Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

Serum Neopterin, Biopterin, Tryptophan, and Kynurenine Levels in Patients with Fabry Disease

Background: Fabry disease is characterized by the accumulation of globotriaosylceramide. Substrate accumulation in lysosomes is thought to trigger an inflammatory response and is responsible for progressive organ damage through the induction of autoimmunity. The levels of pteridine and kynurenine pathway metabolites increase when immune activation is observed and are employed to monitor several diseases and determine prognosis. Aims: To elucidate the effects of immune activation on the pathophysiology of Fabry disease and to investigate the potential utility of pteridine and kynurenine metabolites. Study Design: A prospective case-control study. Methods: In this study, 33 patients with Fabry disease and 33 age-and sex-matched healthy controls were included. Blood pteridine and kynurenine metabolites were studied in both groups. Organ involvement in Fabry disease and its correlation with the pteridine and kynurenine pathways were also investigated. Results: The patients' neopterin and biopterin levels and the tryptophan/kynurenine ratio were statistically higher than those of the healthy control group (p < 0.05). A statistically significant association was found between neopterin levels and hypertrophic cardiomyopathy, cardiac arrhythmias, and GFR values (p = 0.044, p = 0.021, and p = 0.030, respectively), tryptophan and corneal verticillate, hearing loss and tinnitus (p = 0.010, p = 0.009 and p = 0.046, respectively), and kynurenine levels and valvular heart disease (p = 0.020). Conclusion: From the onset of the disease, patients with Fabry disease exhibited elevated levels of inflammation and immune activation. Furthermore, inflammation and immune activation markers can be used as early disease biomarkers.

Myxoma Virus Combination Therapy Enhances Lenalidomide and Bortezomib Treatments for Multiple Myeloma.

This study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.

[Investigation of the Effect of Farnesol on Biofilm Formation by Candida albicans and Candida parapsilosis Complex Isolates]. / Candida albicans ve Candida parapsilosis Kompleks Izolatlarinin Biyofilm Üretimi Üzerine Farnesol Etkisinin Arastirilmasi.

The incidence of infections caused by Candida species has significantly increased over the past three decades. Candida albicans is commonly recognized as the primary causative agent in cases of candidiasis; however, non-albicans Candida species, including Candida parapsilosis, are also frequently defined as pathogens. Treatment-resistant infections arise as a result of biofilm formation, which is one of the effective mechanisms in the pathogenesis of Candida infections. However, the mechanisms of action of farnesol, a quorum sensing (QS) system molecule, on biofilm formation by Candida species remain unclear. This study aimed to demonstrate the changes in the biofilm biomass of C.albicans and C.parapsilosis complex isolates in the presence of farnesol and reveal the expression of the EFG1 and BCR1 genes, which are believed to play a role in the production of QS molecules, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis. C.albicans (n= 91) and C.parapsilosis complex (n= 29) isolates obtained from different clinical samples were included in the study. The minimum inhibitory concentration (MIC) values of farnesol were determined using the broth microdilution method according to the M27-A3 protocol of the Clinical and Laboratory Standards Institute (CLSI). The biofilm biomass of the isolates was examined without farnesol and at the MIC-0 and MIC-2 concentrations of farnesol. Changes in the expression of the biofilm-associated EFG1 and BCR1 genes were investigated using qRT-PCR. According to the results of the study, the MIC values of farnesol were detected in the range of 1-2 mM in 82.4% (n= 75) of the C.albicans isolates and in the range of 0.5-1 mM in 72.4% (n= 21) of the C.parapsilosis complex isolates. Of the C.albicans isolates, 27 (29.7%) exhibited a strong biofilm formation and 58 (63.7%) demonstrated a weaker biofilm formation, while these rates were 34.4% (n= 10) and 62.1% (n= 18), respectively, for the C.parapsilosis complex isolates. At the MIC-0 and MIC-2 concentrations, farnesol was observed to reduce biofilm biomass among C.albicans (n= 24, 88.9%) and C.parapsilosis complex (n= 8, 80.0%) isolates that formed strong biofilms and observed to increase biofilm biomass among those that formed weak biofilms [60.3% (n= 35) and 55.6% (n= 10), respectively]. On completion of the qRT-PCR analysis supporting the results of the biofilm experiment, it was determined that the expressions of the EFG1 and BCR1 genes decreased at the MIC-0 and MIC-2 concentrations of farnesol among the strong biofilm-forming C.albicans and C.parapsilosis complex isolates, but there was an increase in gene expressions among the weak biofilm-forming isolates. In addition to the antifungal effect of farnesol on Candida species, this study provided data on the efficacy of the MIC-0 and MIC-2 concentrations of farnesol against Candida biofilm biomass. Although our results suggest that farnesol can be used as an alternative agent to reduce biofilm formation in Candida infections, they need to be supported by further studies. Moreover, this research has significance as it represents the first study to determine the EFG1 and BCR1 gene expressions among C.parapsilosis complex isolates in the presence of farnesol.

The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study.

OBJECTIVES: Despite the presumed overdiagnosis of papillary thyroid microcarcinoma (PTMC) which has resulted in a new trend toward less-extensive surgery and a preference for active surveillance, the impact of microscopic extrathyroidal extension (mETE) on the clinical outcomes of PTMC is still controversial. This study assessed the impact of mETE on the clinical outcomes of patients with classic subtype PTMC. METHODS: The data of consecutive patients who underwent thyroidectomy and were histopathologically diagnosed as classic subtype PTMC were analyzed. Cox's proportional hazards model was used to assess the impact of contributing variables on persistent/recurrent disease. Disease-free survival was estimated using the Kaplan-Meier method. RESULTS: This study included 1013 patients (84% females), with a mean follow-up period of 62.5 ± 35.3 months. Patients with mETE had a significantly higher rate of locoregional persistent/recurrent disease than patients without mETE (9.8% vs 2.1%, p < 0.001). The disease-free survival rate was significantly lower in patients with mETE than in those without (90.2% vs 97%, Log-Rank p < 0.001). Furthermore, mETE and neck lymph node involvement were independent predictors of persistent/recurrent disease in multivariate analysis (HR: 2.43, 95% CI:1.02-5.81, p = 0.043; HR: 4.38, 95% CI: 1.7-11.2, p = 0.002, respectively). CONCLUSIONS: In patients with the classic subtype of PTMC, mETE is an independent predictor of persistent/recurrent disease and is associated with a lower DFS rate. However, neck lymph node involvement is the strongest predictor of persistent/recurrent disease. Therefore, PTMCs with mETE and neck lymph node involvement are at a higher risk of persistent/recurrent disease than individuals lacking both characteristics.

Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

B-mode ultrasound assessment of carotid artery structural features in patients with normocalcaemic hyperparathyroidism.

INTRODUCTION: Normocalcaemic hyperparathyroidism is a condition first defined in 2008, characterized by normal serum calcium and high parathormone levels. Although normocalcaemic hyperparathyroidism is considered to have a milder clinical picture compared to asymptomatic primary hyperparathyroidism, recent studies have shown that it may be associated with osteoporosis, insulin resistance, metabolic syndrome, and cardiovascular risk factors. Considering that normocalcaemic hyperparathyroidism may pose a cardiovascular risk in the setting of carotid atherosclerosis, we sought to examine the structural features of the carotid artery in patients with normocalcaemic hyperparathyroidism compared to a control group. MATERIAL AND METHODS: After excluding patients with hypertension, diabetes, and dyslipidaemia (other factors contributing to atherosclerosis), 37 (32 females, 5 males) patients with normocalcaemic hyperparathyroidism with a mean age of 51.2 ± 8 (min: 32, max: 66) years and 40 controls (31 females, 9 males) with a mean age of 49.3 ± 7.5 (min: 34, max: 64) years with normal serum albumin-corrected calcium and parathyroid hormone levels were included in the study. Structural features of the carotid artery including intima-media thickness (mean and maximum), lumen diameter, and the presence of plaque were assessed using B-mode ultrasound. RESULTS: On ANCOVA analysis corrected for atherosclerotic factors (body mass index, waist circumference, fasting plasma glucose, serum cholesterol, lipid, and blood pressure), greater mean intima-media thickness was found in patients with normocalcaemic hyperparathyroidism than in controls (0.65 mm vs. 0.59 mm, respectively) (p = 0.023). Maximum carotid intima-media thickness was also greater in patients with normocalcaemic hyperparathyroidism compared to controls (0.80 mm vs. 0.75 mm, respectively) (p = 0.044). The study groups did not show a significant difference in lumen diameter and the presence of carotid plaque. In addition, a negative correlation was found between parathormone (PTH) level and lumen diameter. CONCLUSION: The findings of this study show that as with asymptomatic primary hyperparathyroidism, normocalcaemic hyperparathyroidism may be associated with increased cardiovascular risk by predisposing to atherosclerosis.

Plasma Asymmetric Dimethylarginine (ADMA) and Nitric Oxide (NO) Levels in Patients with Chronic Pansinusitis.

Chronic pansinusitis is a mucosal inflammation of the nose and all paranasal sinuses with severe inflammation of the upper airways. Asymmetric dimethylarginine (ADMA) is associated with oxidative stress. In this study, we aimed to examine the plasma levels and importance of ADMA and nitric oxide (NO) in patients with chronic pansinusitis. The study was conducted with a total of 64 patients. The study group included a total of 40 patients with chronic pansinusitis. (18 females, 22 males) (mean age 32.27 ± 10.02). The control group consisted of 24 patients (11 females and 13 males). The mean age of the patients in the control group was 31.35 ± 6.05 years. Nasal endoscopic examinations were performed in patients with a history of chronic pansinusitis and symptoms of chronic pansinusitis. Later, the diagnosis of chronic pansinusitis was confirmed with coronal paranasal sinus Computed tomography scans. Plasma ADMA levels were measured by ELISA method and NO levels were measured by Griess method. Plasma ADMA and NO levels of the patients and healthy volunteers were measured and the mean plasma levels of the two groups were compared. ADMA levels were significantly higher in the group with chronic pansinusitis compared to the control group (1.23 ± 0.41 µM and 0.28 ± 0.06 µM, respectively) (p < 0.001), while NO levels were significantly lower in the patient group compared to the control group (7.06 ± 1.07 µM and 12.25 ± 0.95, µM, respectively) (p < 0.001). Our results show that the increase in ADMA levels and the decrease in NO levels are associated with chronic pansinusitis. According to these results, increased plasma levels of ADMA in chronic pansinusitis may be useful in clinical use as a sign of increased oxidative stress.

A 5-year surveillance of healthcare-associated infections in a university hospital: A retrospective analysis.

Objectives: "Nosocomial infections" or "healthcare-associated infections" are a significant public health problem around the world. This study aimed to assess the rate of laboratory-confirmed healthcare-associated infections, frequency of nosocomial pathogens, and the antimicrobial resistance patterns of bacterial isolates in a University Hospital. Methods: A retrospective evaluation of healthcare-associated infections in a University Hospital, between the years 2015 and 2019 in Tekirdag, Turkey. Results: During the 5 years, the incidence densities of healthcare-associated infections in intensive care units and clinics were 10.31 and 1.70/1000 patient-days, respectively. The rates of ventilator-associated pneumonia, central line-associated bloodstream infections, and catheter-associated urinary tract infections in intensive care units were 11.57, 4.02, and 1.99 per 1000 device-days, respectively. The most common healthcare-associated infections according to the primary sites were bloodstream infections (55.3%) and pneumonia (20.4%). 67.5% of the isolated microorganisms as nosocomial agents were Gram-negative bacteria, 24.9% of Gram-positive bacteria, and 7.6% of Candida. The most frequently isolated causative agents were Escherichia coli (16.7%) and Pseudomonas aeruginosa (15.7%). The rate of extended-spectrum beta-lactamase production among E. coli isolates was 51.1%. Carbapenem resistance was 29.8% among isolates of P. aeruginosa, 95.1% among isolates of Acinetobacter baumannii, and 18.2% among isolates of Klebsiella pneumoniae. Colistin resistance was 2.4% among isolates of A. baumannii. Vancomycin resistance was 5.3% among isolates of Enterococci. Conclusion: Our study results demonstrate that healthcare-associated infections are predominantly originated by intensive care units. The microorganisms isolated from intensive care units are highly resistant to many antimicrobial agents. The rising incidence of multidrug-resistant microorganisms indicates that more interventions are urgently needed to reduce healthcare-associated infections in our intensive care units.

Altered immune response in organic acidemia.

BACKGROUND: Most patients with organic acidemia suffer from recurrent infections. Although neutropenia has been reported in multiple studies, other components of the immune system have not been evaluated thoroughly. This study was conducted to assess the immune status of patients with organic acidemia (OA). METHODS: Thirty-three patients with OA who were followed up in Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Nutrition and Metabolism Department and a total of 32 age- and sex-matched healthy controls were enrolled to the study. The demographic and clinical data were recorded retrospectively from patient files. Complete blood counts, immunoglobulins, and lymphocyte immunophenotyping were recorded prospectively in a symptom- (infection-) free period. RESULTS: Of the 33 patients enrolled to the study, 21 (88%) were diagnosed with methylmalonic acidemia, 10 (33%) with propionic acidemia, and two (6.6%) with isovaleric acidemia. The mean age of the patients with OA and healthy subjects were 5.89 ± 4.11 years and 5.34 ± 4.36, respectively (P = 0.602). Twenty-nine (88%) of the patients had experienced frequent hospital admission, 13 (39%) were admitted to pediatric intensive care unit, and 18 (55%) suffered from sepsis. Naïve helper T cells and recent thymic emigrants were significantly lower in OAs (P < 0.001). Various defects in humoral immunity have also been documented including memory B cells and immunoglobulins. CONCLUSIONS: Patients with OAs may show adaptive immune defects rendering them susceptible to infections. Metabolic reprogramming based on nutritional modifications may be a promising therapeutic option in the future.

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study.

OBJECTIVE: Although the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up. METHODS: In this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons. RESULTS: This study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease. CONCLUSION: Applying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.

The Impact of Various Breast Sizes of Women on Vertebral Column and Spinopelvic Parameters.

AIM: To find out the anatomical changes in spine and pelvis, and the impact of various breast sizes of women on the quality of life. MATERIAL AND METHODS: Sixty women with back pain volunteered to participate in this study. Their body mass index (BMI) was calculated. Clinical evaluation of the pain was assessed using the Oswestry Disability Index and visual analogue scale. Breast volumes were measured using the Grossman Rounder device. Scoliosis radiograms were obtained, and the cervical lordosis, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic incidence and pelvic tilt angles were measured in patients. The relationship between the increasing breast size and BMI was investigated through all these parameters. RESULTS: Increase in breast size positively changes the sagittal balance (r=0.356, p=0.005) and increases cervical lordosis (r=0.300, p=0.020). Increase in BMI leads to a positive sagittal balance (r=0.329, p=0.010) and increases the pelvic tilt (r=0.460, p=0.000). In patients with a positive sagittal balance, the sacral slope (r=-0.350, p=0.006) and the lumbar lordosis angle decrease (r=-0.552, p=0.000), whereas the pelvic tilt increases (r=0.298, p=0.021). CONCLUSION: Macromastia has an impact on cervical lordosis and sagittal balance, while indirectly impacting the pelvic tilt rather than the thoracic kyphosis and lumbar lordosis.

Predictive value of noninvasive indices in chronic hepatitis B virus-related fibrosis.

OBJECTIVES: Despite being an invasive method, liver biopsy followed by pathological grading remains the gold standard in evaluating liver fibrosis resulting from chronic hepatitis B virus (HBV) infection. The present study aims to evaluate the utility of biochemical parameters and their derived indices in predicting development of fibrosis related to HBV infection. PATIENTS AND METHODS: Pathology results and biochemical parameters of patients who underwent liver biopsy were retrieved from electronic archive records dated 2010-2019 and evaluated retrospectively. Pathological fibrosis grading was performed as per Ishak scoring, with scores of 1-2 considered as mild fibrosis and 3-6 as advanced fibrosis. RESULTS: The mean age of 302 patients was 37.69 ± 11.33 years. Of the 302 patients, 230 (76.2%) had mild fibrosis and 72 (23.8%) had advanced fibrosis. Age-platelet index, aspartate aminotransferase/platelet ratio index, fibrosis-4 (FIB-4), modified fibrosis-4, platelets count, aspartate aminotransferase to alanine aminotransferase ratio/platelet ratio index, Goteborg University Cirrhosis Index and King's score were markedly and significantly higher in patients with advanced fibrosis than those with mild fibrosis. FIB-4, age-platelet index and King's score had higher (>80%) area under the curve values than other indices in the receiver operating characteristics analysis. Evaluation of sensitivity, specificity and accuracy of these indices with the specified cut-off values revealed 87% sensitivity with FIB-4, 70% specificity with King's score and 72% accuracy with the age-platelet index. CONCLUSION: In this study, the highest rates of sensitivity, specificity and accuracy in distinguishing and predicting liver fibrosis were observed with the noninvasive indices FIB-4, King's score and the age-platelet index, respectively.

The association of TSH-receptor antibody with the clinical and laboratory parameters in patients with newly diagnosed Graves' hyperthyroidism: experience from a tertiary referral center including a large number of patients with TSH-receptor antibody-negative patients with Graves' hyperthyroidism.

INTRODUCTION: Although the TSH-receptor antibody (TRAb) plays a central role in the pathogenesis of Graves' disease (GD), the association between TRAb at first diagnosis and clinical and laboratory parameters is not well known. On the other hand, a minority of patients with GD may be TRAb negative, and there is a lack of adequate evidence to demonstrate the clinical and laboratory characteristics of these patients. Therefore, we aimed to investigate the association of TRAb at the initial diagnosis of GD with the clinical and laboratory parameters in a large number of patients with GD and to compare the clinical and laboratory parameters between patients with high TRAb levels and TRAb-negative patients. MATERIAL AND METHODS: This study included 440 patients [326 (74%) female, 114 (26%) male]. All patients were classified according to gender, age, smoking habit, and TRAb levels. RESULTS: TRAb levels were significantly higher in male compared to female patients and in smokers compared to non-smokers. Smoking male patients had the highest TRAb levels. In regression analysis, goiter size, male gender, cigarette smoking, Graves' orbitopathy, fT3, and anti-TPO antibody levels were independently associated with high TRAb levels, while age at diagnosis and fT4 levels were not independently associated with high TRAb levels. TRAb-negative GD was diagnosed in 80 (18%) patients. TRA-negative patients had markedly less severe clinical and laboratory hyperthyroidism compared to patients with high TRAb levels. Moreover, the smoking habit was significantly lower in patients with TRAb-negative GD. CONCLUSIONS: According to our study results, TRAb levels at the initial diagnosis of GD are differently associated with clinical and laboratory parameters. Male patients and smoking patients with GD tended to have markedly higher TRAb levels and more severe clinical hyperthyroidism. Therefore, besides other contributing factors, male gender and smoking may affect TRAb levels and consequently the severity of hyperthyroidism in patients with GD. Furthermore, male gender and smoking may have a synergistic effect on TRAb levels and consequently on the severity of hyperthyroidism in patients with GD.

The frequency of Cushing's disease, ACTH-independent Cushing's syndrome and autonomous cortisol secretion among Turkish patients with obesity.

OBJECTIVE: The frequency of Cushing's disease (CD), ACTH-independent Cushing's syndrome (CS) and autonomous cortisol secretion (ACS) in patients with obesity is not well known. Therefore, in the present study, we aimed to assess the frequency of CD, CS and ACS among the patients with obesity. METHODS: This study included 813 patients (683 female, mean age 46.47±14.23 yr; mean body mass index (BMI) 37.31±6.50 kg/m2). Patients with obesity were classified further to stages 1, 2, and 3, according to BMI. All patients underwent a low dose dexamethasone suppression test (LDDST). The patients with CD, CS, and ACS and patients with simple obesity were compared concerning gender, age, type-2 diabetes, hypertension (HT) and hyperlipidemia (HL). RESULTS: Forty-four (5.4%) out of 813 patients were diagnosed as CD, CS or ACS. CD, CS, and ACS were diagnosed in four (0.4%), two (0.2%), and 33 (4%) patients, respectively. When patients with CD, CS and ACS were compared to the patients with simple obesity, older age at diagnosis, the presence of stage-1 obesity, the presence of HT, and uncontrolled type-2 diabetes were more frequent in patients with CD, CS and ACS (p=0.001, p=0.007, p=0.004, and p=0.0026, respectively). CONCLUSION: The frequency of CD, CS, and ACS is high among patients with obesity. Screening for CD, CS, and ACS in patients with stage-I obesity who are older than 50 years of age with uncontrolled type-2 diabetes and HT may be a reasonable approach.

Relationship between the infarct localization and left ventricular rotation parameters following acute ST-segment elevation myocardial infarction.

OBJECTIVE: This study was an investigation of the role of left ventricular (LV) apical rotation seen in the early period after myocardial infarction (MI) in predicting infarct localization. METHODS: A total of 124 patients with a ST-Segment elevation myocardial infarction (STEMI) diagnosis who underwent primary percutaneous coronary intervention (PCI) and 50 healthy volunteers with similar demographic characteristics were included in the study. The relationship between 2-dimenstional speckle tracking echocardiography (STE)-guided LV apical rotation angle measurements and technetium-99m sestamibi-single-photon emission computed tomography (SPECT)-guided infarct localization was evaluated. Conventional echocardiography and STE were performed on average 2 days after PCI, and gated SPECT myocardial perfusion imaging (MPI) was performed within an average of 60 days. RESULTS: The apical rotation angle was lower in patients with an anterior MI compared with those who had an inferior MI and the control group (AntMI-InfMI: 6.51±2.4°, AntMI-Control: 13.20±2.5°, InfMI-Control: 14.3±2.1°; p value: 0.00, 0.00, 0.15, respectively). SPECT MPI analysis revealed the presence of an LV apical scar in all patients with acute anterior MI, but only 14 of those with inferior MI group (usually the inferoapical wall). The apical rotation angle recorded in patients with apical scar was lower than that of the patients without apical scar (7.6±2.8° and 14.5±2°, respectively; p=0.00). Receiver operating characteristic curve analysis yielded an area under the curve for apical rotation of 0.799 (p<0.01). The optimal cutoff value of 12.1° had a sensitivity of 78.3% and a specificity of 68.2% for predicting LV apical scar following STEMI. CONCLUSION: Detection of apical rotation angle decrease in the early period after STEMI may be useful in predicting extension of infarct scarring to the LV apex.

Can the development of atrial fibrillation in patients with ischemic heart failure with low ejection fraction be predicted?

OBJECTIVE: Our aim is to determine the triggering factors of paroxysmal atrial fibrillation (PAF) in ischemic heart failure (HF) patients with low ejection fraction (EF). METHODS: Sixty patients were included in this study. Echocardiography and 24-hours Holter monitoring were performed after measurement of serum NT-pro BNP concentration. The patients were classified into two groups concerning the occurrence of PAF on Holter recordings. Biochemical and echocardiographic parameters of patients with and without PAF were compared. RESULTS: PAF was detected in 28 (46%) patients. Patients with PAF demonstrated higher NT-pro BNP levels, mitral and aortic regurgitation velocities, E/A, E/E', pulmonary capillary wedge pressure, pulmonary artery systolic pressure, left atrial volume and volume indices. NT-pro BNP was established as the predictor of PAF (OR=1.23, 95% CI: 1.08-1.42; p=0.001). ROC analysis showed an NT-pro BNP value of 2188 pg/mL as cut-off value with 68% sensitivity and 84% specificity [Area under the ROC curve (AUC)=0.826, CI 95%: 0.724-0.927; p<0.001]. CONCLUSION: The triggering factors for AF are increased intracardiac pressures, left atrial dilatation and increased wall tension. As an indicator of increased wall tension, elevated levels of NT-pro BNP predict the development of PAF.

The effect of gender on response to antithyroid drugs and risk of relapse after discontinuation of the antithyroid drugs in patients with Graves' hyperthyroidism: a multicentre study.

INTRODUCTION: The outcome of medical treatment in patients with Graves' disease (GD) is generally difficult to predict. In this study, we examined the hypothesis that gender may affect the outcome of treatment with antithyroid drugs (ATDs). MATERIAL AND METHODS: This is a retrospective multicentre study including 717 (514 female and 203 male) patients with the first episode of GD treated for at least 12 months. Patients were classified as relapse, poorly controlled (several episodes of hyperthyroidism followed by euthyroidism and rarely hypothyroidism, occurring after titration of ATDs), and remission. RESULTS: During the mean follow-up time of 26.75 ± 21.25 months (between 1 and 120 months), 269 (37.5%), 176 (24.5%), and 272 (37.9%) patients experienced a relapse, a poorly controlled disease, and remained in remission, respectively. During the follow-up time, 223 (43.4%) of the female and only 49 (24%) of the male patients remained in remission. Relapse and poorly controlled disease (non-remitting GD) were more common in male compared to female patients with GD (hazard ratio 1.26, 95% CI: 1.03-1.53, p = 0.025). Graves' disease in male patients tended to relapse earlier, and male patients tended to have larger goiter sizes at diagnosis as well. The smoking habit was also significantly more frequent in males compared to female patients with GD. CONCLUSION: Male patients with GD have a markedly higher frequency of relapse and poorly controlled disease, as compared to female patients. Larger goiter sizes and higher frequency of smoking may contribute to the higher frequency of relapse and poorly controlled disease in male patients.

Is Overweight a Risk of Early Atherosclerosis in Childhood?

We measured brachial artery flow-mediated dilatation (FMD) and common carotid intima-media thickness (cIMT) in overweight (n = 67) and normal weight children (n = 115, controls). Age at examination ranged from 72 to 182 months (mean 123 ± 27). Compared to controls, the overweight children had increased weight, waist and hip circumference, systolic and diastolic blood pressures (all P < .001), right and left mean cIMT (mm; 0.58 [0.42-0.68] vs 0.44 [0.3-0.64], P < .001 and 0.56 [0.32-0.70] vs 0.44 [0.3-0.60], P < .001), respectively, and decreased FMD (%; 6.25 [3.33-19.05] vs 7.69 [3.45-16], P < .001). The cIMT and FMD were closely related to the serum insulin concentrations. Age, waist circumferences, and serum triglycerides were independent predictive risk factors for increased cIMT, and fasting glucose and BMI were independent predictive variables for decreased FMD. Overweight children are also potentially at risk of early atherosclerosis as much as obese children.

The gut microbiome in epilepsy.

The close relationship between epilepsy and autoimmune diseases and the fact that the cause of epilepsy is idiopathic in 60% of cases suggest that intestinal microbiota may play a role in the etiology of epilepsy. In this study, we analyzed and compared the intestinal microbiota composition of patients with idiopathic focal epilepsy (n = 30) and healthy volunteer group (n = 10) by 16s ribosomal DNA sequencing. Proteobacteria phylum was found to be higher in patients with epilepsy (25.4%) than in healthy volunteers group (1.5%). The genera of Campylobacter, Delftia, Haemophilus, Lautropia, Neisseria among Proteobacteria phylum were found to be statistically significantly higher in patients with epilepsy than in healthy volunteers (p < 0.05). Fusobacteria phylum was detected in 10.6% of the patients with epilepsy but not in the healthy volunteer group. The genus of the Fusobacteria phylum was found as Leptotrichia and Fusobacterium. In our study, taxonomic drift and significant differences in the intestinal microbiota of patients with epilepsy according to healthy volunteer group showed that autoimmune mechanisms and inflammation may have a role in the etiology of epilepsy. Our data should be supported by other studies as to the role of the intestinal microbiome in the prevention and treatment of epilepsy.