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Abstract A growing body of evidence suggests the role of male hypogonadism as a possible harbinger for poor clinical outcomes across hospitalized Covid-19 patients. Accordingly, we sought to investigate the impact of dysregulated hypothalamic-pituitary–gonadal axis on the severity of the clinical manifestations for hospitalized Covid-19 patients matched with healthy controls through a systematic review and meta-analysis. Databases were searched from inception to March 2022. A standardized mean difference (SMD) meta-analysis focused on hospitalized Covid-19 patients and healthy controls was developed for studies who reported total testosterone (TT) and luteinizing hormone (LH) levels at hospital admission. Overall, n = 18 series with n = 1575 patients between 2020 and 2022 were reviewed. A significant decrease in SMD of TT levels in Covid-19 patients compared to paired controls was observed (− 3.25 nmol/L, 95%CI − 0.57 and − 5.93). This reduction was even more consistent when matching severe Covid-19 patients with controls (− 5.04 nmol/L, 95%CI − 1.26 and − 8.82) but similar for Covid-19 survivors and non-survivors (− 3.04 nmol/L, 95%CI − 2.04 and − 4.05). No significant variation was observed for serum LH levels across studies. Patient related comorbidities, year of the pandemic, and total lymphocyte count were associated with the observed estimates. TT levels may be a useful serum marker of poor outcomes among Covid-19 patients. These findings may support the development of ad-hoc clinical trials in the Covid-19 risk-group classification and subsequent disease monitoring. The interplay between TT and immune response should be evaluated in future researches.

Background: Contrast-enhanced ultrasound (CEUS) is a diagnostic tool that is gaining popularity for its ability to improve overall diagnostic accuracy in bladder cancer (BC) staging. Our aim is to determine the cumulative diagnostic performance of CEUS in predicting preoperative muscle invasiveness using a comprehensive systematic review and pooled meta-analysis. Methods: A systematic review until October 2023 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patients with BC suspicion were offered CEUS before the transurethral resection of the bladder tumor (TURBT). The diagnostic performance of CEUS was evaluated based on non-muscle-invasive bladder cancer (NMIBC) vs. muscle-invasive bladder cancer (MIBC) confirmed at the final histopathological examination after TURBT. The outcomes were determined through pooled sensitivity, specificity, pooled positive likelihood ratio (PLR+), negative likelihood ratio (PLR−), and area under the summary receiver operating characteristic (SROC) along with their respective 95% confidence intervals (CI). Results: Overall, five studies were included. In these studies, a total of 362 patients underwent CEUS prior to TURBT. The pooled sensitivity and specificity were 0.88 (95% CI: 0.81–0.93) and 0.88 (95% CI: 0.82–0.92), respectively. SROC curve depicted a diagnostic accuracy of 0.94 (95% CI: 0.81–0.98). The pooled PLR+ and PLR− were 7.3 (95% CI: 4.8–11.2) and 0.14 (95% CI: 0.08–0.23), respectively. Conclusions: Our meta-analysis indicates that CEUS is highly accurate in the diagnosis and staging for BC. Beyond its accuracy, CEUS offers the advantage of being a cost-effective, safe, and versatile imaging tool.

Contrast-enhanced ultrasound (CEUS) is an advanced imaging technique that integrates conventional US with the intravenous injection of specific US contrast agents (UCAs), combining the non-invasiveness of US with the higher accuracy of contrast-enhanced imaging. In contrast with magnetic resonance imaging (MRI), computed tomography (CT) and cystoscopy, CEUS has few contraindications, and UCAs are non-nephrotoxic agents that can be safely used in patients with kidney failure. CEUS is a well-established method for the detection of liver lesions and for echocardiography, and its indications are expanding. The updated 2018 WFUMB-EFSUMB guidelines have added the urinary bladder under non-hepatic applications of CEUS. The technique is able to distinguish between benign tissue, such as clots or hematoma, and malignant lesions by perfusing the mass with contrast agent. Thanks to the different perfusion rates of the various layers of the bladder wall, CEUS is also able to predict tumor invasion depth and stage. Despite that, current urological guidelines do not include CEUS as a plausible imaging technique for bladder urothelial carcinoma. The main reason for this omission might be the presence of scarce randomized evidence and the absence of large validated series. In this review, we describe the rationale behind the use of CEUS in bladder cancer and the added value of this imaging technique in the detection and staging of bladder lesions. In addition, we researched the available literature on the topic and then described the results of randomized clinical trials and a meta-analysis investigating the accuracy of CEUS in bladder cancer diagnosis and staging. The reported studies show that CEUS is a highly accurate diagnostic and staging tool for BC, reaching levels of specificity and sensitivity in differentiating between Ta-T1, or low-grade BC, and T2, or high-grade BC, that are comparable to those shown by the reference standard methods. Nonetheless, several limitations were found and are highlighted in this review. The aim of this study is to further validate and promote the use of CEUS as a quick, economic and effective diagnostic tool for this high-impact disease.

Background: Cyclothymia seems to be often associated with coexisting ADHD symptoms, although this comorbidity is understudied. Emotional dysregulation is a core symptom of both conditions. Methods: Adult subjects with cyclothymia were consecutively enrolled at the outpatient service of the Second Psychiatry Unit of the Pisa University Hospital (Italy). Screening for ADHD was performed using the Adult ADHD Self-Report Scale (ASRS). We analyzed differences in sociodemographic and clinical characteristics between subjects with and without ADHD symptomatology. Results: Of the total sample of 107 subjects, 43 % screened positive for ADHD. ADHD+ subjects were significantly younger than ADHD- subjects, had a lower level of education, a higher prevalence of psychiatric comorbidity, and a more frequent family history for ADHD and alcohol use disorder. In addition, ADHD+ subjects scored higher than ADHD- subjects on the affective instability, negative emotionality, and emotional impulsivity subscales of the RIPoSt-40 questionnaire, as well as on the 40‐item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-40) total score. They also showed a stronger association with the cyclothymic and depressive subscales of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) scale. Limitations: the small sample size, the cross-sectional nature of the study, the use of self-report questionnaires, and the use of a screening test to assess comorbidity with ADHD symptomatology. Conclusions: ADHD symptomatology is very common in cyclothymic individuals, and emotional dysregulation blurs the diagnostic boundaries between the two disorders. Several clinical features suggest the need for systematic evaluation of ADHD in patients with cyclothymic disorder.