Background: Gender differences in aging among people with HIV (PWH) remain poorly characterized. Women with HIV (WWH) may experience more complex aging trajectories, due to the interplay of biological, clinical, and psychosocial factors. In this context, we aimed to investigate gender-specific determinants of frailty among older people with HIV, with a particular focus on women, to better inform tailored clinical care. Methods: Cross-sectional analysis of the Over50 Cohort, including PWH aged ≥50 years from two tertiary hospitals in Spain. Participants underwent a comprehensive geriatric assessment across demographic, clinical, functional, cognitive, psychological, and social domains. Gender-stratified multivariable analyses examined frailty (by Fried criteria) and associated factors. Results: Among 588 participants, 139 (23.6%) were cisgender WWH. Despite younger age and better immune status, WWH showed higher prevalence of frailty (17% vs. 9%), musculoskeletal disease (47% vs. 28%), depressive symptoms (45% vs. 30%), sleep disturbances (10% vs. 5%), and cognitive complaints (23% vs. 11%). Men with HIV (MWH) more frequently had cardiovascular (48% vs. 35%) and renal disease (22% vs. 15%). In multivariable models, frailty in WWH was independently associated with musculoskeletal disease (OR 3.85), cognitive impairment (OR 3.21), depressive symptoms (OR 2.67), and malnutrition (OR 2.14). In MWH, frailty was associated with musculoskeletal disease, cognitive impairment, malnutrition, and older age. Conclusions: Frailty exhibits gender-specific patterns: a multidimensional phenotype in WWH versus age-driven in MWH, supporting tailored, gender-responsive care integrating geriatric, mental, and musculoskeletal health.

Background: Bartonella henselae infection has been associated with a broad spectrum of neurological and autonomic manifestations, although its impact on autonomic nervous system function remains insufficiently characterized, and the aim of this study was to evaluate autonomic function in patients with polymorphic symptoms and Bartonella henselae IgM seroreactivity. Methods: In this cross-sectional study, 75 patients were compared with 75 age- and sex-matched healthy controls, and all participants underwent cardiovascular autonomic reflex testing, short-term (5 min) and long-term (24 h) heart rate variability analysis, and 24 h ambulatory blood pressure monitoring, while head-up tilt testing was performed in the Bartonella group. Results: Abnormal autonomic reflex tests were significantly more frequent in the Bartonella IgM-seroreactive group, particularly those reflecting parasympathetic function, while heart rate variability analysis demonstrated reduced high-frequency components and lower long-term variability indices, and head-up tilt testing revealed heterogeneous hemodynamic responses including orthostatic hypotension and pronounced blood pressure variability, with ambulatory monitoring additionally showing higher nighttime blood pressure values and reduced nocturnal dipping. Conclusions: These findings indicate a consistent pattern of autonomic imbalance characterized predominantly by parasympathetic impairment and altered blood pressure regulation in patients with Bartonella henselae IgM seroreactivity, although further studies are required to clarify underlying mechanisms and clinical implications.

No previous sub-Saharan studies have compared patients with community-acquired pneumonia (CAP) and COVID-19 pneumonia, the focus of this study. Consecutive adult patients hospitalized with CAP (n = 59) or COVID-19 pneumonia (n = 74) were compared regarding multiple characteristics, including cardiac biomarkers. In multivariable logistic regression analysis, differences were noted among various clinical features. Troponin I concentrations (p = 0.00028) and the Troponin I/NT-pro BNP ratio (p = 0.00048) were significantly higher in COVID-19 compared with CAP. After adjustment for age, these differences remained significant (troponin I p = 0.0019; ratio p = 0.00054), while BNP concentrations were now higher in CAP (p = 0.009). PCA demonstrated that BNP and NT-pro BNP contributed most strongly to the dominant cardiac biomarker signature, suggesting shared cardiopulmonary stress across both diseases. Exploratory subgroup analyses suggested higher troponin I levels among people living with HIV and COVID-19, although interaction modelling did not demonstrate significant effect modification by HIV status. Both CAP and COVID-19 pneumonia were associated with evidence of cardiac stress; however, COVID-19 demonstrated a relatively stronger myocardial injury signature characterized by higher troponin I concentrations and an increased Troponin I/NT-pro BNP ratio while CAP had evidence of greater hemodynamic cardiac strain, as evidenced by the higher levels of BNP. The findings suggest that the mechanisms of cardiac involvement may differ between viral and bacterial respiratory infections.

Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, immune dysregulation, and increased susceptibility to infections. Obesity may influence these processes and has been proposed as a potential contributor to the so-called "obesity paradox", although its effects on immune competence, viral burden, and survival are not yet fully understood. Seventy patients with severe to very severe COPD (GOLD stage 3-4) were stratified according to BMI (<30 vs. ≥30 kg/m²). Clinical and functional parameters were assessed together with biomarkers of oxidative stress, DNA damage, systemic inflammation, and T-cell subsets. A comprehensive viral panel, including Torque Teno virus (TTV), was also analyzed. Five-year survival was evaluated using Kaplan-Meier curves and Cox regression models. Patients with BMI ≥ 30 showed higher lymphocyte counts and increased CD4⁺ and CD8⁺ T-cell levels, accompanied by lower systemic inflammatory indices. No significant differences were observed in oxidative stress or DNA damage markers. In addition, TTV viremia (≥4 log₁₀ copies/mL) was more frequently observed among patients with lower BMI. Despite these differences, five-year survival did not significantly differ between the two groups. These findings suggest that BMI alone may have limited value as a predictor of outcomes in patients with advanced COPD. Conversely, immune-inflammatory indices and viral burden, particularly TTV viremia, could provide complementary information for risk assessment and may deserve further investigation as potential tools for personalized patient stratification.

To evaluate associations between polymorphisms in CYP3A4 (*1B, *22), CYP3A5 (*3), CYP2J2 (*7, rs11572325), ABCB1 (c.1236C>T, c.2677G>T/A, c.3435C>T, rs4148738) and ABCG2 (c.421C>A) and the occurrence of bleeding or occlusive events in patients receiving rivaroxaban in real-world clinical practice.

A nested case-control study, divided into two substudies (bleeding and thromboembolic events), was conducted within a prospective cohort of 385 adults receiving rivaroxaban at University Hospital Centre Zagreb (September 2021-September 2024). Bleeding events were classified per ISTH criteria, and genotyping was performed using TaqMan real-time PCR. Cases and controls were balanced using entropy balancing, and associations were estimated with Bayesian logistic regression under a skeptical prior N(0, 0.355); LASSO regression was used to identify clinical and genetic predictors of outcomes.

In total, 71 patients (18.4%) experienced bleeding events, most frequently gastrointestinal (47.9%), while 314 patients served as controls. No pharmacogenomic variant showed a clear association with bleeding risk (raw and balanced odds ratios 0.80-1.35; 95% credible intervals crossing 1.0). LASSO regression identified age (OR 2.00 per decade), gastrointestinal comorbidity (OR 8.77), and eGFR as the dominant predictors of bleeding. Twenty-one patients experienced occlusive events (15 venous, 6 arterial); however, the low event count precluded meaningful pharmacogenomic analysis.

Individual pharmacogenomic variants in CYP3A4, CYP3A5, CYP2J2, ABCB1, and ABCG2 together with pharmacogenetic-based phenotypes were not associated with clinically relevant bleeding in rivaroxaban-treated patients. Traditional clinical risk factors, particularly advanced age and gastrointestinal comorbidity, remain the dominant determinants of adverse outcomes. Routine pharmacogenomic testing to guide rivaroxaban dosing is not currently supported.

Vascular stents are crucial devices in the treatment of cardiovascular diseases, and their structural design and function critically affect therapeutic efficacy and patient prognosis. Conventional stents can effectively restore vascular patency by providing mechanical support to blood vessels. However, they still face significant challenges including restenosis, thrombosis, and limited adaptability to complex patient-specific lesion characteristics. To address these limitations, drug delivery offers an important strategy to modulate the pathological microenvironment, enhance long-term vascular healing, and reduce systemic side effects. Meanwhile, advances in computational simulations have provided powerful tools for optimizing stent design through structural mechanics, hemodynamics, and drug release modeling. Computational approaches enable the rational design of stent architectures with improved mechanical stability, vascular compatibility, and therapeutic regulation. Consequently, the development of vascular stents is evolving toward the synergistic integration of drug delivery, structural optimization, and intelligent design. This review summarizes the latest advances in functional vascular stents, clinical applications and computational design. This work aims to provide valuable insights for the engineering of efficient, precise, and intelligent vascular stents for cardiovascular therapies.

Natural products derived from plants, animals, and microorganisms have long been used as nutritional supplements and are increasingly recognized for their potential role in preventing and managing human diseases. This narrative review aims to summarize current evidence on the therapeutic relevance of natural products as dietary supplements across major disease categories and to highlight their mechanisms of action, clinical efficacy, and safety considerations.

A narrative literature review was conducted using peer-reviewed articles, systematic reviews, and clinical studies focusing on natural products used as nutritional supplements in disease management. Relevant data were analyzed thematically, with emphasis on bioactive compounds, mechanisms of action, and evidence from preclinical and clinical research.

Natural products, particularly plant-derived polyphenols, flavonoids, terpenoids, omega-3 fatty acids, and probiotic-derived metabolites, exhibit diverse biological activities, including antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial effects. Evidence suggests potential benefits in cardiovascular diseases, metabolic disorders such as diabetes and obesity, neurodegenerative conditions, certain cancers, gastrointestinal disorders, and infectious diseases. However, clinical efficacy varies depending on compound type, dosage, and formulation. Key limitations include low bioavailability, variability in composition, and insufficient large-scale clinical trials. Safety concerns such as herb-drug interactions and lack of standardization remain significant challenges.

Natural products as nutritional supplements represent a promising adjunct strategy in the prevention and management of various human diseases. While preclinical and early clinical evidence is encouraging, stronger clinical validation, improved standardization, and clearer regulatory frameworks are required to fully integrate these agents into evidence-based medical practice.

Background and Objectives: Hyperphosphatemia is a key component of chronic kidney disease-mineral and bone disorder and is associated with higher rates of cardiovascular events and mortality in patients undergoing dialysis. Phosphate binders are essential for phosphorus reduction, and their evaluation relies on several factors, such as chemical composition, binding capacity, and safety profile. Unfortunately, long-term management is hindered by high pill burden and poor adherence. Magnesium phosphate binders have proven effectiveness in reducing phosphate levels. Nevertheless, despite their efficacy, they are not widely used in clinical settings because of concerns related to their use. This study assessed the efficacy of low-dose magnesium carbonate as a phosphate binder in patients undergoing chronic dialysis, focusing on its biochemical control, tolerability, and cost-effectiveness. Materials and Methods: A prospective observational study was conducted on 54 hemodialysis patients with end-stage renal disease at a single dialysis center. Patients were taking either 250 mg magnesium carbonate or 2400 mg sevelamer carbonate for 3 months. Results: Both groups showed decreased phosphorus levels, with a 14.2% significant reduction in the magnesium carbonate group (p < 0.001) and a 5.1% reduction in the sevelamer carbonate group. At the end of the study, no significant differences were observed between the groups (p = 0.682). In the magnesium carbonate group at month 3, compared to baseline, no significant differences were detected in other laboratory parameters reflecting calcium-phosphorus metabolism (Ca-p = 0.681, PTH-p = 0.126). Simultaneously, good compliance without clinically relevant gastrointestinal side effects was observed, including the absence of clinically significant hypermagnesemia. Conclusions: The phosphorus-lowering potential of low-dose magnesium carbonate is non-inferior to that of low-dose sevelamer carbonate. However, its favorable safety profile, low incidence of adverse effects, and cost-effectiveness make it a promising option in clinical practice, further highlighting the need for better recognition by physicians.

Takotsubo syndrome (TTS) is an acute disorder characterized by transient left ventricular dysfunction with typical regional wall motion abnormalities, most commonly apical ballooning. It accounts for 1-3% of all suspected acute coronary syndromes and up to 5-6% in women presenting with ST-segment elevation myocardial infarction requiring coronary angiography to exclude obstructive coronary artery disease. The pathophysiology of TTS is complex and not fully elucidated, with sympathetic hyperactivation playing a central role through calcium dysregulation, oxidative stress, and metabolic alterations. Both clinical and experimental data demonstrate the importance of inflammation, with cell infiltration and persistent immune activation exceeding the acute phase. Increasing evidence highlights the impact of coronary microvascular disfunction (CMVD) as a secondary phenomenon, with some findings that support its role as a causative substrate. Beyond well-known predisposing conditions such as female sex, postmenopausal age, and neurological and psychiatric disorders with the trigger of a physical or psychological event, numerous case reports associate the syndrome with chronic autoimmune diseases, even if clear experimental evidence remains poor and worthy of further study. Echocardiography and advanced imaging techniques, including cardiac magnetic resonance and positron emission tomography, have provided insights into transient CMVD, reversible myocardial edema, and metabolic impairment, strengthening our knowledge of the syndrome as a dynamic process. It is also of growing interest to perform invasive hemodynamic assessment to explain the increase in microvascular resistance. This review offers a comprehensive and up-to-date overview of these techniques in the context of TTS. Since clinically, TTS may be associated with significant morbidity and mortality, with some unexplained cases of long-term myocardial disfunction or even recurrence, a deeper understanding of the interplay between catecholamines, inflammation, immune substrate, and CMVD may improve risk stratification and lead to the development of targeted therapeutic strategies.

As the primary active constituent of the traditional Chinese medicinal herb Ligusticum chuanxiong, Tetramethylpyrazine (TMP) has demonstrated broad therapeutic potential across multiple disease areas. Its clinical applications span cardiovascular and cerebrovascular disorders, oncology, hepatorenal protection, and respiratory diseases. The mechanisms of action involve antiplatelet aggregation, anti-inflammatory, antioxidant, and anti-apoptotic effects, as well as modulation of autophagy and multiple signaling pathways. Despite its pleiotropic efficacy, the clinical utility of TMP is constrained by unfavorable pharmacokinetic properties, including rapid metabolism and limited oral bioavailability. To overcome these limitations, researchers have developed various TMP derivatives, which exhibit significantly improved metabolic stability and enhanced pharmacological activity. This review summarizes recent advances in TMP and its derivatives over the past five years, aiming to provide insights for the future development of novel TMP-based therapeutics.