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Background: Breast cancer has been a disease in which treatment strategy has changed over time under the influence of different hypotheses and evidence for more than a century. We analyzed the contribution of radiotherapy to disease-free survival and overall survival by classifying according to stage, 1-3 lymph node involvement, and molecular subgroups., Methods: Following the approval of the Institutional Review Board, records of patients with breast cancer who were admitted to University School of Medicine Departments of Radiation Oncology and Medical Oncology between July 1999 and December 2020 were reviewed. Using data propensity score matching was performed between the groups that did and did not receive radiotherapy using an optimal matching algorithm (optimum, 1:1). Disease-free survival and overall survival after propensity score matching were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was used to estimate hazard ratios., Results: In the radiotherapy and non-radiotherapy groups, disease-free survival was 257.42 ± 5.46 (246.72- 268.13), 208,96 ± 8,15 (192,97-224,94) months respectively, (p = < 0.001), overall survival was 272,46 ± 8,68 (255,43-289,49), 219,05 ± 7,32 (204,70-233,41) months respectively (p = .002). We compared the 19 N1 patient groups who received radiotherapy with the 19 patients who did not receive radiotherapy and calculated the disease-free survival times was 202,21 ± 10,50 (181,62-222,79) and 148,82 ± 24,91 (99,99-197,65) months respectively (p = .011) and overall survival times was 200,85 ± 12,79 (175,77-225,92) and 166,90 ± 20,39 (126,93-206,82) months respectively (p = .055). We examined disease-free survival and overall survival times in both groups according to Luminal A, Luminal B, TNBC, and HER2-enriched subgroups. In the Luminal B subgroup, the disease-free survival duration in the groups receiving radiotherapy and not receiving radiotherapy was 264.83 ± 4.95 (255.13-274.54) and 187.09 ± 11.06 (165.41-208.78) months (p < .001), and overall survival times were 252.29 ± 10.54 (231.62-272.97) and 197.74 ± 9.72 (178.69-216.80) months (p = .001) respectively., Conclusions: Thanks to studies proving that RT increases long-term survival rates in breast cancer as a result of reducing locoregional recurrence and systemic metastasis rates, it has been understood that the spectrum hypothesis is the hypothesis that most accurately describes breast cancer to date. We found that patients with Luminal B invasive breast cancer benefited significantly more from RT compared to other subgroups., (© 2024. The Author(s).)

Significant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS "nuclear" and AUS "other" is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely "high-risk group" than the group including other subcategories, namely "low-risk group" (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories., (© 2024. The Author(s).)

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.

Purpose: The literature contains different information about the prognosis of invasive lobular carcinoma of breast cancer (BC). We aimed to address the inconsistency by comparatively examining the clinical features and prognosis of invasive lobular carcinoma patients in our university and to report our experience by dividing our patients into various subgroups., Patients and Methods: Records of patients with BC admitted to Trakya University School of Medicine Department of Oncology between July 1999 and December 2021 were reviewed. The patients were divided into three groups (No-Special Type BC, Invasive Lobular Special Type BC, No-Lobular Special Type BC). Patient characteristics, treatment methods and oncological results are presented. Survival curves were generated using the Kaplan-Meier method. Statistical significance of survival among the selected variables was compared by using the log-rank test., Results: The patients in our study consisted of 2142 female and 15 male BC patients. There were 1814 patients with No-Special Type BC, 193 patients with Invasive Lobular Special Type BC, and 150 patients with No-Lobular Special Type BC. The duration of disease-free survival (DFS) was 226.5 months for the No-Special Type BC group, 216.7 months for the No-Lobular Special Type BC group, and 197.2 months for the Invasive Lobular Special Type BC group, whereas the duration of overall survival (OS) was 233.2 months for the No-Special Type BC group, 227.9 for the No-Lobular Special Type BC group, and 209.8 for the Invasive Lobular Special Type BC group. The duration of both DFS and OS was the lowest in the Invasive Lobular Special Type BC group. Multivariate factors that were significant risk factors for OS were Invasive Lobular Special Type BC histopathology (p = .045), T stage, N stage, stage, skin infiltration, positive surgical margins, high histological grade, and mitotic index. Modified radical mastectomy, chemotherapy, radiotherapy and use of tamoxifen and aromatase inhibitors for more than 5 years were significant protective factors for overall survival., Conclusion: The histopathological subgroup with the worst prognosis in our study was Invasive Lobular Special Type BC. Duration of DFS and OS were significantly shorter in Invasive Lobular Special Type BC than No-Lobular Special Type BC group. The classification of Invasive Lobular BC under the title of Special Type BC should be reconsidered and a more accurate treatment and follow-up process may be required., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cosar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Due to their semiological similarities, psychogenic nonepileptic seizures (PNESs) can occasionally hardly be differentiated from epileptic seizures (ESs), and long-term video-electroencephalographic monitoring (VEM) is needed for the differential diagnosis., Objective: To investigate the time of the first clinical event and its distribution on the days of VEM in ES and PNES patients., Methods: In total, a consecutive series of 48 PNES and 51 ES patients matched for gender and age were retrospectively and consecutively evaluated. The time distribution of the seizures during the day was noted. Seizure latency was determined as the time in hours from the start of the video-electroencephalographic recording to the first clinical event., Results: The seizure latency was significantly shorter in PNES patients compared to ES patients ( p  < 0.001). Seventy-two percent of PNES patients and 49.1% of ES patients had their first seizure in the 24 hours of video-EEG recording ( p  = 0.023). Recording longer than 48 hours was required for 12.5% of PNES patients and 37.3% of ES patients ( p  = 0.006). While ESs were almost evenly distributed throughout the day, most PNESs occurred during the evening hours ( p  = 0.011)., Conclusion: We observed that the PNESs appeared earlier than the ESs in the VEM and were concentrated during daylight hours. Although not strictly reliable, seizure latency can contribute to the differential diagnosis of ES and PNES., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Maternal stress, depression and anxiety are associated with atopic dermatitis (AD) in offspring. However, the relationship between maternal obsessive compulsive symptoms (OCS) and AD in their children is unclear., Aim: To investigate whether maternal OCS are associated with AD in offspring., Material and Methods: A total of 75 children with AD diagnosed by the paediatric allergist and 76 healthy children and their mothers were included in the study. A Turkish version of the Maudsley Obsessive Compulsive Inventory (MOCI-T) was used to assess OCS of mothers in both groups., Results: Total MOCI-T score and slowness, doubt, and rumination subscale scores were higher in the AD group than in the healthy group ( p = 0.007, p = 0.001, p = 0.012 and p = 0.011, respectively) but washing/cleaning and checking subscale scores did not reach a statistically significant difference ( p = 0.203 and p = 0.053, respectively). There was no correlation between SCORing Atopic Dermatitis (SCORAD) and MOCI-T/subscales scores., Conclusions: Our study provides evidence for associations between maternal OCS and infantile AD. The findings support recommendations for psychosocial support of mothers of children with AD., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

In our study, we aimed to investigate the relationship between microRNA (miRNA) expression levels and serum iron (Fe), copper (Cu), and zinc (Zn) levels in Multiple sclerosis (MS) patients. Total RNA was isolated from peripheral venous blood containing ethylenediaminetetraacetic acid (EDTA) of MS patients and controls. Total RNA was labeled with Cy3-CTP fluorescent dye. Hybridization of samples was performed on microarray slides and arrays were scanned. Data argument and bioinformatics analysis were performed. Atomic absorption spectrophotometer method was used to measure serum Fe, Cu, and Zn levels. In our study, in bioinformatics analysis, although differently expressed miRNAs were not detected between 16 MS patients and 16 controls, hsa-miR-744-5p upregulation was detected between 4 MS patients and 4 controls. This may be stem from the patient group consisting of MS patients who have never had an attack for 1 year. Serum iron levels were detected significantly higher in the 16 MS patients compared to the 16 controls. This may be stem from the increase in iron accumulation based on inflammation in MS disease. According to the findings in our study, hsa-miR-744-5p upregulation has been determined as an early diagnostic biomarker for the development together of insulin resistance, diabetes mellitus associated with insulin signaling, and Alzheimer's diseases. Therefore, hsa-miR-744-5p is recommended as an important biomarker for the development together of diabetes mellitus, Alzheimer's disease, and MS disease. In addition, increased serum Fe levels may be suggested as an important biomarker for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and MS disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To compare the incidence of postoperative neuropsychological dysfunction in patients managed with cerebral saturation monitoring versus traditional approaches., Material and Methods: A hundred patients undergoing elective intracranial surgery were divided into two groups to receive intraoperative management via cerebral saturation monitoring (Group O) or the conventional approach (Group C). The postoperative neuropsychological function was evaluated by the antisaccadic eye movement test (ASEM) and the Mini-Mental State Examination (MMSE). These tests were performed preoperatively and postoperatively on the first, second, and fifth days. The time for the modified Aldrete score to reach 9 (MAS 9), adverse effects, and pain using a Visual Analog Scale (VAS) scores were recorded., Results: Patient characteristics and surgery data were not statistically different. The MAS 9 of group O was significantly lower than that of group C (p < 0.001). The MMSE at the postoperative 1, 2, and 5 days were significantly higher in Group O compared to Group C (p < 0.001). ASEM was similar between groups. Group O was subdivided according to the type of surgery applied with diagnosis, and there were no statistically significant between-group differences in terms of areas under the curve for the cerebral regional oxygen saturation. There was no between-group difference regarding the mean arterial pressure at any time perioperatively. The heart rate at 80, 90, 100, and 110 min intraoperatively was significantly higher in group C than in Group O., Conclusion: Intraoperative cerebral oxygenation monitoring can reduce patient mortality and morbidity by allowing early postoperative neurological evaluation to detect potential neurocognitive deficits.

Aims: Diabetic nephropathy is one of the major complications of Type 2 diabetes mellitus. In this study, we aimed to investigate the effects of angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C gene polymorphisms on the development of diabetic nephropathy in patients with type 2 diabetes mellitus., Methods: This study included 100 type‑2 diabetes mellitus patients with diabetic nephropathy patients (patient group) and 99 type‑2 diabetes mellitus patients without diabetic nephropathy (control group). Polymerase chain reaction and restriction fragment length polymorphism methods were used to identify polymorphisms in the angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C genes., Results: There was no significant difference in genotype frequencies of M235T gene polymorphism between patient and control groups (χ2 = 4.01, df = 2, p = 0.13). There was no significant difference in genotype frequencies of T174M gene polymorphism between patient and control groups (X2 = 0.36, df = 2, p = 0.83). There was no significant difference in genotype frequencies of A1166C gene polymorphism between patient and control groups (χ2 = 0.51, df = 2, p = 0.77)., Conclusions: The results showed no significant difference in angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C gene polymorphisms between the patient and control groups. Future studies are needed to validate the results of this study and to explore underlying mechanisms (Tab. 3, Fig. 3, Ref. 35). Text in PDF www.elis.sk Keywords: type 2 diabetes mellitus, diabetic nephropathy, angiotensinogen gene polymorphism, angiotensin type 1 receptor, gene polymorphism.

Purpose: Many studies report the triple negative breast cancer (TNBC) as the worst subgroup, as such patients do not benefit from anti-hormonal therapy and human epidermal growth factor receptor 2 (HER2) antagonists. While HER2 overexpression was a poor prognostic factor in breast cancer before trastuzumab (Herceptin) was available, TNBC is often reported as the worst BC subgroup since targeted therapy is currently not possible. Since the patience-specific experiences and the current literature did not always align, we aimed to determine the BC subgroup with the shortest survival in our center., Methods: The records of patients with BC who were admitted to Trakya University Faculty of Medicine Department of Medical and Radiation Oncology between July 1999 and December 2019 were reviewed. Patients were divided into four main groups (Luminal A, Luminal B, TNBC, and HER2-enriched) according to the St Gallen International Consensus Panel and four subgroups in accordance with estrogen receptor, progestin receptor and HER2 positivity. Patient characteristics, treatment characteristics and clinical outcomes of the four main subgroups were evaluated. Survival curves were generated using the Kaplan-Meier method, and the significance of survival differences among the selected variables was compared by using the Log rank test. Factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression analysis., Results: Statistical analysis was performed on 2017 patients, after excluding patients with phyllodes tumor, carcinoma-in-situ and missing information from a total of 2474 patients with BC. There were 952 (47.1%) patients in the Luminal A group, 236 (34.1%) in the Luminal B group, 236 (11.7%) in the TNBC group and 142 (7.1%) patients in the HER2 enriched group. HER2-enriched patients had the shortest survival (p < 0.001), with 113.70 ± 7.17 months of DFS and 125.45 ± 3.03 months of OS. For patients who received Herceptin, DFS was 101.50 ± 6.4 months and OS was 118.14 ± 6.16. Patients who did not receive Herceptin had 92.79 ± 18 months of DFS and 94.44 ± 15.23 months of OS., Conclusion: The HER2-enriched subgroup had the worst prognosis despite receiving targeted therapy. While the duration of DFS and OS had no significant difference between TNBC and Luminal A-B subgroups, HER2 enriched subgroup had significantly shorter survival when compared to any other subgroup. HER2-enriched subgroup had a 10-fold greater risk of death compared to the Luminal A subgroup., Competing Interests: The authors declare that they have no conflicts of interest., (© 2022 Cosar et al.)

Background/aim: Exercise enhances endothelium-dependent vasodilation; however, it is unclear whether intermittent exercise has a different effect on vascular endothelial function compared to continuous exercise. This study aimed to compare vascular endothelial function following intermittent exercise including short rest intervals with continuous exercise, both at the anaerobic threshold level., Materials and Methods: Peak oxygen consumption (VO 2 peak) and anaerobic threshold were measured in physically active healthy young men (n = 12) by breath-by-breath analysis. After completion of intermittent exercise consisting of eight 1-min long intervals at the anaerobic threshold intensity with 75-s rest periods, total work was calculated. Equivalent work was done during continuous exercise. Immediately after the two exercise periods, venous blood lactate, endothelial nitric oxide synthase (eNOS), endothelin-1, N-terminal proANP (NTproANP), N-terminal proBNP (NTproBNP), and N-terminal proCNP (NTproCNP) levels were measured. Brachial artery flow-mediated dilatation (FMD) was measured before exercise and 30 min after exercise., Results: Mean VO 2 peak level was 33.42 ± 5.9 ml/min/kg and anaerobic threshold level was 47.33 ± 5.85%. Lactate levels following continuous exercise were higher than levels following intermittent exercise (27.76 ± 7.43 mg/dl, 18.54 ± 4.87 mg/dl respectively; p˂0.05). Endothelin-1, eNOS, NTproANP, NTproBNP, and NTproCNP levels were similar after both modalities of exercise (p > 0.05). No significant difference was found in FMD response when comparing intermittent and continuous exercise (7.05 ± 15.11%, 2.49 ± 16.24% respectively; p > 0.05)., Conclusion: Since blood lactate levels are higher following continuous exercise, individuals who find difficulty exercising may prefer an intermittent form of exercise. However, both intermittent and continuous exercise at the anaerobic threshold level seem to not produce a significant acute change in endothelial function in healthy men., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Selma Arzu Vardar reports financial support and equipment, drugs, or supplies were provided by 10.13039/501100007104Trakya University., (© 2022 The Authors. Published by Elsevier B.V.)

PURPOSE This article will examine the usefulness of diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI) on the assessment of axillary lymph nodes (ALN) of breast cancer patients. METHODS Axillary lymph nodes in 66 breast cancer patients were examined by DTI and DWI, and the largest lymph node with increased cortical thickness in axilla was selected. Morphological features, apparent diffusion coefficient (ADC), volume anisotropy, and fractional anisotropy values were measured by using a special software. Imaging findings and histopathological results were recorded. RESULTS Metastatic ALN were detected in 43 (65.1%) patients. Cortical thickness of the metastatic ALN was significantly higher than the non-metastatic ALNs (P < .001), and the long-axis-to-shortaxis ratio was significantly lower in metastatic ALNs (P < .001). There was a statistically significant difference between the ALN status and fatty hilum presence (P < .001). Apparent diffusion coefficient values of metastatic ALNs were statistically lower than those of non-metastatic ALNs (P < .001) using a cutoff value of 1.26 × 10-3 mm2 /s for b=500 ADC and 1.21 × 10-3 mm2 /s for b=800 ADC which had 97.7% sensitivity and 91.3% specificity. Fractional anisotropy and volume anisotropy values were significantly different between both groups. A cutoff value of 0.47 for b-500 fractional anisotropy had 83.7% sensitivity, 69.6% specificity 69.6% positive predictive value, and 83.7% negative predictive value. A cutoff value of 0.33 for b=500 volume anisotropy had 76.7% sensitivity, 78.3% specificity, 86.8% positive predictive value, and 64.3% negative predictive value. CONCLUSION Apparent diffusion coefficient value of metastatic ALNs was found to be significantly lower than those of non-metastatic ALN, and DTI metrics of metastatic ALN were found to be significantly higher than those of non-metastatic ALN. Overall, ADC had a better diagnostic performance than morphological features, fractional anisotropy, and volume anisotropy. Diffusion tensor imagingderived diffusion metrics may be used to complement breast magnetic resonance imaging in the future after further standardization of the imaging parameters.

Background: The goal of this study is to determine the role of MTHFR (C677T, A1298C) and MGP (G-7A, T-138C) gene variations in DN development., Methods: There were 61 DN patients and 55 healthy controls in this study. The genotype distributions of these gene variations were determined using PCR and RFLP methods., Results: According to our study, there was no significant relationship between these gene variations and DN ( p  > 0.05). The allele frequencies of the MTHFR C677T gene variation in the control group were found significantly different from the Hardy-Weinberg distribution ( p  < 0.05). According to combined genotype analysis, GA-TT combined genotype of MGP (G-7A/T-138C) gene variations was observed significantly more in the patient group with DN. The GA-TT combined genotype of MGP (G-7A/T-138C) gene variations was differ significantly between these groups (OR: 2.359, %95 CI: 1.094-5.087, p  = 0.028)., Conclusion: In our study, although MTHFR and MGP gene variations were not risk factors, the GA-TT combined genotype of the MGP (G-7A/T-138C) gene variation was detected as an important risk factor for DN., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2022.)

Several studies have reported differences in radiation toxicity between the sexes, but these differences have not been tested with respect to histopathology and genes. This animal study aimed to show an association between histopathological findings of radiation-induced lung toxicity and the genes ATM, SOD2, TGF-β1, XRCC1, XRCC3 and HHR2. In all, 120 animals were randomly divided into 2 control groups (male and female) and experimental groups comprising fifteen rats stratified by sex, radiotherapy (0 Gy vs. 10 Gy), and time to sacrifice (6, 12, and 24 weeks postirradiation). Histopathological evaluations for lung injury, namely, intra-alveolar edema, alveolar neutrophils, intra-alveolar erythrocytes, activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis, and collapse were performed under a light microscope using a grid system; the evaluations were semi quantitatively scored. Then, the alveolar wall thickness was measured. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to determine gene expression differences in ATM, TGF-β1, XRCC1, XRCC3, SOD2 and HHR2L among the groups. Histopathological data showed that radiation-induced acute, subacute, and chronic lung toxicity were worse in male rats. The expression levels of the evaluated genes were significantly higher in females than males in the control group, but this difference was lost over time after radiotherapy. Less toxicity in females may be attributable to the fact that the expression of the evaluated genes was higher in normal lung tissue in females than in males and the changes in gene expression patterns in the postradiotherapy period played a protective role in females. Additional data related to pulmonary function, lung weights, imaging, or outcomes are needed to support this data that is based on histopathology alone., (©2022 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background: The noise in an operating room may have a detrimental effect on human cognitive functions, and it may cause perioperative anxiety with prolonged exposure. The aim of this study was to investigate the effects of music therapy and use of earplugs and normal noise level in the operating room under general anesthesia of pediatric patients on hemodynamic parameters and postoperative emergence delirium., Methods: One hundred and five pediatric patients were involved in this study. The patients were randomly divided into three groups. Group N was exposed to the ambient operating room noise, group S received earplugs from an independent anesthesiologist, and group M used a CD player. The preoperative anxiety levels of children were evaluated with the Modified Yale Preoperative Anxiety Scale (M-YPAS). Mean arterial pressure (MAP) and heart rate were recorded at 30-minute periods until the completion of surgery, end of surgery and postoperatively. During each measurement, noise level recordings were performed using sonometer. Pediatric Anesthesia Emergency Delirium (PAED) score was evaluated after postoperative extubation., Results: M-YPAS was similar between groups. The MAP at 30 and 60 min intraoperatively, at end of surgery, and at 5, 10, and 15 min postoperatively was significantly lower in group S than in group N. There were no differences in heart rate among the groups. Postoperative PAED score was not significantly different among the groups., Conclusions: The music therapy was not more effective than silence and operating noise room in reducing PAED score postoperatively in pediatric patients., Trial Registration Number: ClinicalTrials.gov Registry (NCT03544502)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The morphology of the circle of Willis in adults has been thoroughly discussed in scientific literature. However, the morphology of the circle of Willis in pediatric patients is under-researched., Objectives: We aimed to establish reference data for the morphology and variations of the circle of Willis in a population consisting of all pediatric age subgroups and to evaluate the possible temporal evolution of the circle of Willis in pediatric patients along with the variations between pediatric and adult populations., Materials and Methods: Our patient cohort included 263 pediatric patients ages 1-215 months. A total of 273 magnetic resonance (MR) angiography images were retrospectively analyzed for all circle of Willis vessels to compare the incidence of complete cases and variation frequency based on gender and age group., Result: In our study of 273 MR angiograms from all age ranges in the pediatric population, we found a 56.1% circle of Willis completion rate. Overall completion rates were statistically significantly higher in the toddler and preschool age groups. The lowest completion rate was in the newborn-infant group (40%)., Conclusion: Circle of Willis completion rates and variations in pediatric populations are similar to those in adult populations; completion rates rise in toddler and preschooler age groups and decline as children grow into the school-age and adolescent period., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim of this study is to investigate of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patient with colorectal cancer. Mateials and Methods. Genotype distributions of GSTM1 gene variations were determined using real-time polymerase chain reaction method. Serum trace element levels were determined using atomic absorption spectrophotometer method and plasma MDA levels were measurement by spectrophotometric method., Results: Serum Cu levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GA heterozygous genotype of the GSTM1 (rs 112,778,559) gene variation compared to healthy controls (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in patients carrying GG homozygous genotype of the GSTM1 (rs 112778559) gene variation compared to healthy controls carrying same genotype (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GG homozygous genotype of the GSTM1 (rs 12068997) gene variation compared to healthy controls (p < 0.05). On the other hand, serum Se levels were detected significantly lower in CRC patients carrying GA heterozygous and GG homozygous genotypes for GSTM1 (rs 112,778,559) and (rs 12,068,997) gene variations compared to healthy controls (p < 0.05)., Conclusion: In our study, the evaluation of serum Cu, Zn and Se trace element levels and plasma MDA levels according to GSTM1 gene variations genotype distributions were enabled to obtain important biomarkers in terms of CRC development and progression., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Ischemic stroke is a clinical condition characterized by focal or global cerebral dysfunction resulting from inhibition of brain blood flow. Genetic factors play an important role in the pathogenesis of ischemic stroke. As a result of IL-18 (-607 C/A, -137 G/C) gene variations, it is thought that binding of transcription factors may be affected and IL-18 mRNA expression can be modulated. Therefore, the purpose of our study is to investigate the roles of IL-18 (-607 C/A), IL-18 (-137 G/C) gene variations in the development of ischemic stroke in Trakya Region of Turkey., Methods: Our study was performed with 90 ischemic stroke patients and 89 healthy controls. Genotype distributions of IL-18 (-607 C/A, -137 G/C) gene variations were determined using polymerase chain reaction (PCR) method., Results: GC genotype and CA genotype of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations were determined higher significantly in patent group as compared with other genotypes. However, the statistically significant difference was not determined between patients with ischemic stroke and healthy control groups in terms of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations ( p > 0,05). Allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) in patient and control groups were significantly different from the Hardy-Weinberg distribution ( p < .001 for all)., Conclusion: Although these gene variations' genotype distributions were not determined as a genetic risk factor for the development of ischemic stroke, allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) in patient and control groups were significantly different from the Hardy-Weinberg distribution.

Objective: To assess antibody response to inactivated COVID-19 vaccine in patients with immune-mediated diseases (IMD) among hospital workers and people aged 65 and older., Methods: In this cross-sectional study, we studied 82 hospital workers with IMD (mean age: 42.2 ± 10.0 years) and 300 (mean age: 41.7 ± 9.9 years) controls. Among + 65 aged population, we studied 22 (mean age: 71.4 ± 4.5 years) patients and 47 controls (mean age: 70.9 ± 4.8 years). All study subjects had a negative history for COVID-19. Sera were obtained after at least 21 days following the second vaccination. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method., Results: Patients with IMD were significantly less likely to have detectable antibodies than healthy controls both among the hospital workers (92.7% vs 99.7%, p < 0.001) and elderly population (77.3% vs 97.9%, p = 0.011). Among patients with IMD, those using immunosuppressive or immune-modulating drugs (64/75, 85.3%) were significantly less likely to have detectable antibodies compared to those off treatment (29/29, 100%) (p = 0.029). Additionally, a negative association between age and the antibody titer categories among patients (r = - 0.352; p < 0.001) and controls (r = - 0.258; p < 0.001) were demonstrated., Conclusions: Among hospital workers, the vast majority of patients with IMD and immunocompetent controls developed a significant humoral response following the administration of the second dose of inactivated COVID-19 vaccine. This was also true for the elderly population, albeit with lower antibody titers. Immunosuppressive use, particularly rituximab significantly reduced antibody titers. Antibody titers were significantly lower among those aged ≥ 60 years both in patient and control populations. Whether these individuals should get a booster dose warrants further studies.

Objectives: Vaccination against COVID-19 emerges as an effective strategy for combating the pandemic. While many of our patients with rheumatic diseases (RD) wonder whether it is safe to get the vaccine, vaccine hesitancy is rising among the general population. We assessed the willingness to get vaccination and its probable predictors among patients with RD compared to healthcare workers and a sample from the general population., Methods: We conducted a web-based questionnaire survey in a cross-sectional design in 3 groups of participants just before the mass vaccination program in Istanbul, Turkey. The questionnaire sought socio-demographic variables, COVID-19 related risk factors, willingness to get vaccination, and concerns and thoughts about vaccine. COVID-19 anxiety scale (CAS) was also evaluated., Results: We studied in total 732 patients with RD (Group 1), 763 individuals representing general population (Group 2) and 320 hospital workers (Group 3). Dysfunctional anxiety related to COVID-19 was found in 4.9%, 3.8% and 4.1%, in Group 1, 2 and 3, respectively. Of the patients with RD, 29.2% were willing to be vaccinated, 19.0% were unwilling and 51.8% were undecided. These were somewhat similar among the general population (yes: 34.6%, no: 23.3% and unsure: 42.1%), with significantly less undecided individuals (p < 0.001). On the other hand, hospital workers were significantly more willing (yes: 52.5%, no: 20.9% and unsure: 26.6%) (p < 0.001). Main concerns were probable side effects, unknown scientific results and having no trust. Being male, older age, working in a hospital, not having contracted COVID-19 and high scores on CAS were found to be independently associated with willingness., Conclusions: The low rate of vaccine acceptance among patients with RD, as well as general population sampling is worrying. Healthcare policies should aim to implement communication, promote confidence and increase demand for COVID-19 vaccine.

Background: The association between arginase I (ARG1) and arginase II (ARG2) genes and asthma has been reported in previous studies, but associations between polymorphisms in ARG genes and preschool wheezing (PSW) phenotypes are still unknown., Objective: To examine the association between genetic variation in ARG1 and ARG2 genes and PSW phenotypes., Methods: We enrolled 83 patients and 86 healthy controls. The patient group included two subgroups: episodic wheezing (EW) (n = 42, median age 41 months) and multiple-trigger wheezing (MW) (n = 41, median age 39 months). We genotyped six single nucleotide polymorphisms (SNPs) in ARG1 and six SNPs in ARG2. Eighteen haplotypes for ARG1 and 31 haplotypes for ARG2 were constituted, and the distributions of SNPs and haplotypes in patients and controls were analyzed., Results: The frequency of the homozygote cytosine-cytosine (CC) genotype of ARG1 rs2781667T>C SNP and the ARG1 haplotype 4 in the MW group was significantly higher than the EW group (p = .002; odd ratios [OR]: 5.25; confidence interval [CI]: 1.9-14.51 and p < .001; OR: 7.77; CI: 2.54-23.74, respectively). The frequency of the ARG1 haplotype 5 was significantly higher but the frequency of ARG1 haplotype 9 was significantly lower in the all patients than in the healty controls (p = .019; OR: 10.34; CI: 1.28-83.53 and p = .015; OR: 0.093; CI:0.01-0.74, respectively). The frequency of the ARG1 haplotype 2 was significantly higher in the EW group than in the MW group (p = .014; OR: 5.68; CI: 1.48-21.8)., Conclusion: Variations in ARG1 may potentially be related to phenotypes and risk of PSW., (© 2020 Wiley Periodicals LLC.)

We hypothesized that patients with rheumatic diseases (RD) would have increased psychological distress during the COVID-19 outbreak; therefore, assessed their psychological symptoms and changes in their routine. A web-based questionnaire survey was conducted in a cross-sectional design in three groups of participants: (1.) patients with RD, (2.) hospital workers, and (3.) high-school teachers/academic staff. Psychiatric status was evaluated using Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised scale. Overall response rate was 34.7%. We studied 771 patients with RD, 535 hospital workers, and 917 teachers/academic staff. Most of the patients with RD were unwilling to go to the hospital (86%), while 22% discontinued their medications. Biological DMARDS were the most frequent drugs whose doses were altered. Only 4% were willing to take hydroxychloroquine for protection. Moreover, the frequency of anxiety (20%), depression (43%), and post-traumatic stress (28%) among patients with RD were found to be comparable to that found among the teachers/academic staff (23%, 43% and 29%, respectively), whereas significantly less than that observed among the hospital workers (40%, 62%, and 46%, respectively) (p < 0.001). Female gender, use of social media, having a comorbid disease, or a psychiatric disorder were found to be independently associated with psychiatric symptoms in total study population. The majority of the patients were unwilling to attend outpatient visits and one-fifth skipped or stopped their immunosuppressive agents. Psychiatric symptoms in patient's and teacher's populations were of considerable clinical concern, despite being significantly lower than that observed among the hospital workers.

Purpose: 18F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) combined with computed tomography (CT) scan is accepted as a standard tool in the staging of oesophageal cancer (OC). Histological subtype of tumour is known to be a major determinant of prognosis and metabolic behaviour. In this study, we aimed to evaluate the effect of histological subtypes of OC on standard uptake value (SUV max ), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) obtained by PET/CT, and also to compare this effect with prognosis., Material and Methods: Images and clinical course data of 57 patients who were diagnosed with EC and treated in our hospital between 2009 and 2016 were evaluated in a retrospective manner. PET/CT images were re-analysed in terms of metabolic parameters, and observations were compared with histological subtypes., Results: No significant difference was observed between histological subtypes with SUV max , overall survival (OS), or progression-free survival (PFS). Thus, MTV was observed to be related with histological subtype; MTV values of adenocancer patients were significantly higher than those of squamous cell cancer patients., Conclusions: Metabolic tumour volume was related with histological subtype of OC, but clinical staging, TLG, and SUV max values were not related with histological subtype, which may suggest the use of MTV as a routine parameter for OC and inclusion of MTV observations in prognostic scoring., Competing Interests: The authors report no conflict of interest., (Copyright © Polish Medical Society of Radiology 2020.)

Background: Food allergy is associated with stress, anxiety, and impairment in quality of life in both children and families. This study aimed to assess the anxiety of mothers in the case of suspected food allergy in their children and the influence of Internet usage on their levels of anxiety and food elimination., Methods: Ninety-two patients aged 0-2 years presented at a pediatric allergy department following either a physicians' presumptive diagnosis or family's suspicion of food allergy (Group 1) and 99 healthy controls (Group 2) were evaluated. The clinical diagnosis of food allergy was confirmed or excluded by oral food challenge (OFC). The validated Turkish version of Spielberger State-Trait Anxiety Inventory (STAI) was applied to the mothers of both groups on admission and to Group 1 3 months after OFC., Results: The state and trait anxiety (STAI-S and STAI-T) scores were significantly higher in Group 1 than Group 2 (P < 0.001, z = 5.410, and P = 0.021, z = 2.304, respectively). Seventy-nine mothers (85.9%) had been eliminating foods on admission. Thirty-seven (40.2%) mothers had eliminated foods on their own. The performance of food allergy-related Web searches was significantly higher among mothers who eliminated foods by themselves than those who did not (P = 0.004, χ 2  = 8.391, df = 1). The second STAI-S score was significantly lower among mothers whose children's food allergy diagnosis was excluded than confirmed (effect size = 1.06 (95% CI: 0.56-1.57), P = 0.001, z = 3.442)., Conclusion: It is important to make a correct food allergy diagnosis with a detailed allergy work-up, including OFC, to avoid anxiety and not cause unnecessary food elimination., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: Lower extremity (LE) deep venous thrombosis (DVT) is the main feature of vascular involvement in Behçet disease (BD). We thought that vein wall thickness (VWT) could be a surrogate marker for venous inflammation and hence predict future vascular involvement. We assessed VWT in proximal LE veins in BD patients without DVT, BD patients with DVT, and healthy controls in a formal, masked protocol., Methods: We studied 50 (43 male and 7 female) BD patients with LE DVT (group 1), 50 (43 male and 7 female) BD patients without any vascular involvement (group 2), and 50 (43 male and 7 female) age- and sex-matched apparently healthy controls (group 3). Two radiologists blinded to the diagnosis of BD used ultrasound to measure VWT of common femoral vein, femoral vein, and great saphenous vein in both legs. Interobserver reliability was assessed using the intraclass correlation coefficient and Bland-Altman plots., Results: There was good agreement between the two observers. The mean VWT was significantly increased in both BD patients with LE DVT and those without apparent vascular involvement compared with the healthy controls, whereas those with LE DVT had the highest VWT., Conclusions: VWT of proximal deep and superficial LE veins is increased among the BD patients without any clinical and radiologic vascular involvement. This information, after prospective work, might be useful in management and elucidating disease mechanisms in vascular BD., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The p-value is commonly misused. We hypothesised that a close cooperation with a statistician would go along with a more proper use of p-values. We considered a close cooperation present, when a statistician was a coauthor, or a formal statistical help was acknowledged in a study report., Methods: Randomised controlled trials published in 2015-16 in 4 widely read rheumatology journals were searched for a close cooperation with a statistician, the inclusion of effect sizes, confidence intervals, exact rather than relative p-values and the omission of p-values in tables depicting trial entry data., Results: There were only 28/133 (21%) articles in which a formal statistical help was acknowledged (Group I). The rest (Group II) gave no acknowledgement of a close cooperation. Reporting of effect sizes (96% vs. 71%) and exact p-values (88% vs. 69%) were more in Group I (p=0.01, and p=0.08, respectively)., Conclusions: While a formal acknowledgement of a close cooperation was notably infrequent at 21%, this went along with improvement in some aspects of p-value reporting. If substantiated by further studies, we propose that a formally acknowledged statistical help should improve p-value reporting. Like all professionals, statisticians would like their name/office to be formally associated with their good work.

Background: Environmental and dietary factors during pregnancy may affect development of infantile atopic dermatitis (AD). This study analyzed whether maternal consumption of selected Turkish fermented foods (FF) and other factors during pregnancy affect the development of AD during the first 2 years of life., Methods: Eighty-four children with physician-diagnosed AD (aged between 2 and 24 months) and mothers, and 56 similarly aged, healthy children and mothers were studied. Physician-administered questionnaires retrospectively surveyed maternal consumption of FF during pregnancy. The intake frequency of 8 selected Turkish FF was classified as either (1) daily or (2) less than daily. Other possible demographic and environmental risk factors were also analyzed., Results: Daily maternal consumption of yogurt, fermented olive, and cheese in the control group was significantly higher than the AD group (P < 0.001, P = 0.017, and P = 0.011, respectively). Exposure to environmental tobacco smoking (ETS) was more common in the AD group than the control group (P = 0.025). In multivariate logistic regression analysis, maternal ETS exposure during pregnancy was associated with increased risk of infantile AD, and daily consumption of yogurt was associated with a reduced risk (odds ratio [OR]: 2.60, 95% confidence interval [CI]: 1.11-6.1, and OR: 0.22, CI: 0.09-0.54, respectively). The diversity of consumed FF during pregnancy was found to have a protective effect against infantile AD (OR: 0.27, CI: 0.14-0.53)., Conclusions: Daily maternal intake of yogurt and diversity of consumed Turkish FF during pregnancy may reduce the risk of AD. Maternal tobacco smoke exposure is associated with increased risk of infantile AD., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: The aim of this study was to investigate the frequency of renal calculi in patients with ankylosing spondylitis (AS) and to determine its relationship with disease assessment variables., Methods: The study was designed retrospectively, and it included a cohort of 320 patients with AS diagnosed using the Modified New York Criteria. A total of 119 patients who underwent renal ultrasonography (USG), in who the erythrocyte sedimentation rate, C-reactive protein, blood calcium, phosphorus, Vitamin D, parathormone, and urinary calcium excretion were measured, and who also had lateral cervical and lumbar radiography in the same time period were extracted from the cohort. All patients' demographic characteristics and the results of blood and urine tests were recorded. The Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Mobility Index (BASMI), and Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were evaluated in all patients., Results: Thirteen of the 119 patients had renal calculi confirmed by USG data. The frequency of nephrolithiasis detected by USG was 10.9% in patients with AS. The disease lasted significantly longer in patients with renal calculi ([nephrolithiasis (+): 18.39±8.72 years; nephrolithiasis (-): 12.02±8.43 years, p=0.01]). The BASMI total score was significantly higher in the group of patients with renal calculi. There was not any significant difference in terms of blood samples, HLA-B27, BASDAI, BASFI, and mSASSS between groups., Conclusion: The frequency of renal stones is increased in patients with AS compared to healthy population. Especially patients who had AS for a long time and higher BASMI values are more susceptible to renal calculi. It is important to point out that the results of this type of studies would be more reliable if the study is conducted on large patient groups and population-based prevalence., Competing Interests: Conflict of Interest: The authors declare no conflict of interest., (Copyright: © 2019 by Istanbul Northern Anatolian Association of Public Hospitals.)

Objective: To evaluate the possible effects of prenatal steroid administration on Doppler parameters of the umbilical artery, uterine artery, middle cerebral artery, and ductus venosus, the cerebroplacental ratio, and the amniotic fluid index in preterm fetuses., Methods: The present prospective observational study was performed at the Perinatology Department of Trakya University, Edirne, Turkey, between June 1, 2015, and September 1, 2016. It included patients with healthy singleton pregnancies who had received betamethasone at 24-34 weeks of pregnancy. Doppler parameters were measured before (0 hours) and 24, 48, and 72 hours after the administration of betamethasone (two intramuscular doses of 12 mg each, administered 24 hours apart)., Results: There were 68 patients included. Pairwise comparisons demonstrated that, at 72 hours after betamethasone administration, the umbilical artery resistance index (P=0.038), the middle cerebral artery systolic/diastolic velocity ratio (P=0.007), and the amniotic fluid index (P=0.017) were reduced, whereas the end-diastolic velocity of the middle cerebral artery was increased (P=0.012), compared with baseline values., Conclusion: Betamethasone had favorable effects on fetal cerebral circulation, with increased end-diastolic velocity in the middle cerebral artery; this could represent a positive effect on cerebral blood circulation and decreased flow resistance in the umbilical artery., (© 2018 International Federation of Gynecology and Obstetrics.)

Introduction: Among head and neck cancers, those of the oral cavity and oropharynx are the second most prevalent following the larynx. This study aimed to research immunohistochemical expression of survivin, HPV positivity and microvessel density in tumors and their relationships with prognosis., Material and Methods: Pathological materials and demographic properties of 46 patients were retrospectively evaluated. Survivin, HPV and CD34 (for microvessel density evaluation) antibodies were applied tumoral tissues. Survival times, clinical stage and differentiation were evaluated., Results: In univariate analysis, we observed that survivin, microvessel density and stage were significantly associated with survival time ( p < 0.05). In multivariate analysis, only survivin and microvessel density were associated with survival time ( p < 0.05). But we did not find significant correlation between neither tumor differentiation nor HPV positivity and survival ( p > 0.05)., Conclusions: Survivin levels and microvessel density were found to be effective prognostic factors and were related to survival in oral cavity and oropharyngeal cancers. Treatments targeting survivin expression and angiogenesis might be employed against these tumor groups.

Paraoxonase-1 (PON1) and PON3 (PON3) are anti-atherosclerotic enzymes, synthesized primarily in liver and bound to HDL in circulation. The aim of the present study was to investigate the effects of therapeutic doses of lipoic acid on PON1 and PON3 protein levels, mRNA expression and arylesterase activity in liver. We treated HepG2 cells with 10, 40 and 200 μM lipoic acid for 72 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. PON1 and PON3 protein levels were measured by Western blotting, their mRNA expression was measured by quantitative PCR and arylesterase activity was measured spectrophotometrically. 200 µM lipoic acid caused a significant increase on PON1 and PON3 protein levels and arylesterase activity as compared with control, 10 µM and 40 µM lipoic acid-treated cells. 200 µM lipoic acid also caused a significant decrease on PON1 mRNA expression whereas on a significant increase PON3 mRNA expression as compared with control, 10 µM and 40 µM lipoic acid-treated cells. Our study showed that although lipoic acid up-regulates PON3 but down-regulates PON1 mRNA expression, it increases both PON1 and PON3 protein levels and arylesterase activity in HepG2 cells. We can report that lipoic acid may be useful for preventing atherosclerosis at therapeutic doses.

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

Experimental and clinical data strongly suggests that nitric oxide (NO) plays a pivotal role in migraine. This is also supported by studies of migraine induced by substances that release NO. NO is synthesized from L-arginine by endothelial NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is the major endogenous competitive inhibitor of NOS. Symmetric dimethylarginine (SDMA) is an inactive stereoisomer of ADMA. It may reduce NO production by competing with arginine for cellular uptake. The aim of this study was to measure the levels of ADMA, SDMA and L-arginine in migraine patients during the interictal period. One hundred migraine patients and 100 healthy volunteers were recruited. The patients were in the interictal period and classified into two groups as having migraine with aura and migraine without aura. Their serum ADMA, SDMA and L-arginine levels were measured by high-performance liquid chromotography (HPLC) method. ADMA, SDMA and L-arginine levels were significantly higher in migraine patients compared to the control group. But there was no difference between the patients with and without aura. These results suggest that NOS inhibitors and L-arginine/NO pathway plays an important role in migraine pathopysiology.

Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis.

Objective: This meta-analysis investigates the effect of aromatherapy massage on pain in primary dysmenorrhea., Methods: Randomized controlled trials were searched by keywords in several databases (Pubmed, ISI Web of Sciences, and Google Scholar). Six randomized controlled trials that included 362 participants with primary dysmenorrhea, comparing abdominal aromatherapy massage (n = 184) with massage with placebo oils (n = 178), were analyzed in the meta-analysis. The change in the visual analogue scale (VAS) pain score from the first menstruation cycle to the second cycle at the first menstruation day was used as the primary outcome., Results: Aromatherapy massage with essential oils was superior to massage with placebo oils (standardized mean difference = -1.06 [95% CI: -1.55 to -0.55])., Conclusion: Abdominal aromatherapy massage with essential oils is an effective complementary method to relieve pain in primary dysmenorrhea., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Incidental papillary thyroid carcinomas (IPTCs) consist of a significant portion of increasing incidence in papillary thyroid carcinomas. This study investigated the clinicopathological features of IPTCs from different perspectives and by comparing nonincidental PTCs (NIPTCs) in patients who underwent total thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was present in 27.9% of 308 patients. IPTCs were significantly accompanied by lymphocytic thyroiditis (LT), particularly, multinodular hyperplasia (MNH). IPTCs were more common in older patients (51.3 years vs. 47.2 years) and in female patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour size, lymphatic vessel invasion (2.6% vs. 97.4%), extrathyroidal extension (4.3% vs. 95.7%), lymph node metastasis (3.6% vs. 96.4%), multifocality (21.2% vs. 78.8%), bilaterality (5.3% vs. 94.7%), and BRAFV600 mutation (6.7% vs. 93.3%). Older age, bilaterality, encapsulation, and radioactive iodine (RAI) were significantly more common in IPTCs > 5 mm than in those ≤ 5 mm. In conclusion, IPTCs are more commonly associated with LT and MNH. IPTCs may have a more favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may have benefits in the management of IPTCs.

Background: Differentiated thyroid carcinomas (DTC) account for most of the thyroid cancers. The emergence of DTC may be affected by various predisposing genetic alterations and environmental factors The aim of this study was to investigate the role of VEGF C936T and IL-8 A251T gene polymorphisms in the pathogenesis and metastasis of differentiated thyroid cancer., Methods: The study consisted of 101 patients DTC patients and 109 healthy controls. The parameters of the stage of cancer of the DTC patients at the time of diagnosis (TNM) were recorded. DNA was isolated from blood using a DNA isolation kit. VEGF C936T and IL-8 A251T gene polymorphisms were determined using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Distributions of gene polymorphisms were evaluated according to the Hardy-Weinberg principle., Results: The TT genotype from the VEGF C936T genotype distributions was higher in the control group than in the DTC group (p < 0.05). In contrast, the IL-8 A-251T genotype distributions were similar in both groups. No relationship was found between either cytokine gene polymorphism or the DTC stages. The frequency of IL-8 TT was higher in the DTC group with lymph gland metastasis (TT 92%) than in the group without lymph gland metastasis (TT 45.9%) (p < 0.05)., Conclusions: We consider that the VEGF 936 TT genotype may play a protective role in the development of DTC and that the IL-8 A-251 TT genotype may contribute to the DTC lymph node metastasis. Therefore, these genotypes may hold a key to the evaluation of thyroid nodules and the metastasis of DTC.

Epilepsy patients whose seizures cannot be controlled by treatment have a lower quality of life (QoL). The aim of the present study was to compare the potential factors affecting the QoL in patients who were seizure-free with medication or who had drug-resistant epilepsy. The study included 46 drug-resistant and 42 seizure-free epilepsy patients. The demographic and clinical features of the patients were investigated for their effects on patient QoL. The QoL was assessed by the QoL in Epilepsy Inventory-89 and depression was detected by the Beck Depression Inventory. The QoL was significantly lower in the drug-resistant patients than in the seizure-free epilepsy patients (p < 0.001). Depression, lower education level, and unemployment were associated with lower QoL scores (p < 0.001, p < 0.01, p < 0.001, respectively). After adjusting for lower education level and unemployment, depression remained as an independent factor affecting QoL (p < 0.05). In addition to their efforts to control and stop seizures, clinicians should remain aware of depression and treat it effectively to improve the QoL of drug-resistant epilepsy patients.

Tumor-associated macrophages (TAMs) are one of the most noticeable elements of the tumor microenvironment. The present study investigated the relationships between the density of CD163 immunolabeled M2-like TAMs with other histological properties of the tumor microenvironment and clinipathological features in 90 patients with papillary thyroid carcinomas (PTC). The percentage of TAMs was higher in tumors with significant lymphocytic tumor response (p = 0.020), in tumors with a significant degree of stromal tumor response (p = 0.014), those with infiltrative tumor borders (p = 0.029), in conventional variant papillary carcinoma (p = 0.032), and in patients with autoantibodies for thyroid peroxidase (p = 0.014). The tumors associated with lymphocytic thyroiditis had lower numbers of TAMs (p = 0.027). In conclusion, for the first time, the present study attempts to establish a full assessment of interactions of CD163 expressing M2-like TAMs with the triad of primary tumor- tumor microenvironment- tumor behavior and above all, with markers of autoimmunity. Thus, these alternatively polarized macrophages may act in tumor progression and dissemination according to their various products, which may be ordered by tumor cells or neighboring immune cells. The molecular studies may reveal their roles in various tumors and may improve the therapy strategies targeting TAMs in various malignant tumors, including PTCs.

Purpose: The aim of this prospective study was to determine the efficacy of intraarticular levobupivacaine with and without intravenous dexketoprofen trometamol for postarthroscopy analgesia., Methods: Sixty patients who underwent arthroscopic knee surgery were randomly assigned to three treatment groups. When the surgical procedure was completed, patients received the following treatments: group I (n = 20) patients received 20 mL intraarticular normal saline and 2 mL intravenous dexketoprofen trometamol (50 mg); group II (n = 20) patients received 20 mL intraarticular 0.5 % levobupivacaine (100 mg) and 2 mL intravenous normal saline; and group III (n = 20) patients received 20 mL intraarticular 0.5 % levobupivacaine (100 mg) and 2 mL intravenous dexketoprofen trometamol (50 mg). The visual analogue scale (VAS) was used, and the total analgesic consumption was assessed at 1, 2, 4, 6, 12, and 24 h post-operatively., Results: The VAS scores at 1, 2, 4, 6, 12, and 24 h post-operatively were significantly increased in group I and group II compared with group III (p < 0.05). The average VAS score during the first 24 h post-operatively was significantly lower in group III than in group I and group II (p < 0.001). Total meperidine consumption was significantly lower in group III than in groups I and II (p < 0.001)., Conclusion: Intraarticular levobupivacaine with adjuvant intravenous dexketoprofen trometamol administration provided better pain relief and less analgesic requirement after arthroscopic knee surgery during the first 24 h than that induced by dexketoprofen alone or levobupivacaine intraarticular alone., Level of Evidence: II.

Vascular involvement can be seen in up to 40% of patients with Behcet syndrome (BS), the lower-extremity vein thrombosis (LEVT) being the most common type. The aim of the current study was to compare venous Doppler findings and clinical features between BS patients with LEVT and control patients diagnosed as having LEVT due to other causes.All consecutive 78 patients (71 men, 7 women; mean age 38.6 ± 10.3 years) with LEVT due to BS and 50 control patients (29 men, 21 women; mean age 42.0 ± 12.5 years) who had LEVT due to other causes, or idiopathic, were studied with the help of a Doppler ultrasonography after a detailed clinical examination. Patterns of venous disease were identified by cluster analyses. Clinical features of chronic venous disease were assessed using 2 classification systems. Venous claudication was also assessed.Patients with BS were more likely to be men, had significantly earlier age of onset of thrombosis, and were treated mainly with immunosuppressives and less frequently with anticoagulants. Furthermore, they had significantly more bilateral involvement, less complete recanalization, and more frequent collateral formation. While control patients had a disorganized pattern of venous involvement, BS patients had a contiguous and symmetric pattern, involving all deep and superficial veins of the lower extremities, with less affinity for crural veins. Clinical assessment, as measured by the 2 classification systems, also indicated a more severe disease among the BS patients. In line, 51% of the BS patients suffered from severe post-thrombotic syndrome (PTS) and 32% from venous claudication, whereas these were present in 8% and 12%, respectively, among the controls. Among BS patients, a longer duration of thrombosis, bilateral femoral vein involvement, and using no anticoagulation along with immunosuppressive treatment when first diagnosed were found to be associated independently with severe PTS.Lower-extremity vein thrombosis associated with BS, when compared to LEVT due to other causes, had distinctive demographic and ultrasonographic characteristics, and had clinically a more severe disease course.

Objectives: To investigate the frequency of Behçet's syndrome (BS) with pulmonary artery aneurysms (PAA) publications, the most lethal complication of BS, as reported from different countries and to provide a review of diagnostic techniques, treatment approaches and prognosis., Methods: Countries from each continent with a population of 4 million and over were chosen (n=128). A PubMed search for "BS, PAA and the country name" was conducted and 23 countries with BS and PAA were identified. The full texts of articles (n=91) were analysed for data including gender, age, accompanying vascular findings, diagnostic techniques, treatment modalities and mortality rates., Results: A total of 207 (183 males, 24 females) patients with BS and PAA were reported in 91 articles originating from 23 countries. As expected there was a significant correlation (r=0.88, p<0.001) between the total number of articles about BS (n=4431) and those related to PAA and BS. In a simple linear regression analysis the number of BS and PAA articles from Japan was significantly below the identity line while in Turkey there was a propensity to publish more articles related to PAA than expected. One hundred and sixteen patients (56%) were treated with immunosuppressive therapy. Biologics were used only in 5 patients (2%). Of the 207 patients, 62 (30%) died., Conclusions: PAA is mostly reported as case reports from countries where BS is common. PAA might be uncommon in Japan. The prognosis of PAA could be getting better.

Prophylactic lymph node dissection is still controversial due to the potentially surgery-related morbidity in management of papillary thyroid carcinomas. So, some histopathological predictors for lymph node metastasis in thyroidectomy specimens may reveal importance. The objective of this study was to define histomorphological indicators of lymph node metastasis in the patients who had been performed thyroidectomy without lymph node dissection. Clinicopathological features of patients archived in Department of Pathology at Trakya University Medical Faculty were reviewed. A total of 211 patients who had been diagnosed as papillary carcinoma and had been performed total thyroidectomy/lobectomy with central/cervical lymph node dissection were included in the study. Clinical features (age, gender, preoperative/postoperative clinical, and laboratory findings) and histopathological features (histological variant, tumor size, focality, extrathyroidal extension, tumor border, lateral tubular growth, intraglandular dissemination, stromal and lymphocytic tumor response, lymphocytic thyroiditis, lymphovascular invasion, lymph node metastasis, number of metastatic lymph nodes, extranodal extension, size of the metastatic foci) were evaluated. Male gender, conventional variant, tumor size greater than 10 mm, multifocality, extrathyroidal extension, lateral tubular growth, intraglandular dissemination, lymphocytic and stromal tumor response, and absence of lymphocytic thyroiditis were predictive, and older age (≥45 years) and follicular variant PTC were protective for lymph node metastasis. In order to optimize the management of papillary thyroid carcinomas, pathologists should search for the clues of lymph node metastasis particularly intraglandular dissemination, lateral tubular growth, tumor border and lymphocytic/stromal tumor response, multifocality, concomitant lymphocytic thyroiditis besides the actual prognostic criteria especially in younger aged male patients.

Atherosclerosis-induced premature vascular diseases are the leading cause of mortality among patients with chronic kidney disease (CKD). The pathogenetic mechanism of atherosclerosis in patients with CKD has not been fully explained. Experimental studies have demonstrated that high dietary sodium intake not only increases circulatory volume and blood pressure, but also facilitates development of atherosclerosis by reducing production-bioavailability of nitric oxide due to oxidative stress and accordingly by enhancing endothelial and arterial stiffness. In this study, we investigated the relationship between sodium consumption and carotid artery intima-media thickness, which is the indicator of atherosclerosis, by determining daily urinary sodium excretion, which is a reliable indicator of sodium consumption, in our patient group. Our patient group included 193 patients with stage 2-4 non-diabetic CKD and without a history of atherosclerotic disease. We determined that 77% of our patients have been consuming more than 2  g of sodium per day, which is the upper limit of sodium consumption recommended for patients with CKD. We determined a positive linear correlation between carotid artery intima-media thickness and patient age (p < 0.001), C-reactive protein (p < 0.001), urinary sodium excretion (p < 0.001), body mass index (p = 0.002), systolic blood pressure (p = 0.002), hemoglobin (p = 0.030), triglycerides (p = 0.043), and diastolic blood pressure (p = 0.049). We also found a negative linear correlation between carotid artery intima-media thickness and glomerular filtration rate (p = 0.008). We found that urinary sodium excretion is the determinant of intima-media thickness even if all factors associated with intima-media thickness are adjusted, and that intima-media thickness increases by 0.031 (0.004-0.059) mm per 2  g increase in daily sodium excretion, independent from overall factors (p = 0.025). Our results reveal a relation between urinary sodium excretion and carotid artery intima-media thickness and suggest that excessive sodium consumption predisposes development of atherosclerosis in patients with CKD.

Background: The cause of early-accelerated atherosclerosis development observed in Chronic Kidney Disease (CKD) is not fully understood. The determination of the relationship between the levels of fibroblast growth factor 23 (FGF-23) and the development of endothelial dysfunction, left ventricular hypertrophy, and myocardial infarction lends support to the possibility that FGF-23 plays a role in the development of atherosclerosis in CKD. Only a few studies, however, have been conducted that analyze the relationship between FGF-23 levels in the progression of CKD and the development of atherosclerosis, and these studies have generally been limited to those patients receiving dialysis therapy due to end stage renal disease (ESRD)., Methods: In the present study, carotid artery intima-media thicknesses (IMT) were measured ultrasonically as a marker of atherosclerosis in 91 patients with CKD stage 3 - 4 (61 female and 30 male, age between 19 - 65 years, glomerular filtration rate [GFR] 15 - 60 mL/min 1.73 m2, CKD was not related to diabetes mellitus, and without cardiovascular-cerebral disease) in contrast to 36 healthy volunteers (26 female and 10 male, age between 19 - 65 years, GFR > 90 mL/min 1.73 m2, and without any diagnoses of acute or chronic disease), and a possible role of FGF-23 on atherosclerosis was analyzed., Results: Patients were similar to controls with respect to age, gender, smoking status, body mass index, and plasma glucose and lipid profile. On the other hand, IMT measurements (p < 0.00001) and FGF-23 levels (p = 0.00012) were significantly higher in patients than controls. IMT was measured above the subclinical atherosclerosis limit of 0.750 mm in 54% of the patients. Multivariate regression analysis showed that patients' age, high sensitive c-reactive protein (hsCRP), and FGF-23 levels were independent predictors of IMT (p < 0.00001, r = 0.559). Independent of other variables, every 1 μmol/L increase in FGF-23 levels resulted in 0.444 mm increase of IMT measurements in patients with CKD., Conclusions: Our findings suggest that monitoring serum FGF-23 may be useful as a non-invasive indicator of subclinical atherosclerosis in patients with chronic kidney disease.

Objective: Some features of Behçet's syndrome (BS) tend to go together. We aimed to explore the association and timing of various vascular events in both the venous and the arterial vascular tree., Methods: We conducted a chart survey on the type and time of vascular involvement of BS. The cross-relationships of involvement were assessed by phi correlation coefficients. Multiple correspondence analysis was used to identify patterns of vascular involvement. The risk of vascular recurrence was also estimated., Results: We identified 882 patients with vascular involvement among 5970 BS patients (14.7%). Deep vein thrombosis (DVT), almost always in the legs, was the most frequent single vascular event (592/882; 67.1%). The cumulative risk of a recurrent vascular event was 38.4% at 5 years. Patients with extrapulmonary artery involvement (EPAI) were significantly older than those with venous and pulmonary artery involvement (PAI). There were significant correlations between dural sinus thrombosis (DST) and PAI, Budd-Chiari syndrome (BCS) and inferior vena cava syndrome (IVCS) and between IVCS and superior vena cava syndrome (SVCS). Multiple correspondence analysis further indicated clustering of PAI, DST, BCS, IVCS and SVCS. However, EPAI and DVT clustered separately from forms of vascular disease, the separate clustering of the DVT being attributed to its propensity to occur solo., Conclusion: The most common type of vascular involvement in BS is solo DVT, almost always occurring in the legs. Various forms of venous disease in BS segregate together and PAI is included in this group. EPAI segregates separately., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Lumbar puncture (LP) is one of the most common procedures performed in medicine. The aim of this prospective study is to determine the success rate of LP in lateral decubitus with 45-degree head-up tilt position, and compare it with traditional positions like sitting and lateral decubitus., Methods: Three hundred and thirty patients between 25 and 85 years of age who had undergone abdominal, urologic, and lower limb extremities surgeries were enrolled and 300 patients were divided into three different groups. The LP was performed with a 25-G atraumatic needle, either in the standard sitting position (group S, n = 100), lateral decubitus, knee-chest position (group L, n = 100) or lateral decubitus, knee-chest position with a 45-degree head-up tilt (group M, n = 100). The free flow of clear cerebrospinal fluid (CSF) upon first attempt was considered to be evidence of a successful LP., Results: Total LP success rate was significantly higher in group M (85 %) than in groups S and L (70 and 65 %, respectively) (p = 0.004). When the significance between the groups was evaluated according to age, the increase in the LP success rate was not significant for ≤65 and >65 age groups. There were no differences among the three groups in terms of bloody CSF (p = 0.229) and the number of attempts before dural puncture (p = 0.052)., Conclusions: The lateral decubitus in knee-chest position with a 45-degree head-up tilt may be the preferred position for spinal anesthesia in young and elderly patients, due to the high success rate.

Objectives: To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer., Methods: Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast-enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated., Results: CIN was detected in 18/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P = 0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P = 0.005); it was also an independent risk factor (P = 0.017). CIN was significantly more after treatment with bevacizumab/irinotecan (P = 0.021) and in patients with hypertension (P = 0.044)., Conclusions: The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab/irinotecan may be additional risk factors for CIN development., Key Points: • Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. • CIN occurs more often when CT is performed <45 days after chemotherapy. • Hypertension and treatment with bevacizumab appear to be additional risk factors.

The goal of this study was to evaluate the efficacy of CA-125 area under the curve (CA-125 AUC) as a prognostic factor following surgical treatment for ovarian cancer patients. A retrospective analysis was conducted on ninety-five patients with ovarian cancer who had primary treatment in a tertiary center between 2000 and 2010. After either optimal or cytoreductive surgery, all patients underwent adjuvant chemotherapy. CA-125 AUC was calculated for each patient that had a minimum of three CA-125 serum measurements during the treatment period. The mean age at diagnosis and mean survival were 53.9 years (range, 16-75 years) and 35.6 ± 22.9 months (range, 3.1-95.4 months), respectively. The mean (and median) CA-125 AUC of patients of FIGO stages I, II, III, and IV was 53.0 (42.5), 58.06 (58.06), 97.8 (54.6), and 405.2 (149.3) IU/ml day, respectively (p = 0.004). The mean CA-125 AUC was 57.7, 410.1, and 636.3 IU/ml day for patients with a complete response, partial response, and no response/progressive disease to first-line chemotherapy, respectively (p < 0.001). The CA-125 AUC cut-off level for an overall survival of ≥5 years was 99.75 IU/ml day with a sensitivity of 90.9 % (95 % CI, 70.8-98.6) with 1.27 as positive likelihood ratio. Patients who suffer from ovarian cancer, with a lower CA125 AUC, have a better overall survival than those with a higher CA125 AUC. CA-125 AUC could be used as an independent factor for evaluating the treatment efficacy and chemotherapy response.