This article presents recommendations for the use of beta-blockers (BB) according to current guidelines and the underlying evidence. Until the last decade, BBs were recommended as first-line therapies for uncomplicated hypertension. This recommendation was discontinued, because studies indicate an overall lower efficacy compared to other antihypertensive drugs. Current cardiology guidelines include recommendations for the indications of symptomatic heart failure with reduced ejection fraction (HFrEF), angina pectoris, post-myocardial infarction, atrial fibrillation, and for the treatment of resistant hypertension.

Coronary artery calcium (CAC) imaging directly assesses subclinical calcified coronary atherosclerosis but population-wide imaging is not recommended. Simple prescreening may help identify individuals most likely to benefit from CAC imaging. We previously developed a self-report-based model to estimate the probability of CAC ≥100. This study prospectively evaluated a strategy based on this model to select individuals for CAC imaging. We assessed agreement between model-predicted probability and observed prevalence of CAC ≥100 among participants undergoing CT imaging and examined patterns of preventive lipid-lowering therapy.

The PRedict and Identify cOronary atherosclerosis-Now (PRIO-Now) study applied a prospective, two-step, population-based screening approach. Individuals aged 59-60 years were invited to complete a self-report questionnaire. Eligible respondents without previous ischaemic heart disease whose model-predicted probability of CAC ≥100 exceeded the predefined threshold were invited to clinical assessment and non-contrast coronary CT imaging. The primary analysis assessed agreement between model-predicted probabilities and the observed prevalence of CAC ≥100 among CT completers.

Of 8000 invited individuals, 2588 (32%) completed the questionnaire. Of 2375 eligible respondents, 814 were classified as high risk and 563 underwent CT imaging. Among CT completers, the mean predicted probability of CAC ≥100 was 28.3% (95% CI 27.2 to 29.3), compared with an observed prevalence of 28.4% (95% CI 24.8 to 32.4), corresponding to an expected/observed ratio of 0.99 and a Brier score of 0.19. Among participants with CAC ≥100, 64% were not receiving lipid-lowering therapy and 11% had low-density lipoprotein cholesterol ≤1.8 mmol/L.

A self-report-guided strategy enabled targeted CAC imaging in a model-selected cohort. Among participants completing CT imaging, the observed prevalence of CAC ≥100 was comparable with the mean model-predicted probability. These findings suggest that self-report data may support preselection for CAC imaging and help identify opportunities for preventive treatment among individuals with elevated CAC.

A woman in her 80s was referred for evaluation and treatment of progressive paraparesis due to a suspected spinal arteriovenous shunt. During hospitalisation at the referring institution, she developed multiterritory embolic stroke, prompting investigation.Bilateral deep venous thrombosis and a large pulmonary arteriovenous malformation (PAVM) with a high-grade extracardiac right-to-left shunt were identified, supporting paradoxical embolism as the most likely mechanism. Spinal angiography confirmed a spinal epidural arteriovenous fistula (SEDAVF) with venous drainage into intradural spinal veins and the inferior vena cava.Because liquid embolic material used for SEDAVF treatment could potentially migrate into the inferior vena cava and reach the systemic circulation through the PAVM, a staged approach was adopted. Coil embolisation of the PAVM was performed, followed by N-butyl-2-cyanoacrylate embolisation of the SEDAVF without clinically evident complications.This case highlights the importance of treatment planning based on vascular anatomy and haemodynamics in patients with coexisting arteriovenous shunt lesions.

Snakebites frequently cause venom-induced consumption coagulopathy (VICC). While bleeding is common, ischaemic stroke from large-vessel occlusion (LVO) is rare. The coexistence of LVO and active VICC creates a therapeutic paradox, as reperfusion therapies risk catastrophic haemorrhage. We report a woman in her mid-60s who developed left-sided hemiplegia 6 hours after a suspected viper bite. Investigations revealed profound VICC and an acute right middle cerebral artery (M1) occlusion. Due to extreme bleeding risks, standard reperfusion therapies-intravenous thrombolysis and mechanical thrombectomy-were contraindicated. Management prioritised rapid venom neutralisation using polyvalent anti-snake venom and supportive care. Once coagulation parameters normalised, cautious antiplatelet therapy was initiated, resulting in partial neurological recovery. This case highlights a rare clinical dilemma where modern stroke treatments are unsafe due to venom-induced coagulopathy, emphasising the necessity of individualised, risk-balanced management when ischaemic and haemorrhagic risks collide.

Visceral (hepatic) larva migrans is a parasitic disease which predominantly affects children. This usually presents with fever and abdominal pain with occasional respiratory symptoms. Radiologically, hepatic lesions are seen in cases of hepatic visceral larva migrans. However, the lesions causing pseudoaneurysms are uncommon. We report a 3-year-old girl who presented with prolonged fever, abdominal pain and haematemesis. Laboratory investigations demonstrated anaemia, raised eosinophil count, jaundice, elevated serum IgE levels and positive Toxocara serology. Ultrasonography revealed multiple hypoechoic lesions in the liver consistent with abscesses, while abdominal CT angiography demonstrated multiple hepatic artery pseudoaneurysms arising from branches of the hepatic artery. The patient was successfully treated with transarterial embolisation along with albendazole and corticosteroid therapy, resulting in clinical and laboratory improvement. This case highlights the significance of radiological imaging in the diagnosis of visceral larva migrans in children with emphasis on close clinicoradiological integration for accurate identification of the uncommon presentation of this disease and demonstrates the value of CT angiography in identifying life-threatening arterial involvement.

Traditionally, the number and location of cerebral microbleeds (CMBs) are manually calculated based on magnetic resonance imaging (MRI) characteristics such as shape, size, and signal features. Although accurate, manual detection requires expert interpretation and is costly. Therefore, it is necessary to explore an effective auxiliary detection method. In recent years, deep learning (DL) has been increasingly used in the detection of cerebral hemorrhage. Some studies have explored image-based DL models for diagnosing CMBs. Nevertheless, systematic evidence regarding their diagnostic accuracy is lacking.

This review aimed to assess the accuracy of DL models in detecting CMBs and inform the development of intelligent detection tools.

This study was reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and was prospectively registered in PROSPERO (registration ID CRD42024628447). IEEE, Web of Science, Embase, the Cochrane Library, and PubMed were comprehensively searched up to November 1, 2024, and the database search was subsequently updated on July 5, 2026, to collect publicly published original studies on DL for detecting CMBs. The risk of bias of eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Subgroup analyses were performed according to the level of analysis (lesion level and patient level) and the method of obtaining the diagnostic 4-fold table at the lesion level (direct extraction and reconstruction).

At the patient level, 5 studies were included, all of which developed models based on MRI. The meta-analysis results suggested that the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.89 (95% CI 0.76-0.96), 0.86 (95% CI 0.77-0.92), 6.3 (95% CI 3.5-11.6), 0.13 (95% CI 0.05-0.32), and 50 (95% CI 12-212), respectively. At the lesion level, the sensitivity, specificity, PLR, NLR, and DOR were 0.96 (95% CI 0.93-0.98), 0.98 (95% CI 0.94-0.99), 39.5 (95% CI 16.8-92.7), 0.04 (95% CI 0.02-0.07), and 1061 (95% CI 293-3848), respectively. In the subgroup of direct extraction of the diagnostic 4-fold tables at the lesion level, the sensitivity, specificity, PLR, NLR, and DOR were 0.98 (95% CI 0.95-0.99), 0.98 (95% CI 0.90-0.99), 40.2 (95% CI 9.3-79.9), 0.02 (95% CI 0.01-0.05), and 1738 (95% CI 174-17,385), respectively. In the subgroup of reconstruction of the diagnostic 4-fold tables at the lesion level, the sensitivity, specificity, PLR, NLR, and DOR were 0.95 (95% CI 0.89-0.97), 0.98 (95% CI 0.96-0.99), 41.2 (95% CI 21.2-79.9), 0.06 (95% CI 0.03-0.12), and 736 (95% CI 224-2418), respectively.

DL models based on MRI appear to show favorable diagnostic performance in detecting CMBs. Given the small number of included studies, more multicenter studies are warranted to facilitate the development of more generalizable detection tools.

PROSPERO CRD42024628447; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024628447.

Protein carbamylation, a urea-driven post-translational protein modification that increases in chronic kidney disease (CKD), affects diverse mechanisms relevant to the excess morbidity and mortality observed in this population. Given urea's ubiquitous presence in the body, we hypothesized that carbamylation would associate with a broad range of clinical phenotypes, specifically cardiovascular diseases.

Observational cohort study.

3,111 participants from the Chronic Renal Insufficiency Cohort (CRIC).

Carbamylation burden assessed by carbamylated albumin (C-Alb).

Clinical phenotypes, and coronary artery calcification (CAC) prevalence, severity, and progression.

A phenome-wide association study (PheWAS) evaluated associations between C-Alb and clinical phenotypes. Post-PheWAS analyses examined the association of carbamylation with CAC measured by Agatston and total volume scores.

Across 212 phenotypes, multivariable adjusted comparisons identified 47 significant associations between C-Alb and clinical phenotypes after accounting for multiple testing. Blood urea nitrogen showed one of the greatest associations. Among the most significant continuous phenotypes correlated with C-Alb, those within the coronary calcification category exhibited the greatest magnitude of association prompting additional analysis. 1,046 participants had CAC assessments (median age 60 years, 46% female, median eGFR 43) with CAC present in 65% and the highest C-Alb quartile showing the greatest prevalence. Cross-sectional analysis revealed that each SD increase in log-transformed C-Alb associated with 41% greater CAC severity. Longitudinally, among 269 participants with baseline CAC zero, 55 developed incident CAC, while among 389 with baseline CAC > 0, 147 showed ≥50-unit annual CAC progression. C-Alb associated with progressive CAC in multivariable models adjusting for traditional risk factors.

Observational design, residual confounding, and limited power for incident CAC analyses.

Among patients with CKD, our findings showcase a wide range of phenotypic associations with carbamylation, particularly cardiovascular phenotypes. Carbamylation may be an independent risk factor for CAC, suggesting its potential as a therapeutic target to mitigate cardiovascular risk in CKD populations.

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide. Modulation of cholesteryl ester transfer protein (CETP), which plays an important role in exchanging neutral lipids between plasma lipoproteins, became a key target for combating CVDs. However, mixed clinical results of CETP inhibitors suggest the need for new analogues that maintain high CETP binding affinity and provide better therapeutic outcomes. In this study, a focused series of Evacetrapib-inspired tetrahydrobenzazepine analogs was computationally designed, synthesized, and experimentally tested as potential CETP inhibitors. Based on the structure-based docking of curated 24 analogues, the N-alkylated ester derivatives were found to be the most promising subset occluding CETP binding pocket. Molecular dynamics simulation results showed that the designed molecules do not alter the inherent dynamics of CETP, instead reorganize themselves for more persistent and stronger hydrophobic contacts with the protein core. Based on these findings, a common benzazepine intermediate was employed to synthesize the targeted ester analogues by straightforward N-alkylation sequence, followed by characterization using spectroscopic methods, which were tested on fluorescence-based CETP inhibition assay. Of the synthetic analogues, 6d emerged as the most active compound (IC₅₀ of 75.54 ± 8.70 nM). Although the best analogue remained less potent than Evacetrapib, the study suggested a preliminary chain-length-dependent activity pattern, where elongation of the N-alkyl ester chain was associated with improved CETP inhibition. Complementary in silico profiling further indicated that the designed esters occupy a lipophilicity range comparable to clinically evaluated CETP inhibitors. Taken together, these findings establish the N-alkylated benzazepine scaffold as a mechanistically informative lead platform and provide a clear direction for the future design of more potent CETP inhibitors.

Conventional cancer therapies such as chemotherapy primarily rely on apoptosis induction; however, their efficacy is often compromised by the development of apoptosis resistance in tumor cells. A new cyclometalated iridium complex, IrOAc, was designed and synthesized in this study. Its improved red-light absorption in the 650-700 nm biological window offers potential advantages for the treatment of deep-seated and hypoxic tumors. Upon irradiation, IrOAc generates reactive oxygen species (ROS) via both Type I and Type II photodynamic pathways, disrupting cellular redox homeostasis and inducing lipid peroxidation, thereby triggering both potential ferroptosis and apoptosis. In vitro studies demonstrate that IrOAc exhibits markedly enhanced cytotoxicity against RM-1 prostate cancer cells under 650 nm irradiation, along with significant inhibition of colony formation and cell migration. Mechanistic investigations reveal depletion of intracellular glutathione (GSH), downregulation of glutathione peroxidase 4 (GPX4) expression, and characteristic mitochondrial alterations associated with ferroptosis. Notably, IrOAc also promotes caspase-3 activation (cleavage), further facilitating apoptotic cell death. In vivo experiments demonstrate that IrOAc combined with red-light irradiation effectively suppresses tumor growth without inducing noticeable systemic toxicity; this therapeutic effect was accompanied by an increased proportion of splenic CD8⁺ T cells and elevated intratumoral IFN-γ levels, suggesting potential immunomodulatory activity. Collectively, IrOAc represents a promising red-light-responsive photodynamic agent combining chemotherapeutic and photodynamic activities, with favorable biosafety and immunomodulatory potential, offering a novel strategy to overcome tumor resistance and enable precise cancer therapy.