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Summary: Background: Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D. Methods: We included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function. Findings: We analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR 30 mg/g. During a mean follow-up of 2.5 year, eGFR declined significantly less in the dapagliflozin vs comparator group by 1.81 ml/min/1.73 m2 (95% C.I. from 1.13 to 2.48; p

Obesity has been recognized as a potential risk factor for the carcinogenesis of differentiated thyroid cancer (DTC). The aim of this observational study was to investigate the prognostic role of BMI in influencing DTC histopathological aggressiveness and the risk of tumor relapse. We enrolled 257 patients with DTC, consecutively admitted to our Institution between January 2016 and December 2023. The following variables were collected: demographic, anthropometric and clinical parameters, risk factors for DTC, surgical and radioiodine therapy, histopathological features of DTC, and biochemical markers of disease. Tumor recurrence was assessed during short-, medium- and long-term follow-up. According to BMI tertiles (e.g; I: BMI < 23.3 kg/m2; II: 23.3 ≤ BMI < 27.1 kg/m2; III: BMI ≥ 27.1 kg/m2), the clinical and histopathological characteristics did not differ between groups. The multinomial logistic regression analysis showed that BMI was not associated with clinical and histopathological aggressiveness of DTC, independently from sex, age, and risk factors for DTC onset. Moreover, BMI did not constitute a predictor of tumor recurrence during follow-up. In conclusion, BMI does not represent a predictor of clinical and histopathological aggressiveness of DTC. Since it is not a reliable marker of adiposity, BMI cannot be considered alone in evaluating the potential association between obesity and DTC prognosis.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect testicles. Lower testosterone levels have been associated with worse clinical outcomes and higher mortality. Our objective was to evaluate the hypothalamic–pituitary–gonadal axis of men admitted with SARS-CoV-2 pneumonia and its link with the pneumonia-treatment intensification. Short-term changes in hormonal parameters were also assessed. Methods: Men admitted with SARS-CoV-2 pneumonia were recruited in two different hospitals in Piedmont, Italy. In all patients, the assessment of total testosterone (TT), calculated free testosterone (cFT), gonadotropins, inhibin B (InhB), and other biochemical evaluations were performed at admission (T0) and before discharge (T1). Through a review of medical records, clinical history was recorded, including data on pneumonia severity. Results: Thirty-five men (median age 64 [58–74] years) were recruited. Lower TT and cFT levels at T0 were associated with CPAP therapy (p = 0.045 and 0.028, respectively), even after adjusting for age and PaO2/FIO2 ratio in a multivariable analysis. In those discharged alive, lower TT and cFT levels were associated with longer hospital stay (p < 0.01). TT, cFT, and InhB were below the normal range at T0 and significantly increased at T1 (TT 1.98 [1.30–2.72] vs. 2.53 [1.28–3.37] ng/mL, p = 0.038; cFT (0.0441 [0.0256–0.0742] vs. 0.0702 [0.0314–0.0778] ng/mL, p = 0.046; InhB 60.75 [25.35–88.02] vs. 77.05 [51.15–134.50], p < 0.01). Conclusions: Both TT and cFT levels are associated with adverse clinical outcomes in men admitted with SARS-CoV-2 pneumonia. As TT, cFT and InhB levels increase before discharge, short-term functional recovery of steroidogenesis and an indirect improvement of spermatozoa functional status could be hypothesized.

Obesity has been recognized as a potential risk factor for the carcinogenesis of differentiated thyroid cancer (DTC). The aim of this observational study was to investigate the prognostic role of BMI in influencing DTC histopathological aggressiveness and the risk of tumor relapse. We enrolled 257 patients with DTC, consecutively admitted to our Institution between January 2016 and December 2023. The following variables were collected: demographic, anthropometric and clinical parameters, risk factors for DTC, surgical and radioiodine therapy, histopathological features of DTC, and biochemical markers of disease. Tumor recurrence was assessed during short-, medium- and long-term follow-up. According to BMI tertiles (e.g; I: BMI < 23.3 kg/m2; II: 23.3 ≤ BMI < 27.1 kg/m2; III: BMI ≥ 27.1 kg/m2), the clinical and histopathological characteristics did not differ between groups. The multinomial logistic regression analysis showed that BMI was not associated with clinical and histopathological aggressiveness of DTC, independently from sex, age, and risk factors for DTC onset. Moreover, BMI did not constitute a predictor of tumor recurrence during follow-up. In conclusion, BMI does not represent a predictor of clinical and histopathological aggressiveness of DTC. Since it is not a reliable marker of adiposity, BMI cannot be considered alone in evaluating the potential association between obesity and DTC prognosis. [ABSTRACT FROM AUTHOR]

Hypogonadism is a frequent finding among men living with HIV (MLWH) and it seems to occur earlier in comparison with the generalmale population. Although the prevalence of hypogonadism in MLWH has significantly lowered thanks to advancements in medical management, it remains high if compared with age-matched HIV-uninfected men, ranging from 13% to 40% in the age group of 20-60 years. Signs and symptoms of low serum testosterone (T) in MLWH are cause of concern since they are non-specific, of mild-to-moderate degree, and often overlapping with those of infection per se. For these reasons, hypogonadism can be underestimated in the absence of targeted laboratory blood examinations. With regard to the etiological factors involved in the T decrease, emerging evidence has suggested the functional nature of hypogonadism in MLWH, pointing out the mutual relationship between sex steroids, health status, comorbidities, and HIV-related factors. In agreement with this hypothesis, a therapeutic approach aiming at improving or reversing concomitant diseases through lifestyle changes (e.g. physical activity) rather than pharmacological T treatment should be theoretically considered. However, considering both patient's barriers to lifestyle changes to be maintained overtime and the lack of evidence-based data on the efficacy of lifestyle changes in normalizing serum T in MLWH, T therapy remains an option when other non-pharmacological interventions are ineffective as well as for all other functional forms of hypogonadism. From this perspective, the traditional therapeutic management of male hypogonadism in MLWH, especially the role of T supplementation, should be revised in the light of the probable functional nature of hypogonadism by considering a good balance between benefits and harmful. This narrative review presents an overview of current knowledge on hypogonadism in MLWH, deepening the factors driving and taking part in T decrease, providing advice for the clinical approach, and underlining the importance of individualized treatment aiming at optimizing non-gonadal comorbidities and thus avoiding over-, or even unnecessary, treatment with T. [ABSTRACT FROM AUTHOR]

Purpose: The hemoglobin glycation index (HGI) quantifies the mismatch between glycated hemoglobin A1c and average glycemia among individuals. Currently, it is unknown the potential role of HGI in exhaustively evaluating the progression of glucose metabolism/the risk of developing diabetes mellitus. Therefore, this study aimed to investigate the association between HGI and the risk of incident diabetes. Methods: A total of 7,345 participants aged at least 40 years and without diabetes were divided into three groups according to the tertile of their baseline HGI level and followed for a median of 3.24 years to track new-onset diabetes. Using multivariate Cox regression analyses, we explored the association between the HGI, both categorized and continuous, and incident diabetes. Results: During follow-up, 742 subjects (263 males and 479 females) developed diabetes mellitus. Higher HGI was associated with an increased risk of diabetes, even when adjusted for confounding factors, and every standard deviation increase in HGI was associated with a significant risk increase of 30.6% for diabetes (hazard ratio 1.306, 95% confidence interval 1.232-1.384). Conclusions: Participants with a higher HGI were at a higher risk of future diabetes, irrespective of their glycemic conditions. Consequently, HGI may be employed to identify individuals at high risk for diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the complex interactions of thyroid hormone, apelin, and copeptin in the fluid-ion homeostasis of patients with severe transitory hypothyroidism. Methods: In this prospective observational study, 39 patients (ECOG: 0; 11 men, 28 women, mean age: 50.3 ± 14.9 years) were investigated during shortterm severe hypothyroidism due to surgical removal of the thyroid gland and after adequate thyroid replacement therapy. In addition to the routinely available lab tests, copeptin and apelin levels were determined using ELISA. Results: In the hypothyroid state, apelin concentration was lower, while copeptin levels did not differ compared to the euthyroid condition. Apelin showed a positive correlation with copeptin (p = 0.003), sodium (p = 0.002), NT-proBNP (p < 0.001), and fT4 (p < 0.001) and a negative correlation with thyroid-stimulating hormone (TSH) (p < 0.001). In multivariate linear regression models, copeptin and TSH proved to be significant independent predictors of apelin levels, of which TSH had an explanatory power of 48.7%. Aside from apelin, copeptin only correlated with sodium (p = 0.046). Sodium levels were negatively associated with TSH (p = 0.004) and positively with ACTH (p = 0.002) and cortisol (p = 0.047), in addition to copeptin. None of the parameters were independent predictors of serum sodium levels in a multivariate regression model. Conclusions: In short-term severe hypothyroidism, serum apelin level is markedly decreased, which may predispose susceptible patients to hyponatremia, while the level of copeptin is unchanged. TSH and copeptin are independent predictors of apelin concentration, of which TSH is stronger. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect testicles. Lower testosterone levels have been associated with worse clinical outcomes and higher mortality. Our objective was to evaluate the hypothalamic–pituitary–gonadal axis of men admitted with SARS-CoV-2 pneumonia and its link with the pneumonia-treatment intensification. Short-term changes in hormonal parameters were also assessed. Methods: Men admitted with SARS-CoV-2 pneumonia were recruited in two different hospitals in Piedmont, Italy. In all patients, the assessment of total testosterone (TT), calculated free testosterone (cFT), gonadotropins, inhibin B (InhB), and other biochemical evaluations were performed at admission (T0) and before discharge (T1). Through a review of medical records, clinical history was recorded, including data on pneumonia severity. Results: Thirty-five men (median age 64 [58–74] years) were recruited. Lower TT and cFT levels at T0 were associated with CPAP therapy (p = 0.045 and 0.028, respectively), even after adjusting for age and PaO2/FIO2 ratio in a multivariable analysis. In those discharged alive, lower TT and cFT levels were associated with longer hospital stay (p < 0.01). TT, cFT, and InhB were below the normal range at T0 and significantly increased at T1 (TT 1.98 [1.30–2.72] vs. 2.53 [1.28–3.37] ng/mL, p = 0.038; cFT (0.0441 [0.0256–0.0742] vs. 0.0702 [0.0314–0.0778] ng/mL, p = 0.046; InhB 60.75 [25.35–88.02] vs. 77.05 [51.15–134.50], p < 0.01). Conclusions: Both TT and cFT levels are associated with adverse clinical outcomes in men admitted with SARS-CoV-2 pneumonia. As TT, cFT and InhB levels increase before discharge, short-term functional recovery of steroidogenesis and an indirect improvement of spermatozoa functional status could be hypothesized. [ABSTRACT FROM AUTHOR]