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
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.
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
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.
Heart failure with preserved ejection fraction (HFpEF), obesity, type 2 diabetes mellitus are common in elderly patients and are associated with an increased risk of cognitive impairment (CoI). In these patients, the protective metabolic and vascular effects of glucagon-like peptide−1 receptor agonists (GLP-1 RAs) are well established. The aim of this study was to evaluate effects of one-year treatment with oral semaglutide versus DPP-4 inhibitors (DPP4i), as an add-on to the hypoglycaemic therapy, on the incidence of CoI in patients with HFpEF, obesity, and type 2 diabetes. 246 elderly outpatients were recruited and divided into two groups (oral semaglutide vs. DPP4i), accurately matched for age, sex, and body mass index (BMI). At one-year follow-up, 106 new cases of CoI were observed in the entire study population (43.1 events/100 patients/year). A significant difference was found between the two groups: 33 cases with oral semaglutide (26.8 events/100 patients/year) versus 73 cases with DPP4i (59.3 events/100 patients/year), p<0.0001. Logistic regression analysis indicated a 77
A 23-year-old woman presented with sudden, severe vision loss in her right eye following intense emotional crying. Visual acuity was reduced to counting fingers with an unremarkable anterior segment examination. Fundus examination revealed a well-circumscribed, dome-shaped sub-internal limiting membrane hemorrhage involving the macula, with a visible fluid-blood level. Optical coherence tomography confirmed separation of the internal limiting membrane with a hyporeflective blood-filled cavity, consistent with sub-internal limiting membrane hemorrhage. Based on the characteristic imaging findings and a clear history of a Valsalva-like event, Valsalva retinopathy was diagnosed. Given the extensive macular involvement and the presence of fresh, non-clotted hemorrhage, neodymium-doped yttrium aluminum garnet laser membranotomy was performed at the lowest point of the hemorrhagic cavity. Immediate drainage of blood into the vitreous cavity was observed, accompanied by rapid visual improvement. Visual acuity improved to LogMAR 0.5 shortly after the procedure and further to LogMAR 0.2 at one-week follow-up. Subsequent fundus imaging demonstrated near-complete resolution of both sub-internal limiting membrane and intravitreal hemorrhage, and fundus fluorescein angiography showed no retinal structural damage. This case highlights intense emotional crying as a potential trigger for Valsalva retinopathy and supports early laser membranotomy as an effective treatment for macula-involving cases.
Dyspnea is a personal perception of breathing discomfort. The patient self-reported numerical rating scale (NRS) from 1 to 10 is an accurate tool for assessing dyspnea severity following the definition of dyspnea. The Respiratory Distress Observation Scale (RDOS) is an alternative dyspnea severity measurement for patients with impaired communication abilities. This study aims to evaluate the accuracy of RDOS and determine the optimal cutoff point in the emergency department (ED). This cross-sectional observational study was nested in a previous study investigating the inter-rater reliability of RDOS in the EDs of two academic hospitals. The participants were emergency physicians who were the first responders to adult patients presenting with dyspnea. The patient reports NRS, while the physician assesses RDOS using the record forms separately. The study excluded patients with impaired communication. A total of 122 patients and 44 emergency physicians rated RDOS. The overall severity of dyspnea was rated by the total median self-reported NRS as 7 (5, 8), and the total median RDOS as 5 (3, 7). For the diagnostic performance, the highest AUC is 0.783 (95
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, ischemic stroke, peripheral artery disease, and calcific aortic valve stenosis. Structurally, Lp(a) consists of an LDL-like particle covalently bound to apolipoprotein(a), a plasminogen-like glycoprotein that confers distinct biological properties. In particular, Lp(a) is the main circulating carrier of oxidized phospholipids, which promote endothelial dysfunction and vascular inflammation. Lp(a) contributes to vascular injury through multiple mechanisms, including lipid retention within the arterial wall, inflammatory activation, impairment of fibrinolysis, and vascular calcification. These processes contribute to plaque development and progression. Circulating Lp(a) levels are largely determined by genetic variability within the LPA gene, particularly by kringle IV type 2 copy number variation, which influences apolipoprotein(a) isoform size and secretion. Despite its clinical relevance, therapeutic options specifically targeting Lp(a) remain limited. Lipoprotein apheresis is the main available strategy for a substantial reduction in selected high-risk patients, while conventional lipid-lowering therapies have minimal effects and PCSK9 inhibitors provide only partial reductions. However, several targeted therapies are currently under investigation. Antisense oligonucleotides and small interfering RNAs reduce hepatic LPA expression and achieve marked reductions in circulating Lp(a) levels, and novel small molecule agents interfere with Lp(a) particle formation. Gene-editing strategies are a potential future approach for long-term Lp(a) reduction. In conclusion, Lp(a) is a key determinant of residual cardiovascular risk. A better understanding of its pathophysiology and the development of targeted therapies may improve cardiovascular risk stratification and prevention strategies.
Emergency department (ED) overcrowding is a persistent global challenge associated with adverse patient outcomes and system inefficiencies. Boarding and access block, which delay the transfer of admitted patients to inpatient beds, represent its most critical manifestations. While overcrowding has traditionally been attributed to rising demand and ED inefficiencies, growing evidence identifies downstream constraints in hospital capacity and patient flow as major drivers. A non-systematic literature search was conducted using PubMed and Web of Science focusing on studies published between January 1990 and December 2025 related to ED overcrowding, boarding, hospital overcrowding, access block, patient flow, and hospital capacity. The literature was narratively synthesized and organized according to the input–throughput–output framework to examine system-level determinants and interventions and to explore overcrowding as a hospital-wide phenomenon. Interventions targeting input and throughput processes improve local ED performance metrics but often fail to reduce overcrowding when output capacity remains constrained. Conversely, high inpatient-bed occupancy, delayed discharge processes, and inefficient hospital-wide patient flow are frequently associated with access block and boarding. Overall, the literature supports the interpretation of ED overcrowding as a manifestation of hospital-wide dysfunction. High-performing hospitals prioritize patient flow as an institutional focus and adopt a system-level approach, characterized by executive leadership involvement, real-time data monitoring, and shared accountability across departments. Boarding may be better understood as the clinical manifestation of system-level failure in hospital patient flow rather than an ED-specific issue. The way out requires a shift from ED-centered interventions to coordinated, hospital-wide strategies, recognizing that the responsibility for timely and safe patient flow lies with the entire organization.
The BAN-ADHF score is a recently developed measure designed to predict low diuretic efficiency and adverse outcomes using eight simple routinely available clinical and laboratory variables. However, its performance in real-world settings remains understudied. This is a retrospective analysis using data from the Spanish Heart Failure Registry (RICA), a nationwide, prospective cohort of patients admitted for ADHF to internal medicine departments. Only patients with complete data to calculate the BAN-ADHF score were included. Patients were classified into low BAN-ADHF (< 12) and high BAN-ADHF (≥ 12) groups. The primary endpoint was all-cause mortality. Secondary endpoints included the composite of mortality and/or heart failure (HF) readmission and length of hospital stay. A total of 2110 were eligible. High BAN-ADHF patients (17.5
The objective is to describe patterns of noncommunicable disease (NCD) service delivery and the operational roles of the different Emergency Medical Team (EMT) types—Type1 mobile (outpatient mobile primary care), Type1 fixed (outpatient static primary care), and Type2 (inpatient and surgical care)—in NCD care during the emergency response in Gaza throughout 2024–2025. This study analyzed routinely collected aggregate data from the World Health Organization EMT Minimum Data Set reported by EMTs across Gaza between January 2024 and December 2025. A total of 317,624 NCD consultations were included. Consultations for hypertension, diabetes, asthma/chronic obstructive pulmonary disease, cardiovascular disease, and epilepsy were examined across the different EMT types. Temporal trends were analyzed across six predefined conflict phases using non-parametric statistical testing. Statistically significant differences were observed for NCD consultations across EMT types, suggesting complementary roles. Type1 mobile teams showed the highest proportions of new diagnoses, indicating a frontline case-detection role. Type1 fixed teams demonstrated intermediate follow-up new diagnosis ratios, functioning primarily as chronic disease management hubs. Type2 teams managed the highest burden of acute exacerbations (87.6
The primary aim of this study was to develop a clinical scoring system for predicting centrally located pulmonary embolism in patients with confirmed acute pulmonary embolism. The secondary objectives were to evaluate the association between the THROMPE score and 30-day mortality. This retrospective study included 531 adult patients who presented to the emergency department with suspected pulmonary embolism and underwent computed tomography pulmonary angiography. Independent predictors of centrally located pulmonary embolism were identified using multivariate logistic regression analysis to develop the THROMPE score. Receiver operating characteristic analysis was used to determine optimal cutoff values, assess the diagnostic performance of the THROMPE score and compare its performance with that of the Pulmonary Embolism Severity Index (PESI). Among the 365 patients diagnosed with PE, 47 (12.9
To evaluate the impact of health literacy on medication adherence of hyperlipidemic outpatients, considering age, gender, perceived health, adverse drug reaction and lipid-lowering treatment. To examine the impact of a modifiable factor—health literacy (HL)—on medication adherence (MA), a cross-sectional observational study was conducted in outpatient lipid clinic (January to June 2025). The exposure of interest was HL, assessed using the Brief Health Literacy Screening Items scale. The primary outcome was MA, measured with the Morisky Medication Adherence Scale. 621completed questionnaires were analysed (age 61.2 ± 13.8 years; male 58.1
