Medicine and Pharmacology

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.

Abstract: Background: Mean arterial pressure (MAP) is widely used to guide hemodynamic management, yet it provides limited insight into the underlying physiological determinants of circulation. Identical MAP values may reflect markedly different states of cardiac output and vascular tone. The arterial pressure waveform contains rich physiological information beyond static pressure values, but this information is rarely quantified in a simple, continuous, and interpretable manner. Objective: To evaluate the relationship between a novel arterial waveform–derived metric, the Pulse Energy Ratio (PER), and reference cardiac output in a large intraoperative dataset. Methods: We performed a retrospective observational analysis using the VitalDB database, including 248 patients with concurrent high-resolution arterial pressure waveforms and cardiac output measurements obtained from an EV1000 volumetric monitoring system. PER was calculated as the area of the arterial waveform above the diastolic baseline normalized to the diastolic pressure–time integral for each cardiac cycle. Beat-level and rolling 10-beat averaged PER values (PERC) were analyzed. Correlations with cardiac output were assessed using aggregated time-segment data to account for repeated measures, with additional sensitivity analyses including first-differenced signals and mixed-effects modeling. Results: PER demonstrated strong positive correlation with cardiac output across a wide range of intraoperative conditions. Beat-level PER correlated with cardiac output at r = 0.781, while PERC showed r = 0.797. Rolling 10-beat averaging further strengthened these relationships (PER r = 0.834; PERC r = 0.822; all p < 0.001). These associations remained consistent across multiple analytic approaches designed to account for temporal dependence and within-subject clustering. Conclusions: The Pulse Energy Ratio is a physiologically grounded, waveform-derived metric that correlates strongly with cardiac output without requiring calibration or additional hardware. By quantifying the pulsatile component of the arterial waveform, PER may provide continuous insight into the interaction between forward flow and vascular tone. This approach has the potential to enhance interpretation of arterial pressure and support more physiologically informed hemodynamic monitoring, warranting prospective validation.

Abstract: Background and Objectives: Human immunodeficiency virus (HIV) infection is associated with immune dysregulation, which may influence the development of autoimmune diseases. However, population-based evidence on the prevalence of autoimmune diseases in individuals living with HIV remains limited, particularly in Asian populations. This study aimed to evaluate the prevalence of autoimmune diseases in individuals living with HIV in Korea using nationwide population-based data. Materials and Methods: We conducted a cross-sectional analysis using the Health Insurance Review and Assessment Service National Patient Samples from 2012 to 2015, including 4,851,064 individuals aged ≥15 years. HIV infection and autoimmune diseases were identified using ICD-10 codes. The prevalence of autoimmune diseases in individuals with HIV infection was compared with that in the general population. Antiretroviral therapy (ART) status was determined based on prescription records. Results: A total of 1,023 individuals were identified with HIV infection, all of whom were receiving antiretroviral therapy. The overall prevalence of autoimmune diseases was 4.37% in males and 2.38% in females with HIV, without significant differences compared to controls. However, the prevalence of Behçet’s disease, ulcerative colitis, and primary biliary cholangitis was significantly higher in males with HIV (P &lt; 0.05), while dermatomyositis was significantly more prevalent in females with HIV (P &lt; 0.001). Conclusions: Although the overall prevalence of autoimmune diseases was not significantly increased in individuals living with HIV, specific autoimmune diseases showed higher prevalence in this population. These findings suggest that clinicians should consider autoimmune dis-eases in the differential diagnosis of patients with HIV and highlight the need for further research on underlying immunological mechanisms.

Abstract: This study aims to present a series of cases reports of- knee arthritis occurring following COVID-19 RNA vaccination and to examine the potential role of these Spike protein-based RNA vaccines in the development of this arthritis. Although musculoskeletal disorders have been reported in connection with COVID-19 vaccines, post-vaccination arthritis is not yet listed. Given the different and specific mechanisms of Spike protein-based RNA vaccines and viral vector-based DNA vaccines, we report 7 cases that question the role of COVID-19 vaccines in the onset of early or late-onset knee arthritis observed following one or more injections. All patients (5 early onset and 2 late-onset cases) were examined in the same department and underwent a comprehensive assessment to investigate the usual causes of unilateral or bilateral oligoarthritis; none of them had a previous predisposition to rheumatic disease. No inflammatory rheumatic disease was detected, nor did any develop after a follow-up period of at least 24 months. A double-check of medical histories (both prior to and following diagnosis) was carried out by consulting the general medical database for all patients described. Post-vaccination serological monitoring of blood and synovial fluid to detect the presence of anti-spike antibodies has been requested for all patients and a synovial biopsy was performed in four of them. All patients showed improvement following low-dose prednisolone treatment within two months, but in some patients the symptoms persist. Anti-Spike antibody levels were found to be elevated in blood and synovial fluid samples from all patients. Synovial biopsies reveal chronic histiocytic (CD68+) and plasmocytic infiltration (CD3+) accompanied by neovascularisation. The similar timeline, progression and clinical manifestations of this knee arthritis might suggest a pathogenic role for the spike protein and/or an overproduction of anti-spike antibodies following mRNA vaccination.

Abstract: The COVID-19 pandemic has disrupted the lives of the world's population, resulting in over 7 million deaths. It was immediately noted that obese and/or diabetic subjects and frail elderly individuals with multiple comorbidities were more likely to have a more severe disease course. The cause of the increased morbidity and mortality in obese and/or diabetic subjects was found to be related to the presence of insulin resistance in these individuals. Furthermore, it was also discovered that COVID-19, particularly in its more severe forms, was capable of causing de novo type 1 and type 2 diabetes as well as worsening the disease course, if already present. This review aims to highlight the most accredited possible mechanisms by which subjects with insulin resistance may have a more severe disease course and those by which SARS-CoV-2 infection may cause new onset of diabetes or worsening of existing diabetes. To write this manuscript, the authors independently reviewed and compared the results of peer-reviewed and impacted journal publications, written in English, selected from the most well-known search platforms such as PubMed, Scopus, Science Direct, Google Scholar, and ResearchGate, using the following keywords: SARS-CoV-2, COVID-19, Insulin resistance, Glucose metabolism, Obesity, Diabetes, Hospitalization, Mortality.

Abstract: Background: Respiratory syncytial virus (RSV) is a serious disease in older adults with comorbidities; however, comparative data across epidemic waves, both clinically and in terms of inflammatory profiles and their diagnostic and prognostic utility, remain limited. Methods: We conducted a retrospective study of adults hospitalized with RSV infection across two epidemic waves (2022–2023 and 2024–2025). Clinical characteristics, comorbidities, severity scores, and outcomes were collected. Serum interleukin-6 (IL-6), C-reactive protein (CRP), and hematological parameters were analyzed and compared with healthy controls. Results: A total of 152 patients were included (81 in wave 1 and 71 in wave 2). Patients in wave 2 were older and had a higher burden of comorbidities, although ICU admission and in-hospital mortality were similar across waves. RSV induced a consistent systemic inflammatory response in both waves, characterized by elevated IL-6 and CRP levels, neutrophilia, lymphopenia, and increased neutrophil-to-lymphocyte ratio, without relevant inter-wave differences. All biomarkers demonstrated good diagnostic performance. The neutrophil-to-lymphocyte ratio, showed the highest accuracy, while IL-6 exhibited excellent rule-in capacity due to perfect specificity. However, none of the evaluated biomarkers were associated with disease severity (McCabe index) or in-hospital mortality. Conclusion: RSV infection in older adults is associated with a stable inflammatory signature across epidemic waves. Although biomarkers showed strong diagnostic utility, they lacked clinical prognostic value. We suggest that disease severity is mainly driven by host-related factors, particularly comorbidities, rather than differences in inflammatory response, highlighting the need for improved preventive and risk stratification strategies in this population.

Abstract:

Background: Overlapping endemic infections often present with non-specific systemic features, which could initially lead to delayed recognition and inappropriate treatment. Strongyloides stercoralis and Coccidioides spp. are rarely encountered together, yet both may cause pulmonary disease, constitutional symptoms, and eosinophilia, complicating diagnosis. Corticosteroid exposure in particular can unmask severe strongyloidiasis, highlighting the importance of early detection. Case Presentation: We present the case of a 30-year-old man from the Dominican Republic with recent travel to Brazil and Mexico, who presented with a 3-week history of fever, cough, myalgias, rash, and 13-pound weight loss. Initial treatment for presumed asthma exacerbation and bacterial pneumonia with corticosteroids and multiple antibiotics failed to relieve symptoms. Laboratory evaluation revealed marked eosinophilia (absolute eosinophil count 3,400/µL) and elevated inflammatory markers. Chest CT demonstrated diffuse bilateral tree-in-bud and micronodular opacities. Bronchoalveolar lavage contained 44% eosinophils. Serologic testing was positive for Strongyloides IgG, Coccidioides IgM/IgG, and β-D-glucan. The patient improved with ivermectin and fluconazole but experienced a relapse of coccidioidomycosis after antifungal discontinuation, requiring reinitiation of long-term azole therapy. Discussion: Coinfection with Strongyloides stercoralis and Coccidioides spp. poses a difficult diagnosis due to overlapping respiratory and systemic manifestations that could mimic common bacterial, fungal or allergic processes. Corticosteroid exposure can precipitate Strongyloides hyperinfection while promoting fungal proliferation, worsening disease severity. Recognition of eosinophilia in patients with a compatible travel history should prompt evaluation for parasitic and fungal etiologies. This case emphasizes the need for early serologic testing and targeted therapy while providing close follow-up to prevent relapses and complications in overlapping endemic infections. Conclusion: This case shows the difficulty of diagnosing overlapping infections like Strongyloides stercoralis and Coccidioides, which can easily be mistaken for bacterial pneumonia. It highlights the risk of giving corticosteroids before ruling out parasitic diseases and stresses the value of screening those at risk. The patient’s relapse after stopping treatment reflects the chronic nature of coccidioidomycosis and the need for close follow-up. Clinicians should keep an open, exposure-based approach when evaluating unexplained pulmonary symptoms, especially in people from endemic areas. This case underscores the importance of broad differentials, timely diagnosis, and long-term monitoring in patients with complex overlapping infections.

Abstract: Glycemic variability has become a critical predictor of diabetes progression and complications, surpassing traditional single-point measures such as fasting plasma glucose or glycated hemoglobin in capturing dynamic glucose level patterns. Continuous glucose monitoring (CGM) enables a detailed assessment of glycemic variability, which may reveal early dysregulation that is invisible to conventional tests. This study applies functional data analysis to evaluate the effects of a culturally tailored dietary intervention on CGM data from a prediabetic older adult. Over two consecutive weeks, CGM captured baseline glucose dynamics and post-intervention changes. The results indicated significant reductions in both mean glucose levels and variability throughout the intervention, highlighting meaningful changes in glycemic control attributable to culturally tailored dietary interventions. Furthermore, these results underscore the potential of combining CGM with advanced statistical methodologies to improve early detection and guide personalized interventions in the management of prediabetes.

Abstract: Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease globally, mirroring the in-creasing prevalence of obesity, insulin resistance, and type 2 diabetes. Early detection of hepatic steatosis is vital for cardiometabolic risk assessment; however, conventional imaging is costly and impractical for population screening. This study aimed to devel-op interpretable machine-learning models to predict ultrasound-detected hepatic ste-atosis within the MASLD spectrum using routinely available clinical and biochemical data. Methods: We analyzed data from 644 adults, 50% of whom had ultra-sound-detected hepatic steatosis. Preprocessing, imputation, and feature selection were implemented within a single scikit-learn pipeline to avoid information leakage. An Elastic Net–regularized logistic regression identified the top 20 predictors, which were subsequently used across nine supervised machine learning (ML) classifiers. Model performance was evaluated via repeated stratified 5-fold cross-validation (25 resamples) using accuracy, F1 score, sensitivity, specificity, Youden’s J, balanced accu-racy, and Area Under the Receiver Operating Characteristic Curve (AUROC). Inter-pretability was assessed using SHapley Additive exPlanations (SHAP). Results: Par-ticipants with ultrasound-detected hepatic steatosis exhibited greater adiposity, insu-lin resistance, and dyslipidemia compared with controls [p < 0.05 for body mass index (BMI), waist circumference, glucose, glycated hemoglobin (HbA1c), triglycerides]. Elastic Net selection highlighted Weight, Ponderal Index, Fibrosis-4 Index (FIB-4), blood urea nitrogen (BUN)/Creatinine ratio, Aspartate Aminotransferase to Platelet Ratio Index (APRI), and Visceral Adiposity Index as the strongest predictors. Logistic Regression and Gradient Boosting achieved the best performance (accuracy = 0.65 ± 0.03; AUROC = 0.71 ± 0.04; balanced accuracy = 0.66 ± 0.06), outperforming rule-based indices such as Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) reported in the literature. SHAP analysis confirmed clinically coherent feature effects, with higher anthropometric and hepatic injury indices increasing the predicted probability of ul-trasound-detected hepatic steatosis. Conclusions: Routinely available clinical and bi-ochemical parameters can predict hepatic steatosis with moderate accuracy using transparent, interpretable ML models. Logistic Regression and Gradient Boosting pro-vided best discrimination and robust internal performance, offering a pragmatic, low-cost approach for early identification of ultrasound-detected hepatic steatosis within the MASLD spectrum in primary and metabolic care settings.

Abstract: Cytomegalovirus (CMV) infects most of the population and remains dormant after a self-limited illness at the time of infection. It can cause severe illness in immunocompromised patients. CMV DNAemia in non-HIV-infected, non-solid organ/bone marrow transplant (NHNT) hosts is poorly characterized, with limited clinical insights. We aim to describe the clinical presentation, prognostic indicators, and outcomes of CMV DNAemia among NHNT patients. We used the TriNetX international patient database to identify adult patients diagnosed with CMV DNAemia from 2016 until March 2023. We evaluated hospitalization, intensive care unit (ICU) level care, and all-cause mortality at 30 days and 1 year. We also completed a post-propensity score analysis comparing clinical characteristics of survivors versus non-survivors at 90 days. We identified 1123 NHNT patients with CMV DNAemia, most commonly those with neoplasms (63%). Venous thromboembolism occurred in 31% of the population. The 30-day hospitalization and all-cause mortality rates were 35% and 14%, respectively. After propensity score matching, dyspnea, weakness, purpura, acute respiratory failure, malnutrition, encephalopathy, hypotension, CMV viral load, and ferritin were associated with increased 90-day all-cause mortality. CMV DNAemia in NHNT patients is associated with substantial morbidity and all-cause mortality. Further studies are warranted to clarify whether CMV DNAemia is a causative factor or an incidental finding in this population.

Abstract: Introduction and Purpose. Aquatic organisms, including invertebrates such as sponges, mollusks, and jellyfish, are sources of environmentally friendly marine collagen and low-molecular-weight bioactive oligopeptides, purified using advanced technologies. Since the early 2010s, numerous high-quality experimental and human studies have explored the properties of hydrolyzed marine collagen fragments as systemic functional ingredients in regenerative medicine. The purpose of this review is to discuss these properties and the rationale behind them, with a focus on wound healing. Mechanisms underlying chronic wound healing may offer a strong foundation for the still-missing, high-level clinical studies, particularly in patients with diabetic and pressure ulcers. Methods. This review examines only academically significant studies published in PubMed-indexed journals with significant impact factors, supplemented by a few contributions from Google Scholar for methodologically sound in vitro and animal studies. Results. Activation of skin fibroblasts and other mesenchymal cells underpins the systemic regenerative properties of highly purified hydrolyzed marine collagens. For example, 50 µg/mL of hydrolyzed marine collagen peptides nearly replicated in vitro the accelerated cell migration induced by 10 µg/mL of recombinant human epidermal growth factor. Faster wound healing, associated with increased collagen neosynthesis, is accompanied by increased immunohistochemical expression of platelet-endothelial cell adhesion molecule-1, basic fibroblast growth factor, and transforming growth factor β-1. The potential supportive role of collagen hydrolysates in managing insulin resistance could benefit the treatment of chronic diabetic and pressure ulcers. Conclusions. An increasing number of preclinical and human studies highlight the systemic regenerative properties of hydrolyzed marine collagens and their excellent safety profile. The evidence for their regenerative properties in aesthetic skin rejuvenation appears solid. Preclinical evidence is also growing for wound-healing support. Unfortunately, sound clinical studies confirming the experimental evidence in everyday wound care practice are still lacking, with long-term safety as a primary concern.

Abstract:

Background/Objectives: Irreversible organ damage is a central determinant of long-term outcomes in systemic lupus erythematosus (SLE). We aimed to define patterns of long-term damage accrual and identify dominant predictors of damage severity and mortality in a contemporary SLE cohort. Methods: This retrospective single-center study (2014-2023) included adult patients fulfilling 2019 EULAR/ACR SLE classification criteria. Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), at last follow-up and categorized as none (0), mild–moderate (1–2), or severe (≥3). Various variables were assessed, including sociodemographic, disease-related characteristics, comorbidities, hospitalizations, emergency department visits, and all-cause mortality. Multivariable logistic regression and Cox models were applied. Results: Among 182 patients (84.1% female; mean follow-up 15.6±11.4 years), 59.5% accrued damage, including 30.8% with severe damage. Damage predominantly involved cardiovascular, ocular, neuropsychiatric, and musculoskeletal domains. It was associated with older age, longer disease duration, hematologic and renal involvement, and corticosteroids and immunosuppressive medications. In multivariable analysis, antiphospholipid syndrome (APS) and hypertension emerged as the dominant independent predictors of damage accrual with an odds ratio of 15.70 (95% CI 4.26-57.89, p<0.001) and 6.46 (95% CI 2.54-16.40, p<0.001), respectively. Mortality increased with damage severity (16.1% in SDI≥3, 1.9% in SDI 1–2, none in SDI=0; p<0.0001). Damage was also associated with increased hospitalizations. Conclusion: Damage accrual is common and strongly predicts mortality. APS and hypertension emerge as dominant, modifiable drivers, supporting integrated cardiovascular and thrombotic risk management in SLE.

Abstract: Lung disease is a major global health challenge causing millions of deaths annually. Early diagnosis and treatment of lung disease is crucial for effective treatment, preventing mortality and reducing long-term morbidity. While most existing diagnostic research primarily utilizes unimodal medical image data, this approach often provides limited information. To incorporate additional clinical information in the diagnosis, multimodal strategies are increasingly being explored. Medical image and clinical data are the key medical information utilized by physicians to diagnose lung disease in addition to physical examination. In this work, we propose a comprehensive multimodal machine learning framework for lung disease detection that integrates structured clinical data with medical imaging modalities specifically, chest X-rays and computed tomography scans. The methodology includes robust data preprocessing, feature extraction using VGG16 for images and multiple techniques (mutual information, principal component analysis, and random forest) for clinical data, followed by fusion and classification using both classical machine learning and deep learning models. We introduce and evaluate a newly collected lung disease dataset comprising over 27,635 records combining imaging and clinical data from Ethiopian hospitals. Experiments conducted show that unimodal chest X-Ray image based detection achieves 95.28% accuracy while multimodal chest X-ray and clinical data based detection achieves accuracy 98.88%. Similar results are obtained for computed tomography scan based experiments with 97.62% for unimodal and 98.91% for multimodal detection. This study demonstrated the critical importance of multimodal data fusion in developing more accurate and clinically viable diagnostic system for lung diseases.

Abstract: Background/Objectives: Ceftaroline fosamil (CFT) is a fifth-generation cephalosporin approved in Spain for skin and soft tissue infections and community-acquired pneumonia. CFT may also be useful against endovascular infections. This real-world study aimed to evaluate its effectiveness and safety in patients with Gram-positive (GP) infective endocarditis (IE). Methods: This observational, retrospective multicenter study enrolled adults with GP-IE treated with CFT for ≥48 h. Recruitment extended from CFT incorporation in participating hospitals through May 2024. Data were gathered on demographic, clinical, and microbiological variables, adverse effects, overall and IE-related mortality, relapses, and a composite unfavorable outcome. Results: Seventy-six patients (65.8% male) were enrolled, with a mean age of 68.9±12.8 yrs and age-adjusted Charlson index of 4; 55.3% had previous moderate/severe valvular heart disease, 35.5% had atrial fibrillation, 34.2% chronic heart failure, 17.1% chronic kidney disease, and 22.4% septic shock. IE was native valve-related in 53.9%, involving aortic valve in 38.2% and mitral in 30.3%. Staphylococcus aureus was isolated in 50.7%, being methicillin-resistant in 57.9% of cases. CFT was salvage therapy in 64.9% and combined with other antibiotics in 94.8%. Valve replacement was indicated in 63.6% but performed in only 34.7% of these. At six months, adverse effect rate was 9.2%, overall crude mortality 37.7%; infection-related mortality 28.9%, and composite unfavorable outcome 40.1%. In multivariate analysis, mortality-related factors were age-adjusted Charlson index, septic shock, and methicillin- sensitive S. aureus. Conclusions: CFT proved effective and safe for the real-life treatment of GP-related IE in clinically complex patients with high comorbidity and previous antibiotic therapy failures.

Abstract: Gestational diabetes (GDM) is associated with long term risk of diabetes and cardiovascular disease. Offspring of mothers with GDM also have elevated cardiometabolic risk in their lifetime. This article reviews risk factors that may predict progression to Type 2 or Type 1 diabetes after history of GDM, recurrence risk of GDM in a future pregnancy and discusses what evidence is available for risk mitigation in reducing long term adverse health outcomes in both mothers with GDM and their children.

Abstract: Background/Aim: Albuminuria is an established marker of endothelial dysfunction and an independent predictor of cardiovascular risk. Polycystic ovary syndrome (PCOS) is associated with early metabolic and vascular abnormalities; however, whether urinary albumin excretion differs across PCOS phenotypes remains unclear. This study aimed to evaluate urinary albumin excretion using the urinary albumin-to-creatinine ratio (U-ACR) across distinct PCOS phenotypes and to examine its association with metabolic parameters. Materials and Methods: In this cross-sectional study, 180 women aged 18-35 years with PCOS and 51 age-matched healthy controls were included. PCOS phenotypes were classified according to the Rotterdam criteria as Phenotype A (n = 96), Phenotype B (n = 19), Phenotype C (n = 35), and Phenotype D (n = 30). Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-IR). Urinary albumin and creatinine levels were measured in morning urine samples, and U-ACR was calculated. Results: Age was comparable across all groups. Body mass index, waist circumference, diastolic blood pressure, and HOMA-IR were significantly higher in Phenotype A compared with controls and other phenotypes, indicating a more adverse metabolic profile. Serum creatinine levels were similar across all groups. Despite this unfavorable metabolic profile in Phenotype A, U-ACR was significantly elevated only in Phenotype B compared with controls (p = 0.018) and Phenotype D (p = 0.016). No significant correlations were observed between U-ACR and age, body mass index, or HOMA-IR. When participants were categorized according to U-ACR levels (< 30, 30-299.9, and ≥ 300 mg/g creatinine), no significant differences in category distribution were observed between the total PCOS cohort, phenotype subgroups, and controls. Conclusion: Among PCOS phenotypes, U-ACR elevation was observed exclusively in Phenotype B despite similar renal function markers. Notably, this occurred even though Phenotype A exhibited a more adverse metabolic profile, suggesting a dissociation between metabolic burden and early microvascular involvement across PCOS phenotypes. These findings indicate that vascular risk in PCOS may be phenotype-dependent and support the potential value of phenotype-oriented cardiovascular risk assessment.

Abstract: Background: Hypernatremia is an infrequent but clinically relevant electrolyte disorder in older adults and is associated with poor outcomes. Patients managed through Hospital-at-Home (HaH) programs, particularly those living in institutional settings, are especially vulnerable due to functional dependency and cognitive impairment. Evidence regarding the prevalence and prognostic impact of hypernatremia in HaH settings remains limited; Methods: We conducted a retrospective observational cohort study including all patients admitted to a Hospital-at-Home unit between 2019 and 2024. Patients were classified according to care setting as home-dwelling or institutionalized. Hypernatremia was defined as a serum sodium concentration &gt;145 mmol/L. Sociodemographic, functional (Barthel Index), and cognitive (Global Deterioration Scale) variables were collected. Mortality during HaH admission and at 30, 60, and 90 days was analyzed, and survival was assessed using Kaplan–Meier methods.; Results: A total of 4,501 patients were included, of whom 2,701 were treated at home and 1,800 in institutional settings. Hypernatremia was significantly more prevalent among institutionalized patients than among home-dwelling patients (3.1% vs. 0.8%, p &lt; 0.001). Institutionalized patients with hypernatremia showed greater functional dependency (Barthel Index 11 vs. 15, p = 0.041) and more advanced cognitive impairment (GDS 6 vs. 5.5, p = 0.033) compared with those without hypernatremia. Mortality among institutionalized patients with hypernatremia was high, reaching 32.9% during HaH admission, 61.2% at 30 days, 70.6% at 60 days, and approximately 79% at 90 days. Kaplan–Meier analysis demonstrated a rapid decline in survival during the first month following diagnosis.; Conclusions: In Hospital-at-Home programs, hypernatremia is more prevalent among institutionalized older adults and is strongly associated with severe functional and cognitive impairment and very high short- and medium-term mortality. These findings suggest that hypernatremia should be considered a marker of advanced frailty rather than an isolated electrolyte disturbance and highlight the need for enhanced preventive and monitoring strategies in institutional and HaH care settings.

Abstract: Peripheral artery disease (PAD) is a pervasive atherosclerotic condition affecting well over 100 million adults worldwide and associated with major functional limitations, reduced quality of life, and elevated risks of myocardial infarction, stroke, limb events, and mortality. Exercise therapy—preferably supervised or delivered through structured, monitored home based programs—is a first line, guideline endorsed therapy that improves walking performance and patient reported outcomes and contributes to comprehensive secondary prevention. This review synthesizes mechanistic underpinnings (endothelial, angiogenic, metabolic, autonomic) and appraises the comparative effectiveness, safety, and implementation models of supervised exercise therapy (SET), structured home based and hybrid programs, and alternative modalities in PAD. Finally, we summarize policy aspects and persistent gaps to guide clinical practice and future research.

Abstract: Background/Objectives: Advanced Glycation End Products (AGEs) are the end products of the Maillard reaction, derived from reduced sugars and proteins, lipids or DNA. AGEs accumulate in dermal collagen and elastin, causing several changes: skin stiffening and loss of elasticity, stimulation of inflammation and the result of accelerated photo- and chronological aging, manifested by skin yellowing, wrinkles, and dryness. High Fre-quency Ultrasound (HFU) offers precise and non-invasive assessments of structural and inflammatory changes in the skin: it measures the thickness of the epidermis and dermis, echogenicity and the hypoechoic band under the epidermis. The aim of the study is to correlate AGEs levels in biological fluids with ultrasonographic measurements of sun-exposed skin and non-sun-exposed tissue. Methods: Patients (N=113) were enrolled and demographic, clinical, and anthropometric measurements were recorded: age, gender, body mass index (BMI), waist circumference, and Fitzpatrick skin type. Venous blood, urine and salivary samples were harvested. The following AGEs were assessed in biological fluids (plasma, saliva, urine): Fruc-tose-Lysine, Pyridine, Methyl-Glyoxal-H1, Carboxyethyl-lysine, Carboxymethyllysine, Arginine, Lysine. The tissue glycation process of collagen fibers was indirectly evaluated with a 22 MHz HFU ultrasound device (DUB cutis, Taberna Pro Medicum, Lüneburg, Germany). The assessment was performed on sun-exposed skin (left zygomatic area) and on non-sun-exposed tissue (non-keratinized mucosa of the lower lip). For the sun-exposed skin of the zygomatic area, including the epidermis, dermis, and subcuta-neous tissue (hypodermis), tissue depth (thickness), pixel count (px), and density (au-tomatic) were recorded. The non-sun-exposed tissue examined was the oral mucosa on the inner surface of the lower lip including the non-keratinized epithelium, lamina propria, and submucosa. Results: The study evidences a weak positive correlation between UV exposed dermis collagen and serum Pyr, salivary MG-H1, salivary Arg and salivary Lys. Between bio-fluid AGEs and the degree of pixelation of dermal collagen exposed to UV rays, we determined weak direct correlations with salivary MG-H1 and salivary CML. Significant indirect weak and medium correlations were found between dermal collagen density affected by UV exposure with serum CEL, Arg, Lys, weak direct correlation with sali-vary MG-H1 and salivary CML. Regarding the density of the dermis affected by UV exposure, we found a weak indirect correlation with salivary FruLys, MG-H1, CML and Lys . Conclusions: HFU ultrasound assessment revealed structural changes in the cervi-co-facial dermis, which were associated with increased AGEs, suggesting that gly-cation-induced tissue remodeling can be detected non-invasively. This data obtained might be the based for future studies on the clinical utility of the combined assessment of AGEs and skin changes by HFU as modern, rapid and non-invasive tools to identify patients at increased cardiovascular risk.