Machine Learning May Be An Alternative To BIPSS In The Differential Diagnosis Of ACTH-Dependent Cushing's Syndrome.

OBJECTIVE: This study aimed to develop machine learning (ML) algorithms for the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) based on biochemical and radiological features. METHODS: Logistic regression algorithms were used for ML, and the area under the receiver operating characteristics curve (AUROC) was used to measure performance. We used Shapley Contributed Comments (SHAP) values, which help explain the results of the ML models to identify the meaning of each feature and facilitate interpretation. RESULTS: A total of 106 patients, 80 with Cushing's disease (CD) and 26 with ectopic ACTH syndrome (EAS), were enrolled in the study. The ML task was created to classify patients with ACTH-dependent CS into CD and EAS. The average AUROC value obtained in the cross-validation of the logistic regression model created for the classification task was 0.850. The diagnostic accuracy of the algorithm was 86%. The SHAP values indicated that the most important determinants for the model were the 2-day 2-mg dexamethasone suppression test, the > 50% suppression in the 8-mg high-dose dexamethasone test, late-night salivary cortisol, and the diameter of the pituitary adenoma. We have also made our algorithm available to all clinicians via a user-friendly interface. CONCLUSION: ML algorithms have the potential to serve as an alternative decision support tool to invasive procedures in the differential diagnosis of ACTH-dependent CS.

Serum Lipoprotein(a) Is Not Associated with Graves' Ophthalmopathy.

Aim: To investigate the relationship of serum lipoprotein(a) [Lp(a)] and other serum lipids with presence of Graves' ophthalmopathy (GO). Methods: A total of 99 consecutive patients diagnosed with Graves' disease (GD), aged 18-65 years, who had not received prior treatment for GO, thyroid surgery, or radioactive iodine therapy, were recruited between June 2020 and July 2022. In addition, 56 healthy controls (HCs) were included as the control group. All patients underwent an ophthalmological examination, and were classified based on the presence of GO into the GO group (n = 45) and no GO group (n = 54). Fasting blood samples were collected from all participants to analyze serum lipid parameters, including Lp(a), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Results: The median serum levels of Lp(a) were 5.7 [4.3-9.2] in the GO group, 6.7 [3.7-9.9] in the no GO group, and 4.7 [3-7.6] in the HC group. The intergroup comparisons of serum Lp(a) levels showed no significant result. The serum levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were also similar between the groups (P > 0.05 for all). However, when analyzing only euthyroid GD patients and the control group, the serum LDL cholesterol levels were found to be significantly higher in the euthyroid GO group [median: 132 interquartile range (IQR) (110-148) mg/dL] than in the HCs [median: 96 IQR (94-118) mg/dL] (P = 0.002). Conclusion: The findings of our study did not support the association between serum Lp(a) levels and GO.

Is There A Connection Between Primary Hypophysitis and Celiac Disease?

AIM: To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD). METHODS: The study was retrospective and patients with PH followed in our clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic, pathologic, and radiologic findings and treatment modalities were assessed. Patients diagnosed with CD in the Gastroenterology outpatient clinic in 2020-2022 were included in the study as a control group. Information such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA) DQ2/8 information, CD-specific antibody levels, pathologic results of duodenal biopsy, treatment received, follow-up status, additional diseases, hormone use, and surgical history was obtained from patient records at PH.In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD were measured. RESULTS: The study included 19 patients with lymphocytic hypophysitis, 30 celiac patients, and 30 healthy controls. When patients diagnosed with lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was found in the pathologic findings. The detection rate of HLA-DQ2/8 was 80% in celiac patients and 42% in PH (p=0.044). (APA and AAVP antibodies associated with PH were tested in two separate groups of patients and in the control group. APA and anti-arginine vasopressin (AAVP) levels in PH, CD and healthy controls, respectively M [IQR]: 542 [178-607];164 [125-243]; 82 [74-107] ng/dL (p=0.001), 174 [52-218]; 60 [47-82]; 59 [48-76] ng/dL (p=0.008) were detected. The presence of an HLA-DQ2/8 haplotype correlates with posterior hypophysitis and panhypophysitis (r=0.598, p=0.04 and r=0.657, p=0.02, respectively). CONCLUSION: Although patients with PH were found to have significant levels of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary antibodies were detected in celiac patients compared with healthy controls, but no hypophysitis clinic was observed at follow-up. Although these findings suggest that the two diseases may share a common genetic and autoimmune basis, the development of the disease may be partially explained by exposure to environmental factors.

Acromegaly increases depressive symptoms and reduces quality of life of cohabitants.

PURPOSE: To assess how living with patients with acromegaly affects people's psychology and quality of life (QoL). METHODS: Acromegaly patients and their cohabitants included in this study. Patients were administered Acromegaly Quality of Life Questionnaire (AcroQoL), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). Cohabitants were administered quality of life questionnaire (SF-36), BAI, BDI, and Zarit Caregiver Burden Interview (ZBI). RESULTS: This study included 84 patients with acromegaly and 84 cohabitants. Sixty-nine patients (n = 84, 82.1%) had an acromegalic appearance. Cohabitants who were affected by the acromegalic appearance had higher BAI, BDI, and ZBI scores than those who were not affected (p < 0.001 for all). Cohabitants who were affected by the acromegalic appearance had a significantly lower SF-36 score (p = 0.015). The BAI (r=-0.535, p < 0.001), BDI (r=-0.592, p < 0.001), and ZBI (r=-0.465, p < 0.001) scores of the cohabitants showed a negative correlation with AcroQoL. SF-36 scores showed correlation with AcroQoL (r = 0.387, p < 0.001). CONCLUSION: The chronic process of acromegaly and the external appearance of patients with this disease can negatively affect both the patients and the people living with them. Physicians being aware of this effect and taking counteractive measures may contribute positively to the course of acromegaly.

The Association between Serum 25-Hydroxyvitamin D3 Levels and Pro-Inflammatory Markers in New-Onset Type 2 Diabetes Mellitus and Prediabetes.

In this study, we aimed to reveal the pro-inflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabetes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy participants. We measured the levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in the serum of the participants. ANOVA Bonferroni and Kruskal-Wallis Dunn tests were used to compare the inflammation markers and vitamin D levels between the groups. Based on covariance analysis with age, gender and BMI, the Vit D levels of the T2DM group were significantly lower (p < 0.003). Pro-inflammatory markers and CRP were significantly higher in prediabetic and diabetic subjects. In the prediabetes group, IL-1ß, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In the T2DM group, IL-1ß, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the pro-inflammatory effects of Vit D deficiency and insufficiency in new-onset type 2 diabetes mellitus and prediabetes.

The effect of radioiodine therapy on blood cell count in patients with differentiated thyroid cancer.

PURPOSE: This study aimed to investigate the long-term effects of radioiodine treatment (RAI) on blood cell counts in patients with differentiated thyroid cancer (DTC) and to describe the characteristics of patients at high risk for blood cell count abnormalities. METHODS: The study included patients with DTC who underwent RAI treatment between 2007 and 2017. Patients with regular complete blood counts for at least 5 years were included, while those with diseases or treatments that could influence blood count parameters were excluded. Blood cell count abnormalities were defined according to the Common Terminology Criteria for Adverse Events version 5.0, and factors influencing these abnormalities were examined. RESULTS: A total of 225 patients were analyzed. The mean age at diagnosis was 45.8 ± 13.9 years, and 76.5% of patients were female. In the first year after RAI, leukocyte, neutrophil, and lymphocyte counts were significantly reduced compared with baseline values. The leukocyte and neutrophil counts returned to baseline values by the third year, while the decrease in lymphocytes continued until the fifth year. Blood cell count abnormalities developed in 16 patients (7.1%) within the first year after RAI. Risk factors for blood cell count abnormalities within the first year after RAI included male sex, older age, T4, N1, and M1 disease, as well as higher RAI doses. In logistic regression analysis, only RAI dose remained independently associated with blood cell count abnormalities. CONCLUSION: These results suggest an association between RAI dose and blood cell count abnormalities, characterized by mild lymphopenia, and indicate that the risk of mild lymphopenia persists over time. Careful consideration should be given when planning high-dose RAI for patients at a high risk of blood cell count abnormalities, such as males with metastatic disease and of advanced age.

Changing presentation of acromegaly in half a century: a single-center experience.

OBJECTIVE: Investigate the changes in the characteristics of presentation, in patients with acromegaly over a period of approximately half a century. METHODS: The medical records of patients diagnosed with acromegaly between 1980 and 2023 were retrospectively reviewed. The collected data were examined to assess any changes observed over the years and a comparison was made between the characteristics of patients diagnosed in the last decade and those diagnosed in previous years. RESULTS: A total of 570 patients were included in the study, 210 (37%) patients were diagnosed in the last decade. Patients diagnosed before 2014 had longer symptom duration before diagnosis, advanced age, larger pituitary adenomas, higher incidence of cavernous sinus invasion, and higher GH and IGF-1 levels than those diagnosed last decade (p < 0.05, for all). Furthermore, the patients diagnosed before 2014 had a lower rate of surgical remission (p < 0.001), and a higher prevalence of comorbidities such as diabetes, hypertension, colon polyps, and thyroid cancer at the time of diagnosis (p < 0.05, for all). CONCLUSION: There may be a trend for earlier detection of patients with acromegaly.

The Role of NF-κB, PPAR-α, and PPAR-γ in Older Adults with Metabolic Syndrome.

The etiopathogenesis of metabolic syndrome (MetS) has not been fully understood yet, and chronic low-grade inflammation is thought to be associated with the development of complications related to MetS. We aimed to investigate the role of Nuclear factor Kappa B ( NF-κB ), Peroxisome Proliferator-Activated Receptor- α and γ (PPAR-α, and PPAR-γ) which are the main markers of inflammation in older adults with MetS. A total of 269 patients aged≥18, 188 patients with MetS who met the diagnostic criteria of the International Diabetes Federation, and 81 controls who applied to geriatrics and general internal medicine outpatient clinics for various reasons were included in the study. Patients were separated into four groups: young with MetS (< 60, n=76), elderly with MetS (≥60, n=96), young control (< 60, n=31), elderly controls (≥60, n=38). Carotid intima-media thickness (CIMT) and NF-κB , PPAR-α, and PPAR-γ plasma levels were measured in all of the participants. Age and sex distribution were similar between MetS and control groups. C-reactive protein (CRP), NF-κB levels (p=0.001) and CIMT (p<0,001) of MetS group were significantly higher than in the control groups. On the other hand, the PPAR-γ (p=0.008) and PPAR-α (p=0.003) levels were significantly lower in MetS. ROC analysis revealed that the NF-κB, PPAR-α, and PPAR-γ could be used to indicate MetS in younger adults (AUC: 0.735, p<0.000; AUC: 0.653, p=0.003), whereas it could not be an indicator in older adults (AUC: 0.617, p=0.079; AUC:0.530, p=0.613). It seems that these markers have important roles in MetS-related inflammation. In our results, suggest that the indicator feature of NF-κB , PPAR-α and PPAR-γ in recognizing MetS in young individuals is lost in older adults with Mets.

Antibody Response to Inactive SARS-CoV-2 Vaccination in a Cohort of Elderly Patients Living with Obesity.

INTRODUCTION: Obesity and aging negatively affect the immune system and host defense mechanisms, increasing vulnerability to and worsening prognosis of infectious diseases, leading to vaccine failure. Our aim was to investigate the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigens and the risk factors affecting antibody levels in elderly patients living with obesity (PwO) after inactive SARS-CoV-2 vaccine (CoronaVac) administration. METHODS: One hundred twenty-three consecutive elderly patients with obesity (age ≥65 years, body mass index [BMI] ≥30 kg/m2) and 47 adults with obesity (age 18-64 years, BMI ≥30 kg/m2) admitted between August and November 2021 were enrolled. Seventy-five nonobese elderly people (age ≥65 years, BMI 18.5-29.9 kg/m2) and 105 nonobese adults (age 18-64 years, BMI 18.5-29.9 kg/m2) were recruited from subjects who visited the Vaccination Unit. SARS-CoV-2 spike protein antibody titers were measured in patients with obesity and nonobese controls who received two doses of CoronaVac. RESULTS: SARS-CoV-2 levels of patients with obesity were found to be significantly lower than those of nonobese elderly individuals who had non-prior infection. There was no difference in SARS-CoV-2 levels between patients with obesity and nonobese individuals with prior infection. Age and SARS-CoV-2 level were found to be highly correlated in the correlation analysis in the group of elderly individuals (r: -0.184). In multivariate regression analysis, when SARS-CoV-2 immunoglobulin class G (IgG) was regressed on age, sex, BMI, type 2 diabetes mellitus, and hypertension (HT), HT was found to be an independent factor of the SARS-CoV-2 level (ß: -2,730). CONCLUSION: In the non-prior infection group, elderly patients with obesity generated significantly reduced antibody titers against SARS-CoV-2 spike antigen after CoronaVac vaccine compared to nonobese people. It is anticipated that the results obtained will provide invaluable information about SARS-CoV-2 vaccination strategies in this vulnerable population. Antibody titers may be measured, and booster doses should be delivered accordingly in elderly PwO for optimal protection.

Do not forget the kidney in graves' disease.

PURPOSE: To investigate the prevalence of microalbuminuria and factors associated with microalbuminuria in Graves' Disease (GD). METHODS: This cross-sectional and single-center study included 99 patients with GD and 47 healthy controls (HC). Exclusion criteria such as active infection, uncontrolled diabetes, and chronic kidney disease were applied to the participants. The participants' clinical findings, comorbidities, drug use, laboratory tests, and thyroid antibody levels were recorded. Spot urine samples were collected and stored at - 80 â„ƒ to analyze the presence of microalbuminuria. RESULTS: The prevalence of microalbuminuria in patients with GD was 12.1%. The median microalbumin/creatinine ratio in spot urine (UACR) in patients with GD (9.49 mg/g [5.09-18.10]) was higher than in the HC group (7.99 mg/g [3.48-12.88], p = 0.033). UACR was correlated with thyroid-stimulating hormone receptor antibody (TRAb), thyroid-stimulating hormone (TSH), and free triiodothyronine (FT3) levels (p = 0.020, p = 0.006, p = 0.009 respectively). In the regression analysis, only the relationship between TRAb level and UACR remained (p = 0.040). CONCLUSION: This study demonstrates an increased prevalence of microalbuminuria in patients with GD. There was a significant correlation between microalbuminuria and TRAb level in patients with GD. This relationship suggests that one of the underlying mechanisms of microalbuminuria seen in patients with GD may be autoimmunity.

Does the Association of Hashimoto's Thyroiditis with Differentiated Thyroid Cancer Really Have a Protective Role?

The study is an investigation of aggressive tumor features, prognosis, and disease-specific mortality rates of differentiated thyroid cancer (DTC) in the presence of concomitant Hashimoto's Thyroiditis (HT). The data of patients with DTC followed in our tertiary care center between 2000-2022 were analyzed. Variables such as patient age, gender, preoperative serum autoantibody levels, tumor characteristics, and treatment modalities were obtained from medical records. The diagnosis of HT was based either on the presence of a positive result in the pathological examination and/or on antibody positivity. A total of 637 patients [mean±SD age, 44.9±13.5 years; 485 women [76.1%)] were included in the analysis. The overall prevalence of coexistent HT was 22.9% (n=146). The disease-specific mortality associated with DTC was 2.9%. DTC patients with HT compared to those without; have more positive lymphovascular invasion (p<0.001), and lymph node metastases (p<0.001). According to the Kaplan-Meier curves, disease-specific survival rates among DTC patients without HT were significantly higher than patients with HT (log-rank p=0.002). The disease-specific mortality rate was 4.79% in DTC patients with HT, it was 1.43% in those without HT. Hashimoto thyroiditis was not associated with a 10-year recurrence-free survival (p=0.059). Differentiated thyroid cancers with concomitant HT are associated with some aggressive tumor features (such as lymphovascular invasion and nodal metastasis) and lower survival. In staging systems based on tumor risk factors, it may be useful to evaluate the presence of concomitant HT as a prognostic factor.

Visceral Adiposity Index as an Indicator of Cardiometabolic Risk in Patients with Congenital Adrenal Hyperplasia.

Aim: To evaluate the cardiometabolic risk in patients with CAH (21 (OH) enzyme deficiency) on the basis of the visceral adiposity index (VAI), which indicates dysfunction of the visceral adipose tissue (VAT). Materials and Methods: A total of 41 patients and 38 body mass index (BMI), age, and gender-matched healthy controls (HC) were included. The patients' and HCs' age, gender, waist circumference (WC), BMI information and total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG) values, smoking, and medication history were obtained from medical charts. Weight, height, WC, and blood pressure levels were measured. Patients' and HCs' BMI, Framingham risk scores (FRS), VAI and Ferriman-Gallwey scores were calculated. The patients' and HCs' age, gender TC, HDL, and TG, androstenedione, dehydroepiandrosterone sulfate (DHEASO4), 17 hydroxyprogesterone (17(OH)P) values, smoking, and medication history were obtained from medical charts. Body fat and muscle mass levels were measured with Tanita T 6360. Results: Gender distribution, mean age, and BMI of patients with CAH were 34/7, 30 ± 8, 27 ± 5.4; HC subjects 30/8, 30 ± 6, 27 ± 3.8 (P = 0.9, 0.6, 0.9, respectively). The VAI values of patients with a diagnosis of CAH 3.7 (2.3-6.9) were found to be significantly higher than those of HC patients 2.5 (1.8-3.9; P = 0.02). The mean glucocorticoid doses of the patients were 17 ± 9 mg/day. The glucocorticoid dose level was determined as independent risk factor on the FRS (P = 0.03, ß = 0.04) and VAI (P = 0.018, ß = 0.17). Conclusion: Glucocorticoid dose optimization should be done more carefully to improve metabolic and cardiovascular outcomes in CAH patients.

Relationship Between Carotid Intima-Media Thickness and Osteoporosis in Type 2 Diabetic Patients: Cross-Sectional Study in the Third-Level Center.

Aim: Although atherosclerosis and osteoporosis (OP) are seen in elderly patients, it is still a matter of research whether there is an age-independent relationship between them. In our study, we planned to investigate the relationship between carotid intima-media thickness (CIMT), OP, and bone turnover parameters in patients with type 2 diabetes mellitus (DM2) of both sexes. Materials and Methods: A total of 69 patients and 40 healthy volunteers with chronic diseases such as DM2, hypertension, hyperlipidemia, and OP. Group 1 had 27 patients with DM2 and OP, group 2 had 42 patients with DM2 and no OP, and group 3 had 40 healthy volunteers without DM2 and OP. Results: In the control group, CIMT was measured lower than the patients with DM2 (0.8 + 0.1 and 1.1 + 0.3, P < 0.001, respectively). Femur T score and lumbar T score values of patients with DM2 were lower than the control group (-0.48 + 1.1 and 0.7 + 0.6, P < 0.001, and -1.3 + 1.5 and 0.6 + 0.5, P < 0.001, respectively). Bone turnover markers in DM2 compared to the control group (C-terminal telopeptide of type 1 collagen: 240.9 ± 211.1 and 606.5 ± 200.8, P < 0.001; bone-specific alkaline phosphatase: 47.9 ± 15.5 and 431.5 ± 140, P < 0.001; and osteocalcin: 13.2 ± 5.0 and 19.7 ± 9.2, P < 0.001, respectively) were lower. Patients with femoral region (TSF) T score and lumbar region (TSL) T score below -2.5 were found to have higher CIMT values than those without (1.2 ± 0.23 mm and 0.9 ± 0.23 mm, P = 0.006, and 1.1 ± 0.28 mm and 0.95 ± 0.21 mm, P = 0.003, respectively). In linear regression analysis, age (ß = 0.01, P < 0.001), OP (ß = 0.166, P = 0.001), and DDM2 (ß = 0.222, P = 0.04) were found to be effective on CIMT, while DM2 (ß) = -0.754, P < 0.001), CIMT (ß = -0.258, P = 0.021), body mass index (ß = 0.355, P = 0.028), and age (ß = -0.229, P = 0.029) were found to be independent factors on TSF. Conclusion: Bone turnover and bone mineral density are decreased in DM2 patients. In addition, subclinical atherosclerosis is more common in DM2 patients. Findings suggest that there is a relationship between subclinical atherosclerosis and OP due to metabolic factors other than age.

Risk Factors Influencing Seroconversion after Inactive SARS-CoV-2 Vaccination in People Living with Obesity.

INTRODUCTION: The aim of this study was to investigate the antibody titers against SARS-CoV-2 spike antigens and the risk factors affecting antibody levels in people living with obesity (PwO) after inactive SARS-CoV-2 vaccine (CoronaVac) administration. METHODS: 169 consecutive patients with obesity who visited the Center for Obesity Management at Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty Hospitals, between May and August 2021, were invited to the study. The nonobese control group was recruited from 191 subjects who visited the Cerrahpasa Hospitals Vaccination Unit. The study group and the nonobese control group have already received two doses of inactive SARS-CoV-2 vaccine. The SARS-CoV-2 IgG nucleocapsid antibody test was administered to patients and control subjects to discover those who had prior SARS-CoV-2 infection. Forty-one patients who had prior infection and received two doses of vaccine were also included in the study as a subgroup. Blood samples were taken on the 3rd to 4th week after the second vaccination. SARS-CoV-2 IgG antibody titers were determined by quantitative serological methods. RESULTS: Antibody titers against SARS-CoV-2 spike antigen of individuals with BMI ≥30.0 kg/m2 were significantly lower than those with BMI <30 kg/m2 (p = 0.001) in the study group. Moreover, the antibody titers in people with BMI ≥30.0 kg/m2 were significantly lower than in those having a BMI <30.0 kg/m2 in the subgroup (p = 0.03). Age (p = 0.03), BMI (p = 0.006), and hypertension (p = 0.03) were found to be independent risk factors for antibody response in PwO. Women with non-prior SARS-CoV-2 infection showed a significantly higher antibody response then men (p = 0.001). CONCLUSION: SARS-CoV-2-Immunoglobulin G antibody levels against inactive (CoronaVac) vaccine were found to be lower in PwO compared to nonobese individuals. Antibody titers may be measured, and booster doses should be delivered accordingly in PwO for optimal protection.

Antibody Response to SARS-CoV-2 Vaccines in People with Severe Obesity.

AIM: Obesity is a disease complicating the course of COVID-19 and SARS-CoV-2 vaccine effectiveness in adults with obesity may be compromised. Our aim is to investigate the spike-protein receptor-binding domain antibody titers against BNT162b2 mRNA and inactivated SARS-CoV-2 (CoronaVac) vaccines in people with severe obesity. It is anticipated that the results to be obtained may provide invaluable information about future SARS-CoV-2 vaccination strategies in this vulnerable population. METHODS: A total of 124 consecutive patients with severe obesity (age > 18 years, BMI ≥ 40 kg/m2) presenting between August and November 2021 were enrolled. The normal weight control group (age > 18, BMI 18.5-24.9 kg/m2) was recruited from 166 subjects who visited the vaccination unit. SARS-CoV-2 spike-protein antibody titers were measured in patients with severe obesity and in normal weight controls who received two doses of BNT162b2, or CoronaVac vaccines. SARS-CoV-2 IgG Nucleocapsid Protein antibody (NCP Ab) testing was performed to discover prior SARS-CoV-2 infection. Blood samples were taken from individuals at 4th week and after 2nd dose of vaccination. SARS-CoV-2 IgG antibody titers were determined by quantitative serological methods. RESULTS: A total of 290 individuals (220 female, 70 male) who have received two doses of BNT162b2 or CoronaVac vaccines were enrolled in the study. Seventy had prior SARS-CoV-2 infection. In 220 subjects (non-prior infection) vaccinated with BNT162b2 or CoronaVac, the antibody titers against SARS-CoV-2 spike antigen of patients with severe obesity were significantly lower than normal weight controls (p = 0.001, p = 0.001 respectively). In seventy subjects with prior SARS-CoV-2 infection, spike antigen antibody titers in patients with severe obesity, vaccinated with BNT162b2 or CoronaVac, were not significantly different from normal weight controls (p = 0.1, p = 0.1 respectively). In patients with severe obesity, with and without prior SARS-CoV-2 infection, spike antigen antibody levels of those vaccinated with BNT162b2 were found to be significantly higher than those vaccinated with CoronaVac (p = 0.043, p < 0.001 respectively). CONCLUSION: Patients with severe obesity generated significantly reduced antibody titers against SARS-CoV-2 spike antigen after CoronaVac and BNT162b2 vaccines compared to people with normal weight. Antibody levels in patients with severe obesity vaccinated with BNT162b2 were found to be significantly higher than those vaccinated with CoronaVac. People living with severe obesity should be prioritized for COVID-19 vaccination and BNT162b2 vaccine may be recommended for this vulnerable population.

Machine learning as a clinical decision support tool for patients with acromegaly.

OBJECTIVE: To develop machine learning (ML) models that predict postoperative remission, remission at last visit, and resistance to somatostatin receptor ligands (SRL) in patients with acromegaly and to determine the clinical features associated with the prognosis. METHODS: We studied outcomes using the area under the receiver operating characteristics (AUROC) values, which were reported as the performance metric. To determine the importance of each feature and easy interpretation, Shapley Additive explanations (SHAP) values, which help explain the outputs of ML models, are used. RESULTS: One-hundred fifty-two patients with acromegaly were included in the final analysis. The mean AUROC values resulting from 100 independent replications were 0.728 for postoperative 3 months remission status classification, 0.879 for remission at last visit classification, and 0.753 for SRL resistance status classification. Extreme gradient boosting model demonstrated that preoperative growth hormone (GH) level, age at operation, and preoperative tumor size were the most important predictors for early remission; resistance to SRL and preoperative tumor size represented the most important predictors of remission at last visit, and postoperative 3-month insulin-like growth factor 1 (IGF1) and GH levels (random and nadir) together with the sparsely granulated somatotroph adenoma subtype served as the most important predictors of SRL resistance. CONCLUSIONS: ML models may serve as valuable tools in the prediction of remission and SRL resistance.

Fertility Desire and Motivation Among Individuals with Gender Dysphoria: A Comparative Study.

Despite receiving Gender-Affirming Hormone Therapy or Gender-Affirming Surgery, which may adversely impact their fertility, people with Gender Dysphoria (GD) may desire to form families. In this study, we aimed to quantitatively display fertility desire from the perspective of these individuals, despite all the legal challenges they face. The single center, cross-sectional comparative study included individuals with GD and cisgender volunteers. A Sociodemographic Data Form, the Fertility Desire Data Form, the Childbearing Motivations Scale and the Fertility Desire Scale were used. Of the 414 participants, 171 were individuals with GD (110 FtM; 61 MtF) and 243 were cisgender volunteers (142 cis-males; 101 cis-females). While 22% of the people with GD stated that they had regrets about not undergoing fertility preservation, 16% stated that they would like this process if it were legal. People with GD, particularly MtF, want to have children more than cisgenders. Moreover, people with MtF exhibited less negative motivations toward becoming parents, despite having reservations regarding the socioeconomic aspect of parenthood. Our findings indicate that fertility desire in people with GD is not less in comparison to cisgender people. Healthcare professionals should not forget to offer fertility preservation options as part of clinical practice before Gender-Affirming Therapy.

The Effects of Diabetic Polyneuropathy and Autonomic Neuropathy on Bone Turnover.

Background: The effect of diabetic polyneuropathy (DPN) and autonomic neuropathy (AN) on bone turnover in type 2 diabetes mellitus (DM) is uncertain due to the lack of data. In this study, we tried to determine the effect of DPN and AN on bone metabolism. Materials and Methods: The study included patients with type 2 DM (aged 18-80 years) and age-matched healthy individuals who presented to the Departments of Metabolism and Diabetes, Geriatrics, and General Internal Medicine, Cerrahpasa Medical School, Istanbul University. The patients were examined to find out whether they had AN, and neuropathy scores were recorded by exploring peripheral neuropathy. Bone mineral density was measured by dual-energy X-ray (DXA). Demographic characteristics, the presence of microvascular complications, and biochemical data were obtained from patients' files. Serum cross-linked C-telopeptide (Ctx), osteocalcin, and bone-specific alkaline phosphatase (B-ALP) were analyzed. Results: The study comprised a total of 64 patients: 23 had type 2 DM and osteoporosis (OP) (duration of diabetes 10.1 ± 7 years; mean age 63 ± 9.1 years; female/male 18/5; Group 1), 41 had type 2 DM and non-OP (duration of diabetes 10.3 ± 7.6 years; mean age 58 ± 7.4 years; female/male 30/11; Group 2), and 26 healthy volunteers made up the control group (mean age 62 ± 11.9 years; female/male 14/12; Group 3). The bone turnover parameters were lower in type 2 DM individuals. The levels of osteocalcin (13.3 ± 5.2 ng/mL) and B-ALP (44.7 ± 10.9 IU/L) in patients with type 2 DM were lower than those of healthy subjects: osteocalcin (20.6 ± 10 ng/mL) and B-ALP (111 ± 31.4 IU/L; P = 0.001 and P = 0.000, respectively). Ctx levels (193.5 ± 49.3; 207.6 ± 40 ng/mL) were recorded to be similar (P = 0.2). AN was also noted as a risk factor for OP. For patients without AN, the likelihood of developing OP (odds ratio) was 0.7. The corresponding ratio for patients with AN was 9.3. Conclusions: Among the independent variables, the neuropathy score was determined to have an impact on bone turnover. AN was identified to be a significant risk factor for OP.

TransCOVID: Does Gender-Affirming Hormone Therapy Play a Role in Contracting COVID-19?

Based on the possible effects of androgens on the course of COVID-19, it can be posited that Gender-Affirming Hormone Therapy (GAHT) may affect the course of the disease in people with GD. We aimed to investigate the relationship between GAHT and contracting COVID-19, as well as the severity of the disease in individuals with Gender Dysphoria (GD). The single center, cross-sectional, web-based survey was completed by people with GD who received GAHT. The questionnaire contained three parts: a sociodemographic data form; a GAHT data form; a COVID-19-related data form. Of the 238 participants, 179 were individuals with female-to-male (FtM) and 59 male-to-female (MtF) GD. We detected that the risk of contracting COVID-19 increased 3.46 times in people with FtM GD, who had received testosterone therapy, in comparison to people with MtF GD, who received estrogen and anti-androgen therapy. Additionally, people with FtM GD who contracted COVID-19 had received longer testosterone therapy when compared to those who did not contract COVID-19. Our findings indicate that individuals with FtM GD who receive testosterone treatment within the scope of GAHT are at higher risk of contracting COVID-19 and that the clinicians who follow-up on GAHT should be more careful about this issue.

Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival.

BACKGROUND: Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes. METHODS: The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case-control study of surviving and non-surviving patients was conducted. RESULTS: Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2-52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p=0.015) and prolonged neutropenia (p=0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p=0.001 and p=0.001, adjusted r(2)=0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p<0.001). Time to active treatment had a significant effect on the course of infection (p=0.014). CONCLUSION: Earlier active treatment with colistin based regimens and microbiological and clinical response within 7 days are major predictors of survival in cases of BSIs due to CRE. Rectal screening offers the advantage of earlier recognition and prompt empirical treatment.