Fasting before elective abdominal ultrasound is widely recommended to improve image quality or visualization of abdominal structures although supporting evidence is limited. We examined whether fasting is associated with improved diagnostic or image quality-related outcomes in adult abdominal ultrasound. We conducted a systematic review and meta-analysis (PROSPERO CRD42024568514) of studies comparing fasting and non-fasting conditions in adults undergoing elective abdominal ultrasound (search date July 18, 2025; 5 databases). Study quality and risk of bias were assessed, and randomized trials were pooled using random effects models. Real-world preparation recommendations were evaluated across international ultrasound society guidelines and patient-facing sources. 14 studies (9 randomized trials, 5 observational studies; 2,208 participants) met the inclusion criteria. Five randomized trials were eligible for meta-analysis; three were included in the primary analysis (n = 378). Two trials contributed organ-specific outcomes to sensitivity analyses. Fasting did not improve overall diagnostic sufficiency, defined as adequate visualization to answer the clinical question without repeat imaging (OR 0.97, 95% CI 0.51-1.86, p = 0.92; I2 = 0%). Significant effects were limited to gallbladder visibility and detectability of the common bile duct, with no consistent benefit otherwise. Risk of bias was moderate and overall certainty of evidence was low. Real-world fasting instructions were highly variable and rarely evidence-based. Fasting before elective abdominal ultrasound does not improve diagnostic sufficiency. Observed benefits were limited to the biliary tract. Given the low certainty of evidence and limited observed benefits beyond the biliary tract, strict and prolonged fasting recommendations should be reconsidered.

Tenecteplase (TNK) is a modified variant of alteplase (TPA) that offers advantages such as a long plasma half-life and high fibrin specificity. Previous studies have demonstrated the noninferiority of TNK to TPA in patients with acute ischemic stroke (AIS). Although very elderly patients (aged ≥ 80 years) represent a significant proportion of AIS cases, research on the safety and efficacy of TNK in this population remains limited. Therefore, this study aimed to evaluate the comparative efficacy and safety of TNK versus TPA in treating AIS in very elderly patients. We conducted a meta-analysis of randomized controlled trials (RCTs) from Embase, PubMed, and the Cochrane Library up to May 20th, 2026. The outcomes included modified Rankin Scale (mRS) scores of 0-1 and 0-2 at 90 days, symptomatic intracranial hemorrhage (SICH), all-cause mortality, and parenchymal hematoma. We also performed subgroup analysis to assess the effects of patient race. We utilized mainly Review Manager 5.4 software to conduct the data synthesis and statistical analysis. Five RCTs (EXTEND-IA TNK, AcT, ATTEST-2, TRACE-2, and ORIGINAL) involving 1307 very elderly patients were included. Pooled analysis showed that TNK was associated with higher odds of excellent and good functional outcomes at 90 days compared with TPA (excellent: odds ratio (OR) 1.85, 95% confidence interval (CI) 1.06-3.23, p = 0.03, I[2] = 75%; good: OR 1.35, 95% CI: 1.06-1.71, p = 0.01, I[2] = 3%). Leave-one-out sensitivity analysis showed that the association between TNK and excellent functional outcomes was no longer statistically significant after exclusion of the ORIGINAL trial (OR 1.38, 95% CI 0.91-2.08, p = 0.13, I[2] = 52%). No statistically significant differences were observed between TNK and TPA in SICH (OR 1.00, 95% CI 0.54-1.89, I[2] = 0%), 90-day mortality (OR 0.84, 95% CI 0.63-1.11, I[2] = 0%), or parenchymal hematoma (OR 0.73, 95% CI 0.30-1.74, I[2] = 5%). In this pooled analysis of noninferiority-designed RCTs, TNK was associated with a trend toward improved functional outcomes compared with TPA in very elderly patients with AIS. However, the statistical significance of the excellent functional outcome was dependent on the inclusion of the ORIGINAL trial, and the association was no longer significant after its exclusion. This finding, combined with the high heterogeneity and small sample sizes, and the high risk of bias related to deviations from intended interventions in most included trials, suggests that the results should be regarded as hypothesis-generating. As all included trials were designed as noninferiority studies, adequately powered superiority trials are warranted to confirm the potential benefit of TNK over TPA in this population.Affiliation [1] has been split into two different affiliations. Please check if action taken is appropriate and amend if necessary.Thank you for checking. The splitting of Affiliation [1] into two separate affiliations is not appropriate. Although its institutional components are separated by semicolons, they collectively constitute one complete affiliation and should remain under a single affiliation number. The official English name has recently been updated. Please replace Affiliation [1] in its entirety with the following: "Neurology Department, Beijing Hospital, National Center for Gerontology; National Clinical Research Center for Gerontology; The Key Laboratory of Geriatrics of NHC; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China" Please also remove all Chinese text currently displayed in Affiliation [1]. We are unable to correct it directly because the editing window closes unexpectedly whenever we click on Affiliation [1] in the online proofing system. We confirm that the wording above is the correct and complete form of Affiliation [1]. Please retain it as a single affiliation and do not split it.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.We have checked the authors and their respective affiliations. Please note the following corrections: The former Affiliation [3], which has been marked for deletion in the proof, should be removed completely.Keying Zhang's previous affiliation did not include the name of her department. We have now added the department name to make her affiliation complete. Please retain the revised affiliation, including the newly added department information.After the deletion of the former Affiliation [3], the former Affiliation [4], which corresponds to Keying Zhang, should be renumbered as Affiliation [3]. Accordingly, Keying Zhang's affiliation number should also be changed from [4] to [3].We are unable to make this renumbering in the online proofing system. Please make the necessary corrections during production. The final affiliation list should contain only Affiliations [1], [2], and [3], with no Affiliation [4].

Comprehensive intra-cohort comparisons of pre-interventional prognostic scores for gastrointestinal bleeding (GIB) are lacking. We compared 12 pre-interventional scores [Glasgow-Blatchford Score (GBS), modified GBS (mGBS), AIMS65, Pre-Rockall, ABC, Harbinger, T-Score, Canuka, SHA2PE, Oakland, NOBLADS, and Modified Early Warning Score (MEWS)] for predicting 30-day mortality and intensive care unit (ICU) admission in emergency department patients with upper GIB (UGIB) and lower GIB (LGIB). This retrospective, single-center cohort study evaluated 2020 patients with GIB between January 2014 and March 2025, categorized into UGIB (n = 1524) and LGIB (n = 496) groups. Primary outcomes were 30-day mortality and ICU admission. Scores were evaluated in two ways: an indication-restricted analysis, in which each score was applied only to the bleeding location for which it was developed, and a comprehensive analysis, in which all 12 scores were applied to both subgroups. Discriminative performance was assessed using the area under the curve (AUC); the highest-performing scores per outcome were compared using DeLong's method. For 30-day mortality, AIMS65 showed the highest discrimination in UGIB (AUC = 0.850) and NOBLADS in LGIB (0.809) in the indication-restricted analysis. In the comprehensive analysis, AIMS65 again showed the highest discrimination (AUC = 0.850) in UGIB, outperforming NOBLADS (AUC = 0.812; p = 0.035), ABC (AUC = 0.801; p = 0.023), and Pre-Rockall (AUC = 0.798; p = 0.033), but not Canuka (AUC = 0.821; p = 0.124). For LGIB, GBS achieved the highest AUC (0.851), followed by MEWS (0.841) and mGBS (0.832), with no significant pairwise differences among the top five scores. For ICU admission, the highest-performing scores demonstrated moderate discrimination in the comprehensive analysis (AUC range, 0.755-0.788 in UGIB; 0.746-0.768 in LGIB). AIMS65 showed the highest discrimination for 30-day mortality in UGIB in both analyses, whereas no score demonstrated clear superiority in LGIB. NOBLADS ranked highest within its original indication in LGIB and retained strong discrimination when applied to UGIB, supporting its potential role as a location-independent mortality predictor. No score reliably predicted ICU admission, indicating a persistent gap in pre-interventional risk stratification.

Refractory lupus nephritis (LN) remains a major therapeutic challenge and a leading cause of progression to end-stage kidney disease (ESKD) in systemic lupus erythematosus (SLE). To characterize a large multicenter cohort of refractory LN, evaluate therapeutic strategies used after non-response, and determine long-term renal outcomes. Multicenter longitudinal cohort including 68 patients with refractory LN from several Spanish centers. Refractoriness was defined according to the GLOSEN consensus as failure to reduce proteinuria by > 25% or worsening of proteinuria and/or renal function after ≥3 months of triple immunosuppressive therapy. Demographic, clinical, histological, therapeutic and outcome data were collected. The cohort included 68 patients (61 women), mean age 34.5 [27-45] years. Renal biopsy showed predominantly proliferative classes (III-IV and mixed forms). Extrarenal involvement was frequent, mainly articular (82.3%), hematological (70.6%) and cutaneous (60.3%). Before non-response, most patients had received corticosteroids (98.5%), mycophenolate mofetil (82.3%), antimalarials (91.2%) and cyclophosphamide (36.8%). Non-response occurred after 16.1 ± 9.5 months and was due to persistent proteinuria (61.8%), worsening renal function (25%) or both (13.2%). Over 12 months, creatinine remained stable, from 0.96 to 1.02 mg/dL (p = 0.726), C3 increased from 56.3 to 85.55 mg/dL (p < 0.001), C4 rose from 0.82 to 1.02 mg/dL (p < 0.001), while proteinuria decreased from 1.9 ± 0.5 to 0.57 ± 0.24 g/24 h (p < 0.001). After treatment modification or intensification-including tacrolimus (39.7%), rituximab (27.9%) and belimumab (27.9%), 41 patients (60.3%) achieved LN remission during a mean follow-up of 59.7 ± 46 months. Ten patients progressed to ESKD (6 requiring hemodialysis and 4 undergoing kidney transplantation). Infections were the most frequent complication (30.9%). Therapeutic escalation allowed LN remission in a substantial proportion patients with refractory LN; however. the risk of progression to ESKD remained high. These findings highlight the need for earlier recognition of non-response and more effective treatment strategies to prevent irreversible renal damage.

Rheumatoid arthritis (RA) patients face increased cardiovascular (CV) risk, yet existing 10-year estimation tools often underperform. This study evaluated whether unsupervised machine learning (uML) clustering can identify distinct RA patient phenotypes with varying major cardiovascular events (MACE) potentially improving risk stratification. A cross-sectional, multi-center cohort of RA patients meeting the 2010 ACR/EULAR classification criteria and without prior CV events was enrolled in January 2019 and followed-up for MACE incidence over 5 years. Clinical and demographic data, including traditional CV risk factors and SCORE2 estimates, were collected. Factor Analysis of Mixed Data (FAMD), a generalization of principal component analysis for mixed data types, was applied in Python (ver.3.9) using Prince (ver.0.7.1). Missing data observations were excluded. Bootstrapped eigenvalue distribution determined the number of FAMD components for clustering, followed by Hierarchical Clustering on Principal Components using Ward's criterion and Euclidean distance. An XGBoost model assessed feature importance, while ANOVA and Chi-square tests evaluated cluster differences. Among 951 RA patients (mean age 61.8 ± 10.5 years; 81.1% female; median disease duration 120 months), 9 MACE occurred (incidence: 1.89/1000 patient-years). Four clusters emerged: Cluster 1 (high HAQ, steroid use, high cholesterol), Cluster 2 (low disease activity, BMI, diabetes, hypertension, SCORE2), Cluster 3 (predominantly male, < 10-year disease duration, csDMARDs; no MACE cases), and Cluster 4 (longer disease duration, hypertension, high triglycerides, lipid-lowering agents, TNFi; highest MACE incidence).uML clustering identified distinct RA phenotypes, complementing SCORE2 for improved CV risk stratification and aiding in recognizing patients at elevated MACE risk.

Urinary tract infection (UTI) is a clinically important complication of autosomal dominant polycystic kidney disease (ADPKD), often involving upper urinary tract and cyst infections. However, most epidemiologic data were generated decades ago, prior to contemporary advances in ADPKD management. We evaluated the current risk of incident and recurrent UTI in adults with ADPKD. Using the National Taiwan University Hospital Integrated Medical Database (2006-2021), adults with ADPKD were propensity score matched (1:4) to individuals without cystic kidney disease by age, sex, and chronic kidney disease (CKD) stage. Participants with prior UTI were excluded. Incident UTI was identified using validated International Classification of Disease codes. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) controlling for demographics, comorbidities, medications, and estimated glomerular filtration rate. Recurrent UTI (≥ 2 episodes) risk was assessed in sensitivity analyses. The cohort included 1,044 patients with ADPKD and 4,176 matched controls (mean follow-up 4.2 years). Incident UTI occurred in 17.9% of ADPKD patients and 15.6% of controls (45.96 vs. 36.24 per 1,000 patient-years). This represented an absolute difference of 2.3 percentage points. ADPKD was independently associated with increased incident UTI risk (aHR 1.20, 95% confidence internal (CI) 1.02-1.42). The association was more pronounced in males (aHR 1.59) and in CKD stages 3b-5 (aHR 1.51). ADPKD was also associated with recurrent UTI (incidence rate ratio 1.32, 95% CI 1.15-1.51). In the contemporary era, ADPKD remains independently associated with increased risk of incident and recurrent UTI, although the absolute increase in UTI incidence was moderate. Targeted surveillance and preventive strategies may be warranted in high-risk subgroups.

Diabetes mellitus is associated with a persistent prothrombotic state driven by platelet hyperreactivity, endothelial dysfunction, oxidative stress, and chronic low‑grade inflammation, all of which contribute to increased cardiovascular (CV) risk. Importantly, a substantial residual thrombotic risk persists even with optimal glycemic control, indicating that glucose lowering alone is insufficient to prevent vascular complications. In this context, antidiabetic therapies have emerged as important modulators of CV risk beyond their metabolic effects. Several drug classes-including metformin, thiazolidinediones, DPP‑4 inhibitors, SGLT‑2 inhibitors, and GLP‑1 receptor agonists-have been shown to influence platelet activity, endothelial function, and inflammatory pathways. These effects are mediated through mechanisms such as enhanced nitric oxide bioavailability, reduced oxidative stress, attenuation of platelet activation, and modulation of vascular inflammation. Among these, GLP‑1 receptor agonists exert particularly pronounced effects on endothelial function, oxidative stress, and platelet reactivity, alongside robust reductions in CV events. More broadly, accumulating experimental and clinical evidence indicates that several antidiabetic agents exert clinically meaningful antithrombotic actions, contributing to decreased rates of major CV events and heart failure. However, these benefits vary across drug classes and patient populations. This highlights the importance of an individualized therapeutic approach in type 2 diabetes, where treatment selection should account not only for glycemic targets but also for CV and thrombotic risk. Choosing agents with proven CV benefit may optimize overall risk reduction and improve long‑term outcomes. This narrative review aims to critically examine the available experimental and clinical evidence on the effects of antidiabetic drugs on platelet function, thrombosis, and thrombo-inflammatory pathways, highlighting the mechanisms that may contribute to cardiovascular protection beyond glucose lowering.

Myocardial infarction (MI) remains a major driver of incident heart failure (HF) despite timely reperfusion and guideline-directed medical therapy. Current treatments, largely centered on neurohormonal blockades, attenuate maladaptive pathways but do not restore endogenous cardioprotective systems. Among these, the natriuretic peptide (NP) network plays a central role in counteracting fibrosis, hypertrophy, sodium retention, and microvascular dysfunction. In advanced HF, impaired prohormone processing, corin dysfunction, and abnormal glycosylation lead to the predominance of biologically less-active NP forms despite elevated circulating levels, resulting in "functional NP deficiency" and insufficient NP-cGMP signaling. From a mechanistic perspective, NP biology can be organized into two complementary axes. The cGMP-dependent axis comprises ANP and BNP signaling via NPR-A and CNP via NPR-B, mediating natriuretic, vasodilatory, and antifibrotic effects. The cGMP-independent axis includes NPR C-mediated signaling and the actions of the ANP mid-sequence fragment proANP31-67, which exerts antifibrotic and cardioprotective effects through a cyclooxygenase-2/prostaglandin E2/EP4 pathway with minimal systemic hypotension. Nanomedicine offers a strategy to restore these complementary pathways with improved spatiotemporal precision. Lipid and polymeric nanoparticles, biomimetic carriers, and extracellular vesicles can protect NP-derived cargo, prolong bioavailability, and enhance functional cardiac targeting while limiting off-target exposure, although current evidence is largely preclinical. In this review, we examine NP biology in post-ischemic remodeling, the concept of functional NP deficiency, and emerging nano-enabled delivery approaches as potential add-on interventions to contemporary HF therapy. We propose dual-axis "nano-hormonal" strategies integrating cGMP-dependent and cGMP-independent signaling as a testable paradigm for targeted modulation of post-MI remodeling.

Long COVID imposes a substantial public health burden following the SARS-CoV-2 pandemic, yet the contribution of electronic cigarette (e-cigarette) use, alone or alongside cigarette smoking, remains inadequately characterized in population-representative data. We conducted a cross-sectional analysis of 9274 adults aged 16 years and older from the pooled 2023-2024 Scottish Health Survey, a nationally representative household survey. Cigarette smoking and e-cigarette use were classified into seven mutually exclusive categories, and the outcome was survey-defined self-reported Long COVID, based on symptoms persisting for more than four weeks after first having COVID-19. Survey-weighted logistic regression was used to estimate crude and adjusted odds ratios, with adjustment for survey year, age group, sex, area deprivation, ethnicity, alcohol use, and educational attainment. Overall, 7.4% of adults reported Long COVID. Compared with never cigarette/e-cigarette users, adjusted odds were higher among former cigarette smokers currently using neither product (adjusted odds ratio 1.40, 95% confidence interval 1.12-1.76) and among former smokers currently using e-cigarettes exclusively (1.56, 1.09-2.24). No statistically detectable associations were observed among former e-cigarette users who had never smoked, current e-cigarette users who had never smoked, exclusive current cigarette smokers, or dual users. The two elevated associations persisted after additional adjustment for asthma, chronic obstructive pulmonary disease, diabetes, and cardiovascular disease. The observed pattern may reflect previous cigarette exposure, health-related smoking cessation or switching, reverse causation, and residual selection or confounding; the cross-sectional design does not permit an independent contribution of e-cigarette use to be determined.