Medicine and Pharmacology

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic disorder shaped by inter-organ crosstalk: dynamic, bidirectional communication through which the liver and endocrine organs, gut, adipose tissue, brain, kidney, skeletal muscle, and bone exchange signals to coordinate metabolism, immunity, and tissue homeostasis. Across these axes, neural circuits, hormones, cytokines, adipokines, hepatokines, myokines, osteokines, bile acids, microbial metabolites, lipids, extracellular vesicles, and microRNAs integrate nutrient handling, insulin action, immunity, mitochondrial function, and tissue remodeling. Perturbation of these networks converts physiological homeostasis into self-reinforcing loops of substrate overflow, endocrine dysregulation, dysbiosis, inflammation, and fibrogenesis, while hepatic dysfunction propagates renal, neurocognitive, cardiometabolic, and musculoskeletal complications. This framework helps explain why individuals with comparable steatosis show divergent trajectories of metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, extrahepatic disease, and treatment response. It also highlights tractable points of intervention, including restoration of adipose buffering, modulation of gut microbial and bile-acid signaling, correction of endocrine drivers, preservation of muscle and bone, and integrated cardio–kidney–liver risk reduction across different disease stages and clinical phenotypes. We argue that precision hepatology should move beyond isolated assessment of liver fat and fibrosis towards multidimensional phenotyping of dominant crosstalk mechanisms. Longitudinal multi-omic studies and trials incorporating outcomes across organs are now required to distinguish causal signals from disease correlates, define clinically actionable endotypes, and test whether targeting one node can restore durable metabolic and functional resilience throughout the interconnected MASLD network, while improving patient-centered outcomes across the disease course.

Abstract: Background/Objectives: Diabetic foot syndrome (DFS) is a serious complication of diabetes that poses a high risk of morbidity/mortality. The management of these patients requires a multidisciplinary team approach, as these patients are “complex” and “fragile”. Despite this, the rate of re-amputation remains high. This study aims to evaluate the degree of multidimensional complexity in patients with DFS using specific tools and to determine if it is an additional risk factor for amputation. Methods: The study was conducted on a cohort of 115 patients referred to a Tertiary Center of University Hospital of Modena from January to December 2021. The study used 12 variables to assess patients, including age, sex, caregiver presence, BARTHEL INDEX, LAWTON-BRODY SCALE, Mini Mental State Examination, Cumulative Illness Rating Scale (CIRS), SINBAD system, Malnutrition Universal Screening Tool and Italian National Association of Social Workers Tool. All patients were taken care of by the Multidisciplinary Team in order to standardize care according to the updated guidelines. Patients were classified based on amputation and revascularization status. Statistical analyses were performed using R software version 4.1.1. Results: The analysis showed that a greater clinical complexity and more severe ulcer had a greater risk of amputation (respectively OR 3.13, p 0.035 and OR 1.53, p 0.015). The study confirms the predictive value of tools such as CIRS and SINBAD in amputation risk stratification for patients with DFS. Conclusions: Although limitations, due to a small sample size, the use of multidisciplinary approach and multidimensional evaluation tools can identify “unconventional” risk factors that, if modified, could delay and/or reduce the risk of amputation. Further studies are needed to investigate the role of caregiving in the prevention of amputation in patients with DFS.

Abstract: Many people take more than one medicine at a time — a spoon of cough syrup, a fever tablet, a cold-and-flu sachet — often on the same afternoon, and sometimes with a drink of alcohol. This is casually called a “medicine cocktail.” This article explains, in plain school-textbook language, why such combinations can be harmful. It corrects a common misunderstanding: dangerous combinations usually do not arise because two drugs meet in a glass and brew a brand-new poison. Far more often the harm comes from duplicated active ingredients, additive effects, or the way the body chemically transforms a drug once it is swallowed. We examine what makes any molecule “poisonous,” the small number of cases where a genuinely toxic new molecule is formed, and — in an expanded central section — why alcohol is the single most dangerous thing to mix with everyday medicines. Every worked example ends with a short, simple “what to avoid” box written for school students. All chemical changes are given as balanced equations.

Abstract: Increasingly sophisticated genetic panels have disproportionately increased the identification rate of novel gene variants in Mendelian conditions. In Fabry disease (FD), this phenomenon is particularly relevant because the pathogenicity of individual gene variants has an impact on treatment proposal. In fact, FD is characterized by a phenotypical heterogeneity depending on patients' biological sex and the underlying GLA mutation. This represents the main reason why integrating genetic data with phenotypic expression is challenging, and defining the pathogenic role of novel variants remains complex. The early discrimination between pathogenic and non-pathogenic GLA variants is crucial to enable timely initiation of treatments such as Enzyme Replacement Therapy (ERT), which has been shown to significantly slow down the progression of the disease. In fact, the most severe cases of FD have a significantly compromised quality of life up to reduced life expectancy, especially with regard to cardiac and renal complications. In recent years, some GLA variants have been reclassified following investigation and clinical observations by multidisciplinary working groups that have made it possible to better define if they are pathogenic or not. Regardless of the clinical scenario leading to the identification of a novel GLA variant (i.e., family screening, neonatal screening, clinical profile suggestive of FD, incidental finding), any genetic finding becomes relevant when it is complemented by laboratory, clinical and instrumental investigations that require a concerted effort among the many health care professionals involved in the diagnostic process. The present work summarizes the outcomes of a series of expert meetings with the aim to provide some shared and practical indications for managing the genetic report of a novel GLA variant so to promptly start the most suitable diagnostic journey and assess corresponding phenotype and clinical characterization.

Abstract: Background: Acute myeloid leukemia (AML) remains a treatment challenge due to the systemic toxicity of conventional chemotherapy. Venetoclax, a selective BCL-2 inhibitor, shows promise in the treatment of AML; however, its clinical efficacy is limited due to inadequate pharmacokinetic properties. PEG-PLGA-based polymeric nanoparticles provide a biocompatible platform for improving drug stability, controlling release behavior, and potentially enhancing intracellular drug availability. Methods: The physicochemical properties of VEN-PEG-PLGA nanoparticles were evaluated by dynamic light scattering (DLS), scanning electron microscopy (SEM), drug loading analysis, and in vitro drug release. Antileukemic activity was assessed in THP-1 cells using the CCK-8 cytotoxicity assay, propidium iodide (PI)-based cell cycle analysis, Annexin V-FITC/PI apoptosis assay, and Western blot analysis of Bcl-2, cleaved caspase-3, cleaved caspase-9, ERK1/2, phospho-ERK1/2 (p-ERK1/2), NF-κB, and phospho-NF-κB (p-NF-κB). Results: VEN-PEG-PLGA nanoparticles exhibited a mean particle size of 186 ± 4 nm with a polydispersity index of 0.195 ± 0.005, 89% loading efficiency, and 6.26% loading capacity. The nanoparticles demonstrated a pH-responsive drug release profile, reaching approximately 72–74% cumulative release at pH 7.4 and 88–89% at pH 5.5 after 96 h. In THP-1 cells, both free venetoclax and VEN-PEG-PLGA na-noparticles exhibited concentration-dependent cytotoxicity, although free venetoclax showed greater cytotoxicity, with EC₅₀ values of 5.59 × 10⁻⁷ M and 1.35 × 10⁻⁶ M, respectively. Cell cycle analysis demonstrated an increase in the G0/G1 cell population from 49.30% in the control group to 61.04% following treatment with VEN-PEG-PLGA nanoparticles, accompanied by a reduction in the G2/M phase. Annexin V-FITC/PI analysis showed that VEN-PEG-PLGA nanoparticles in-creased the proportion of late apoptotic cells to 36.99%, compared with 22.13% following free venetoclax treatment. Western blot analysis demonstrated reduced Bcl-2, ERK1/2, phos-pho-ERK1/2, and phospho-NF-κB expression, together with increased cleaved caspase-3 and cleaved caspase-9 expression in both treatment groups, with these changes being more pronounced in the VEN-PEG-PLGA nanoparticle-treated group. Conclusions: Venetoclax-loaded PEG-PLGA nanoparticles modulated apoptosis-related responses, cell cycle progression, and BCL-2/ERK1/2/NF-κB-associated signaling pathways in THP-1 cells. These findings provide preliminary in vitro evidence supporting further preclinical evaluation of VEN-PEG-PLGA na-noparticles in AML models.

Abstract: Background/Objectives The accurate estimation of glomerular filtration rate (GFR) is essential for assessing trends in the prevalence (CKD), yet standard serum creatinine (SCr)-based estimates (eGFR_SCr) are limited by individual variations in muscle mass. While demographic surrogates like age and sex are typically used to account for these variations, they often lead to eGFR misclassification in individuals. This study investi-gated whether normalizing SCr to Dual-energy X-ray absorptiometry (DEXA)-derived Lean Mass Index (LMI) improves the association with cardiometabolic risk. Methods We analyzed data from 11,143 adults (mean age 46.0 ± 17.2 years) in the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort. Individual SCr concentrations were normalized to sex- and age-specific LMI reference values to calculate LMI-adjusted eGFR (eGFR_LMISCr). The strength of associations between eGFR_SCr and eGFR_LMISCr with cardiometabolic risk factors (dyslipidemia, hypertension, pre-diabetes/diabetes, and metabolic syndrome) was compared using age- and sex-adjusted logistic regression with bootstrap resampling. Results While eGFR_SCr and eGFR_LMISCr were highly correlated (R2 = 0.897), LMI adjust-ment led to significant reclassification between CKD stages G1, G2, and G3a. eGFR_LMISCr demonstrated significantly stronger associations with dyslipidemia, arterial hyperten-sion, pre-diabetes/diabetes, and metabolic syndrome compared to standard eGFR_SCr. Longitudinal analysis showed that LMI adjustment stabilizes eGFR change estimates, particularly in younger men. Conclusion Adjusting serum creatinine for LMI signifi-cantly enhances the epidemiological utility of GFR estimation. GFR_LMISCr improves car-diometabolic risk stratification, potentially offering a valuable method to "salvage" the utility and comparability of eGFR_SCr in historic cohorts in early-stage filtration impair-ment in settings where DEXA but not Cystatin C is available.

Abstract: Bladder cancer is one of the most common malignancies of the urinary tract and remains a major global health burden because of its high incidence, frequent recurrence, and substantial healthcare costs associated with lifelong surveillance. The disease exhibits remarkable clinical and biological heterogeneity, ranging from low-risk non–muscle-invasive bladder cancer (NMIBC) to highly aggressive muscle-invasive and metastatic urothelial carcinoma. Consequently, there is an urgent need for more accurate approaches to early diagnosis, individualized risk stratification, treatment selection, and long-term disease monitoring. Recent advances in artificial intelligence (AI), machine learning, and deep learning have created new opportunities to improve bladder cancer management across the entire continuum of care. AI-assisted approaches have demonstrated promising applications in cystoscopy, urine cytology, digital pathology, radiomics, and multimodal clinical decision support. These technologies have the potential to improve tumor detection, reduce interobserver variability, integrate heterogeneous clinical and molecular data, and generate individualized predictions of recurrence, progression, and therapeutic response. Despite encouraging progress, several important barriers continue to limit routine clinical implementation. Most published AI models are based on retrospective datasets, while external validation across diverse healthcare systems remains limited. Additional challenges include variability in imaging protocols and biomarker platforms, limited model interpretability, regulatory and ethical considerations, and integration into existing clinical workflows. Overall, AI has the potential to become an integral component of precision bladder cancer care. Continued development of large multicenter datasets, prospective clinical validation, standardized reporting, and seamless integration into routine clinical practice will be essential to fully realize the benefits of AI for improving diagnosis, risk prediction, treatment selection, survivorship, and long-term patient outcomes.

Abstract: Background/Objectives: Finerenone improves cardiovascular and renal outcomes in diabetic kidney disease (DKD), but hyperkalemia remains a key safety concern. Patients with elevated baseline potassium levels (≥ 4.9 mEq/L) are largely excluded from clinical trials, and real-world data in this population are scarce. Methods: In this retrospective multicenter cohort study derived from the FINE-TURK cohort, adults with DKD who initiated finerenone with baseline serum potassium ≥ 4.9 mEq/L were included. The primary outcome was clinically significant hyperkalemia (CSH) (≥ 5.5 mEq/L) within three months. Multivariable logistic regression analyses were used to identify associated factors, with multiple sensitivity analyses performed. Results: 166 patients were included, of whom 47 (28.3%) had baseline potassium levels between 5.1 to 5.5 mEq/L. Of the 166 patients, 35 (21.1%) developed CSH, and 10 (6%) patients had follow-up potassium ≥ 6.0 mEq/L. 126 (76.8%) patients required no intervention, 24 (14.6%) were initiated on potassium binders, and finerenone was discontinued only in 12 (7.3%) patients. Baseline eGFR, baseline urinary albumin, loop diuretic use and 20mg finerenone dose were associated with CSH. In contrast, baseline serum potassium was not associated with CSH. Conclusions: In patients with DKD and elevated baseline potassium levels, finerenone initiation was associated with manageable rates of hyperkalemia. Our findings support the cautious use of finerenone in selected patients under close monitoring, as well as highlight the need for a multidimensional approach to hyperkalemia risk assessment.

Abstract: Background: Sarcopenia is highly prevalent among older adults with chronic kidney disease (CKD) and is associated with adverse clinical outcomes. The finger-ring (Yubi-wakka) test is a simple anthropometric screening tool based on calf circumference; however, its performance in older adults with CKD remains unclear. This study aimed to investigate the association of the finger-ring test with low muscle mass, sarcopenia, and comprehensive geriatric assessment parameters and to evaluate its diagnostic performance for identifying low muscle mass in older adults with CKD. Methods: This cross-sectional study included 115 patients aged ≥65 years with CKD who were evaluated in geriatric and nephrology inpatient services. After excluding two participants with missing finger-ring measurements, 113 individuals were analyzed. Muscle mass was assessed using bioelectrical impedance analysis and low muscle mass was defined according to EWGSOP2-based Turkish cut-off values. Demographic characteristics, anthropometric measurements, laboratory findings, and comprehensive geriatric assessment parameters were recorded. Correlation analyses, logistic regression models, receiver operating characteristic (ROC) analyses, and likelihood-ratio tests were performed. Results: Among 113 participants, 62 were classified as finger-ring positive (FR=0) and 51 as finger-ring negative (FR=1). Low muscle mass was significantly more frequent in the FR=0 group than in the FR=1 group (51.6% vs. 24.0%, p=0.005). Finger-ring test results showed strong correlations with calf circumference (rho=0.689, p< 0.001) and body mass index (BMI) (rho=0.631, p< 0.001), whereas the correlation with muscle mass was modest (rho=0.250, p=0.008). For detecting low muscle mass, the finger-ring test demonstrated an area under the curve (AUC) of 0.643 (95% CI 0.554–0.732), sensitivity of 72.7%, specificity of 55.9%, positive predictive value of 51.6%, and negative predictive value of 76.0%. In multivariable analyses, BMI remained the strongest independent determinant of finger-ring test results, whereas the association with muscle mass lost statistical significance after BMI adjustment. Adding age and sex significantly improved discrimination, while the contribution of nutritional status was limited. Conclusions: The finger-ring test is associated with low muscle mass in older adults with CKD; however, its diagnostic performance is modest and appears to be substantially influenced by body size and calf circumference. Therefore, the finger-ring test should be considered a simple adjunctive screening tool rather than a stand-alone method for identifying low muscle mass in this population.

Abstract: Background: The widespread success of antiretroviral therapy (ART) has transformed HIV into a chronic condition, shifting clinical attention toward aging-associated comorbidities, including autoimmune and rheumatologic diseases. However, the epidemiology, clinical spectrum, and treatment outcomes of these conditions in older people living with HIV (PLH) remain incompletely characterized. Objective: This scoping review aimed to map contemporary evidence on autoimmune and rheumatologic diseases in aging PLH in the ART era, with emphasis on epidemiology, clinical phenotypes, diagnostic challenges, and therapeutic outcomes. Methods: A systematic search of PubMed, Embase, and Scopus was conducted for studies published from January 1, 2021, onward. Eligible studies included adult PLH with autoimmune or rheumatologic conditions and were screened according to PRISMA-ScR methodology. Case reports, non-human studies, and studies published before 2021 were excluded. Data were extracted narratively from included studies. Results: The search yielded 438 records, of which 134 duplicates were removed. After title, abstract, and full-text screening, 8 studies were included. The evidence identified a heterogeneous spectrum of autoimmune and rheumatologic manifestations in PLH, including systemic lupus erythematosus, reactive arthritis, psoriatic arthritis, rheumatic heart disease, immune thrombocytopenia, renal immune-mediated pathology, and myasthenia gravis. Contemporary data suggest that biologic and targeted small-molecule therapies are generally effective and well tolerated in selected PLH, although opportunistic infections and transient viral load increases have been reported with some agents. Conclusion: Autoimmune and rheumatologic diseases in aging PLH represent an emerging ART-era challenge. Prospective studies and multidisciplinary guidelines are needed to optimize diagnosis and treatment.

Abstract: Autoimmune rheumatic diseases are still treated predominantly through broad or targeted suppression of inflammatory pathways, yet durable restoration of self-tolerance remains a central unmet therapeutic goal. This narrative review examines restoration of immune tolerance as an emerging translational framework in rheumatology, integrating checkpoint agonism, antigen-specific immunotherapy, regulatory cell-based strategies, and immune-reset approaches within a unified therapeutic perspective. Rather than treating these strategies as isolated innovations, the review evaluates how each attempts to restore, reinforce, or reconfigure immune restraint at distinct biological levels, spanning inhibitory receptor signaling, antigen-selective non-responsiveness, dominant regulatory control, and deeper reconfiguration of pathogenic immune architecture. Their relevance is considered across rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, and systemic sclerosis, with emphasis on mechanistic rationale, translational maturity, disease-specific therapeutic fit, biomarkers, therapeutic timing, and major barriers to clinical implementation. Collectively, these approaches suggest a shift in rheumatology from repeated control of inflammatory consequences toward more selective and potentially durable recalibration of autoreactive immunity. Although the field remains biologically and clinically immature, restoration of immune tolerance is emerging as an important organizing principle for the development of more precise and potentially disease-modifying therapies in autoimmune rheumatic disease.

Abstract: Objectives: Streptococcus pneumoniae is a major respiratory pathogen. Reports during the COVID-19 era suggest decreased pneumococcal activity. This study aimed to assess the frequency of S. pneumoniae in adult sputum cultures and its antimicrobial susceptibility in a tertiary care hospital. Materials and Methods: This retrospective laboratory-based study was conducted in a tertiary care hospital in Turkey. Sputum cultures from adult patients between October 1, 2021, and October 1, 2023, were analyzed. Demographic, clinical, and antimicrobial susceptibility data of culture-confirmed cases were obtained from medical records. Results: Among 3,433 sputum cultures, only three (0.087%; 95% CI: 0.018%–0.255%) yielded S. pneumoniae. All patients were male with comorbidities such as cardiovascular disease, COPD, or diabetes. Pneumonia developed during hospitalization for non-infectious conditions. All isolates were susceptible to fluoroquinolones, rifampicin, tetracycline, and ceftriaxone; one showed resistance to macrolides and clindamycin. No multidrug resistance was detected. Conclusion: An extremely low pneumococcal isolation rate was observed during the COVID-19 and post-pandemic period. These findings align with global reports of reduced pneumococcal activity. Continued surveillance is essential to monitor epidemiological trends and resistance patterns.

Abstract: Background/Objectives: Acute pulmonary embolism (PE) is a major cause of cardio-vascular mortality, with prognosis influenced by hemodynamic status, comorbidities, and biomarker profiles. Although several laboratory markers have demonstrated prog-nostic relevance in PE, it remains unclear whether their predictive performance differs in patients with active malignancy. This study aimed to identify laboratory predictors of in-hospital mortality in acute PE and to evaluate the modifying effect of malignancy on biomarker-based prognostic stratification. Methods: This retrospective multicenter cohort study included 2803 consecutive patients with computed tomography-confirmed acute PE enrolled in the Regional Pulmonary Embolism Registry (REPER) between January 2015 and April 2026. Univariate and multivariable logistic regression analyses were performed to identify predictors of in-hospital mortality in the overall cohort and in subgroups stratified by malignancy status. Interaction analyses were used to assess effect modification by malignancy. Results: Active malignancy was present in 14.02% of patients, while overall in-hospital mortality was 14.93%. In the overall cohort, multivariable analysis identified malignancy (OR 1.698, 95% CI 1.128–2.555, p = 0.011), C-reactive protein (CRP), glucose, creatinine clearance (CrCl), platelet count, and white blood cell count as independent predictors of in-hospital mortality (BNP was excluded from multivariable models due to missing data). Mortality was significantly higher in patients with ma-lignancy compared with those without (20.9% vs. 13.2%, p < 0.001). In patients with malignancy, CRP and glucose remained independent predictors, whereas in non-malignant patients, CRP, glucose, and CrCl were independently associated with mortality. Significant interaction effects were observed for CrCl, age, glucose, and white blood cell count. Conclusions: Malignancy is an important predictor of in-hospital mortality in acute PE and may partially influence the prognostic performance of certain conventional biomarkers. These findings suggest that while standard risk markers remain broadly reliable, specific parameters might benefit from a cautious, malignancy-aware interpretation.

Abstract: Aim: Severe aortic stenosis (AS) with cardiogenic shock (CS) presents a complex clinical challenge. For these patients, the optimal management strategy- either direct transcatheter aortic valve replacement (TAVR) or a staged approach with balloon aortic valvuloplasty (BAV) as a bridge to TAVR (BAV-TAVR) is uncertain. We aimed to compare the outcomes of these two strategies. Methods: We conducted a retrospective cohort study using TriNetX database. In this study, we identified patients with CS undergoing TAVR or BAV-TAVR. After matching propensity scores, 198 patients were analyzed in each group (total 396). The primary outcome was major adverse cardiovascular events (MACE) at 30 days, 1 year, and 3 years. Results: The analysis included 396 matched patients (198 in each cohort). There was no significant difference in the primary endpoint of MACE at 30 days between the staged BAV and direct TAVR groups (HR 1.14; 95% CI 0.79–1.64; p=0.91), and this finding was consistent at 1 and 3 years with HR 1.20 and 1.17 respectively. Similarly, no differences were observed in secondary outcomes including all-cause mortality, stroke, and new permanent pacemaker implantation, at 30 days, 1, and 3 years. Conclusion: For patients with severe AS complicated by CS, a staged strategy of using BAV-TAVR resulted in comparable short and long-term outcomes to direct TAVR. These findings suggest that BAV is a viable and safe bridging option in high-risk patients whose immediate candidacy for definitive therapy is uncertain.

Abstract: The rapid expansion of biologic therapies for immune-mediated inflammatory diseases has raised significant clinical concerns regarding malignancy risk, particularly for patients with a history of cancer. This narrative review explores the safety of targeted therapies across dermatology, rheumatology, respiratory medicine, and gastroenterology to guide clinicians in these therapeutic dilemmas. We conducted a non-systematic review of the literature, prioritizing longitudinal registry and real-world cohort data over clinical trials to better capture malignancy outcomes with long latency periods. Results indicate that tumor necrosis factor (TNF) inhibitors, which have the most extensive evidence base, do not consistently demonstrate an increased risk of overall malignancy or recurrence across specialties. Newer agents, including interleukin (IL)-17 and IL-23 inhibitors, show particularly reassuring safety profiles in both trial and registry data, with some evidence suggesting a potential reduction in certain cancer incidences. While dupilumab is associated with the potential unmasking of cutaneous T-cell lymphoma, overall cancer rates remain stable among users. Most clinical guidelines support an individualized, multidisciplinary approach involving oncology consultation. We conclude that current biologic therapies generally pose a lower malignancy risk compared to older systemic treatments. Future management requires validated decision frameworks and mandatory participation in real-world registries to refine long-term safety assessments.

Abstract: Background: Peripheral intravenous catheters (PIVCs) are the most frequently inserted intravascular devices globally (~2 billion per year), yet their infectious complications—and particularly hematogenous distant infections—remain systematically underestimated and excluded from mainstream catheter-associated bloodstream infection (CABSI) surveillance. We present the first systematic review and meta-analysis specifically focused on hematogenous distant complications as the primary outcome. Methods: A systematic search of PubMed, EMBASE, CINAHL, and the Cochrane Library (no date restriction through April 2025) was conducted following PRISMA 2020 guidelines. Random-effects meta-analysis with Freeman–Tukey double-arcsine transformation was used for proportion outcomes; pooled incidence rates per catheter and per 1000 catheter-days were computed. Primary outcomes were infective endocarditis (IE), osteomyelitis, septic arthritis, epidural abscess, and septic emboli attributable to PIVC-related bacteremia. Results: Sixty-seven studies (n = 1,247,430 PIVCs; 2,547,841 catheter-days) met inclusion criteria. Pooled PIVC-BSI incidence was 0.028% per catheter (95% CI 0.009–0.081; I² = 96.8%) in high-income settings and 2.41/1000 catheter-days (95% CI 1.97–2.89) in low-/middle-income country ICUs. Among PIVC-related Staphylococcus aureus bacteremia (PIVC-SAB) episodes, the pooled metastatic complication rate was 37.2% (95% CI 24.1–51.6%; I² = 71.4%). IE developed in 6–23% of PIVC-SAB cases. Thirty-day all-cause mortality ranged from 12.9% to 25.0% overall; for S. aureus-specific cohorts it reached 18.3–26.5%. Dwell time &gt; 96 h (OR 3.16, 95% CI 1.73–5.77), antecubital fossa insertion (OR 8.20, 95% CI 3.10–21.70), and large-bore gauge ≤16G (HR 4.65, 95% CI 1.19–18.20) were independently associated with PIVC-BSI in PIVC-specific multivariate analyses. Conclusions: PIVCs cause clinically severe hematogenous distant infections in approximately one-third of bacteremia episodes, with 30-day mortality equivalent to central venous catheter bloodstream infections. Current national surveillance systems that exclude PIVCs produce a critical undercount of catheter-attributable infections and deaths. Mandatory bundle-based PIVC care, inclusion of PIVCs in national BSI surveillance, and dedicated prospective studies quantifying the burden of hematogenous complications are urgently warranted.

Abstract: Background/Objectives: Coexistence of systemic sclerosis and sarcoidosis is very ra-re. Both are systemic autoimmune diseases with lung involvement but with different pathogenesis. In contrast to findings of mid- to upper-lobe interstitial lung disease (ILD) or/with hilar lymphadenopathy in sarcoidosis, the most common lung manifes-tation of systemic sclerosis is lower-lobe ILD, which is typically characterized by a nonspecific interstitial pneumonia pattern. Distinction between lung involvement re-lated to each disease is crucial due to different therapeutic approach Methods We present herein a serie of three overlap cases: two with sarcoidosis onset before the diagnosis of systemic sclerosis and the other with systemic sclerosis onset before sarcoidos. Results: A review of cases of concomitant sarcoidosis and systemic sclerosis is dis-cussed, including the pathophysiology of each disease with shared pathways leading to the development of both conditions in one patient Conclusions: The systemic sclerosis-sarcoidosis overlap is a high-risk phenotype. Early recognition and a personalized, aggressive therapeutic approach are essential to alter the natural history of these two converging fibrotic and granulomatous processes.

Abstract: Background: Cardiovascular (CV) risk is increased in psoriatic arthritis (PsA), yet vascular assessment has largely focused on carotid arteries, potentially underestimat-ing systemic atherosclerosis. Objective: To characterize the distribution and concord-ance of atherosclerotic plaques across carotid, femoral, and aortic territories in PsA and evaluate their incremental value over SCORE2. Methods: In this cross-sectional study, 250 unselected patients with PsA underwent carotid and femoral ultrasound and ab-dominal X-ray. Plaque prevalence and multiterritorial involvement (≥2 vascular beds) were assessed. Agreement between territories was evaluated using Cohen’s κ. In pa-tients aged 50–69 years, the incremental value of vascular territories over SCORE2 was evaluated using ROC curves, bootstrap-corrected decision curve analysis (DCA), and reclassification metrics (IDI and continuous NRI). Results: Plaques were detected in carotid (36.0%), femoral (62.8%), and aortic (31.6%) territories, with multiterritorial involvement in 43.2%. Agreement between vascular beds was moderate (κ ≈ 0.35). Notably, 48.1% of patients without carotid plaques had femoral involvement. SCORE2 categories showed a strong gradient with plaque prevalence (p < 0.0001). In patients aged 50–69 years, adding vascular imaging improved discrimination for multiterrito-rial disease (AUC 0.73 vs 0.86–0.90). Reclassification analyses showed greater im-provement for carotid and aortic plaque (IDI 0.28; NRI 1.24–1.33) than femoral plaque (IDI 0.21; NRI 1.11). Bootstrap-corrected DCA confirmed improved net benefit. Con-clusions: The incremental value of vascular imaging over SCORE2 is pheno-type-dependent, with femoral plaque enhancing detection of subclinical disease and carotid/aortic plaque better identifying multiterritorial burden. These findings support a tailored, multiterritorial approach to CV risk assessment in PsA.

Abstract: This study investigated the molecular epidemiological characteristics of Cryptococcus neoformans (C. neoformans) isolates from AIDS patients with cryptococcal meningitis (CM) in southern China and examined their associations with clinical features and outcomes. A total of 100 clinical isolates were identified by MALDI-TOF MS and genotyped by multilocus sequence typing (MLST). Antifungal susceptibility to five agents was assessed using the FUNGUS 3 system. Baseline demographic, clinical manifestations, radiological, and laboratory data were collected from the corresponding 100 patients, and outcomes were evaluated at weeks 4, 12, 24, and 48. Seven sequence types (STs) were identified: ST5 (83/100, 83.0%), ST4 (5/100, 5.0%), ST31 (3/100, 3.0%), ST43 (1/100, 1.0%), ST93 (4/100, 4.0%), ST395 (1/100, 1.0%), and a presumptive novel ST685 (3/100, 3.0%). Most patients were male (80.0%), and headache was the most common symptom (85.0%). Susceptibility rates for 5-flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole were 98.9% (94/95), 71.9% (69/96), 82.3% (79/96), 59.4% (41/69), and 86.8% (59/68), respectively. Cumulative mortality reached 16%, 33%, 37%, and 39% at weeks 4, 12, 24, and 48. No significant differences were observed between 83 patients infected with ST5 and 17 patients with non-ST5 in clinical presentations or antifungal susceptibility. However, patients infected with ST5 exhibited consistently better survival rates across all time points, whereas those infected with ST93 showed the highest 12-week mortality. Accordingly, ST5 is the dominant sequence type of C. neoformans in HIV-associated CM in southern China; meanwhile, non-ST5 types could have worse prognosis, indicating ST sequence typing may act as a prognostic biomarker in AIDS patients with CM.

Abstract: Introduction: A major health issue in individuals living at high altitude regions is an increase in the number of red blood cells (RBCs). This condition generates a series of physiological alterations, including the nervous system, where damage can occur due to increased blood viscosity. This increased viscosity, in turn, could compromise oxygen uptake, potentially leading to a degree of cognitive impairment. Objective: To determine the association between exposure to chronic hypoxia and sleep quality with the degree of cognitive impairment (IQ) in a young adult population residing at different altitude levels. Methodology: Two hundred apparently healthy subjects of both sexes, aged 21 to 26 years, permanently residing in four cities at different altitudes—Lima, Arequipa, Puno, and La Rinconada (50 participants per location)—were evaluated. Physiological variables such as oxygen saturation (SpO2), blood pressure (BP), heart rate (HR), and hemoglobin (Hb) and hematocrit (Hct) levels were measured. Cognitive impairment was assessed using the Montreal Cognitive Assessment (MoCA), and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). ANOVA, chi-square, and linear regression models were used to analyze correlations. Results: Hemoglobin (Hb) levels increased gradually with altitude, reaching a maximum of 19.47 ± 3.01 g/dL in La Rinconada, while SpO2 decreased to 81.64% at the same site. Moderate to severe cognitive impairment was a finding exclusive to the La Rinconada population (5100 m), where only 10% of subjects remained unaffected. Regression analysis showed that for each unit increase in Hb, the MoCA score decreased by 0.59 points, indicating that elevated Hb levels were associated with varying degrees of cognitive impairment. No association was found between sleep quality and the degree of cognitive impairment. Conclusions: Chronic exposure to severe hypoxia (>5000 m) is associated with a greater presence of cognitive impairment, while sleep quality is not associated with any degree of cognitive impairment.