenesis. Main molecular inflammatory pathways and their nuclear transcription factors such as NF kappa B, play an important role in the pathogenesis of both atherosclerosis and cancer. Altered expression of proteases associated with thrombolysis plays a role in atherosclerotic plaque progression and in the process of cancer invasion and metastasis [1-3]. The relationship between HDL-cholesterol and cancer incidence and mortality is controversial [4]. There are limited studies on directly affecting HDL-cholesterol levels and cancer mortality. Low HDL-cholesterol has been identified as a poor prognostic factor in many cancers [5]. A relationship has been found between low HDL-cholesterol levels and prostate cancer [6]. After monocytes enter the tissue, they can transform into tumor-associated macrophages. It has been found that breast and skin cancers play a role in the progression and metastasis myelomonocytic cells in mouse models [7]. Metastasis-associated macrophages cause tumor progression in metastasis [8]. Overactivation of monocytes can increase oxidative stress and increase inflammation. HDL-cholesterol has an impressive effect on monocyte migration by showing anti-inflammatory and antioxidant properties.
Monocyte/HDL-cholesterol has been used as an oxidative stress inflammation marker. HDL-cholesterol neutralizes the pro-inflammatory and pro-oxidant effects of monocytes by inhibiting the migration of macrophages and the oxidation of low-density lipoprotein cholesterol (LDL-C) molecules [9]. Therefore, features such as monocyte count (MHR) and HDL-cholesterol ratio may indicate the patient’s inflammatory status. Consistent with this, the association between increased MHR and cases of atherosclerosis has been demonstrated. MHR has emerged as a new cardiovascular prognostic marker in previous studies.
Prostate cancer has a high mortality rate despite new treatment modalities. Inflammation is responsible for the etiopathogenesis and progression of many cancers. Monocyte/HDL-cholesterol is a marker of inflammation. Prostate cancer most commonly causes bone metastases. This study aimed to determine the predictability of bone metastasis with Monocyte/HDL-cholesterol ratio in prostate cancer patients.
Material and Methods
Sample Collection and Processing
Routinely checked blood lipid and hemogram profiles and PSA value, which are biochemical parameters, were scanned and recorded until 2017 June-October 2020. Data belong to patients aged over 18 years having histopathologically diagnosed prostate cancer. Prostate cancer bone metastasis was detected on a whole-body bone scan. Patients with hematological diseases, those using lipid-lowering drugs, and having lipid metabolism disorders were excluded from the study.
Statistical Analysis
A detailed statistical analysis was performed for the monocyte HDL ratio (MHR), neutrophile lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and thrombocyte lymphocyte ratio (TLR). Results are presented in the form of tables. Levene’s test was applied where required.
Ethical permission
Ethical permission for this study has been granted by the Afyonkarahisar Health Sciences University, committee of clinical research ethics dated 02.04.2021 meeting number 2021/4 encoded 217-2011/KAEK-2. As seen in Table 3, there is no significant difference between the patients’ metastasis status and the ratio of monocytes/HDL (p=.752;p>0.05) and ratios of monocytes/lymphocyte (p=.065;p>0.05). However, a statistically significant difference was determined between the patients’ metastasis/non-metastasis status and the neutrophil/lymphocyte ratio (t(93)=2.089; p=.040; p<0.05). According to this result, it was observed that neutrophil/lymphocyte levels (x=5.18) of patients with metastasis of prostate cancer were higher than those in which prostate cancer did not metastasize (x=3.33). A statistically significant difference was determined between the patients’ metastasis/non-metastasis status and the platelet/lymphocyte ratio (t(93)=2.586;p=.012;p<0.05). According to this result, it was seen that the platelet/lymphocyte levels (x=251.36) of the patients with metastasis of prostate cancer were higher than the patients without metastasis (x=189.36).
Results
As seen in Table 1, it was found that the disease metastasized in 54.7% of the patients participating in the study, while the disease did not metastasize in 45.3%. As seen in Table 2, there is no statistically significant relationship between the patients’ metastasis/non-metastasis and monocyte/HDL-C, neutrophil/lymphocyte and monocyte/lymphocyte ratios. However, there is a statistically significant negative low-level correlation between the presence or absence of metastasis and the platelet/lymphocyte ratio. As seen in Table 3, there is no significant difference between the patients’ metastasis status and the ratio of monocytes/HDL (p=.752;p>0.05) and ratios of monocytes/lymphocyte (p=.065;p>0.05). However, a statistically significant difference was determined between the patients’ metastasis/non-metastasis status and the neutrophil/lymphocyte ratio (t(93)=2.089; p=.040; p<0.05). According to this result, it was observed that neutrophil/lymphocyte levels (x=5.18) of patients with metastasis of prostate cancer were higher than those in which prostate cancer did not metastasize (x=3.33). A statistically significant difference was determined between the patients’ metastasis/non-metastasis status and the platelet/lymphocyte ratio (t(93)=2.586;p=.012;p<0.05). According to this result, it was seen that the platelet/lymphocyte levels (x =251.36) of the patients with metastasis of prostate cancer were higher than the patients without metastasis (x=189.36).Discussion
There was no statistically significant relationship found between patients’ metastasis as shown in Table 1. However, there was a statistically significant negative and low-level correlation between patients’ metastasis with their thrombocyte/lymphocyte ratio. The inflammatory response has been linked to tumor metastasis and the survival effect in many cancers. Studies have determined that hematological parameters of cancer patients, including monocyte-neutrophil-platelet ratio, are associated with prognosis. Wang et al. showed that peripheral monocyte count predicts poor clinical results and aggressive tumor characteristics in patients with castration-resistant prostate cancer [CRPC] [10]. Similarly, Shigeta et al. has reported that high absolute monocyte counts predicted poor prognosis and aggressive tumor characteristics in CPRC patients [11]. In addition, the effect of immune cell ratio, such as the neutrophil/lymphocyte ratio [NLR], on the prognosis in gastric cancer has been reported [12]. In the study conducted by Ceyaln et al., bone metastasis has been predicted in high NLR prostate cancer [13]. In the study by Jing-Ya et al., higher NLR and PLR [platelet-lymphocyte ratio] were found in patients with higher bone metastasis [14]. In the current study, in accordance with these studies, inflammatory markers with NLR and PLR were found to be high in patients with bone metastasis.
Circulating monocytes play an important role in the metastasis process in prostate cancer [15]. An increase in the peripheral monocyte count and lymph node metastasis has also been increased [16]. In the current study, no difference was found in the MLR rate in both groups. However, in the study conducted by Azeb et al., peripheral monocyte count was not found to be associated with metastasis [17] that agrees with the results obtained in the current study.
No significant differences were found between metastasized and non-metastasized patients’ data i.e., MHR (p = 0.752; p> 0.05), MLR (p = 0.065; p> 0.05). However, a statistically significant difference was found between the patients’ presence or absence of metastasis and the neutrophil / lymphocyte ratio (t (93) = 2.089; p = 0.040; p <0.05). According to this result, it was observed that the neutrophil / lymphocyte levels [x = 5.18] of the metastasized patients were higher than in the patients whose prostate cancer did not metastasize [x= 3.33]. A statistically significant difference was determined between the non-metastasized patients and TLR [t [93] = 2.586; p =0.012; p <0.05]. According to this result, it was observed that the thrombocyte / lymphocyte levels [x = 251.36] of the metastasized patients were higher than the patients whose prostate cancer did not metastasize [x = 189.36].
Abnormal lipid metabolism is being investigated as one of the important mechanisms in carcinogenesis. As a result of defects in lipid and lipoprotein metabolism, metabolic syndrome and obesity have been found to affect cancer risk and prognosis [18, 19].
High- and low-density serum lipoproteins have been found to act as key lipoprotein transporters of cholesterol to cancer cells through receptor-mediated mechanisms. Low LDL-C has been shown in some studies associated with a higher risk of malignancy.
Some studies have found a relationship between HDL-C and cancer incidence. It may contribute to tumor progression [20]. There is a positive association between low HDL-C and breast cancer risk in postmenopausal breast cancer [21]. Pre-treatment low HDL-C levels were found to be associated with poor prognosis in non-small-cell lung carcinoma.
Epidemiological studies of the relationship between HDL-C and the prostate are contradictory. While some studies present a relationship, others deny it [22,23]. HDL-C prostate cancer risk and disease severity are controversial in the literature.
Low HDL-C and high triglycerides were found to be associated with higher grade in prostate cancer [24]. In conclusion, the hypothesis of this study was to determine the effect of MHR used as an inflammatory marker on predicting bone metastasis. Also, the association between increased MHR and cases of atherosclerosis has been demonstrated. MHR has emerged as a new cardiovascular prognostic marker in the previous studies [25]. There are limited studies in the literature on the MHR in cancer. It was found to be high in differentiated thyroid cancer. The relationship between monocyte metastasis and HDL-C metastasis cancer is controversial in the literature. There is a need to expand this study on a large scale by increasing the number of patients.
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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2. Stoll G, Bendszus M. Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke. 2006; 37(7): 1923-32.
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6. Van Hemelrijck M, Walldius G, Jungner I, Hammar N, Garmo H, Binda E, et al. Low levels of apolipoprotein A-I and HDL are associated with risk of prostate cancer in the Swedish AMORIS study. Cancer Causes Control. 2011; 22(7): 1011-9.
7. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, et al. CCL2 CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis, Nature. 2011; 8: 475 (7355): 222-5.
8. Binzhi Q, Yan D, Jae HI, Ruth J, Yiyu Z, Jiufeng L, Richard A, et al. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One. 2009; 4 (8): 6562.
9. Tardif JC, Grégoire J, L’Allier PL, Ibrahim R, Lespérance J, Heinonen TM, et al. Effect of Rhdl on atherosclerosis-safety and efficacy [ERASE] investigators. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007; 297 (15): 1675–82.
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11. Shigeta K, Kosaka T, Kitano S, Yasumizu Y, Miyazaki Y. High absolute monocyte count predicts poor clinical outcome in patients with castration-resistant prostate cancer treated with docetaxel chemotherapy. Ann Surg Oncol. 2016; (23): 4115- 22.
12. Zhang LX, Wei ZJ, Xu AM, Zang JH. Can the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio be beneficial in predicting lymph node metastasis and promising prognostic markers of gastric cancer patients? Tumor maker retrospective study. Int J Surg. 2018; 56: 320-7.
13. Yeşim C, Sevil T, Sait Ş, Banu S, Zehra ÖC. Neutrophil/Lymphocyte and Platelet/Lymphocyte Rates Predict Bone Metastasis in Prostate Cancer Patients? J Urol Surg. 2019; 6 (2): 105- 10.
14. Jing-Ya Z, Peng G, Peng-Yu Z, Meng Z, Li R. Role of Neutrophil to Lymphocyte Ratio or Platelet to Lymphocyte Ratio in Prediction of Bone Metastasis of Prostate Cancer. Clin Lab. 2019; (5): 1-65.
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16. Jia-Wei Z, Yun-Hua M, Yang L, Hai-Tao L, Chandni CS, Yue-Wu Fu, et al. A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer. Asian J Androl. 2021; 23(4):409-14.
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Download attachments: 10.4328:ACAM.20985
Utku Dönem Gündoğdu, Fuzuli Tuğrul, Funda Karabağ Çoban. Clinical effect of monocyte/high-density lipoprotein ratio on the prediction of bone metastases in patients with prostate cancer. Ann Clin Anal Med 2022;13(4):457-460
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Factors predicting hyperimmune response in COVID-19 patients presenting to the emergency department
Seref Emre Atıs 1, Mustafa Uguz 2
1 Department of Emergency Medicine, Faculty of Medicine, Karabuk University, Karabuk, 2 Department of Infectious Disease, Mersin City Hospital, Mersin, Turkey
DOI: 10.4328/ACAM.21127 Received: 2022-02-25 Accepted: 2022-03-25 Published Online: 2022-03-25 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):461-464
Corresponding Author: Seref Emre Atıs, Sirinevler, Alparslan Cd., No:1, 78200, Karabuk Merkez, Karabuk, Turkey. E-mail: dremreatis@gmail.com P: +90 506 928 81 86 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5094-6000
Aim: The aim of this study is to determine the predictive parameters that can be used in the early determination of hyperimmune response syndrome in the Emergency Department.
Material and Methods: This is a cross-sectional, retrospective study. Patients over the age of 18 who were admitted to the emergency department with a pre-diagnosis of COVID-19, and who were admitted to the intensive care unit were included in the study. Demographic data and laboratory findings were obtained from the hospital information system and patient files. Patients’ thoracic computerized tomography images were classified into two groups. The classic involvement includes bilateral basal ground-glass opacities, crazy paving, reverse halo, per lobular pattern, and peripheral consolidation. All other images were included as non-classic COVID-19 involvement.
Results: A total of 202 patients were included. Hyperimmune response development was detected in 74 (36.6%) patients. When laboratory values were examined, ferritin and ALT values were found to be higher, WBC and lymphocyte values were found to be lower in patients who developed a hyperimmune response (p<0.01, p<0.01, p=0.038 and p=0.004, respectively). In the logistic regression analysis of the values that can be effective in the development of the hyperimmune response, classic imaging had a statistically significant effect (Odds ratio 0.449 [95% confidence interval, CI = 0.244-0.827], non-classic vs classic[reference]). No statistically significant effect was found in the analysis of other values.
Discussion: Classical chest tomography findings can be useful as a preliminary parameter in the development of hyperimmune response.
Keywords: COVID-19, Emergency, Cytokine, Ferritin, Lymphocyte
Introduction
The SARS-CoV-2 virus emerged as atypical pneumonia cases clustered in China at the end of 2019. The virus spread rapidly between countries and continents in the following months, and the World Health Organization (WHO) declared it as a pandemic. The Coronavirus infectious disease (COVID-19) continues to affect the whole world after two years [1].
Around 6 million cases have been reported worldwide, and the number of cases still increase. Unfortunately, clinical treatment modalities for COVID-19 do not currently exist and clinical studies to identify the treatment are ongoing [2,3].
Currently, the generally accepted view is that hyperimmune response syndrome triggered by SARS-CoV-2 leads to a severe disease course, and treatment efforts are coordinated accordingly [4]. This syndrome caused by COVID-19 has not yet been defined clearly, despite its association with mortality and morbidity [5]. Considering that routine measurement of elevated cytokine levels during a hyperimmune response syndrome at the time of admission is impractical and cost-ineffective, identification of early predictive biomarkers is needed. Unfortunately, parameters such as age, radiological imaging, and comorbidities used to predict disease severity cannot be used with the same efficiency in determining the presence of a hyperimmune response syndrome [6]. Anti-inflammatory treatment approaches to be used in the early stages of a cytokine storm may reduce lung damage and respiratory failure developing throughout the disease course of COVID-19 [7]. Interleukin inhibitors have been used in the early stages of the disease for this purpose [8].
In the present study, we aimed to investigate certain parameters at the time of admission in Emergency Service patients hospitalized in the intensive care unit (ICU) and to examine the relationship between the parameters in the early identification of hyperimmune response syndrome and the need for treatment.
Material and Methods
Study Design:
This research was designed as a cross-sectional, retrospective study. Patients presenting to the Emergency Department of a tertiary hospital between October 31, 2020, and January 01, 2021, were included in the study. Ethics committee approval was obtained for the study (Approval no:2021/740).
Patient Selection:
We included patients aged >18 years who tested positive for COVID-19 via the real-time polymerase chain reaction (rt-PCR) after presenting to the emergency department with a preliminary diagnosis of COVID-19 and were admitted to the intensive care unit (ICU). Patients aged <18 years, those with a negative rt-PCR test result for COVID-19, and patients initially admitted to other units or were discharged were excluded from the study. ICU hospitalization criteria were considered as respiratory rate ≥30/min, severe respiratory distress [dyspnea, use of extra respiratory muscles], oxygen saturation in room air ≤ 90% [PaO2/FiO2 <300 in a patient receiving oxygen]).
Data Collection:
Demographic data (age and sex) and laboratory findings (creatinine, ferritin, fibrinogen, D-dimer, ALT, CRP, procalcitonin, albumin, leukocyte, lymphocyte, neutrophil, and platelet count) were obtained from the hospital information system and patient files. Based on these values, the systemic immune-inflammatory index value (neutrophil value × platelet value/lymphocyte value) and neutrophil/albumin ratio were calculated for each patient.
Thoracic computed tomography (CT) findings were classified in accordance with the British Society of Thoracic Imaging (BSTI) classification system (available at: http://www.bsti.org.uk/media/resources/files/BSTI_COVID_CT_Proforma_v2_13.04.2020.docx). This system includes four different groups. These are categorized as normal, indeterminate, possible/classic, and non-COVID. The possible/classic involvement classification includes bilateral basal ground-glass opacities, crazy paving, reverse halo, per lobular pattern, and peripheral consolidation. In the present research, patients who were classified as possible/classic according to BTSI criteria were included in the research as classic COVID-19 involvement, and all other classifications were included as non-classic COVID-19 involvement. Hyperimmune response syndrome was considered as patients with prolonged persistent fever despite treatment, elevated CRP or CRP progression during treatment, ferritin elevation, D-dimer elevation, existing lymphopenia, and thrombocytopenia or occurring under treatment, impaired liver function tests, and patients showing a hyperimmune response. The patients were divided into two groups as patients with and without a hyperimmune response.
Primary Outcome:
The primary outcome of this research was to determine the effectiveness of parameters at admission (to the emergency service) in predicting the development of a hyperimmune response in patients hospitalized in the ICU with the diagnosis of COVID-19. The secondary outcome of the research was to identify the correlation between these parameters and mortality.
Statistical analysis:
IBM SPSS Statistics 22 (IBM SPSS, Turkey) program was used for statistical analysis of the data obtained in the research. The Shapiro–Wilk test was used to check whether the parameters were normally distributed. Descriptive statistical methods (mean, standard deviation, median and interquartile range, and frequency) were used to present the data. Quantitative parameters were compared between the groups using the Mann–Whitney U test. The Chi-square test was used to compare qualitative parameters between the groups. Logistic regression analysis was used to determine independent parameters affecting the hyperimmune response. P < 0.05 indicated statistical significance in all analyses.
Results
Among the 220 patients considered for the study, 18 were excluded owing to missing or incomplete laboratory data. The study was completed with 202 patients, 128 (63.4%) of whom were men. The mean age of patients was 61 years (±15).
A total of 74 (36.6%) patients received treatment as they presented with a hyperimmune response. The mean age of patients with a hyperimmune response was lower than that of patients without a hyperimmune response (p = 0.025). Examining laboratory parameters of the patients revealed that ferritin and ALT values were higher (p < 0.001 and p < 0.001, respectively), whereas WBC and lymphocyte values were lower (p = 0.038 and p = 0.004, respectively) in patients who developed a hyperimmune response compared with those who did not. Demographic characteristics and laboratory parameters of the patients are summarized in Table 1.
When the thoracic CT scans of the patients at the time of admission were examined, it was found that classic involvement was found in 58.1% of patients who developed a hyperimmune response, while this rate was 36.7% in patients who did not (p = 0.003) (Table 2).
In the logistic regression analysis of the values that can be effective in the development of the hyperimmune response, classic imaging had a statistically significant influence (Odds ratio = 0.449 [95% confidence interval, CI = 0.244-0.827], non-
classic vs classic [reference]). No statistically significant effect was found in the analysis of other values (Table 3).
Discussion
In the present study, classical CT involvement was more common in patients with the hyperimmune response at admission compared to patients who did not develop a hyperimmune response. Also, in the logistic regression analysis, the non-classical CT imaging had a negative influence on the development of a hyperimmune response. A significant correlation was found between the severity of CT findings and the course of COVID-19 and inflammatory cytokine levels [9,10]. Jin et al. graded computered tomography imaging from 0 (normal) to 4 (several stages of pneumonia) in COVID-19 patients. They found that clinical outcomes were worse in the high-grade group [11]. In another study, it was determined that high initial lung CT scores of the patients were an independent risk factor for patient discharge (Odds ratio = 0.41 [95% confidence interval, CI = 0.18-0.92]) [12].
In the present study, the WBC and lymphocyte levels at the time of admission to the hospital were lower in patients who developed hyperimmune response syndrome in the ICU compared with those who did not. Consistent with this finding, in a systematic review of 3939 patients in 28 different studies, the change in WBC and lymphocyte levels was examined in patients with mild and severe SARS-COV-2 infection and it was found that lymphocyte levels were significantly lower in severe patients [13]. Caricchio et al. found that ALT values were higher and lymphocyte levels were lower in patients who developed a hyperimmune response compared with those who did not [14]. Zhou et al. investigated the role of biochemical parameters in predicting the severity of COVID-19 and reported that a high ferritin level was useful in predicting severe disease [15]. Similarly, in a meta-analysis conducted by Cheng et al., it was reported that a ferritin level above 397 ng/ml was associated with severe COVID-19 disease [16]. However, WBC, lymphocyte, and ferritin values were not detected as independent factors according to logistic regression analysis. This discordance can be explained by the fact that the present study was conducted among patients already followed in the ICU, whereas the abovementioned studies compared mild–moderate–severe COVID-19 patients. Considering the severe course of COVID-19 in the patients included in the present research, high WBC, lymphocyte, and ferritin values in both groups are an expected result.
Conclusion:
Classical chest tomography findings can be useful as a preliminary parameter in the development of hyperimmune response. Although WBC and lymphocyte counts are high and ferritin value is low in patients with hyperimmune response, these three parameters are not independent predictors for its the development.
Limitations:
This research was designed as a retrospective study and conducted in a single center. The patients’ comorbidities were not included in the study. Patients admitted to the ward were not included in the study.
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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Emotional characteristics of mothers of children admitted with anorexia complaint
Veli Yildirim 1, Fatih Battal 2
1 Department of Child Psychiatry, Special Clinic, Mersin, 2 Department of Pediatrics, Medical School, Canakkale Onsekiz Mart University, Canakkale, Turkey
DOI: 10.4328/ACAM.20500 Received: 2021-01-23 Accepted: 2022-02-18 Published Online: 2022-03-26 Printed: 2022-04-01 Ann Clin Anal Med 2022;13(4):465-469
Corresponding Author: Veli Yildirim, Department of Child Psychiatry, Special Clinic, Yenişehir, Mersin, Turkey. E-mail: drveliyildirim@gmail.com P: +90 553 099 56 90 F: 324 241 00 92 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4001-6237
Aim: It is aimed to compare the emotional characteristics of the mother and the emotional characteristics of the mother mostly in the families of children with no appetite.
Material and Methods: Among the children who came to the outpatient clinic for routine checks, mothers of 56 first consecutive children between the ages of 3-8 who had been suffering from anorexia for the last three months were included in the study. The first 39 consecutive healthy children were taken as the control group. A personal information form, Eating Attitude Test (EAT), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Brief Symptom Inventory (BSI), Young Schema Questionnaire (YSQ) and Family Assessment Device (FAD) that measures anxiety levels were given to all mothers who agreed to participate in the study.
Results: There was no difference between the control group and the mothers of children with anorexia in terms of EAT, STAI and BDI. According to the BSI scores of the mothers of children with anorexia, depression and anxiety symptom levels were found to be higher than in the control group (p<0.05). The scheme of abandonment from the subtests of YSQ was found to be different between the case and the control group (p=0.041). According to the subtests of FAD, it was determined that the mothers of children with anorexia had problems with family functions, problem solving, communication and roles.
Discussion: We suggest that all family members should be involved, especially in communication, roles and problem solving in the family. In the anorexia problem, especially the approach in which the child and father will be evaluated is especially useful.
Keywords: Anorexia, Eating Attitude, Depression Inventory, Symptom Inventory, Schema Questionnaire, Family Evaluation
Introduction
Children who do not have an organic problem, who applied to the outpatient clinic with anorexia and eating rejection, were defined as infancy anorexia in DSM-IV, and were evaluated in detail in the pediatric psychiatry outpatient clinics in DSM-V in terms of avoidant/ restrictive nutrient intake disorder [1]. It is reported that 30% of applicants with anorexia complaints have organic problems. However, it should not be overlooked that factors related to psychological and social anorexia may also occur in children with organic problems. Indeed, if anorexia occurs in relation to another condition or disorder, if this condition or disorder is more severe than it may cause, and the impact of these factors should be evaluated by the child psychiatrist [2-6].
Whether an organic diagnosis is evaluated or not, mothers often play the leading role in the diet. There are many studies on infants’ anorexia, eating rejection, or eating/nutritional disorders that reveal problems in mother-child interaction. In the studies examining mother-child interaction during feeding, separation anxiety, depression, somatic symptoms and attachment crises were found in children with anorexia, and anxiety, depression and inappropriate nutritional attitudes were found higher in mothers [7-9].
Anorexia is a very common problem in pediatrics outpatient clinics. It has been reported that anorexia and nutritional problems are seen at high rates such as 25% in normally developing children, 80% in children with developmental retardation and 90% in children with autism [9]. The huge difference between the rates of application to the pediatrics outpatient clinic due to anorexia is that psychosocial factors are less thought by families and pediatricians. For this reason, hypothesis has been established that it can be very useful to refer children to psychiatry to think about psychological factors with questionnaires after organic examinations.
In this study, it was aimed to evaluate the emotional characteristics of the mothers of the children brought to the clinic with the complaint of anorexia.
Material and Methods
This study was followed up at the Canakkale Onsekiz Mart University Medical Faculty Hospital, the healthy Child outpatient clinic, and was applied to 3-8 years old children and their mothers who applied to the outpatient clinic for control purposes. Among the children who came to the outpatient clinic for routine controls, mothers of the first 56 children who agreed to participate in the study, who had been suffering from anorexia for the past three months, were taken as the study group. The first 39 healthy children who applied to the robust child outpatient clinic who came to the routine development follow-up and did not have anorexia complaints were taken as the control group. Children with chronic disease and/or children with any current disease were excluded from the study. Approval was obtained from Canakkale Onsekiz Mart University Clinical Research Ethics Committee Presidency with the decision numbered 2015-20 on 09.12.2015 for our research no. 2011-KAEK-27/2015-153.
Criteria for inclusion in the research were as follow:
1- Being in the normal percentile in the growth curve of the child during the physical examination
2. The child does not have any chronic disease
3. Having healthy children between the ages of 3-8
4. Agree to participate in the study
Criteria for exclusion from the research:
1. Having neurodevelopmental psychiatric diseases such as hyperactivity and autism
2. No motor mental retardation or anatomical defect affecting nutrition
3. No catabolic diseases such as tuberculosis, immunodeficiency
4. Infection causing chronic gastrointestinal symptoms such as nausea, vomiting, dysphagia, gastroesophageal reflux disease, esophagitis, gastritis, duodenitis, peptic ulcers, gastroenteropathy, causes of chronic diarrhea, malabsorption (Celiac, etc.), food reactions, chronic constipation, functional bowel diseases not having parasites.
5. People with known nutritional deficiency, severe malnutrition, iron deficiency anemia
6. Anorexigenic drug use
7. Causes that disrupt metabolism. Metabolic diseases: Hereditary fructose intolerance, urea cycle defects, organic acidemias… etc.
8. Those with long-term enteral or parenteral anamnesis
9. Supportive radiological and laboratory findings suggestive of organic causes.
All mothers who agreed to participate in the study were given a Personal information form, Family Assessment Device (FAD), Eating Attitude Test (EAT), State- Trait Anxiety Inventory(STAI), Beck Depression Inventory (BDI), Young Schema Questionnaire (YSQ) and Brief Symptom Inventory (BSI).
Personal information form:
With the “Personal Information Form” prepared by the researchers, questions were asked including socio-demographic characteristics such as gender, age, education level of the mother, social security, place of residence, information about work, age, education level, diseases, divorce separation, and previous history of psychosocial symptoms.
Family Assessment Device (FAD):
McMaster Family Assessment Device (FAD). The FAD is a 60-item self-report questionnaire used by clinicians and researchers to evaluate family functioning. FAD was completed by all household members aged 12 years and older [10]. TThere are studies in which attitude of the family was assessed by administering FAD only to mother [11]. The FAD was designed to assess whole family functioning according to multiple family members’ perceptions. Validity and reliability in Turkish have been fulfilled [12]. The scale involved seven subscales: general function, problem solving, communication, roles, affective responsiveness, affective involvement, and behavioral control [10].
Eating Attitudes Test (EAT):
The EAT contains 40 items, including items related to symptoms and behaviors common to patients with eating disorders, and provides an index of the severity of the disorder. Validity and reliability in Turkish have been fulfilled [13].
State-Trait Anxiety Inventory (STAI):
State-Trait Anxiety Inventory is a self-report questionnaire consisting of 2 sub-scales (state anxiety and trait anxiety), each including 20 items evaluating the level of anxiety. The State anxiety (STAI-S) describes the person’s feelings at a specific moment and under particular conditions, whereas trait anxiety scale (STAI-T) is used to describe how subjects generally feel. Responses to each item in the anxiety questionnaire are assigned a score from 1 to 4. Possible scores vary from 20 to 80, with higher scores indicating more anxiety [14].
Beck Depression Inventory (BDI):
Beck Depression Inventory has been used in numerous studies of depression and was completed on all major assessment points [15]. Validity and reliability in Turkish have been fulfilled [16].
Young Schema questionnaire-Short Form-3 (YSQ-SF3):
YSQ-SF3 was developed and determined early maladaptive schemas by Young et al. [17]. The scale contains 90 items. There are 5 schema domains and 18 different maladaptive schemas. Each item is rated on a 7-point scale ranging from 1 (entirely untrue for me) to 7 (describes me perfectly). Higher scores represent more maladaptive schemas. Validity and reliability in Turkish have been fulfilled [18].
Brief Symptom Inventory (BSI):
The Symptom Checklist-90-Revised is a 90-item self-report symptom inventory, and is a measure of current psychological symptom status and is scored on nine subscales. Validity and reliability in Turkish have been fulfilled [19].
Statistical analysis
SPSS 13 computer program was used for statistical analysis in the study. Variables that receive continuous values in the study will have a mean, standard deviation, maximum and minimum values. In variables that show normal distribution from continuous variables, comparisons between the two groups were used, independent of parametric tests. The Mann-Whitney U test was used for comparison of variables that do not show a normal distribution between the two groups. The significance level of 95% (p <0.05) will be accepted in the study.
Results
The average age of 56 children in the case group was 3.7 ± 1.3 years, and 3.9 ± 1.2 years of 39 children in the control group. There were 49 girls (87.5%) and 7 boys (12.5%) children in the case group with anorexia. There were 36 (92.3%) girls and 3 (7.7%) girls in the control group without anorexia. There was no significant difference in terms of gender and age in the two groups (p>0.05).
The average age of the mothers was 33.1 ± 4.8 years in the case group and 31.5 ± 4.6 in the control group. The mean age of the mothers in the case group during the birth of the child was 29.3 ± 4.8, and the control group was 27.1 ± 3.6. There was no significant difference between the two groups in terms of the average age of the mothers for participation in the study and at birth (p>0.05). The average age of the fathers was 36.5 ± 6.0 in the case group and 34.5 ± 5.0 in the control group. There was no significant difference between the two groups in terms of the average age of the fathers’ participation in the study (p>0.05).
While 22 (39.3%) in the case group and 16 (41.0%) in the control group had secondary or lower education; 34 (60.7%) mothers in the case group and 23 (59.0%) mothers in the control group received education in high school and above. The difference between the education levels of the mothers in the case and control groups was not significant (p>0.05).
There was no significant difference between the two groups in terms of whether mothers worked or not, and a history of mental and physical illness in mothers. There was no significant difference between the two groups in terms of whether fathers worked or not, and a history of mental and physical illness in fathers. There was no significant difference between the groups in terms of mental illness history in mothers. There was no significant difference between the groups in terms of the physical disease history of the mothers.
The results of Eating Attitude Scale, Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI-1-2) and Family Assessment Device (FAD) applied to mothers are shown in Table 1. The mean of BDI Depression scores of mothers of children with anorexia and mothers of children without anorexia was not significant (p = 0.67). There was no difference between the mothers of anorexia children and the mothers of anorexia mothers’ eating attitude scale (p = 0.42), anxiety (p = 0.54) and anxiety (p = 0.63) anxiety scale scores. When the FES subscale scores were examined, there was no difference between the two groups in terms of showing the required attention (p = 0.25), emotional reaction (p = 0.07) and behavioral control (p = 0.41), while problem solving (p = 0.001), communication (p = 0.01), roles (p = 0.02) and general functions (p = 0.02) were found to be significantly different (Table 1).
A comparison of the Brief Symptom Inventory (BSI) subscale scores with and without anorexia is shown in Table 2. In the subscales of the short symptom inventory, anxiety, depression, additional items, total score and severity index were significantly higher in the case group (p<0.05).
The comparison of mean Young Schema subscale scores with and without anorexia is shown in Table 3. In the scheme scale, the abandonment score was higher in those without anorexia (p = 0.041).
Discussion
The anorexia complaint most often peaks between 6 and 36 months, the period of meeting new foods. Nutrition is a process influenced by many environmental, biological, social and psychological factors. Environmental factors include the uncertainty of mutually transmitted messages during feeding and/or play, excessive controlling or insensitive attitude of the caregiver, the primary caregiver not being open to cooperation, and the interaction between the caregiver and the baby [20].
Among these risk factors, parental anxiety and depression levels were evaluated in our study. In the subgroup tests of BSI used in our study, there was no significant difference in BDI and STAI scores, although the anxiety and depression scores were found to be high in the mothers of children with anorexia. Unlu et al. found that there was a significant difference in the mothers of children with FAD, BDI and STAI anorexia [8]. Ammaniti et al. stated that anxiety and depressive symptoms were significantly higher in the parents of children with anorexia of 6-36 months [21]. This may be related to the average age of children in our study group.
Unlu et al. reported that BDI scores were not different between those with and without malnutrition in the study group [8]. In addition, in terms of anxiety, Spielberg described the STAI scale as a relatively high anxiety in adults and above 40 points [22]. Both our control and anxiety group are above this value, suggesting that our control group is also anxious group.
Interaction and dynamics within the family are very important for anorexia in the child, not the direct parent or child [23]. Considering the FAD scores given for family evaluation in our study, there was a significant difference in FAD alt scale scores in terms of problem solving (p = 0.001), communication (p = 0.01), roles (p = 0.02) and general functions (p = 0.02). In our study, the fact that children with anorexia in the FAD general function subscale were significantly higher than that of the control group suggests that mothers perceive all family functions as unhealthy. We suggest that comparing the FAD score to siblings over the age of 12, if there is any other caregiver who lives with the father and the family and can provide additional information to the literature. In our study, it was applied only to the mother considering that the mother fed the child and the evaluation of the mother was more important. Unlu et al. found that FAD problem solving subscale score was significantly higher in the mothers of children with famous and anorexia than the control group [8]. Similarly, in our study, problem-solving scores were found to be significantly higher in this subscale. It may be thought that mothers of children with anorexia apply wrong methods to solve the eating problem of their mothers, or they cannot continue to use the right methods in sufficient time and to a sufficient degree.
In our study, the fact that the FAD communication subscale score was significantly higher in the families of children with anorexia compared to the control group indicates the relationship between communication problems in the family or mother-child relationship in anorexia. Problems in mutual communication suggest that the mother may misunderstand her child’s wishes or needs, and exaggerated, and overly rigid reactions may force the child to eat unwanted amounts rather than appropriate answers [24].
Limitations of our study: The choice of the control group as a hospital caused higher anxiety levels. The absence of the child, father, older siblings, or even grandparents in extended families may have caused mothers to enter a defensive setup, which would emphasize factors other than herself when she filled in the questionnaire.
Conclusion
In conclusion, depression and anxiety scores were higher in BSI in mothers of children with anorexia or refusal to eat. When we think that both groups are formed in an anxious mother group, it is concluded that the dynamics within the family such as roles, communication and problem solving are important in the family, and it is useful to carry out further studies on these issues according to the FAD scale filled by the mother. Family functions and mother-child interaction should be evaluated well in children with anorexia. In treatment approaches, considering the only problem as a mother, there will be incomplete and incorrect evaluation. In an assessment, in which the mother is taken to the center, it will be difficult to give healthy results. It is concluded in our study that the roles of everyone in the family should be evaluated.It can be argued that efforts to solve the problems, in which the mother has difficulties but cannot find support, the mother and child cannot establish emotional communication during conflicts, the efforts are regarded inadequate, or cannot be solved or comprehended, are important.
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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Download attachments: 10.4328:ACAM.20500
Veli Yildirim, Fatih Battal. Emotional characteristics of mothers of children admitted with anorexia complaint. Ann Clin Anal Med 2022;13(4):465-469
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