Metabolic dysfunction-associated steatotic liver disease (MASLD) is frequently accompanied by hepatic fibrosis and systemic cardiovascular complications; however, the mechanistic interplay between coagulation abnormalities and disease progression remains poorly defined. Here, analyses of liver tissues and plasma from patients with MASLD, together with complementary mouse models, suggest an important role of immunothrombosis in fibrotic progression. In MASLD mouse models, pharmacological anticoagulation with dabigatran or aspirin attenuates fibrosis but increases systemic bleeding risk, highlighting the need for more selective strategies. Mechanistically, neutrophil extracellular traps (NETs) promote localized fibrin deposition within the hepatic microvasculature, leading to impaired microcirculation and liver sinusoidal endothelial cell (LSEC) capillarization associated with increased Piezo1-dependent mechanosensation, thereby exacerbating fibrosis. Further investigation identifies neutrophil-derived fibrinogen-like protein 2 (FGL2) as a key upstream regulator of NETs formation through interaction with histone deacetylase 11 (HDAC11), promoting histone H3 deacetylation and facilitating PAD4-mediated citrullination to drive NETs release. Genetic disruption of FGL2 or NETs inhibition restores LSEC fenestration, improves microvascular hemodynamics, and attenuates fibrosis without increasing systemic bleeding risk. Together, these findings define an immunothrombotic axis linking neutrophil-derived FGL2-HDAC11 signaling to NETs formation and endothelial dysfunction in MASLD, providing mechanistic insight into the interplay between coagulation and metabolic liver disease.

G3BP1, GTPase activating protein (SH3 domain) binding protein 1, is a core component of stress granules. Homozygous null mutations in the G3bp1 gene result in embryonic lethality, underscoring its essential role in development. While various post-translational modifications regulate G3BP1 activity, here we first report that G3BP1 undergoes succinylation (Suc) at Lys (K)411 in mouse hearts (corresponding to human K413). G3BP1-Suc level was diminished in Myosin binding protein C3 (Mybpc3) knockout and transverse aortic constriction (TAC) operated mice, which developed heart failure (HF). Site-directed mutagenesis confirmed that the K413R mutation compromised the overall Suc level of G3BP1 in vitro. Mice injected with AAV9-G3BP1 (WT) developed typical phenotypes of dilated cardiomyopathy (DCM) and HF when compared to mice injected with AAV9-Ctrl and -G3BP1 (K411R) mice, suggesting a possible loss of functional effect of de-Suc at K411. Moreover, Homozygous knock-in G3bp1 (K411R) mice exhibited compromised cardiac parameters compared to WT littermates. De novo G3BP1 mutation (p.E411G) from a DCM patient disrupts Suc at K413. Mechanistically, G3BP1 de-Suc at K413 induced Rraga expression and impaired TSC1/2 and IDE binding, ultimately leading to excessive activation of the PI3K-AKT-mTOR signaling axis. We demonstrate a critical role for G3BP1 Suc at K413 in cardiac function by modulating the PI3K-AKT-mTOR pathway, providing new insights into the non-canonical function of G3BP1 in cardiomyopathy and HF pathogenesis.

BACKGROUND: Left ventricular hypertrophy (LVH) is a critical complication of hypertension that correlates with increased morbimortality. Its pathophysiology is complex and multifaceted likely involving various players that are still to be determined, particularly those with proinflammatory and profibrotic effects. Complement C1q/tumor necrosis factor-related protein 1 (CTRP1) is an antihypotensive adipokine that has recently been linked to adverse cardiometabolic changes and may contribute to the development of LVH. OBJECTIVE: To explore the relationship between CTRP1 and LVH in patients with essential hypertension. METHODS: A total of 360 patients with mild-to-moderate essential hypertension were enrolled from Ruijin Hospital between December 2015 and November 2017. Participants were divided into two groups: those with hypertension alone (n = 183) and those with hypertension complicated by LVH (n = 177). Plasma levels of CTRP1, adiponectin, and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assay (ELISA). The left ventricular mass index (LVMI) was calculated from echocardiographic measurements. Patients were further stratified by sex and by CTRP1 tertiles for subgroup analysis. RESULTS: Patients with hypertension and LVH showed significantly higher levels of CTRP1, IL-6, and LVMI compared to those with hypertension alone. In contrast, adiponectin levels were significantly lower in the LVH group. CTRP1 levels were positively correlated with LVMI in both males and females. Furthermore, patients in the highest CTRP1 tertile exhibited progressively elevated SBP, DBP, CRP, IL-6, and LVMI. Multivariate logistic regression analysis identified CTRP1, IL-6, and adiponectin as independent factors associated with LVH. CONCLUSION: CTRP1 is independently associated with left ventricular hypertrophy in patients with essential hypertension, demonstrating a dose-response relationship with cardiac hypertrophy and inflammatory markers.

BACKGROUND Infective endocarditis is challenging to diagnose when blood cultures are negative, and its symptoms are nonspecific. Bartonella species are fastidious intracellular bacteria that can cause culture-negative endocarditis and immune-mediated complications such as glomerulonephritis, often mimicking ANCA-associated glomerulonephritis. CASE REPORT A 25-year-old man who underwent a Ross procedure for congenital aortic stenosis performed in childhood presented with 1 month of night sweats, abdominal pain, and intermittent nausea. Initial evaluation revealed elevated creatinine, pancytopenia, proteinuria, microscopic hematuria, and splenomegaly. Serologies showed positive c-ANCA and elevated PR3 antibodies. A presumed diagnosis of ANCA-associated glomerulonephritis led to initiation of high-dose steroids and planned rituximab. Kidney biopsy demonstrated crescentic glomerulonephritis with C3-dominant immune complex deposition, atypical for pauci-immune disease, prompting discontinuation of steroids. Further infectious workup revealed high Bartonella henselae IgM and IgG titers. The patient met the criteria for possible infective endocarditis under the 2023 Duke-ISCVID criteria. Transesophageal echocardiography showed valvular abnormalities without definite vegetations, although only a prior transthoracic echocardiogram was available for comparison. The patient was treated with doxycycline and rifampin for 12 weeks, resulting in clinical and laboratory improvement. CONCLUSIONS This case demonstrates that Bartonella endocarditis can closely mimic ANCA-associated glomerulonephritis and rapidly progressive glomerulonephritis. In patients with systemic symptoms, positive ANCA serologies, and negative cultures, occult infection must be a key consideration, especially in patients at high risk for infective endocarditis. A careful exposure history, including pets, travel, and dental procedures, can provide crucial diagnostic clues. Early recognition and targeted antimicrobial therapy are essential to prevent irreversible organ damage and avoid inappropriate immunosuppression.

AIMS: Heart failure (HF) and acute myocardial infarction (AMI) may contribute to cancer development through shared and disease-related pathophysiological pathways. We investigated the mid-term risk of incident cancer in patients with HF or AMI using a large, real-world dataset. METHODS: Adults with a first hospitalization for acute HF or AMI between October 2015 and October 2024 were included from the TriNetX Global Collaborative Research Network. Patients with prior or concurrent cancer were excluded. Each cohort was matched 1:1 with controls without HF or AMI using propensity score matching. The primary end-point was any new cancer diagnosis occurring during follow-up, starting 6 months after the index hospitalization. RESULTS: After matching, 120 783 patients with HF and 7896 patients with AMI were included. Over a median follow-up of 13 months in the HF cohort and 16 months in the AMI cohort (after the 6-month landmark), both groups showed an higher incidence of cancer compared with controls (HF: HR 2.80 [95% CI, 2.69; 2.91]; AMI: HR 2.02 [95% CI, 1.71; 2.39]; both P < .001). In both cohorts, the excess risk was more pronounced for haematologic than for solid malignancies (HF: HR: 6.78 vs 2.53; AMI: HR: 4.45 vs 1.77). HF with preserved ejection fraction was associated with a slightly higher cancer incidence than HF with reduced or mildly reduced ejection fraction (HR 1.10 [95% CI, 1.04; 1.17], P = .002), whereas no difference was observed between ST and non-ST segment elevation AMI. CONCLUSIONS: In this large, real-world cohort, both HF and AMI were associated with an increased incidence of cancer, particularly haematologic malignancies. HF was associated with a greater excess risk than AMI. These findings are hypothesis-generating and warrant further investigation.

AIMS: Inflammation contributes to the pathophysiology of heart failure (HF), yet the global prevalence of elevated high sensitivity C-reactive protein (hsCRP) in patients with HF across the ejection fraction (EF) spectrum remains unclear. We sought to characterize the prevalence and clinical correlates of high inflammatory risk (defined as hsCRP ≥2 mg/L) in a global real-world HF cohort across the EF spectrum. METHODS AND RESULTS: POSEIDON prospectively enrolled 18,904 individuals across 317 sites in 18 countries (2023-2025) at routine visits, including 11,809 with HF and available hsCRP (3714 with preserved EF [HFpEF], 2176 with mildly reduced EF [HFmrEF], 5919 with reduced EF [HFrEF]), and excluding those with recent infections. Elevated hsCRP (≥2 mg/L) was found in 1442 (38.8%) patients with HFpEF, 830 (38.1%) with HFmrEF, and 2263 (38.2%) with HFrEF. Within each HF subtype, patients with elevated hsCRP were more likely to be female and to have chronic kidney disease, obesity, worse functional class, and higher N-terminal pro-B-type natriuretic peptide levels. In multivariable analyses, independent predictors of elevated hsCRP included smoking, rheumatic/autoimmune/inflammatory disease, obesity, reduced eGFR, dyslipidaemia and worse NYHA class. These predictors were consistent across HF subtypes (interaction p>0.05), except body mass index, which was more strongly associated with hsCRP in HFpEF (interaction p=0.001). Interleukin-6 correlated moderately with hsCRP across all HF subtypes. CONCLUSIONS: In a global HF population, high inflammatory risk is present in approximately 4 in 10 patients and is associated with more severe HF and a cardio-kidney-metabolic phenotype. These findings were consistent across HF subtypes.

BACKGROUND: Obesity is linked to heart failure, particularly with preserved ejection fraction, but is associated with lower natriuretic peptide levels, potentially leading to underdiagnosis. AIMS: To examine the association between adiposity measures-body mass index, waist circumference, and waist-to-height ratio-and N-terminal pro-B-type natriuretic peptide levels, and to determine if lower cut-offs should be used to rule out heart failure in individuals with obesity. METHODS: PORTHOS is a 2023 population-based study in Portugal including adults aged 50 years or older. Participants underwent N-terminal pro-B-type natriuretic peptide screening, followed by clinical and echocardiographic assessment in those with levels >= 125 pg/mL, self-reported heart failure, or a 5% random sample with levels <125 pg/mL. RESULTS: Among 2498 participants, obesity prevalence range from 25% using body mass index ≥30 kg/m² to >70% using waist-to-height ratio ≥0.6. Body mass index showed a strong inverse association with N-terminal pro-B-type natriuretic peptide, with approximately 50 pg/mL lower levels per 5 kg/m² increase. Individuals with obesity and peptide levels < 125 pg/mL had higher odds of heart failure symptoms (odds ratio 1.97, 95% confidence interval 1.15-3.38) and echocardiographic abnormalities (odds ratio 3.63, 95% confidence interval 1.27-10.4) than lean participants with levels >= 125 pg/mL, despite being 9 years younger and having fourfold lower median peptide levels (59 vs 235 pg/mL). CONCLUSIONS: Obesity is associated with lower N-terminal pro-B-type natriuretic peptide levels despite a higher burden of symptoms and structural abnormalities. Fixed cut-offs do not reliably exclude heart failure in individuals with obesity.

IMPORTANCE: Digitalis glycosides may be used as additional therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with reduced EF (HFrEF). OBJECTIVE: To assess the effect of digitalis glycosides on clinical outcomes in patients with HFmrEF or HFrEF. DATA SOURCES AND STUDY SELECTION: PubMed was searched from inception to March 1, 2026, using medical subject headings and keywords related to digitalis glycosides and HF. The review was restricted to placebo-controlled randomized clinical trials including more than 1000 patients and articles published in the English language. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 reviewers who followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Risk of bias was assessed with the Cochrane Risk of Bias tool (version 2). A fixed-effects model was used to estimate the hazard ratios (HRs) with 95% CIs. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of time to cardiovascular death or first worsening HF event. Secondary outcomes included individual components of the composite outcome and time to all-cause death. RESULTS: A total of 3 studies met the inclusion criteria and included 9013 patients with HFmrEF or HFrEF (weighted mean age, 64.5 [weighted SD, 11.2] years; 22% female and 78% male). The composite outcome of cardiovascular death or first worsening HF event occurred in 1852 of 4510 patients (41%) in the digitalis glycoside group vs 2037 of 4503 patients (45%) in the placebo group (HR, 0.85 [95% CI, 0.80-0.90]; P < .001). First worsening HF event occurred in 1183 (26%) patients in the digitalis glycoside group vs 1474 (33%) patients in the placebo group (HR, 0.75 [95% CI, 0.69-0.81]; P < .001). There were 1224 cardiovascular events in the digitalis glycoside group vs 1224 in the placebo group (27% of participants in each group; HR, 0.99 [95% CI, 0.92-1.07]; P = .81) and there were 1466 vs 1497, respectively, all-cause deaths (32% of participants vs 33%; HR, 0.97 [95% CI, 0.90-1.04]; P = .41). There was no statistically significant heterogeneity by trial, type of digitalis glycoside treatment, or extent of background HF therapy. CONCLUSIONS AND RELEVANCE: Treatment with digitalis glycosides was associated with a lower risk of the composite of cardiovascular death or first worsening HF event in patients with HFmrEF or HFrEF, mainly through a lower risk of worsening HF events. There was no statistically significant interaction with important study characteristics, including the extent of HF background therapy or type of digitalis glycosides treatment. These results suggest digitalis glycosides may be used as additional medical therapy to reduce worsening HF events in patients with HFmrEF or HFrEF.

IMPORTANCE: Heart failure is the most common cause of death in patients with rheumatic heart disease. The efficacy and safety of digoxin in this population are not known. OBJECTIVE: To determine if digoxin, compared with placebo, improves the composite of death or new-onset or worsening heart failure in patients with symptomatic rheumatic heart disease. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, placebo-controlled trial enrolling patients with rheumatic heart disease who additionally had heart failure or atrial fibrillation or were already taking digoxin at 12 tertiary care hospitals in India between February 25, 2022, and August 31, 2024; median follow-up was 2.1 years (until December 15, 2025). INTERVENTIONS: Patients were randomized in a 1:1 ratio, stratified by baseline rhythm, to receive oral digoxin, 0.125 to 0.25 mg once daily (n = 885), or matching placebo (n = 884). MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of all-cause death or new-onset or worsening heart failure within 36 months of follow-up or until study end, whichever occurred first. Key secondary outcomes were all-cause death, new-onset or worsening heart failure, and a composite of heart failure-related death or new-onset or worsening heart failure. RESULTS: Of 1769 enrolled patients, 1759 took at least 1 dose of the study medication and were included in the primary analysis. The mean age was 46 years and 72% were female. Most patients (81.5%) had mixed lesions involving multiple valves, with 85% having moderate to severe mitral stenosis. Atrial fibrillation was present in 70%, and 90% were in New York Heart Association class II to IV. The primary composite outcome occurred in 276 patients (31.4%) receiving digoxin and 312 (35.5%) receiving placebo (hazard ratio, 0.82; 95% CI, 0.70-0.97; P = .02). New-onset or worsening heart failure occurred in 227 patients (25.8%) receiving digoxin and in 257 (29.2%) receiving placebo (hazard ratio, 0.82; 95% CI, 0.69-0.98). Most episodes of worsening heart failure were treated with augmentation of oral or intravenous diuretics without hospitalization. Death from any cause occurred in 88 patients (10%) receiving digoxin and 91 (10.4%) receiving placebo (hazard ratio, 0.94; 95% CI, 0.70-1.26). Ten patients receiving digoxin (1.1%) and 1 receiving placebo permanently discontinued study medication due to suspected digoxin toxicity. CONCLUSIONS AND RELEVANCE: In patients with symptomatic rheumatic heart disease, digoxin reduced the risk of a composite of all-cause death or new-onset or worsening heart failure, with little risk of toxicity. TRIAL REGISTRATION: CTRI Identifier: CTRI/2021/04/032858.

BACKGROUND: For decades inflammation has been postulated to play a key pathophysiological role in heart failure (HF), particularly in HF with preserved ejection fraction (HFpEF). Previous attempts to target inflammation in HF have been unsuccessful, possibly due to the choice of therapeutic target or the characteristics of the patient population studied. We hypothesized that targeting interleukin-6 (IL-6)-a cytokine central to NLRP3 inflammasome activation that is associated with both the onset and progression of HF-may be beneficial in patients with HF and circulating evidence of cardiovascular inflammation, but without overtly reduced ejection fraction (EF). We describe the rationale and design of two clinical trials (ATHENA and HERMES) investigating ziltivekimab, a human monoclonal antibody directed against the IL-6 ligand, in patients with HF and mildly reduced or preserved EF (HFmrEF/HFpEF) and cardiovascular inflammation. METHODS: ATHENA (n=673) and HERMES (n=4900) are international, multicenter, double-blind, placebo-controlled trials randomising adults with HFpEF/HFmrEF and cardiovascular inflammation (hsCRP ≥2mg/L) to ziltivekimab 15 mg or placebo, administered subcutaneously once-monthly on top of standard of care. Eligible participants have a left ventricular ejection fraction >40%, elevated NTproBNP and serum high sensitivity C reactive protein ≥2 mg/L. The primary endpoint in ATHENA is the change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at 12 months. The primary endpoint in HERMES is time to first composite of cardiovascular death, hospitalisation for HF or urgent HF visit. ATHENA has a fixed duration of 12 months whereas the HERMES trial is event-driven (approximately 845 adjudicated primary events) with a minimum exposure of 6 months from randomisation to last treatment visit. CONCLUSIONS: ATHENA and HERMES will investigate the effect of ziltivekimab in HFpEF/HFmrEF and cardiovascular inflammation. ATHENA will determine the effect of ziltivekimab on health status. HERMES will determine the efficacy and safety of ziltivekimab on morbidity and mortality.

BACKGROUND AND AIMS: Whether digoxin withdrawal is safe in patients with heart failure (HF) optimized on contemporary guideline-recommended medical therapy remains unknown. This prespecified analysis of the DECISION trial evaluated outcomes following blinded withdrawal of digoxin or placebo. METHODS: In DECISION, 1001 patients were randomized to low-dose digoxin or placebo and treated for a median of 36.5 months. At the end of the study, 587 patients on active treatment (digoxin 288, placebo 299) underwent blinded withdrawal with an in-person follow-up visit at six weeks. All events were adjudicated. RESULTS: During the pre-withdrawal phase (100 days), incidence rates of cardiovascular (CV) death or worsening HF events were 5.7 versus 6.5 events per 100 patient-years in the digoxin versus placebo group; rate ratio 0.88:95%CI [0.24-3.10]. Following withdrawal, the incidence rate increased markedly in patients withdrawn from digoxin but not placebo (42.8 vs. 5.9 events per 100 patient-years; time period-by-treatment interaction, P=0.036). Fourteen events (12 hospitalizations and 2 urgent HF visits) occurred in the digoxin withdrawal arm versus two (one HF hospitalization and one CV death) in the placebo withdrawal arm (RR 7.37, 95% CI 1.56-34.88; P=0.012). Withdrawal of digoxin was accompanied by an increase in heart rate (p=0.003), reduction in systolic blood pressure (p=0.014) and rise in NT-proBNP (p=0.002). CONCLUSIONS: Discontinuation of digoxin after long-term treatment is associated with clinical deterioration in patients with HF and a reduced or mildly reduced ejection fraction. These findings warrant caution when stopping digoxin.

AIMS: Heart failure (HF) is a common sequela of type 2 diabetes (diabetes), and models have been developed for its prediction. We aimed to synthesize the available evidence by performing a systematic review and meta-analysis of models predicting incident HF and HF hospitalization (HFH) in individuals with diabetes. METHODS: We searched MEDLINE and EMBASE for multivariable models predicting HF or HFH in patients with diabetes from inception to 2 December 2025. Discrimination metrics from models validated in ≥3 cohorts were pooled using Bayesian meta-analysis. Heterogeneity was assessed using 95% prediction intervals (PI), and risk of bias with PROBAST. RESULTS: In total, 65 studies describing 56 HF and 44 HFH prediction models were included. Following exclusion of studies at high risk of bias, two HF models (RECODe (0.711, 95% CI 0.651-0.767) and DMRS (0.758, 95% CI 0.684-0.827)) and two HFH models (WATCH-DM 2022 (r) (0.705, 95% CI, 0.624-0.795), WATCH-DM 2022(i) (0.718, 95% CI 0.587-0.850)) had acceptable prediction performance, while one HFH model had good performance (DM-CURE (0.837, 95% CI 0.757-0.913). Of these, none reported a prediction horizon of less than ten years. For all models, regardless of risk of bias, none were prospectively tested, and only three underwent clinical utility analysis. CONCLUSION: While some HF and HFH models in diabetes show acceptable/good long-term discriminative performance, the scarcity of utility analyses and prospective testing limits translation to clinical settings. Prospective evaluation of these models is required to establish clinical utility.

BACKGROUND: Persistent congestion at discharge is associated with worse outcomes in acute decompensated heart failure (ADHF), with impaired lymphatic function contributing to difficult-to-target tissue and organ congestion. METHODS: The safety and effectiveness of the eLym System in ADHF was evaluated in the multicenter, single-arm DELTA-HF trial. A localized reduced-pressure zone at the venous angle was created in 40 patients using an endovenous axial pump to support lymph drainage through the thoracic duct. RESULTS: Forty patients with ADHF (32.5% female, 71±11 years) received therapy. Patients had a median of 2 hospitalizations in the prior 6 months. All were on home daily loop diuretic dose equivalent to ≥80 mg furosemide. Device deployment was successful in all cases (therapy time: 23.1±7.3 hours). Weight decreased by 3.6±2.4 kg during eLym therapy and by 6.8±3.4 kg at discharge. Median modified EVEREST Clinical Congestion Score improved from 5.0 (4.0-6.0) to 2.0 (1.0-4.0) after eLym treatment and to 0 (0-1.0) by discharge, remaining stable through 6 months (change from baseline p-values <0.0001). Serum creatinine remained stable acutely and through 6-months. Freedom from device- or procedure-related serious adverse events was 95%. One patient had a vascular complication causing mediastinal hematoma and death; another required inotropes due to hypotension. At 6 months, two patients experienced three HF hospitalizations and five patients died: four from cardiovascular causes; one from urosepsis. CONCLUSIONS: eLym therapy in ADHF appeared to be safe, with early data suggesting effective, durable decongestion and a low 6-month rehospitalization rate. Randomized controlled trials evaluating eLym therapy are warranted.

BACKGROUND: Acute heart failure (AHF) and respiratory infection (RI) frequently coexist, with the latter commonly regarded as a trigger of AHF decompensation. However, the independent and combined prognostic impact of these conditions on survival is not well studied. We therefore assessed the association of AHF and RI, both separately and in combination, with subsequent mortality. METHODS: Patients discharged with diagnoses of AHF, RI, or both were identified from the PARADISE study, a large cohort of patients hospitalised for acute dyspnoea. Associations with in-hospital and post-discharge mortality were assessed using multivariable binomial logistic regression and Cox proportional hazards models, respectively. RESULTS: Among 11,679 patients, 4,349 (37%) had AHF alone, 5,091 (44%) had RI alone, and 2,239 (19%) had both AHF and RI. In-hospital mortality was highest in patients with concomitant AHF and RI (21.9%), whereas post-discharge mortality was highest among those with AHF (55.2%). After multivariable adjustment, the coexistence of AHF and RI was associated with higher in-hospital mortality compared with AHF alone (adjusted OR [aOR]: 1.62, 1.33-1.98, P<0.001), but not with higher post-discharge mortality (adjusted HR [aHR]: 0.99, 0.88-1.11, P=0.9). Compared with AHF alone, RI alone was not associated with a higher risk of death both during hospitalization (aOR 1.11, 0.89-1.39, P=0.3) and after discharge (aHR 1.07, 0.97-1.17, P=0.2). Results from sensitivity analyses including natriuretic peptides confirm those results. CONCLUSION: Patients with concomitant AHF and RI showed an increased in-hospital risk but no excess post-discharge risk compared with AHF alone, whereas RI alone is not associated with increased mortality both in-hospital and post-discharge.

Gastric cancer remains a major global health challenge, underscoring the need for highly effective and precisely targeted therapies. This study presents a novel biomimetic nanoplatform comprising cancer cell membrane-coated chitosan-stabilized Cu/Pt nanoparticles (CCM@Ch-Cu/PtNPs), designed to enhance tumor specificity and therapeutic efficacy. We characterized the nanocomposite using X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), and transmission electron microscopy (TEM), confirming its bimetallic architecture featuring Cu-rich and Pt-rich surface domains. In vitro, treatment with CCM@Ch-Cu/PtNPs (75 µg/mL) markedly decreased viability and colony formation in AGS and HGC gastric cancer cell lines, induced apoptosis, and triggered reactive oxygen species (ROS) generation, indicating potent cytotoxic activity and disruption of oncogenic pathways. In vivo, systemic administration of CCM@Ch-Cu/PtNPs in a murine gastric cancer model resulted in preferential tumor accumulation, substantial tumor growth inhibition, and prolonged survival, all achieved without detectable organ toxicity. These results support the potential of CCM@Ch-Cu/PtNPs as a theranostic nanomedicine platform for targeted gastric cancer therapy.

BACKGROUND: Childhood-onset Takayasu arteritis (c-TAK) in infants and young children often presents with systemic inflammation rather than ischemic symptoms, and its clinical features overlap with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). To aid in early differentiation, this study compared clinical characteristics and vascular involvement between c-TAK and IVIG-resistant KD in infants and young children. METHODS: This single-center retrospective cohort study included patients under three years old diagnosed with c-TAK or IVIG-resistant KD between June, 2016, and December, 2025. Demographics, clinical presentation, laboratory findings, vascular involvement, immunotherapy, and outcomes were compared between groups. RESULTS: A total of 144 infants and young children were enrolled, including 43 with c-TAK and 101 with IVIG-resistant KD. Compared to the IVIG-resistant KD group, the c-TAK group had a significantly higher proportion of infants (85.7% vs. 29.7%) and females (67.4% vs. 32.7%), longer fever duration (18 [9, 26] vs. 11 [9, 13] days), higher lymphocyte counts (7.09 [5.58, 9.02] vs. 2.92 [2.18, 3.91] × 10⁹/L), and more medium-to-giant coronary artery aneurysms (CAAs; 48.8% vs. 18.8%; all P < 0.001). At the baseline, 76.7% of c-TAK patients received IVIG but experienced recurrent fever. The imaging features in the c-TAK group included vessel wall thickening (95.3%), dilation (79.1%), and stenosis (41.9%). The most commonly involved arteries were the carotid (79.1%), abdominal aorta (69.8%), subclavian (67.4%), and coronary artery (67.4%). Conversely, the IVIG-resistant KD group mainly exhibited CAAs (29.7%). The median follow-up duration was comparable between the two groups (21.0 [11.8, 45.5] vs. 18.0 [12.0, 36.0] months, P = 0.952). By the final follow-up, vascular imaging abnormalities completely resolved in 10.3% of c-TAK patients and 96.9% of IVIG-resistant KD patients. CONCLUSION: In young children, particularly female infants, who present with prolonged fever and a poor response to IVIG, c-TAK should be considered as an important differential diagnosis alongside IVIG-resistant KD. The distribution of vascular involvement, detailed imaging characteristics and regular follow-up may be helpful for the differential diagnosis of these two diseases.

BACKGROUND: Primary Health Care (PHC) is vital to supporting emergency preparedness and health care resilience. There is limited evidence of the impact of crises on PHC services and financing. We aimed to explore the impact of the full-scale invasion of Ukraine in February 2022 on PHC services in the country. METHODS: We used a mixed-methods approach. Survey data were collected using an online questionnaire sent to a sample (n = 86) of PHC providers in Ukraine in January-February 2023. Fifteen providers were then randomly selected for semi-structured interviews from among those that reported an impact of war and from those areas most affected by conflict. Interviews took place in March 2023. RESULTS: 37% of PHC providers reported being affected by the full-scale invasion. Qualitative data revealed greater impacts at the beginning of the invasion, to which facilities adapted by the time of the survey. The most reported disruptions were electricity cuts (76%) and currency depreciation/price increases (72%). The most reported increased medical need was cardiovascular disease (CVD; 58%) (with qualitative data suggesting an increase in CVD among younger patients) followed by mental illnesses and disorders (55%). 59% of PHC providers reported an increase in remote consultations. Among those facilities that reported a change in revenues, the nature of the change depended on the type of ownership. For example, only 9% of private providers reported increased revenues from humanitarian aid, while 79% (n = 58) of public providers indicated an increase in these sources. CONCLUSION: To continue strengthening Ukraine's PHC system, the benefit package must be aligned with clinical guidelines, particularly for CVD and mental health; increases in remote consultations should be closely monitored for quality; and payment systems must be adjusted to ensure equity of financing regardless of provider ownership. These findings offer insights for strengthening PHC and emergency-preparedness in other contexts.

BACKGROUND: Older adults remain highly vulnerable to serious influenza-related complications despite routine vaccination. Whether high-dose quadrivalent influenza vaccine (HD-QIV) offers greater protection than standard-dose quadrivalent influenza vaccine (SD-QIV) against clinically important outcomes remains an important question. METHODS: We conducted a systematic review and pairwise meta-analyses of randomized controlled trials (RCTs) comparing HD-QIV with SD-QIV in adults aged 65 years or older. PubMed, Cochrane Library, Embase, Web of Science, and Scopus were searched up to February 2026. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models. Prespecified subgroup analyses were performed according to baseline cardiovascular disease (CVD) status. RESULTS: Four RCTs comprising 511,890 participants were included. HD-QIV was associated with significantly lower odds of cardio-respiratory hospitalization (OR 0.93, 95% CI [0.90-0.97]) and cardiovascular hospitalization (OR 0.93, 95% CI [0.89-0.98]), with no significant reduction in respiratory hospitalization (OR 0.90, 95% CI [0.80-1.01]). Significant reductions were also observed for hospitalization due to influenza (OR 0.61, 95% CI [0.50-0.74]), laboratory-confirmed influenza hospitalization (OR 0.69, 95% CI [0.56-0.86]), and heart failure hospitalization (OR 0.80, 95% CI [0.69-0.94]). No significant differences were found for all-cause hospitalization (P = 0.12), all-cause mortality (P = 0.413), myocardial infarction (P = 0.753), or serious adverse events (P = 0.419). No significant subgroup differences were observed according to baseline CVD status. CONCLUSIONS: In older adults, HD-QIV was associated with modest but significant reductions in cardio-respiratory and cardiovascular hospitalization, as well as influenza-related and heart failure hospitalizations, without an apparent safety penalty. These findings support preferential use of high-dose influenza vaccination in this population.

BACKGROUND: Myelofibrosis (MF) is a subgroup of Philadelphia chromosome-negative myeloproliferative neoplasms that are associated with an increased risk of cardiovascular disease, including pulmonary hypertension. Here we report the real-world prevalence, risk factors, and clinical outcomes of eRVSP in MF patients. METHODS: A retrospective, single-center cohort study was conducted on 208 patients with MF that were diagnosed between 2013 and 2023. Elevated right ventricular systolic pressure (eRVSP) was defined as RVSP > 35 mmHg. Major adverse cardiac events (MACE) were defined as new-onset congestive heart failure, coronary artery disease requiring intervention, cerebrovascular events, or cardiovascular death after MF diagnosis. Univariate and multivariable Cox proportional hazard ratio regression model with eRVSP status as time-dependent covariate was used to estimate overall survival. RESULTS: Echocardiograms were performed in 208 MF patients, with RVSP estimates available in 156 patients (75%). eRVSP was present in 61 patients (39.1%). Patients with eRVSP were older (65 vs. 62 years, p = 0.053) and had higher rates of baseline hypertension (65.6% vs. 43.2%, p = 0.01), atrial fibrillation (16.4% vs. 4.2%, p = 0.02). MACE after diagnosis of MF occurred in 43 (20.7%) patients and was more frequent in eRVSP patients (36.1% vs. 15.8% p = 0.007), and this was predominantly driven by increased rates of new-onset congestive heart failure (27.9% vs. 8.4%, p = 0.003). In multivariable analysis, the presence of time-dependent eRVSP was associated with reduced survival (aHR: 4.41; 95%CI:2.84-6.85) after adjustment for clinically relevant covariates. CONCLUSIONS: eRVSP was prevalent among MF patients undergoing echocardiogram and this was associated with increased cardiovascular morbidity, particularly HF. Furthermore, eRVSP was associated with inferior survival and underscores the need for targeted screening and management in MF patients with cardiovascular risk factors and diseases. Prospective studies with baseline cardiovascular assessment and echocardiograms in all MF patients will establish true prevalence and may further elucidate the morbidity and mortality implication of eRVSP in MF patients.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular-kidney-metabolic (CKM) syndrome are interrelated conditions with shared pathophysiological features; however, the genetic architecture underlying their relationship has not been fully elucidated. Deciphering this shared genetic basis holds promise for advancing mechanistic insights and therapeutic discovery. METHODS: We performed an integrated genome-wide cross-trait analysis using GWAS summary statistics for MASLD and 38 CKM traits. Our analysis estimated genetic correlations, inferred causal relationships, and identified pleiotropic variants. Candidate causal genes and druggable targets were subsequently prioritized through integrating multi-omics data. RESULTS: MASLD exhibited significant genetic correlations with 16 CKM traits, especially metabolic and cardiovascular conditions. Bidirectional causal relationships were observed between MASLD and T2D, adiposity, and lipid traits. We discovered 116 pleiotropic loci, including 65 shared causal variants such as rs429358 near APOE, which exerted influence across multiple traits. Gene-based analyses prioritized 152 unique candidate pleiotropic genes, enriched in lipid and cholesterol metabolism, and highly expressed in the liver, adipose, and immune-related cell types, such as macrophages and endothelial cells. Multi-omics integration validated 131 genes using eQTL and pQTL data from multiple tissues and cohorts. Notably, FTO and APOE emerged as central pleiotropic hubs, and druggability evaluation highlighted APOE, LPL, PPARG, and GPBAR1 as established therapeutic targets for metabolic diseases. CONCLUSION: This study provides a comprehensive map of the shared genetic architecture between MASLD and CKM syndrome, reveals novel causal genes and repurposable drug targets, and offers insights into precision medicine approaches for cardiometabolic and liver diseases.

BACKGROUND: Since 2019, Dutch hospitals have been developing approaches aiming to bridge the gap between hospital care and community-based lifestyle support. This has led to the introduction of the so called 'Lifestyle Front Office" (LFO) in 2022. The LFO enables healthcare professionals to refer patients for lifestyle and (psycho)social support adjacent to medical treatment in the context of specialist medical care. After a consultation at the LFO, patients are referred to the appropriate community-based lifestyle interventions. LFOs have been quickly adopted in Dutch hospitals, leading to conceptual differences. This study aimed to evaluate similarities, differences and future needs of LFOs in the Netherlands, striving for a more unified concept. METHODS: A cross-sectional survey was sent out between December 2023 and September 2024 to all Dutch hospitals with an operational LFO (n = 17 hospitals). The survey focused on referral processes, patient eligibility criteria, departmental involvement, screening methods, consultation practices, follow-up procedures, financing, and capacity. The collected data were analyzed quantitatively and qualitatively to identify common practice, challenges, and opportunities for improvement. RESULTS: The survey response rate was 82% (14/17). Primary referral groups were patients with lifestyle-related conditions such as obesity, type 2 diabetes mellitus and cardiovascular diseases. Most LFOs conducted pre-visit screenings by using questionnaires, employed lifestyle care coordinators with diverse professional backgrounds, utilized structured tools during consultations and used the electronic patient records for screening and communication. Future needs included the need for (long-term) funding, which was only secured in 21% of the LFOs. Furthermore, inconsistent eligibility criteria, limited capacity, and follow-up procedures were seen as priorities for future attention. CONCLUSION: This study highlights the similarities, differences and future needs of LFOs in the Netherlands. To achieve a more unified concept, LFOs need to better align patient-related eligibility criteria, use of structured tools, referral to community-based support, follow-up strategies and long-term funding. While the LFO concept emphasizes strong inter-organizational collaboration, further research is needed to assess its impact by investigating success rate of referrals and (long-term) health outcomes after referral. Additionally, for maintaining LFOs in the Dutch healthcare system, additional research is required to better understand the barriers and facilitators regarding structural implementation.