Chagas disease (ChD) and Type 2 diabetes (T2D) originate from distinct etiological processes -infectious and metabolic, respectively- yet both share a chronic inflammatory and metabolic imbalance that profoundly impacts immune-endocrine homeostasis. Persistent Trypanosoma cruzi infection in ChD induces sustained immune activation, altered adrenal steroid balance, and tissue remodeling, whereas T2D is characterized by metabolic inflammation, oxidative stress, and insulin resistance. When these two conditions coexist, their overlapping inflammatory, metabolic, and endocrine circuits may act synergistically, amplifying metabolic toxicity, immune exhaustion, and premature immunosenescence. In addition, this comorbidity thus represents the convergence of pathogen-driven and metabolism-driven inflammation, resulting in a disrupted neuroendocrine-immune dialogue and heightened susceptibility to tissue damage, particularly in the heart. Understanding the mechanistic basis of this interplay is crucial, as it highlights shared pathogenic pathways and potential molecular targets for integrated therapeutic interventions. Altogether, recognizing ChD+T2D coexistence as a mechanistic rather than merely epidemiological association provides new insights into the links between chronic infection, metabolic dysfunction, and immune aging-offering a conceptual framework for future studies aimed at restoring immune-metabolic balance and improving disease outcomes, particularly cardiac damage.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease linked to systemic comorbidities such as obesity, diabetes, cardiovascular disease, and inflammatory bowel disease. Non-pharmacological interventions, such as dietary modifications, nutritional supplementation, exercise, and psychological interventions, have emerged as complementary therapies in the management of psoriasis. OBJECTIVES: Review the current and recent evidence and the role of trace elements, vitamins, diet, exercise, and psychological interventions as complementary approaches in the management of patients with psoriasis. MATERIALS AND METHODS: A narrative review was conducted, analyzing clinical trials, meta-analyses, and cohort studies from major databases. RESULTS: Trace elements such as zinc, copper, and selenium, and vitamins including D, E, B-complex, and A, play roles in oxidative stress modulation, immune regulation, and keratinocyte biology. However, the clinical efficacy of micronutrient supplementation remains uncertain due to inconsistent and conflicting findings. Dietary interventions, particularly Mediterranean diet adherence and weight loss through caloric restriction or bariatric surgery, have been associated with reductions in psoriasis severity, although clear clinical protocols are lacking. Aerobic exercise appears beneficial but is underutilized, partially due to psychological and disease-related barriers. Furthermore, psoriasis is associated with a high prevalence of psychological disorders, with the necessity to integrate psychological interventions to optimize disease management. STUDY LIMITATIONS: The available evidence is limited and with heterogeneity in study design, with small sample sizes, observational methodologies, and inconsistent intervention protocols, restricting causal inference and generalizability. CONCLUSION: While non-pharmacological strategies show promise as complementary interventions in psoriasis management, they cannot replace conventional therapy. Further studies are required to confirm their clinical impact. These approaches should be considered as complementary strategies, with individualized patient assessments and continuous follow-up being essential.

BACKGROUND: As overall survival improves in metastatic hormone-sensitive prostate cancer (mHSPC), non-cancer causes of death are increasingly relevant. METHODS: We conducted a real-world multicenter study of patients diagnosed with mHSPC treated with ADT alone or in combination. Causes of death before progression to castration-resistant prostate cancer (CRPC) were classified as cancer- or non-cancer-related. Deaths were classified as non-cancer-related if they occurred in the absence of cancer progression. RESULTS: Among 565 patients, 35 (6.2%) died from non-cancer-related causes without disease progression, mainly infections (34%) and cardiovascular events (20%). CONCLUSIONS: Non-cancer mortality represents a meaningful proportion of deaths in mHSPC, supporting systematic cardiovascular risk evaluation and infection-prevention strategies.

BACKGROUND: Left bundle branch area pacing (LBBAP) has been reported to improve long-term clinical outcomes in patients requiring permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR). Deep septal pacing (DSP) has emerged as a potential alternative to LBBAP. OBJECTIVE: This study investigated whether short-term and long-term clinical outcomes differ between LBBAP and DSP in post-TAVR patients. METHODS: Consecutive patients undergoing LBBAP or DSP following TAVR were retrospectively included at our institution. Short-term clinical outcomes (1-year follow-up) were assessed by echocardiographic measures of reverse remodeling and changes in QRS duration and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. For long-term outcomes, the primary composite endpoint was all-cause mortality or heart failure hospitalization (HFH). Secondary endpoints included HFH and improvement in New York Heart Association (NYHA) class (≥ 2 grades). RESULTS: A total of 82 patients (39 LBBAP and 43 DSP) were observed for a mean duration of 731.8 days. There was no significant difference between two groups in the risk of primary endpoint (23.1% vs. 23.3%, adjusted hazard ratio [aHR] 0.61; 95% CI: 0.23-1.61, p = 0.315) and HFH (17.9% vs. 20.9%, aHR 0.64; 95% CI: 0.22-1.82; p = 0.402). However, LBBAP was a robust predictor of NYHA class improvement compared to DSP (53.8% vs. 27.9%, aHR 2.23; 95% CI: 1.03-4.87, p = 0.043), especially when left bundle branch (LBB) capture was independently confirmed (aHR 2.74, p = 0.006). Both modalities were similarly effective in improving electromechanical and biochemical parameters, including LVEF, LVEDD, QRS duration, and NT-proBNP (all p > 0.05). CONCLUSION: LBBAP and DSP yield comparable risks for the primary composite endpoint and HFH, yet LBBAP provides superior symptomatic relief. Confirmation of left bundle branch capture is advisable to optimize clinical benefits. Liangzhen Qu and Xueting Duan contributed equally to this manuscript.

BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRCD) is among the most important adverse effects of treatment of childhood cancer. In the EARLY study (Early detection of acute and early-onset cARdiovascuLar toxicity in children with cancer using a multiparametric approach), cardiac function in children treated for cancer was monitored during and shortly after treatment, using advanced echocardiography, electrocardiography, and cardiac magnetic resonance (CMR) techniques. METHODS: In this prospective pilot study, 100 children newly diagnosed with childhood cancer receiving anthracyclines as part of their cancer treatment were included. A subgroup of 30 children was included in the CMR sub-study. Echocardiography, electrocardiography, and CMR were performed before (T0), three and a half months after (T1), and one year after (T2) start of anthracycline treatment. In this article, we focus on the methodological aspects of the EARLY study, including patient enrollment and characteristics of the study cohort, as well as the feasibility of advanced echocardiography. CURRENT STATUS: The last patient was included in August 2022. Follow-up for the last patient was finalized in August 2023. Follow-up was completed by 92% of the total study population and 97% of the CMR sub-study. CONCLUSIONS: Protocol adherence was high (92%-97%) and a full collection of data on each included individual was achieved. Advanced echocardiography, i.e., 4D ejection fraction and global longitudinal strain, was feasible in 76% and 69% of measurements, respectively. Cardiac outcomes during and shortly after treatment, as well as associations with known risk factors for CTRCD, such as anthracycline dose, dose of radiotherapy involving the heart, childhood cancer disease profile, age at diagnosis and sex will be reported in a future publication. The feasibility of the study allows for future insight into the correlation between early-onset CTRCD and heart failure during long-term follow-up of childhood cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NL-OMON22737.

INTRODUCTION: The aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD) is an efficacious topical treatment for psoriasis. This study evaluated the efficacy of Cal/BD foam versus ointment in Chinese patients, on the basis of investigator-assessed and patient-reported outcomes (PROs) from a 4-week clinical trial, including post hoc analyses after 2 weeks of treatment. METHODS: A randomized, investigator-blind, active-controlled, parallel-group phase 3 trial was conducted in China. Native Chinese adults (≥ 18 years) with plaque psoriasis involving 2-30% of the body surface area (BSA), with at least mild disease severity according to the Physician's Global Assessment (PGA), and modified Psoriasis Area and Severity Index (mPASI) ≥ 2 were randomized 1:1 to receive either Cal/BD foam or ointment once daily for a 4-week treatment period. Efficacy was assessed at weeks 0, 2, and 4 using mPASI, PGA, BSA, Dermatology Life Quality Index (DLQI), Psoriasis Symptom Inventory (PSI), and Subject's Global Assessment of disease severity (SGA). RESULTS: A total of 302 patients were randomized to each treatment. Both groups had clinically meaningful improvements across all outcome measures from baseline to week 2, with sustained or further improvements at week 4. For Cal/BD foam-treated patients, mean change from baseline in mPASI was -59.87% at week 2 (versus ointment: -54.59%; P = 0.010) and -74.69% at week 4 (versus ointment: -70.22%; P = 0.043). Other investigator-assessed outcomes based on mPASI and PGA showed statistically significant treatment differences favoring Cal/BD foam at week 4. Improvements in PROs (DLQI, PSI, and SGA) were numerically slightly greater with Cal/BD foam than ointment, though not statistically significant. For Cal/BD foam-treated patients, mean change from baseline in DLQI was -3.9 at week 2 (versus ointment: -3.7; P = 0.5012) and -5.5 at week 4 (versus ointment: -5.3; P = 0.5119). CONCLUSIONS: Cal/BD foam showed rapid onset of action with clinically meaningful improvements in signs, symptoms, and quality of life in Chinese patients with plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05919082. Plaque psoriasis is the most common type of psoriasis, a chronic disease affecting the skin and other body systems. Plaques are thick, scaly patches of skin that can be itchy and painful, limiting patients' everyday activities. Plaque psoriasis has a major impact on quality of life, comparable with the impact of other chronic diseases such as cancer and heart disease. Many treatments, such as creams, tablets, and injections, can improve plaque psoriasis, but they do not always work well for everyone. In a clinical trial in China, we tested two treatments-a foam and an ointment-that have the same amount of two active ingredients: calcipotriol (Cal) and betamethasone dipropionate (BD). The goal was to find out if Cal/BD foam, which is the newer treatment, worked as well as Cal/BD ointment in Chinese men and women with plaque psoriasis. The trial participants were randomly distributed into two groups, each with 302 participants. One group applied Cal/BD foam on their plaques and the other group applied Cal/BD ointment, both once daily for 4 weeks. Both groups had meaningful improvements in psoriasis signs and symptoms as well as quality of life already after 2 weeks, with sustained or further improvements after 4 weeks. Overall, the improvements were slightly greater with Cal/BD foam than with Cal/BD ointment.

PURPOSE: The ULTRA trial evaluated the impact of ultra-early and short-term tranexamic acid (TXA) treatment in patients with subarachnoid hemorrhage (SAH) and found no clinical benefit at six months. This post-hoc analysis examines whether TXA improves quality of life (QoL) at three and six months. METHODS: The ULTRA trial was a randomized, controlled, multicenter study conducted from July 2013 to July 2019. Patients received either TXA or standard care. This analysis included patients who completed at least one QoL questionnaire. The primary endpoint was QoL, assessed using the EQ-5D-3L questionnaire at three and six months. Linear mixed models adjusted for confounders were used to analyze the association between TXA and QoL. RESULTS: Of the 955 ULTRA patients, approximately 25% died, and 63% completed at least one QoL questionnaire. At three months, the TXA group had a mean EQ-5D index score of 0.75 versus 0.71 in the control group (p = 0.11) and a mean EQ-5D Visual Analogue Scale (VAS) score of 89 versus 86 (p = 0.10). At six months, the mean EQ-5D index score was 0.84 in the TXA group compared to 0.82 in the control group (p = 0.23), and the mean VAS was 92 in the TXA group compared to 89 in the control group (p = 0.13). CONCLUSION: Ultra-early and short-term TXA did not result in a significant improvement in QoL at three or six months in patients with SAH. Given the lack of benefit on both clinical outcome and QoL, routine use of TXA is not recommended. TRIAL REGISTRATION: Netherlands Trial Register: NTR3272. CLINICALTRIALS: gov: NCT02684812.

Brain arteriovenous malformations (BAVMs) are increasingly recognized as dynamic vascular diseases driven by endothelial genetic alterations and dysregulated signaling pathways, rather than as static structural anomalies. Accumulating evidence from both hereditary and sporadic forms of BAVMs has established endothelial signaling dysfunction as a central pathogenic mechanism underlying aberrant angiogenesis, progressive lesion remodeling, and vascular instability that predisposes to hemorrhage. These insights have fundamentally shifted the conceptual framework of BAVMs toward a pathway-driven disease model. Despite this progress, direct access to biologically informative molecular material from living AVM lesions remains limited, posing a major barrier to detailed mechanistic interrogation and the translation of molecular insights into clinical decision-making. Historically, molecular characterization of AVMs has relied almost exclusively on surgically resected tissue, restricting analyses to selected patient populations and frequently reflecting late-stage disease biology. Such approaches provide limited insight into disease initiation, temporal evolution, or treatment-induced molecular changes. Recent advances in minimally invasive biopsy strategies, particularly those leveraging endovascular access, have begun to overcome these limitations by enabling molecular interrogation of AVMs in vivo. In this mini review, we summarize emerging approaches for molecular profiling of AVMs, with a primary focus on BAVMs, while also drawing on relevant studies in extracranial and other arteriovenous malformations that share common endovascular access routes, technical principles, and translational implications.

The loss of chromosome Y (LOY) in leukocytes is the most prevalent form of clonal mosaicism observed in older men. Previous studies provided multiple pieces of evidence for the effect of LOY on the immune system and connected LOY to elevated risk of all major causes of mortality, including cardiovascular diseases and cancer. Despite these associations, the dynamic effects of LOY across the developmental trajectories of immune cell populations remain unclear. We utilized single-cell RNA-sequencing data from the peripheral blood mononuclear cells of 416 male donors (median age = 68) from the OneK1K cohort. LOY was identified in 45,304 cells (8.76%) and exhibited cell type-specific effects on immune cells along the differentiation trajectories. The largest frequency was detected in monocytes (18.6% in classical and 17.1% in nonclassical) with a progressive decrease along the transition trajectory from 22.6% to 15.8% (p = 2.00 × 10), and a gradual reduction in the expression of nonclassical markers LYPD2 and C1QA. LOY is associated with a profibrotic signature in classical monocytes marked by downregulation of IL1B (log FC = -0.22, p = 2.84 × 10) and MYC-regulated genes (log FC = -0.25, p = 2.22 × 10), consistent with previous observations that LOY-associated macrophages are polarized toward a fibrotic rather than inflammatory phenotype in cardiac and pulmonary injury. Notably, we detected aberrant expression of XIST, the essential X-chromosome-inactivation lncRNA that is not normally expressed in males, and upregulation of genes known to escape X-inactivation, including male-biased cancer-related genes KDM6A, DDX3X, KDM5C, and ZRSR2. Our results indicate associations between LOY and cell type-specific transcriptional changes, including aberrant X-inactivation features.

BACKGROUND: Bioprosthetic mitral valve degeneration is traditionally treated with redo surgical mitral valve replacement (redo-SMVR), but valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) offers a less invasive alternative. METHODS: Systematic review and meta-analysis of studies comparing ViV-TMVR and redo-SMVR. PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane databases (inception to September 2025) were searched. Meta-analyses were conducted with random-effects models to assess patient-relevant outcomes; Kaplan-Meier-derived time-to-event data were pooled to assess late outcomes. RESULTS: Thirteen observational studies met our eligibility criteria, including 15 941 patients (ViV-TMVR: 5465; redo-SMVR: 10476). In comparison with redo-SMVR, ViV-TMVR was associated with lower risk of in-hospital mortality (risk ratio [RR], 0.72 [95% CI, 0.57-0.90]; =0.004), stroke (RR, 0.49 [95% CI, 0.29-0.83]; =0.008), bleeding (RR, 0.43 [95% CI, 0.20-0.94]; =0.035), acute kidney injury (RR, 0.57 [95% CI, 0.42-0.77]; <0.001), permanent pacemaker implantation (RR, 0.30 [95% CI, 0.19-0.49]; <0.001), and shorter hospital length of stay (mean difference,-5.09 days [95% CI, -6.56 to -3.63]; <0.001). There was no statistically significant difference between the groups in terms of 5-year survival (hazard ratio [HR], 0.92 [95% CI, 0.81-1.05]; =0.256); however, the landmark analysis revealed that ViV-TMVR was associated with lower risk of death in the initial 6 months (HR, 0.69 [95% CI, 0.58-0.83]; <0.001) but a higher risk beyond 6 months (HR, 1.47 [95% CI, 1.20-1.79]; <0.001). CONCLUSIONS: In patients amenable to ViV-TMVR, this procedure shows a lower initial risk of death and complications, but higher mortality after 6 months in comparison with redo-SMVR. These findings highlight the importance of striking a balance between upfront surgical risk and estimated life expectancy when selecting interventions.

BACKGROUND & AIMS: Proton pump inhibitor (PPI) use has been associated with metabolic dysfunction associated with steatotic liver disease (MASLD) in multiple studies. While the association is confounded by various risk factors, such as BMI and age, a potential mediating factor of the microbiome has been suggested. In this study, we aimed to identify bacterial clades with the highest mediating potential and evaluate the serially mediated path through microbially derived endogenous ethanol. METHODS: Microbiome mediation analysis of PPI use and MASLD was conducted in two cohorts. In a bariatric surgery cohort ( = 122), liver biopsy-proven steatosis grade and postprandial ethanol concentrations were used as outcomes. In the HELIUS cohort ( = 2440), a general population cohort study, mediation was performed using the Fatty Liver Index (FLI) score. The strongest associations were validated in the FINRISK cohort ( = 7066). RESULTS: Several bacterial taxa, which are predominantly found in the small intestine, showed a potential role in mediating the effects of PPIs on MASLD, postprandial ethanol levels, and FLI score. The Lactobacillales order showed the strongest mediating potential across the outcomes tested in both discovery cohorts. A notable serial mediation pathway was identified, linking PPI use to MASLD via Lactobacillales abundance and postprandial plasma ethanol concentrations. The mediating role of Lactobacillales in the association between PPI use and FLI scores was confirmed in the final study cohort. CONCLUSIONS: Data from multiple cross-sectional cohort studies support a mediating potential of the microbiome in the association between PPI use and hepatic steatosis, independent of alcohol consumption. The effect of PPIs on MASLD appears to be mediated mainly by increased lactic acid bacteria abundance, and is potentially, in part, serially mediated by endogenous ethanol production.

BACKGROUND: The co-occurrence of mirror-image dextrocardia and tetralogy of Fallot (TOF) is a rare congenital condition. Reoperative multivalve surgery in such patients, especially after repaired TOF, presents exceptional challenges due to the mirrored cardiac anatomy and altered surgical field. This case highlights the surgical strategy for concomitant tricuspid, mitral, and pulmonary valve replacement in this unique setting. CASE PRESENTATION: A 14-year-old male patient with a history of corrected TOF and mirror-image dextrocardia presented with progressive heart failure due to severe regurgitation of the tricuspid, mitral, and pulmonary valves. Preoperative imaging confirmed the complex anatomy, with the atria positioned posteriorly, rendering the atrioventricular valve orifices near-vertical during surgery. The patient successfully underwent triple valve replacement under cardiopulmonary bypass. Key technical adaptations were made to select the valve model and position. The postoperative course was uneventful, with significant symptomatic and echocardiographic improvement at discharge and during the two-month and six-month follow-up. CONCLUSION: This case demonstrates that concomitant triple valve replacement is feasible in patients with mirror-image dextrocardia and a history of TOF repair, despite the profound technical challenges posed by the anatomical distortions. Success hinges on meticulous preoperative planning using advanced imaging and the development of an individualized surgical approach. This report provides a valuable reference for managing such complex, high-risk reoperations in the setting of congenital situs inversus.

BACKGROUND: Healthcare-seeking behavior is a key factor in how well a health system performs and how fair it is. In Saudi Arabia, public healthcare services are free, yet many people still choose private healthcare, especially in cities like Riyadh. It is important to understand why people seek care from private clinics to help shape health policies, distribute resources better, and improve services across the healthcare system. OBJECTIVES: This study aimed to examine the frequency of private healthcare use, defined as the reported usual or concurrent use of private healthcare services, and to identify sociodemographic, behavioral, and health-related factors associated with this choice among adults in Riyadh, Saudi Arabia. METHODS: A cross-sectional study was carried out in Riyadh from March to July 2023 using a multistage cluster sampling method. We randomly selected 48 government primary healthcare centers and invited adults aged 18 and older who visited these centers to participate. We collected data electronically with a validated questionnaire that covered sociodemographic details, patterns of healthcare use, reasons for choosing private healthcare, behavioral risk factors, and existing health conditions. We used multivariate logistic regression analysis to find independent predictors of private healthcare use, reporting adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: Of 14,239 participants, 72.4% reported using private healthcare services either as a usual source of care or alongside public services. The multivariable analysis revealed several factors to be positively related to private healthcare utilization. Those who were married were more likely to use private healthcare services (AOR 1.23, 95% CI 1.11-1.36). Those with insurance coverage were threefold higher odds of private healthcare use (AOR 3.51, 95% CI 3.13-3.94). Smokers were more likely to seek private healthcare (AOR 1.60, 95% CI 1.45-1.77) than non-smokers, and those who exercised reported increased utilization (AOR 1.83, 95% CI 1.67-2.00). Obesity was also positively related to private healthcare utilization (AOR 1.38, 95% CI 1.12-1.71), and those with heart disease had substantially higher odds of using private healthcare services (AOR 2.09, 95% CI 1.59-2.76). CONCLUSION: Private healthcare use in Riyadh is common and associated with insurance coverage, marital status, behavioral factors, and certain chronic conditions. These findings provide descriptive insights into factors related to private healthcare utilization among public PHC attendees in Riyadh, without implying causal effects or policy recommendations beyond the scope of the data.

BACKGROUND: A history of prior cardiac surgery (PCS) determines treatment decision and long-term outcomes in patients requiring aortic valve replacement. This study examined patient profiles, treatment-decisions and long-term outcomes of patients under 75 years with PCS undergoing transcatheter and surgical aortic valve implantation/replacement (TAVI, SAVR) in the Netherlands. METHODS: Data from 1,284 patients (ages 50-75 years) with PCS undergoing TAVI or SAVR between 2015 and 2020 were analyzed using data from the Netherlands Heart Registration. Logistic and cox regression identified determinants of treatment selection and long-term mortality. Determinants were considered impactful if they had an odds ratio (OR) or hazard ratio (HR) of ≥ 1.5 or ≤ 0.7 and a prevalence of ≥ 5%. RESULTS: Of 1,284 patients, 690 underwent TAVI (54%) and 594 SAVR (46%). Prior index surgery most frequently involved coronary artery bypass grafting (CABG) (57% in the TAVI group vs 40% in the SAVR group; p < 0.001) and previous aortic valve surgery (25% vs 51%; p < 0.001). TAVI patients were significantly older (median 71 vs. 67 years, p < 0.001) and had a higher EuroSCORE II (median 5.7 vs. 4.4, p = 0.003) than SAVR patients. SAVR was the preferred strategy for intermediate-risk patients (62%), while TAVI was favored in high- and prohibitive-risk patients (62% and 94%, respectively). In descending order of odds ratio, the strongest independent determinants of TAVI selection were left ventricular ejection fraction ≤ 30% ((OR: 4.8; 95% CI: 2.6-8.8), poor mobility ((OR: 3.4; 95% CI: 1.6-7.0) and obesity/cachexia (OR 2.7; 95% CI: 1.6-4.4); the key determinants of SAVR selection were pure native aortic regurgitation (OR: 0.1; 95% CI: 0.1-0.3) and failing surgical bioprosthesis (OR: 0.7; 95% CI: 0.5-1.0. Thirty-day, 1- and 5 year survival after TAVI and SAVR was 97% and 96%, 83% and 91%, and 56% and 83%, respectively (p-value < 0.001). Left ventricular ejection fraction ≤ 30% and chronic lung disease were important mortality determinants for both procedures, with higher odds ratios for mortality in SAVR as compared to in TAVI patients. CONCLUSIONS: In the Netherlands, TAVI and SAVR rates were comparable among patients < 75 years with PCS. Higher-risk patients were directed toward TAVI except for those presenting with pure native aortic regurgitation and bioprosthesis failure who mainly received SAVR. Severe left ventricular dysfunction and chronic lung disease were key mortality predictors for both procedures.

BACKGROUND/OBJECTIVE: Residual cardiovascular risk persists despite intensive statin therapy in patients with established atherosclerotic cardiovascular disease (CVD). Omega-3 fatty acids, particularly high-dose eicosapentaenoic acid (EPA), have been proposed as adjunctive therapy, yet trial results conflict, likely due to formulation differences. We conducted a formulation-focused meta-analysis to determine whether high-dose EPA-dominant supplementation reduces cardiovascular events and to quantify the impact of mixed EPA/docosahexaenoic acid (DHA) regimens on efficacy. METHODS: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched MEDLINE, Embase, CENTRAL, and trial registries through May 2025 for randomized controlled trials, including placebo-controlled and open-label designs, of high-dose EPA-dominant omega-3 (≥ 1.8 g/day; ≥ 50% EPA) in adults with established CVD or other high-risk settings. Six trials (n = 42,738; 31-85% male) were eligible. Random-effects models generated pooled risk ratios (RRs), with I assessing heterogeneity; sensitivity analyses excluded mixed EPA/DHA formulations. Imaging surrogate outcomes were summarized narratively when study modalities were not directly comparable. RESULTS: EPA-based therapy significantly reduced hospitalizations for unstable angina (RR 0.75, 95% CI 0.66-0.87; I = 0%). Overall effects on recurrent myocardial infarction and revascularization were not statistically significant, but both became significant after exclusion of STRENGTH, the only mixed EPA/DHA cardiovascular outcomes trial. No significant effect was observed for ischemic stroke, cardiovascular death, or high-sensitivity C-reactive protein (hs-CRP). CHERRY and EVAPORATE both suggested attenuation of plaque progression, but these imaging studies were not pooled because intravascular ultrasound and coronary computed tomography angiography-derived measures were not directly comparable. CONCLUSION: High-dose EPA-dominant therapy was associated with fewer unstable angina hospitalizations, and formulation appeared to modify clinical benefit. Among blinded, placebo-controlled, cardiovascular outcomes trials, 4 g/day icosapent ethyl is the only formulation independently associated with reduced cardiovascular events. Larger formulation-specific trials are needed to clarify the roles of purified EPA, mixed EPA/DHA regimens, and patient selection. REGISTRATION: PROSPERO identifier number: CRD420251063069.

BACKGROUND: Ongoing neurodevelopmental care is essential for children with congenital heart disease (CHD). Understanding delivery and uptake of neurodevelopmental care pathways can inform implementation and resource planning. This study applied simulation modelling to explore outcomes from a neurodevelopmental care pathway for children with CHD. METHODS: The model was developed using data from a Queensland program to explore health service interactions for neurodevelopmental screening, formal assessment, and early intervention, up to five years. Modelling was intended to provide a baseline understanding of the pathway, rather than evaluating against a reference standard. Hypothetical scenarios explored how changes in screening and referrals influenced the identification of developmental concerns, and how developmental concern severity affected intervention referrals. RESULTS: Based on available data, 58% of the cohort remained under routine surveillance and 25% had accessed early intervention for one or more developmental delays. Scenarios defined by increased screening projected up to 55% of the cohort having a developmental concern identified during screening and 45% having a developmental delay identified following assessment. CONCLUSION: Simulation modelling was useful for understanding outcomes from a neurodevelopmental pathway and how differences in screening and assessment affected health service interactions. Findings may inform policy and resource planning for future neurodevelopmental pathways. IMPACT: This study shows that simulation modelling is a useful approach for evaluating a neurodevelopmental care pathway for children with CHD, to understand movement through neurodevelopmental screening, assessment, and interventions. Scenario-based modelling provides insights into factors influencing pathway engagement, contributing evidence to strengthen understanding of service gaps and areas where improvements can most effectively impact engagement and resourcing. This study identifies neurodevelopmental screening as the most influential stage impacting downstream outcomes, underscoring its importance as a strategic intervention point. This study's approach provides a general framework for evaluating similar pathways and a potential baseline for assessing future policy or service changes.

The gut microbiome supports digestion, immunity, and metabolism; its imbalance (dysbiosis) drives inflammation and metabolic dysfunction, contributing to chronic diseases such as diabetes, cardiovascular disease, inflammatory bowel disease, and autoimmune disorders. Medicinal plants provide a wide range of phytochemicals (such as polyphenols, flavonoids, alkaloids, saponins), which reach the colon and undergo two-sided interactions with microbes in the gut, acting as potential microbiome modulators and substrates of biotransformation into bioactive metabolites. This structured narrative review synthesises evidence from peer-reviewed studies indexed in PubMed, Scopus, and Web of Science over the last 10 years on the role of medicinal plants in microbiome-mediated chronic disease modulation. This literature is organised into three mechanistic axes: (i) perturbations, defined here as measurable shifts in microbial diversity or taxonomic composition relative to a baseline or healthy reference state, together with beneficial taxa enrichment; (ii) alterations in microbial metabolite output, especially short-chain fatty acids (SCFAs) and other immunometabolic mediators; and (iii) downstream host metabolic and immune signalling. Rather than broad descriptive summaries, the literature is organised using an axis-based mechanistic framework, highlighting key translational constraints such as botanical heterogeneity, dose/formulation variability, and inconsistent microbiome endpoint standardisation, that must be addressed to strengthen human evidence and clinical relevance. Illustrative microbiome-mediated processes involve botanicals such as turmeric (curcumin), ginseng (ginsenosides), and green tea (catechins), though evidence strength varies by study design. Future progress requires standardised phytochemical characterisation, microbiome-stratified trials, and integration of multi-omics with artificial intelligence analytics to enhance mechanistic insight, identify responders, and enable personalised plant-based microbiome therapies.

BACKGROUND/AIM: Heart transplantation (HTx) represents the definitive treatment for patients with end-stage heart failure (HF). Neurological complications, particularly cognitive impairment (CI), may influence prognosis, thereby affecting the overall benefits of HTx. CI in HF is associated with disease severity, extracardiac dysfunction, and peri- or intra-operative factors such as prolonged ventilation, cerebral hypoperfusion, and systemic inflammation. However, existing studies on CI in HTx candidates are highly heterogeneous, limiting comparability and highlighting the need for a clearer understanding of its impact in both candidates and recipients. METHODS: This systematic review was registered with PROSPERO (CRD42024549051) and conducted in accordance with PRISMA guidelines. PubMed, Scopus, and Embase were searched for studies published between 2013 and June 2025. Eligible studies assessed cognitive function in adult HF patients undergoing HTx. RESULTS: Of 1188 records screened, eight studies met the inclusion criteria. Most cognitive studies employed the Montreal Cognitive Assessment (MoCA), while two used comprehensive neuropsychological batteries. Evidence confirmed that CI is common among HF and HTx populations. Incorporating cognitive status into frailty assessments enhanced prediction of adverse outcomes, including prolonged hospitalization and reduced survival. Cognitive decline was frequently observed in the immediate post-transplant period, often linked to high-dose immunosuppressive therapy and anemia, while long-term improvements were reported in attention, memory, and executive function. CONCLUSIONS: Cognitive assessment is essential in HTx candidates, as CI has a major impact on survival. Further studies are needed to clarify long-term cognitive trajectories and the role of immunosuppressive therapy in shaping outcomes.

Despite modest improvement, the lifespan of a child on dialysis continues to be 40 years shorter compared to healthy children. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patients. Risk factors for CVD are present even in early stages of chronic kidney disease (CKD) and accelerate as the child's renal function deteriorates. As a result, the highest burden of CVD exists in patients on chronic dialysis. Although dialysis is life-sustaining, the dialysis procedure promotes cardiovascular damage. Both traditional and non-traditional CVD risk factors drive this acceleration. More concerning, the dialysis procedure itself is cardiotoxic. Because of coexisting poor cardiac reserve and altered sympathetic tone in this patient population, dialysis induces repetitive contractile, ischemic injury termed myocardial stunning. This ischemia-reperfusion injury is reversible at first. However, with repetitive episodes, this injury will trigger alterations in cardiac function that decrease contractile function in order to preserve viability. Ultimately, these adaptations lead to remodeling and fibrosis. There is no targeted therapy available to reverse cardiovascular damage in these patients. Intensive monitoring and management of modifiable risks such as hypertension and anemia in the early stages of CKD to optimize cardiovascular health is imperative. However, in late CKD, especially in those patients who are not candidates for preemptive renal transplantation, optimization of the dialysis procedure is critical to prevent acceleration of their CVD burden. Improved assessment of dry weight as well as data-driven fluid management programs may decrease some risk. More importantly, standard implementation of intensified dialysis prescriptions by increasing time or through the addition of convective clearance may mitigate progressive cardiovascular damage and enhance survival. In this review, the pathophysiology of dialysis-induced cardiovascular damage will be reviewed. The management strategies to limit the cardiovascular burden in our patients are also discussed.

BACKGROUND: Central nervous system (CNS) metastases from Wilms tumor (WT) are exceedingly rare. Intracerebral hemorrhage secondary to metastatic WT is even less common, and the management of such cases is further complicated when patients are receiving a direct oral anticoagulant (DOAC) like Rivaroxaban, for which pediatric reversal guidelines are lacking. CASE PRESENTATION: We report on the case of a 5-year-old boy with relapsed stage IV Wilms tumor who presented with rapidly progressive neurological deterioration caused by brain metastases with extensive intraparenchymal and intraventricular hemorrhage while receiving Rivaroxaban due to prior thrombosis. An emergent craniotomy and tumor resection was safely performed after emergent reversal of anticoagulation with Rivaroxaban using Andexanet alfa, administered in this pediatric patient with off-label consent in the setting of a life-threatening intracranial hemorrhage requiring emergent neurosurgical intervention. No excessive intraoperative bleeding was noted. Treatment for relapsed WT according to the SIOP-UMBRELLA-Protocol was initiated. Three weeks after Andexanet alfa treatment, a thrombotic event in the left iliac veins occurred, requiring anticoagulation with unfractionated heparin. CONCLUSIONS: This case highlights the therapeutic challenges of managing intracranial hemorrhage in a pediatric patient requiring emergent neurosurgical debulking in the setting of Rivaroxaban anticoagulation. To our knowledge, this is the second case reporting on Rivaroxaban reversal through Andexanet alfa in children. Early multidisciplinary intervention, meticulous neurosurgical management and continuation of oncologic therapy can lead to favorable outcomes even in such complex presentations.

Alzheimer's disease (AD) is a growing public health concern, with neuroinflammation implicated in its pathogenesis. Allergic rhinitis (AR), a prevalent chronic inflammatory disorder, may contribute to systemic inflammation and potentially influence AD risk. This study sought to critically assess the association between a history of AR and subsequent AD development in a large, representative Taiwanese cohort. Leveraging Taiwan's National Health Insurance Research Database (LHID2010), this nationwide case-control study identified 4,681 individuals aged ≥ 65 years with a first-time AD diagnosis (cases) and 14,043 propensity-score-matched controls. A rigorous definition of prior AR required at least two clinical diagnoses, including one by an otolaryngology specialist. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. The prevalence of prior AR was significantly higher in AD patients than in controls (25.29% vs. 21.01%, p < 0.001). Following meticulous adjustment for demographic variables, socioeconomic status, geographic factors, and medical comorbidities (including hyperlipidemia, diabetes, coronary heart disease, hearing loss, and hypertension), prior AR was robustly associated with elevated odds of AD (adjusted OR = 1.279, 95% CI = 1.182 ~ 1.384). This association remained significant for both males (adjusted OR = 1.196, 95% CI = 1.053 ~ 1.358) and females (adjusted OR = 1.339, 95% CI = 1.210 ~ 1.482). This study suggests a significant association between prior AR and an increased odds of developing AD in an elderly Taiwanese population. These findings highlight chronic peripheral inflammation as a factor potentially associated with neurodegeneration.

We study the deterministic Susceptible-Infected-Susceptible (SIS) epidemic model on weighted graphs. van Mieghem et al. have shown that it is possible to learn an estimated network from a finite time sample of the trajectories of the dynamics that in turn can give an accurate prediction beyond the sample time range, even though the estimated network might be qualitatively far from the ground truth. We give a mathematically rigorous derivation for this phenomenon, notably that for large networks, prediction of the epidemic curves is robust, while reconstructing the underlying network is ill-conditioned. Furthermore, we also provide an explicit formula for the underlying network when reconstruction is possible. At the heart of the explanation, we rely on Szemerédi's weak regularity lemma.