Background/Objectives: Out of 39.9 million adults living with HIV in 2022, 20 million were women. Despite bearing a significant burden, women remain underrepresented in clinical trials, including those for antiretroviral treatments (ART). This study evaluates the safety and efficacy of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimen in a real-life cohort of 99 women with HIV (females with HIV, FWH) over 48 and 96 weeks. Methods: A retrospective cohort study utilized data from the Sardinian HIV Network and Sicilian HIV Cohort (SHiNe-SHiC) research group. The study included FWH, who started B/F/TAF as a treatment switch. The primary objectives were achieving and maintaining an HIV RNA level of <50 copies/mL at 48 and 96 weeks. Secondary objectives included treatment safety, durability, and reasons for discontinuation. Data on demographics, viro-immunological markers, lipid profiles, and treatment interruptions were extracted for analysis. Results: Among the 99 FWH, the median age was 51.9 years, and the median duration of HIV was 15.1 years. At baseline, 80.8% had undetectable HIV-RNA, which increased to 93.8% at 96 weeks. There was a statistically significant increase in CD4 cells/mL (48w p < 0.001, 96w p < 0.001) and CD4/CD8 ratio (48w p < 0.009, 96w p < 0.048), and reductions in total cholesterol (48w p < 0.003, 96w p < 0.006) and LDL (48w p < 0.004, 96w p < 0.009) levels at 48 and 96 weeks. Nine treatment interruptions were noted, with one due to adverse events. The regimen was well-tolerated overall. Conclusions: B/F/TAF demonstrated high efficacy and safety in this real-world cohort of FWH, highlighting the critical need for gender-focused research in HIV treatment. Ensuring equitable access to effective treatment options for women is imperative for the global health community’s efforts to eliminate HIV.

Heart failure (HF) is a growing concern due to the aging population and increasing prevalence of comorbidities. Despite advances in treatment, HF remains a significant burden, necessitating novel therapeutic approaches. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) have emerged as a promising treatment option, demonstrating benefits across the entire spectrum of HF, regardless of left ventricular ejection fraction (LVEF). This review explores the multifaceted mechanisms through which SGLT2is exert cardioprotective effects, including modulation of energy metabolism, reduction of oxidative stress, attenuation of inflammation, and promotion of autophagy. SGLT2is shift myocardial energy substrate utilization from carbohydrates to more efficient fatty acids and ketone bodies, enhancing mitochondrial function and reducing insulin resistance. These inhibitors also mitigate oxidative stress by improving mitochondrial biogenesis, reducing reactive oxygen species (ROS) production, and regulating calcium-signaling pathways. Inflammation, a key driver of HF progression, is alleviated through the suppression of proinflammatory cytokines and modulation of immune cell activity. Additionally, SGLT2is promote autophagy, facilitating the clearance of damaged cellular components and preserving myocardial structure and function. Beyond their glucose-lowering effects, SGLT2is provide significant benefits in patients with chronic kidney disease (CKD) and HF, reducing the progression of CKD and improving overall survival. The pleiotropic actions of SGLT2is highlight their potential as a cornerstone in HF management. Further research is needed to fully elucidate their mechanisms and optimize their use in clinical practice.

Background: Gastrointestinal mucosal damage due to human immunodeficiency virus (HIV) infection leads to microbial translocation and immune activation, contributing to the development of non-infectious comorbidities (NICM) in people living with HIV (PLWH). Additionally, persistent proviral HIV-1 in the gut-associated lymphatic tissue (GALT) can trigger immunological changes in the epithelial environment, impacting the mucosal barrier. However, the role of zonulin, a modulator of epithelial tight junctions in GALT during HIV infection, remains poorly understood. Methods: We measured zonulin in serum and intestinal tissue sections from five treatment-naive (HIV+NAIVE) and 10 cART-treated (HIV+cART) HIV+ individuals, along with 11 controls (CTRL). We compared zonulin levels with clinical characteristics, inflammatory markers (IFN-α, CXCR3, and PD-1), and the viral reservoir in peripheral blood (PB) and terminal ileum (TI). Results: Upon HIV infection, TI was found to harbor more HIV DNA than PB. Circulating zonulin levels were highest in HIV+NAIVE compared to HIV+cART or CTRL. Surprisingly, in the gut tissue sections, zonulin levels were higher in CTRL than in HIV+ individuals. Elevated circulating zonulin levels were found to be correlated with CD4+T-cell depletion in PB and TI, and with intestinal IFN-α. Conclusions: The findings of this study indicate a shift in zonulin levels from the gut to the bloodstream in response to HIV infection. Furthermore, elevated systemic zonulin levels are associated with the depletion of intestinal CD4+ T cells and increased gut inflammation, suggesting a potential link between systemic zonulin and intestinal damage. Gaining insight into the regulation of gut tight junctions during HIV infection could offer valuable understanding for preventing NICM in PLWH.

Purpose: This study aimed to characterize the association between microbial dynamics and excessive exercise. Methods: Swabbed fecal samples, body composition (percent body fat), and swimming logs were collected (n = 94) from a single individual over 107 days as he swam across the Pacific Ocean. The V4 region of the 16S rRNA gene was sequenced, generating 6.2 million amplicon sequence variants. Multivariate analysis was used to analyze the microbial community structure, and machine learning (random forest) was used to model the microbial dynamics over time using R statistical programming. Results: Our findings show a significant reduction in percent fat mass (Pearson; p < 0.01, R = −0.89) and daily swim distance (Spearman; p < 0.01, R = −0.30). Furthermore, the microbial community structure became increasingly similar over time (PERMANOVA; p < 0.01, R = −0.27). Decision-based modeling (random forest) revealed the genera Alistipes, Anaerostipes, Bifidobacterium, Butyricimonas, Lachnospira, Lachnobacterium, and Ruminococcus as important microbial biomarkers of excessive exercise for explaining variations observed throughout the swim (OOB; R = 0.893). Conclusions: We show that microbial community structure and composition accurately classify outcomes of excessive exercise in relation to body composition, blood pressure, and daily swim distance. More importantly, microbial dynamics reveal the microbial taxa significantly associated with increased exercise volume, highlighting specific microbes responsive to excessive swimming.

Background/Objectives: Head and neck cancer (HNC), predominantly squamous cell carcinoma (SCC), presents a significant global health burden. Conventional diagnostic approaches often face challenges in terms of achieving early detection and accurate diagnosis. This review examines recent advancements in hyperspectral imaging (HSI), integrated with computer-aided diagnostic (CAD) techniques, to enhance HNC detection and diagnosis. Methods: A systematic review of seven rigorously selected studies was performed. We focused on CAD algorithms, such as convolutional neural networks (CNNs), support vector machines (SVMs), and linear discriminant analysis (LDA). These are applicable to the hyperspectral imaging of HNC tissues. Results: The meta-analysis findings indicate that LDA surpasses other algorithms, achieving an accuracy of 92%, sensitivity of 91%, and specificity of 93%. CNNs exhibit moderate performance, with an accuracy of 82%, sensitivity of 77%, and specificity of 86%. SVMs demonstrate the lowest performance, with an accuracy of 76% and sensitivity of 48%, but maintain a high specificity level at 89%. Additionally, in vivo studies demonstrate superior performance when compared to ex vivo studies, reporting higher accuracy (81%), sensitivity (83%), and specificity (79%). Conclusion: Despite these promising findings, challenges persist, such as HSI’s sensitivity to external conditions, the need for high-resolution and high-speed imaging, and the lack of comprehensive spectral databases. Future research should emphasize dimensionality reduction techniques, the integration of multiple machine learning models, and the development of extensive spectral libraries to enhance HSI’s clinical utility in HNC diagnostics. This review underscores the transformative potential of HSI and CAD techniques in revolutionizing HNC diagnostics, facilitating more accurate and earlier detection, and improving patient outcomes.

Background: Sepsis is defined as life-threatening organ dysfunction caused by an abnormal host response to infection. The study aimed to evaluate the utility of presepsin (P-SEP) in predicting the risk of death in patients with sepsis at the time of intensive care unit (ICU) admission. Methods: Adult patients were included in the study if they met SEPSIS-3 criteria at ICU admission. Demographic and clinical data were collected. The following inflammatory parameters were determined: C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and presepsin (P-SEP). Material was collected for microbiological testing depending on the suspected source of infection. The primary endpoint was patient death before ICU discharge. The secondary endpoint was a positive microbiological test result. Results: Eighty-six patients were included in the study. Thirty patients (35%) died before discharge from the ICU. There was no difference in P-SEP, CRP, PCT, and IL-6 values between patients who survived and those who died (p > 0.05 for all). P-SEP, CRP, PCT, and IL-6 were determined at ICU admission and did not accurately predict the risk of death in ROC curve analysis (p > 0.05 for all). Confirmation of the location of the focus of bacterial infection by microbiological testing was obtained in 43 (49%) patients. P-SEP, PCT, CRP, and IL-6 were significantly higher in patients with positive microbiological findings. Conclusions: In patients with suspected sepsis admitted to the Intensive Care Unit, presepsin does not accurately predict the risk of in-hospital death, but it can predict a positive microbiological culture.

Acute myeloid leukemia (AML) is a heterogenous malignant hemopathy, and although new drugs have emerged recently, current treatment options still show limited efficacy. Therapy resistance remains a major concern due to its contribution to treatment failure, disease relapse, and increased mortality among patients. The underlying mechanisms of resistance to therapy are not fully understood, and it is crucial to address this challenge to improve therapy. Macrophages are immune cells found within the bone marrow microenvironment (BMME), of critical importance for leukemia development and progression. One defining feature of macrophages is their plasticity, which allows them to adapt to the variations in the microenvironment. While this adaptability is advantageous during wound healing, it can also be exploited in cancer scenarios. Thus, clinical and preclinical investigations that target macrophages as a therapeutic strategy appear promising. Existing research indicates that targeting macrophages could enhance the effectiveness of current AML treatments. This review addresses the importance of macrophages as therapeutic targets including relevant drugs investigated in clinical trials such as pexidartinib, magrolimab or bexmarilimab, but also provides new insights into lesser-known therapies, like macrophage receptor with a collagenous structure (MACRO) inhibitors and Toll-like receptor (TLR) agonists.

Asthma is a chronic respiratory condition predominantly driven by a type 2 immune response. Epithelial-derived alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 orchestrate the activation of downstream Th2 cells and group 2 innate lymphoid cells (ILC2s), along with other immune effector cells. While these alarmins are produced in response to inhaled triggers, such as allergens, respiratory pathogens or particulate matter, disproportionate alarmin production by airway epithelial cells can lead to asthma exacerbations. With alarmins produced upstream of the type 2 inflammatory cascade, understanding the pathways by which these alarmins are regulated and expressed is critical to further explore new therapeutics for the treatment of asthmatic patients. This review emphasizes the critical role of airway epithelium and epithelial-derived alarmins in asthma pathogenesis and highlights the potential of targeting alarmins as a promising therapeutic to improve outcomes for asthma patients.

Background/Objectives: Myocardial involvement has been observed in athletes following SARS-CoV-2 infection. It is unclear if these changes are due to myocardial damage per se or to an interruption in training. The aim of this study was to assess cardiac function and structure in elite athletes before and after infection (INFAt) and compare them to a group of healthy controls (CON). Methods: Transthoracic echocardiography was performed in 32 elite athletes, including 16 INFAt (median 21.0 (19.3–21.5) years, 10 male) before (t0) and 52 days after (t1) mild SARS-CoV-2 infection and 16 sex-, age- and sports type-matched CON. Left and right ventricular global longitudinal strain (LV/RV GLS), RV free wall longitudinal strain (RV FWS) and left atrial strain (LAS) were assessed by an investigator blinded to patient history. Results: INFAt showed no significant changes in echocardiographic parameters between t0 and t1, including LV GLS (−21.8% vs. −21.7%, p = 0.649) and RV GLS (−29.1% vs. −28.7%, p = 0.626). A significant increase was observed in LA reservoir strain (LASr) (35.7% vs. 47.8%, p = 0.012). Compared to CON, INFAt at t1 had significantly higher RV FWS (−33.0% vs. −28.2%, p = 0.011), LASr (47.8% vs. 30.5%, p < 0.001) and LA contraction strain (−12.8% vs. −4.9%, p = 0.050) values. Conclusions: In elite athletes, mild SARS-CoV-2 infection does not significantly impact LV function when compared to their pre-SARS-CoV-2 status and to healthy controls. However, subtle changes in RV and LA strain may indicate temporary or training-related adaptions. Further research is needed, particularly focusing on athletes with more severe infections or prolonged symptoms.

Lung cancer is the leading cause of cancer-related morbidity and mortality. The median survival time for patients with advanced non-small-cell lung cancer before the era of molecular-based personalized treatment was 7.9 months. The discovery of predictive factors and the introduction of molecular diagnostics into daily practice made a breakthrough, enabling several years of survival in patients with advanced disease. The discovery of rearrangements in the ALK gene and ALK tyrosine kinase inhibitors has resulted in a dramatic improvement in the prognosis of patients with this subtype of cancer. Currently, three generations of ALK inhibitors differing in activity, toxicity and degree of penetration into the central nervous system are available in clinical practice. The current state of knowledge on ALK inhibitors used in clinical practice is summarised in this research paper. Methods of diagnosis of abnormalities in ALK have been shown, and the review of research that contributed to the development of the next generation of ALK inhibitors has been presented.