Hidradenitis suppurativa (HS) is increasingly recognized as a progressive inflammatory disease in which recurrent follicular inflammation, tunnel formation and systemic inflammation drive cumulative, largely irreversible tissue damage, quality-of-life impairment and cardiometabolic comorbidity. Despite this, no consensus definition of disease progression exists. This review synthesizes current evidence to propose a working, multidimensional framework for progression in HS and to map its determinants, detection tools and consequences. We frame progression along six complementary dimensions grouped in three blocks-objective severity (Hurley transition, International Hidradenitis Suppurativa Severity Score System [IHS4] category shift), anatomical extension (extra- and intraregional spread) and cumulative disease burden (secondary complications and patient-reported impact)-aligned with current European guidelines for therapeutic escalation. Available longitudinal data show that incidence and speed of progression depend strongly on care setting and assessment method, with tertiary cohorts assessed clinically and by ultrasound reporting incidences of approximately 37% over ~2 years and self-reported community cohorts substantially lower. Independent risk factors cluster into demographic-familial, phenotypic-anatomical, lifestyle-metabolic, laboratory and comorbidity domains, with early-onset disease, smoking, inflammatory bowel disease, Down syndrome and pilonidal sinus as the most consistent signals. Phenotype frameworks converge on a higher-risk profile of male, smoker patients with severe acne and lower-body involvement. Genotype shapes phenotype, with γ-secretase/Notch variants driving an occlusion-dominant course and inflammasome variants (PASH, PAPASH, PAPA, SAPHO) a more systemic one; heritability approaches 77%. Ultrasound refines staging, detects subclinical microtunnels and identifies the inflamed non-draining tunnel that defines a within-lesion window of opportunity. Progression has tangible cutaneous, psychosocial, systemic, metabolic and cardiovascular consequences, making early recognition a clinical imperative; disease modification within a limited therapeutic window remains a plausible and testable paradigm rather than a demonstrated fact.

BACKGROUND: Rat bite fever is a rare infection that can cause severe complications such as infective endocarditis with a mortality rate of 13% if left untreated. CASE SUMMARY: We present the first reported fatal case of rat bite fever requiring mechanical circulatory support in a 48-year-old woman who presented with diarrhea, syncope, and lower back pain. Echocardiogram revealed tricuspid valve endocarditis, a large aortic root abscess, and a moderate-to-large membranous ventricular septal defect. After empiric antibiotics and extensive cardiac surgery, the patient remained in refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation support. Despite maximal supportive measures, the patient ultimately succumbed to her critical illness. DISCUSSION: Rat bite fever often presents with nonspecific symptoms that can delay presentation to medical attention, diagnosis, and targeted treatment. Most cases are caused by Streptobacillus moniliformis and result from rodent bites or exposure to contaminated food or water. Diagnosis can be challenging as the organism is fastidious, difficult to grow, and has limited diagnostic tests available for early detection. TAKE-HOME MESSAGES: Rat bite fever is a potentially fatal infection that presents with nonspecific symptoms. Late presentation can result in catastrophic complications and high mortality.

In 1990, the difference between the longest and the shortest QT interval measured across the twelve leads of the standard electrocardiogram was proposed as a simple and inexpensive index of the spatial heterogeneity of ventricular repolarization. QT dispersion was adopted rapidly and applied to almost every cardiac and to many non-cardiac conditions and was described by its proponents as a potential Holy Grail for the prevention of sudden cardiac death. Within a decade, however, disappointing results from large studies and a series of methodological and conceptual objections had led others to characterise it as the greatest fallacy in electrocardiography of the 1990s. This narrative review reappraises QT dispersion thirty-six years after its description. We examine four separate lines of criticism: the poor reproducibility of T-wave offset determination and the consequent amplification of measurement error in a parameter of small absolute magnitude; the absence of any demonstrated rate dependence, which invalidates the widespread practice of heart-rate correction; the competing local and vectorial explanations of the phenomenon, together with the experimental and clinical evidence that favours projection over regional information; and the inconsistent prognostic performance of the parameter across major cohort studies. We further argue that the failure of QT dispersion is not a failure of the underlying premise that repolarization heterogeneity is arrhythmogenic, but of the specific surface measurement chosen to capture it, and we summarise the contemporary non-invasive markers that have since been developed for the same purpose. We conclude that QT dispersion should not be interpreted as a measure of the dispersion of repolarization duration, and that its residual association with clinical risk is more plausibly explained by projection effects and measurement inaccuracy than by regional electrophysiological information. QT dispersion is still reported without acknowledgement of these objections. Setting them out together with the markers that have replaced the parameter should help readers judge what it can and cannot support.

BACKGROUND: Thrombosis is a multifactorial disorder with a substantial genetic component, yet gene-gene interactions contributing to thrombotic risk remain insufficiently characterized in Southeast Asian populations. Identifying both individual genetic determinants and interaction effects may improve risk stratification, particularly in families with early-onset thrombotic disease. OBJECTIVE: This study aimed to explore individual and interactive genetic contributions to thrombotic events in Vietnamese pedigrees with early-onset venous thromboembolism (VTE) using an integrated analytical framework combining Multifactor Dimensionality Reduction (MDR) and SHapley Additive exPlanations (SHAP). METHODS: A pedigree-based study was conducted among 88 individuals from families with a history of early-onset VTE (<50 years), including 19 affected cases. Genetic variants were identified using next-generation sequencing. Random Forest modeling with SHAP was used to quantify global and local feature contributions, while MDR was applied to detect potential non-linear gene-gene interactions beyond single-locus effects. The Random Forest model was not explicitly adjusted for familial clustering or relatedness; results were therefore interpreted as exploratory. RESULTS: SHAP analysis identified rs1045642 (ABCB1) as the strongest contributor to model-predicted baseline thrombotic risk. MDR analysis suggested that this background susceptibility may be further modified by a two-locus interaction between rs12041331 (PEAR1) and rs1800790 (FGB). Individuals classified within the high-risk MDR genotype combination showed increased odds of thrombosis (OR = 8.00, 95% CI: 1.67-74.96; p = 0.0028), compared with the corresponding single-locus model (OR = 3.73, 95% CI: 0.93-21.48; p = 0.0405). Confidence intervals were wide, reflecting limited precision. CONCLUSION: In this exploratory pedigree-based study, rs1045642 (ABCB1) was associated with baseline thrombotic susceptibility, while a potential interaction between PEAR1 and FGB may further modulate risk in specific genotype combinations. The integration of MDR and SHAP provides an interpretable framework for investigating complex genetic architectures. However, given the small sample size and limited number of events, these findings should be considered hypothesis-generating and require validation in larger independent cohorts.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have achieved remarkable success in treating advanced cancers, yet the accompanying immune-related adverse events (irAEs) pose a major challenge to their clinical application. Growing evidence suggests an association between irAEs and improved clinical outcomes; however, the heterogeneity in this relationship warrants further exploration. CASE PRESENTATION: This article reports two cases of patients with advanced cancer who achieved long-term disease control after experiencing severe irAEs. Case one involved a patient with heavily pretreated Luminal B1 advanced breast cancer who developed Grade 3 immune-related arrhythmia and heart failure following treatment with Toripalimab combined with chemotherapy. Case two involved a patient with ROS1-fusion advanced lung adenocarcinoma who, after developing resistance to Crizotinib, received chemotherapy and Tislelizumab, leading to Grade 3 immune-related hypopituitarism, adrenal insufficiency, and cutaneous toxicity. Both patients were managed with corticosteroids with or without immunosuppressants and discontinued all antitumor therapies. Despite this, they have achieved a partial response (PR) with a duration of response (DoR) of 22 and 37 months, respectively, and both responses are ongoing at the time of this report. CONCLUSION: In this series, two patients with advanced solid tumors achieved durable tumor responses after developing severe irAEs and discontinuing treatment, suggesting that severe irAEs may herald the establishment of long-term immune memory. However, the association between irAEs and efficacy is not straightforward, as the type and severity of irAEs and the use of immunosuppressive intervention all influence the ultimate clinical benefit. In the absence of reliable predictive biomarkers, clinical decisions should not equate irAEs directly with efficacy markers; rather, the benefits and risks of immune activation should be carefully weighed.

BACKGROUND: () is a rare cause of culture-negative infective endocarditis and may present without classic gastrointestinal manifestations, leading to delayed diagnosis and severe valvular destruction. CASE SUMMARY: A 76-year-old man with a prior bioprosthetic aortic valve replacement presented with at least 2 weeks of fatigue, generalized weakness, intermittent chills, and worsening dyspnea, along with approximately 8 kg of unintentional weight loss since the preceding summer; he remained afebrile. Blood cultures remained persistently negative. Transesophageal echocardiography revealed a > 3-cm vegetation, prosthetic valve dehiscence, severe paravalvular regurgitation, and periannular abscess. Despite empiric broad-spectrum antibiotics and urgent surgical evaluation, the patient deteriorated and suffered cardiac arrest. Whole-blood polymerase chain reaction testing collected during hospitalization returned positive for after the patient's death, establishing the diagnosis. DISCUSSION: Whipple endocarditis typically presents as culture-negative disease and often lacks systemic features, delaying recognition. This case highlights the diagnostic challenge posed by in prosthetic valve endocarditis and the value of molecular testing when conventional cultures remain negative. TAKE‐HOME MESSAGE: Early PCR testing should be considered in culture-negative prosthetic endocarditis, as it may establish a diagnosis when conventional cultures and valve tissue are unavailable.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) contributes to vascular calcification and cardiovascular morbidity among maintenance hemodialysis patients. Mineral metabolism abnormalities, particularly hyperphosphatemia and secondary hyperparathyroidism, may adversely affect vascular access patency and increase vascular access-related complications. However, data from sub-Saharan Africa remain limited. This study evaluated the association between abnormalities in mineral metabolism and vascular access complications among maintenance hemodialysis patients in Ethiopia. METHODS: A facility-based cross-sectional study was conducted among 302 maintenance hemodialysis patients in Addis Ababa, Ethiopia. Sociodemographic, clinical, and laboratory data were collected using structured questionnaires and medical record review. Mineral metabolism parameters included serum calcium, serum phosphorus, and intact parathyroid hormone (iPTH) levels. Vascular access complications were assessed clinically and from dialysis records. Multivariable logistic regression analysis was performed to identify factors independently associated with vascular access complications. RESULTS: The mean age of participants was 52.6 ± 14.2 years, and 59.0% were male. Vascular access complications were identified in 72 (23.8%) participants. Hyperphosphatemia, hypocalcemia, and elevated iPTH were present in 28.0%, 27.7%, and 47.4% of patients, respectively. Patients with vascular access complications had significantly higher mean serum phosphorus levels and iPTH concentrations compared with those without complications ( < 0.05). In multivariable analysis, hyperphosphatemia (adjusted odds ratio [AOR] = 2.41, 95% CI: 1.32-4.39), elevated iPTH (AOR = 2.87, 95% CI: 1.58-5.21), and dialysis duration > 24 months (AOR = 1.94, 95% CI: 1.08-3.47) were independently associated with vascular access complications. CONCLUSIONS: Abnormalities in mineral metabolism were significantly associated with vascular access complications among maintenance hemodialysis patients in Ethiopia. Hyperphosphatemia and elevated iPTH emerged as important independent predictors of vascular access dysfunction. Strengthening CKD-MBD management and optimizing mineral metabolism control may help reduce vascular access complications and improve dialysis outcomes in resource-limited settings.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of 90% if not treated promptly. Due to limited clinical experience and sometimes atypical presentation, early detection of TTP is not always easy. The pathophysiological mechanisms underlying TTP can accelerate thrombus formation and vascular occlusion, potentially leading to ischemic damage in various organs, including the heart and pancreas. Considering that the complications caused by these disorders can be life-threatening, the simultaneous manifestation of acute pancreatitis (AP), TTP, and heart damage in the patient may cause a significant risk of mortality if not treated in time and adequately. We report a case involving a 43-year-old patient who presented with symptoms of myocardial infarction (MI) and acute pancreatitis (AP) secondary to thrombotic thrombocytopenic purpura (TTP). The patient was diagnosed based on clinical manifestations, laboratory findings, and imaging studies. Immediate intervention included plasma exchange and supportive care, which led to the stabilization of the patient's condition. This case highlights the importance of actively assessing and monitoring for organ involvement, including pancreatic and cardiac complications, in patients with TTP. Early diagnosis and prompt treatment are critical in reducing the risk of mortality associated with these severe complications.

BACKGROUND Coronary artery disease is associated with long-term systemic inflammation and perioperative multiorgan vulnerability, including transient hepato-renal dysfunction after cardiac surgery. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) provide cardiorenal protection beyond glucose lowering via anti-inflammatory, metabolic, and endothelial effects, but their effect on perioperative liver-related risk markers, including the Model for End-Stage Liver Disease (MELD) score, in off-pump coronary artery bypass grafting (OPCAB) remains uncertain. MATERIAL AND METHODS We retrospectively studied 111 consecutive patients undergoing elective OPCAB in 2024 (chronic hepatic or renal disease excluded). Patients were stratified by long-term preoperative SGLT2i therapy (≥3 months): no SGLT2i (n = 85) vs SGLT2i (n = 26). MELD score, bilirubin, international normalized ratio , and creatinine were assessed preoperatively and on postoperative days 1 and 6. Between-group comparisons used the Mann-Whitney U test; within-group changes were analyzed using the Friedman test, Kendall's W, and Bonferroni post hoc testing RESULTS Baseline MELD and components were comparable. On postoperative day 1, SGLT2i group exhibited lower bilirubin (P < 0.001), INR (P = 0.04), and MELD score (P = 0.03), but higher creatinine (P = 0.002). By day 6, differences attenuated. Within-group analysis showed significant time effects for MELD, INR, and creatinine in both groups, with large effect sizes (W = 0.48-0.88). Total bilirubin changed over time in the control but not the SGLT2i group. CONCLUSIONS Long-term preoperative SGLT2i therapy was associated with distinct perioperative MELD dynamics in OPCAB, with relative preservation of bilirubin and INR despite creatinine changes, suggesting the potential modulation of hepatic function during perioperative stress. Given the observational design and possible confounding, results are hypothesis-generating and warrant prospective confirmation..

Vascular dementia (VaD), the second most common form of dementia, lacks approved disease-modifying therapies. White matter injury and demyelination are major pathological features, and oligodendrocyte-lineage damage directly limits myelin repair. M2-associated microglial responses regulate inflammation, clear cellular and myelin debris, and support oligodendrocyte differentiation and maturation. Single-cell studies, however, have exposed the limitations of the classical M1/M2 dichotomy in brain disease. In this review, M2a-, M2b-, and M2c-like states are interpreted based on experimentally specified inducing conditions and concordant molecular or functional evidence. We examine how these programs relate to oligodendrocyte injury, myelin loss, and white matter repair in VaD. with particular attention to their potentially stage-dependent contributions. Integrating these findings may inform the timing and functional focus of future interventions aimed at preserving oligodendrocyte function and promoting white matter repair in VaD.

Time to event endpoints like time to myocardial infarction, relapse, or death are often of primary interest in clinical trials. To describe the whole disease process and gain a complete picture of treatment effects, methods for recurrent time to event analysis considering terminal events were proposed, i.e. methods considering all events that occur per individual. However, these methods are not often applied in clinical studies. This might be due to the researchers' uncertainties about underlying model assumptions and interpretation of results. We therefore aim to give a comprehensive overview of methods for the analysis of multiple time to events comparing model assumptions and interpretation. We illustrate the methods using a cardiovascular trial and provide the corresponding R code.

5-Flurouracil (5-FU) is still considered as one of the most popular antimetabolite chemotherapy drugs to treat a wide variety of solid tumors. Dose limiting toxicity on major organs, especially cardiovascular system limits the therapeutic use of 5-FU. The current paper addresses the cardioprotective effect of green synthesized selenium nanoparticles through kaempferol (KMP-SeNPs) on the cardiotoxicity induced by 5-FU in a rat model. 35 male Wistar rats were divided equally into five groups, namely control, 5-FU, NaSeO&5-FU, KMP&5-FU, and KMP-SeNPs&5-FU. The 5-FU consumed 5 days induced cardiotoxicity and there were 21 days of oral treatment. The levels of cardiac injury markers, oxidative stress indices, antioxidant enzymes, inflammatory/anti-inflammatory cytokines and apoptotic markers were measured by ELISA, gene expression and immunohistochemistry. The evaluation of cardiac tissue was done by using histopathology. 5-FU caused significant cardiotoxicity detected by increased cardiac enzymes, oxidative stress, inflammatory cytokines, apoptosis, and extensive histopathologic damage. KMP-SeNPs treatment had a great impact on reducing myocardial injury, normalizing cardiac enzymes, decreasing lipid peroxidation and NO generation, reestablishing antioxidant defenses, and increasing Nrf2 signaling and inhibiting Keap-1 expression. The expression of TNF-α, IL-6, NF-κB, Bax, and caspase-3, were significantly decreased, whereas IL-10, FOXP3, and Bcl-2 showed a significant increase, which is evidence of the great anti-inflammatory, as well as anti-apoptotic effect of KMP-SeNPs. Immunohistochemical and histopathology results supported these molecular and biochemical findings to show approximately normal cardiac architecture. KMP-SeNPs are more effective in protecting against 5-FU-induced cardiotoxicity using antioxidant, anti-inflammatory, immunoregulatory, and anti-apoptotic activities.

INTRODUCTION: Intravascular ultrasound (IVUS)-guided femoropopliteal (FP) angioplasty has emerged as a promising imaging-guided strategy in clinical practice. However, current evidence remains heterogeneous, and recently, two randomized controlled trials (RCTs) have provided additional insights into its efficacy. This meta-analysis aims to reevaluate the efficacy of IVUS-guided angioplasty for FP lesions and to better clarify its clinical impact. METHODS: Four databases were systematically searched for studies comparing IVUS-guided angioplasty to angiography-only in FP lesions. Study quality was assessed using the Cochrane Risk of Bias Tool and Newcastle-Ottawa Scale. Meta-analysis was performed using an inverse-variance random-effects model using Rstudio version 2024.09.01. RESULTS: Six high quality studies were included (n = 1544 patients). The risk for primary patency and freedom of clinically driven-target lesion revascularization(cd-TLR) at 1 year was significantly higher in the IVUS-guided group compared to the angiography group (RR 1.27 (95%CI 1.13-1.42, I = 58.6%) and RR 1.10 (95%CI 1.01-1.20, I = 56.8%), respectively), but no significant difference was observed in freedom of amputation and mortality (RR 1.00 (95%CI 0.98-1.01, I2 = 0%) and RR 1.06 (95%CI 0.67-1.70, I2 = 0%), respectively). CONCLUSION: IVUS-guided FP angioplasty improves primary patency and reduced cd-TLR rates. Further studies with longer follow-up duration should be the research focus in order to understand the long-term efficacy.

BACKGROUND: SLE is a chronic autoimmune disease associated with heightened cardiovascular risk. However, the relationship between the triglyceride-glucose (TyG) index and cardiovascular involvement remains unclear. This study aimed to evaluate the association between the TyG index and cardiovascular involvement in SLE. METHODS: We conducted a retrospective cohort study of 991 patients with SLE admitted between 2000 and 2021, spanning 21 years with extended follow-up. Kaplan-Meier curves were used to compare event-free survival across TyG quartiles, and differences between curves were assessed using the log-rank test. Time-to-event analyses were performed using Cox proportional hazards regression models. The proportional hazards assumption was assessed using scaled Schoenfeld residuals. Restricted cubic spline analyses based on Cox models were performed to evaluate the dose-response association between TyG and cardiovascular outcomes. RESULTS: Cardiovascular involvement occurred in 251 patients (25.3%), consisting of 210 inflammatory or lupus-related manifestations and 41 major adverse cardiovascular events (MACE). Elevated TyG correlated with progressively lower event-free survival. An approximately linear association was observed between TyG and both overall cardiovascular involvement and inflammatory/lupus-related cardiovascular manifestations. Each one-unit increase in TyG remained associated with higher risk after multivariable adjustment (adjusted HR 1.36 for both outcomes, both p<0.05). These associations were materially unchanged after accounting for non-proportional covariate effects (overall cardiovascular involvement: HR 1.37, 95% CI 1.10 to 1.71; inflammatory/lupus-related manifestations: HR 1.35, 95% CI 1.06 to 1.74). For the original MACE composite, higher TyG was associated with increased risk in the adjusted analysis; however, this finding was less robust in a post hoc sensitivity analysis excluding heart failure and should be interpreted cautiously because of the limited number of events. CONCLUSION: These findings support the potential value of the TyG index as an accessible marker of cardiometabolic risk in SLE.

OBJECTIVE: To examine whether the outputs of machine learning algorithms designed to predict risk of cardiovascular disease (CVD) address known deficiencies of the Framingham Risk Score (FRS) and improve risk estimates. METHODS: For this critical review, Medline, Embase and IEEE were searched from inception to 1 January 2025. Included were studies describing machine learning algorithms designed to specifically compare output of cardiovascular risk assessment with the FRS. Commentaries, letters, unpublished work or non-peer-reviewed papers were excluded.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two reviewers screened titles and abstracts independently, then populated a purpose-built data extraction form. A subsequent qualitative thematic analysis focused on algorithms' strengths, added value, potential harms, unintended consequences and equity implications.The main outcome assessed was whether, among healthy adults, the algorithm improved CVD risk prediction relative to the FRS. RESULTS: Of 707 studies retrieved, 29 met inclusion criteria. 23 reported improved predictive ability relative to the FRS. Most datasets and/or medical records used included sociodemographic predictors of CVD not included among FRS inputs. Some added costly diagnostic tests like CT angiography to FRS screening indicators. When they were defined, inputs and outcomes such as hypertension or myocardial infarction did not always adhere to FRS values. Statistical significance was generally taken as a proxy for clinical significance. Some algorithms overestimated the number at risk compared with the FRS without discussing whether that larger proportion might be at risk of overdiagnosis rather than CVD, while a few decreased the proportion found to be at risk. CONCLUSIONS: Use of artificial intelligence to improve accuracy of risk assessment for CVD demonstrates the technological capacity to merge known sociodemographic predictors with biologic variables and examine non-linear interactions among these. Still needed to achieve patient benefit is clinical insight, adherence to screening principles and cost-benefit assessment of inputs selected.

BACKGROUND: Dual antiplatelet therapy is indicated in the management of non-ST-elevation acute coronary syndrome (NSTE-ACS) and can be administered before coronary angiography (pre-treatment) or after coronary anatomy is known. Based on clinical trials with rapid access to inpatient coronary angiography, clinical guidelines recommend invasive assessment prior to commencing a second antiplatelet. We aimed to evaluate the impact of a change in clinical policy from routine P2Y inhibitor pre-treatment to no routine pre-treatment on in-hospital outcomes in a UK healthcare context. METHODS: A retrospective observational study of hospitalised NSTE-ACS patients with a planned invasive strategy at a tertiary cardiac centre in Northeast England was conducted. Two cohorts were identified: (1 January 2021 to 31 December 2021) and (1 July 2022 to 30 June 2023). Primary endpoints were in-hospital ST-elevation myocardial infarction (STEMI) and actionable bleeding events, reported as propensity score-adjusted ORs (ORs) and 95% CIs. RESULTS: Of 2506 NSTE-ACS cases, 1219 presented before and 1287 after the policy change, which was adhered to in most cases (84.2%). Median time from admission to angiography was 3.6 days (IQR 1.9, 5.8). In comparison to a strategy, a strategy was associated with greater risk of in-hospital STEMI (1.7% vs 0.4%, adjusted OR 4.40, 95% CI 1.78 to 13.3), but lower risk of actionable bleeding events (0.2% vs 0.9%, adjusted OR 0.18, 95% CI 0.03 to 0.70). There was evidence of pre-treatment effect modification by procedural waiting time on in-hospital STEMI incidence (p for interaction=0.026). CONCLUSION: We observed a greater risk of in-hospital STEMI but lower rates of bleeding following the change from a to a strategy. UK waiting times for in-patient coronary angiography are typically considerably longer than the trials on which guidance is based, which may impact the risk/benefit balance in clinical practice.

BACKGROUND: Percutaneous patent foramen ovale (PFO) closure is an established intervention for secondary prevention of cryptogenic stroke. Increasing evidence indicates that the procedure is associated with a risk of new-onset atrial fibrillation (AF). This study aimed to describe the temporal distribution and clinical factors associated with new-onset AF following percutaneous PFO closure. METHODS: Patients aged ≥16 years undergoing percutaneous PFO closure between 1999 and 2021 at a tertiary care centre were retrospectively included. New-onset AF was identified through systematic review of electronic health records. Descriptives are presented as median with IQR. Time-to-event analysis was performed using cumulative incidence functions and Cox proportional hazards regression. RESULTS: Among 867 patients (median age 51 years (42-58), 47% female), PFO closure was performed for secondary stroke prevention in 86%. During a median follow-up of 11.7 years (6.3-16.8), new-onset AF occurred in 97 patients (11.2%), corresponding to an incidence rate of 1.0 per 100 patient-years. AF diagnoses clustered early after closure, with 26.8% occurring within the first 3 months. In multivariable analysis, higher age at closure (HR 1.05 per year; 95% CI 1.03 to 1.07), larger occluder device size (HR 1.09 per mm; 95% CI 1.03 to 1.16) and any moderate or severe valvular regurgitation (HR 3.70; 95% CI 1.65 to 8.33) were independently associated with new-onset AF. CONCLUSIONS: New-onset AF is common after PFO closure and shows early postprocedural clustering. Increasing age, larger occluder size and valvular regurgitation are independently associated with AF occurrence, underscoring the need for focused rhythm surveillance after closure.

BACKGROUND: Antiretroviral therapy (ART)-treated people with HIV (PWH) have increased risk of heart failure with preserved ejection fraction (HFpEF). The diagnosis of HFpEF relies on cardiac imaging and expertise and is challenging in primary care settings. Further, existing risk prediction tools do not account for HIV-related risk. We developed a practical HFpEF risk prediction tool using data from the Prevalence and Phenotype of HIV-HFpEF in South Africa, a cross-sectional observational study that enrolled 1508 adults aged ≥40 years (1008 PWH on ART ≥1 year and 500 people without HIV (PWoH)) at a primary care clinic in South Africa. METHODS: We used four logistic regression models for HFpEF risk, including demographics, clinical factors, B-type natriuretic peptide (BNP) and ECG abnormalities. We compared the models' area under the receiver operating characteristic curve (AUC) with a random forest classifier, translated the final model into a nomogram-based risk score and evaluated its discrimination and calibration through bootstrap internal validation. RESULTS: The median age was 48 years, 77% female, 42% obese, 38% had hypertension and 7.8% met HFpEF criteria (118 participants; 85 (8.4%) among PWH and 33 (6.6%) among PWoH). Two logistic regression models outperformed the random forest classifier. The model that was used for the nomogram included age, sex, HIV status, smoking, hypertension, body mass index and BNP and showed good discrimination (overfitting-corrected AUC 0.77) with good calibration. CONCLUSIONS: The nomogram-based score, developed using routine clinical information and point-of-care BNP, is practical, accessible and may support screening and identification of individuals at high HFpEF risk for targeted referral for diagnosis and care in a sub-Saharan African primary care setting with a high HIV prevalence.

BACKGROUND: Up to 30% of patients undergoing transcatheter aortic valve implantation (TAVI) have presented to hospital with acute decompensation of aortic stenosis (acute valve syndrome, (AVS)). Such patients conventionally undergo inpatient work-up and treatment by TAVI, associated with prolonged hospital stays, deconditioning and delayed recovery. This study aimed to evaluate the impact and feasibility of an ultra-rapid outpatient pathway for selected, stabilised AVS patients undergoing treatment by TAVI. METHODS: This single-centre cohort study with preimplementation and postimplementation comparison included consecutive AVS patients referred for TAVI over 6 months pre-pathway implementation and 12 months post-pathway implementation. Those meeting prespecified criteria were discharged home for completion of work-up and treatment by TAVI within 2 weeks. The primary efficacy endpoint was length of hospital stay. The primary safety endpoint was death or acute decompensation prior to TAVI. RESULTS: 183 patients were included, of which 105 were evaluated for outpatient treatment after ultra-rapid pathway introduction. 58/105 (55.2%) met criteria for outpatient treatment, the remaining 47/105 (44.8%) were managed as inpatients. There was no significant difference in demographic or echocardiographic characteristics between management pathways. Patients treated as an outpatient had a shorter median total length of hospital stay (outpatient 12 days (IQR 7-17) vs inpatient 20 days (IQR 15-32), p<0.0001), saving an estimated 210 hospital bed-days. There was no significant difference in median time from referral to TAVI (outpatient 15 days (IQR 13-20) vs inpatient 14 days (IQR 10-18), p=0.22), nor in the incidence of the safety endpoint prior to TAVI between pathways (outpatient 6.9% vs inpatient 6.4%, HR 0.97, 95% CI 0.22 to 4.34, p=0.97), or after new pathway implementation (pre-pathway 6.7%, post-pathway 6.7%, HR 0.70, 95% CI 0.17 to 2.80, p=0.61). CONCLUSIONS: An ultra-rapid outpatient pathway for selected AVS patients undergoing treatment by TAVI can successfully reduce total length of hospital stay. Further work is required to validate this approach.

OBJECTIVES: To synthesise barriers and facilitators to reducing sedentary behaviour among stroke survivors and map them to the Theoretical Domains Framework (TDF). DESIGN: A scoping review conducted following Joanna Briggs Institute (JBI) methodology and reported in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis, Scoping Review extension (PRISMA-ScR) guidelines. DATA SOURCES: Nine electronic databases (PubMed, CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, Cochrane Library, CNKI and WanFang) were searched from inception to May 2025. Grey literature was identified through Google Scholar and ProQuest. Updated research was conducted in July 2026. ELIGIBILITY CRITERIA: Studies focusing on barriers and/or facilitators to sedentary behaviour among stroke survivors were included, with no restrictions on study design. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies, extracted data and mapped identified barriers and facilitators to the Theoretical Domains Framework. Frequencies of domains were calculated to summarise distribution patterns. RESULTS: 49 studies were included. A total of 32 barriers and 17 facilitators were identified and mapped to 12 TDF domains. Barriers were reported more frequently than facilitators. The most frequently represented domains included Skills, Environmental Context and Resources, Beliefs about Capabilities, Beliefs about Consequences, Social Influences, Knowledge and Emotion. Common barriers included stroke-related physical and functional limitations, fatigue, inadequate knowledge, low self-efficacy, fear of falling, limited social support and environmental constraints. Key facilitators included sedentary behaviour education, higher self-efficacy, supportive social and physical environments, inpatient rehabilitation and behaviour change strategies that promoted more active lifestyles. CONCLUSIONS: Barriers to reducing sedentary behaviour among stroke survivors include limited knowledge, low motivation, insufficient social support, negative emotions and beliefs and physical limitations. Facilitators include social support, positive beliefs and supportive environmental conditions. Future interventions should comprehensively address these multilevel factors to develop more tailored and feasible behaviour change strategies. REGISTRATION NUMBER: This study was registered with the Open Science Framework website (osf.io/ma8qp).

The growing burden of valvular heart disease has led to increased use of bioprosthetic heart valves (BHVs), yet limited durability remains a major challenge. Although calcification, chronic inflammation and mechanical injury are recognized contributors to BHVs degeneration, their relative contributions and interactions within implanted BHVs remain insufficiently resolved, partly because direct pathological evidence from long-term clinical explants is limited. Here, comparative pathological analysis of long-term failed BHVs and procedurally retrieved non-degenerated valves confirmed pronounced inflammation and reactive oxygen species (ROS) accumulation in the failed leaflets, providing clinically relevant cues for material design. Guided by these findings, we designed a ROS-responsive diclofenac-containing zwitterionic nanogel composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and diclofenac-thioketal acrylate (DTA), and immobilized it onto glutaraldehyde-fixed pericardium (Glut) to construct a multifunctional modified pericardium, termed Glut-MPC-DTA. The nanogel exhibited good colloidal stability in aqueous solution and favorable biocompatibility. Under oxidative conditions, it enabled accelerated ROS-responsive drug release, supporting on-demand anti-inflammatory activity. Compared with Glut, Glut-MPC-DTA improved cytocompatibility and hemocompatibility, reduced platelet, blood-cell and inflammatory-cell adhesion, and markedly inhibited calcification in vivo. It also attenuated inflammatory-cell adhesion and proinflammatory responses in vitro, while suppressing cellular infiltration and proinflammatory responses in vivo. Transcriptomic analysis further revealed a shift toward an immunoregulatory and inflammation-resolving profile, suggesting that effective control of inflammation may alleviate the pro-degenerative interfacial microenvironment and thereby help interrupt the inflammation-driven degenerative cascade, ultimately improving the durability of BHVs. STATEMENT OF SIGNIFICANCE: Bioprosthetic heart valve (BHV) failure remains a major limitation of valve replacement, but many anti-degeneration coatings are designed empirically rather than from the pathology of failed clinical valves. This work is significant because it converts two clinically observed degenerative cues, inflammation and reactive oxygen species (ROS) accumulation, into a disease-responsive biomaterial interface. By integrating a zwitterionic anti-biofouling network with ROS-triggered diclofenac release, the coating is designed to regulate blood/material and cell/material interactions while suppressing the inflammatory microenvironment that promotes calcific degeneration. Beyond improving one valve coating, this study illustrates a pathology-guided design principle for blood-contacting cardiovascular biomaterials: material interfaces can be engineered to sense and counteract local degenerative cues.

BACKGROUND: Standard pulmonary arterial hypertension (PAH) risk models may not fully apply to PAH associated with unrepaired congenital heart disease (PAH-CHD). We aimed to develop and internally validate an interpretable machine learning (ML)-based risk model for adults with unrepaired PAH-CHD, comparing it against the recent European Society of Cardiology (ESC) model. METHODS: Utilizing a nationwide prospective registry in China, we included adults with unrepaired PAH-CHD. Five survival models were trained and internally validated to predict all-cause mortality. The optimal model was interpreted via Shapley Additive exPlanations (SHAP) to identify the top 15 predictors and clinical cutoffs. Novel two-strata and continuous risk models were constructed; predictive accuracy was evaluated using the C-index and survival curves. RESULTS: Among 601 patients (mean age 34; 56.4% Eisenmenger syndrome [ES]), 108 died during a median 76-month follow-up. The random survival forest model achieved the highest predictive performance (bootstrapping C-index 0.773). SHAP identified key predictors, including hemoglobin, body mass index, systolic blood pressure, and diastolic pulmonary artery pressure. The ESC two-strata model classified only 5.0% of patients as "Poorer prognosis" and failed to stratify the non-ES subgroup. The novel ML-derived risk model effectively stratified survival in both ES and non-ES cohorts (log-rank P < 0.001), outperforming the ESC model across all subgroups. CONCLUSIONS: Harnessing the strength of interpretable ML on detecting non-linear correlations, we developed a novel risk stratification model for unrepaired PAH-CHD, outperforming the ESC model. This tool assesses mortality risk regardless of Eisenmenger physiology, facilitating individualized clinical management.

BACKGROUND: Little is known about venous thromboembolism (VTE) and arterial thromboembolism (ATE) risk in melanoma patients receiving immune checkpoint inhibitors (ICI), compared to other therapies. OBJECTIVES: We assessed incidence, risk factors, and impact on survival of thromboembolism (TE) in patients receiving ICI, chemotherapy, or targeted therapy. METHODS: We conducted a cohort study using SEER-Medicare to evaluate TE rates in patients treated 2008-2019 with ICI, chemotherapy, or BRAF/MEK inhibitors within two years after treatment initiation. Associations between TE, treatment, and clinical risk factors were evaluated using weighted competing risk regression (CRR). Overall survival was estimated by Kaplan-Meier and Cox regression models. RESULTS: Among 6,218 patients, 62.1% (3,860) received first line ICI, 30.4% (1,890) chemotherapy, and 7.5% (468) targeted therapy. Cumulative incidence of VTE was similar among all treatment types: 7.7% for ICI, 8.4% for chemo, and 7.4% for targeted therapy at 12 months (p=0.80). Similarly, ATE rates were 5.3% for ICI, 5.0% for chemo, and 6.5% for targeted therapy at 12 months (p=0.30). History of VTE (SHR: 2.81; [95%CI: 2.19-3.61]) and brain metastases (SHR: 1.33 [1.06-1.66]) were associated with increased risk of VTE. When compared to chemotherapy, ICI and targeted therapy had similar VTE risk (p>0.05). For ATE, cardiovascular disease (SHR: 1.49 [1.14-1.93]), diabetes mellitus (SHR: 1.27 [1.04-1.57]), history of ATE (SHR: 1.61 [1.13-2.29]), and antiplatelet therapy (SHR: 1.37 [1.03-1.83]) were associated with increased risk. Patients with VTE or ATE experienced two-fold worse survival (HR: 2.17 [1.64-2.87] and HR: 2.58 [1.92-3.47], respectively). In ICI sub-analysis, combination ipilimumab/nivolumab had higher cumulative incidence of VTE: 11.9% at 12 months, 9.3% for ipilimumab, 7.5% for pembrolizumab, and 5.8% for nivolumab (p<0.05). When compared to nivolumab, combination ipilimumab/nivolumab (SHR: 1.66 [1.09-2.54]) and ipilimumab (SHR: 1.43 [1.03-2.00]) had greater VTE risk. VTE and ATE were associated with worse survival (HR: 3.24 [2.30-4.58] and HR: 1.89 [1.20-2.99], respectively). CONCLUSIONS: ICI, chemotherapy, and targeted therapy are associated with a high incidence of TE; TE is associated with substantial worsening of survival.