The Fibrosis-4 index predicts all-cause mortality in a cohort of patients at high cardiovascular risk partly through glomerular filtration rate reduction

Background and aim: Fibrosis-4 (FIB-4) index is a widely used test for non-invasively assessing liver fibrosis. We aimed to investigate the association between FIB-4 index and risk of all-cause mortality in patients at high cardiovascular (CV) risk and to determine whether coexisting renal dysfunction mediates this association. Methods and results: Single-center prospective study of 994 patients with established or suspected coronary artery disease undergoing coronary angiography, followed for a median of 44 months. Mortality data were obtained through the Italian Health Card Database. At baseline, the median FIB-4 index was greater in deceased vs. alive patients (1.71 vs. 1.38, p < 0.001) and in those with reduced eGFR than in those with normal eGFR (1.65 vs. 1.37, p < 0.001). For each unit increase in the baseline log-FIB-4 index, the risk of all-cause mortality sharply increased during the follow-up (hazard ratio [HR] 2.31, 95%CI 1.31–4.08, p = 0.004). Similarly, assuming the lowest baseline FIB-4 risk category as the reference, the risk of all-cause mortality progressively increased across the indeterminate (HR 1.82, 95%CI 1.18–2.82, p = 0.007) and the highest baseline FIB-4 risk categories (HR 2.33, 95%CI 1.37–3.97; p = 0.002). A causal mediation analysis showed that about one-third of the effect of FIB-4 index on mortality risk was mediated by reduced eGFR (32.8 %, p = 0.01). Conclusions: Increased FIB-4 index predicts the long-term risk of all-cause mortality in patients at high CV risk, and this risk is, at least in part, mediated by reduced eGFR. Further prospective studies are needed to confirm these findings

Association of race with incidence, characteristics, and mortality from incidental prostate cancer: Analysis of two North American contemporary cohorts

Background: Non-Hispanic Black (NHB) men are at higher risk both for incidence and mortality from prostate cancer (PCa) compared to Non-Hispanic White (NHW) men, but these findings arise from biopsy-detected PCa reports. We aimed to compare the incidence, subsequent management and cancer-specific mortality (CSM) of incidental PCa among NHB and NHW men, using two different North American cohorts. Methods: The Surveillance, Epidemiology and End-Result (SEER: 2004-2017) and our institutional Henry Ford Health (HFH: 1995-2022) databases were queried to identify men diagnosed with incidental PCa. Cumulative incidence estimates were used to calculate CSM differences between NHB and NHW men. Competing-risk multivariable regression analysis tested the impact of race on CSM, after accounting for all available covariates. Results: A total of 418 and 6,124 incidental PCa cases were recorded in HFH and SEER database respectively. No pathological differences were observed between NHB and NHW men in both the cohorts, except for prostate-specific antigen (PSA) value at diagnosis, which was higher in NHB men. At 10-years, the CSM rates were 5.5% vs 7.2% in our cohort and 8.6% vs 10.3% in the SEER cohort for NHW and NHB men, respectively (all Gray's test p-value > 0.05). At multivariable, race was not an independent predictor of CSM in our HFH cohort (HR: 1.46, 95% CI: 0.57-3.71, p = 0.6). In the SEER cohort, NHB men were 34% less likely to die from PCa from 1 year to the next (95% CI: 0.49-0.90, p = 0.008), when compared with NHW men. Conclusions: In the comparison of incidental PCa findings between NHB and NHW men, both groups had similar pathological characteristic and survival outcomes. These findings are different from the 'conventional' screening-detected PCa and suggest that racial differences have minimal to no adverse effects on PCa-specific mortality after incidental diagnosis

Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion

The classification of multiple sclerosis (MS) into the two distinct phases of relapsing-remitting and progressive, including primary progressive and secondary progressive phenotypes (PPMS and SPMS, respectively) has long been accepted; however, there are several unmet needs associated with this particular model. The observation that both inflammation and neurodegeneration are present from the onset of MS has resulted in a paradigm shift towards MS as a disease continuum driven by pathological mechanisms underlying clinical progression. Here we report the results from a meeting of Italian MS specialists, exploring the evolving perception of MS pathobiology and its implications for diagnosis and treatment. Insights garnered from the expert panel advocate for a redefined understanding of MS. This expert opinion paper reviews the disease continuum and the intertwined nature of inflammatory and neurodegenerative processes. Also, the need for changes in diagnostic criteria and treatment strategies, including the development of novel biomarkers and new therapies targeting smouldering disease, is discussed

Analysis of the Development of Gender Stereotypes and Sexist Attitudes Within a Group of Italian High School Students and Teachers: A Grounded Theory Investigation

Gender stereotypes and sexist attitudes continue to persist in educational settings, with significant implications for students’ achievement and well-being. This study aimed to investigate the development of gender stereotypes and sexist attitudes among Italian high school students and trainee teachers. A series of focus groups were conducted with a group of Italian school students and trainee teachers to uncover the complex interplay of individ- ual, interpersonal, institutional, and societal factors that contribute to the formation and perpetuation of these biases. Analysis was conducted using a grounded theory approach. The findings reveal a nuanced and multifaceted understanding of the issue, highlighting the critical role of teacher attitudes, peer influence, and broader cultural norms in shaping students’ perceptions and behaviors. This study offers insights for educators, policymak- ers, and researchers seeking to address gender inequities in education and promote more inclusive and equitable learning environments

Global Andrology Forum Clinical Practice Guidelines on the Management of Premature Ejaculation

Purpose: Premature ejaculation (PE) is a commonly encountered male sexual dysfunction (MSD) with various definitions, diagnostic criteria, and treatment options, leading to significant heterogeneity and controversy in its management. This study aimed to explore the global practice patterns of the diagnosis and management of PE. Materials and methods: A cross-sectional, global, online survey on PE was conducted using a questionnaire developed by an international cohort of experts. Results were analyzed using R version 4.1.2. Additionally, expert recommendations were formulated using a modified Delphi method. Results: The survey was completed by 264 participants from 41 countries. The majority of respondents were below the age of 45 years and were urologists focusing on andrology and sexual health. PE diagnosis was primarily based (by 61.5%) on an intravaginal ejaculatory latency time of less than one minute. Lifelong PE was the most common category reported (47.7%), and most respondents (84.2%) observed ante-portas PE in less than 25% of cases. Distinguishing PE from erectile dysfunction was challenging for many respondents (60.7%). Diabetes mellitus was the most common comorbidity (17.1%). Pharmacological therapy was the most common treatment method (34.3%), with dapoxetine being the most preferred medication (37.9%). Surgical methods were infrequently used. Emerging treatments like hyaluronic acid gel glans augmentation were favored by only 11.7%. Patient satisfaction was the primary criterion for successful PE treatment (55.9%), and cost was a significant concern for many (35.5%). Conclusions: This global survey highlights significant diversity in the diagnostic and treatment strategies for PE. Standard diagnostic criteria are generally accepted, off-label medication is widely used in therapy, and the role of surgery is still controversial. A multi-modal therapy approach, tailored to the patient's specific needs, is favored. Further research into the neurobiology of PE and the development of effective and safe options is crucial for improving the management of PE