Almost half a century ago, cardiac surgeons introduced the concept of prosthesis-patient mismatch (PPM), which was defined by indexing the effective orifice area (EOA) to body surface area. Although PPM has demonstrated strong prognostic value following surgical aortic valve replacement (SAVR), its significance in transcatheter aortic valve replacement (TAVR) remains uncertain. In this review, we revisit the concept of PPM and explore the methodological and clinical challenges in its application. Special focus is given to the limitations in interpreting EOA and indexed EOA (EOAi), including flow dependency and imaging variability. We also review the literature evaluating the association between PPM and clinical outcomes after SAVR and TAVR. Finally, we discuss a potential role of alternative metric such as the fitting index.

Arrhythmia is one of the leading causes of mortality and lacks diagnostic and therapeutic options. Electrical activity at the cellular level is difficult to use as a basis for evaluating drug effects on cardiac rhythm. Cardiac organoids, as organized and functional cell clusters, offer significant advantages as models for the pathophysiological mechanisms of arrhythmia or as drug screening platforms. Here, we applied a standardized set of electrophysiological techniques to integrate electrophysiological activity of cardiac organoids, including multielectrode array (MEA), calcium signal optical mapping and patch clamp analysis. We first established cardiac organoids containing cardiomyocyte and endothelial cell components through hiPSC (human induced pluripotent stem cell) induction. Then by this electrophysiological detection protocol, we found that the characteristics of electrical activity and calcium transient signal of cardiac organoids under E-4301, cisapride or ATX-II induction were more similar to cardiac tissue rather than to cardiomyocytes cultured in vitro. Finally, the patch clamp analysis revealed the existence of subpopulations of ventricular-like cardiomyocytes with different electrical activity phenotypes in cardiac organoids, which aligns with the theoretical basis for cardiac rhythm formation. Our findings systematically validated the tissue-like characteristics of cardiac organoids and can be applied to the testing of molecules' effects on cardiac rhythm, thereby screening for novel antiarrhythmic drugs.

We sought to synthesize and evaluate evidence for the overuse of vascular diagnostic imaging tests and procedures in high-income countries as they may be overused in asymptomatic, minimally symptomatic, and/or high-risk patients with limited life expectancy.

After protocol registration (CRD42021257490), we searched MEDLINE, EMBASE, and Evidence-Based Medicine Reviews (January 1st, 2010-May 14th, 2025) for English-language studies that reported the incidence/prevalence of overuse of vascular diagnostic imaging tests and/or procedures in high-income countries; adjusted predictors of overuse; or adjusted associations between overuse and outcomes. Three investigators independently reviewed titles/abstracts and full-texts, extracted data, and assessed risk of bias. Data were pooled using random-effects models. GRADE was used to assess estimate certainty.

Among 11,748 citations, we included 14 studies (n=16,706,904 patients) that examined two unique vascular diagnostic imaging tests and eight unique procedures. The most frequently overused vascular imaging tests included carotid (pooled-cumulative incidence=19%; 95% confidence interval [CI]=10-30%; moderate-certainty) and venous duplex (cumulative incidence=46%; 95% CI=43-48%; moderate-certainty). The most frequently overused vascular procedures included renal artery angioplasty (pooled-cumulative incidence=92%; 95% CI=85-97%; low-certainty) and inferior vena cava filter placement (pooled-cumulative incidence=72%; 95% CI=0-100%; low-certainty). Adjusted-risk factors for carotid duplex overuse included increasing age and higher median neighborhood income quartile. Adjusted risk factors for overuse of endovascular intervention for claudication included ever smoking and end-stage renal disease. Overuse was associated with increased healthcare costs in all studies examining this outcome.

Overuse of vascular diagnostic imaging tests and procedures may be common in high-income countries and associated with increased healthcare costs. However, because the included studies had important limitations, our findings should be confirmed before methods to reduce the above overuse are developed.

Several cardiovascular risk factors and comorbidities have been linked to an increased risk of new-onset atrial fibrillation (NOAF). However, the relationship between peripheral artery disease (PAD) and NOAF has been less extensively investigated.

The purpose of this study was to estimate the risk of NOAF in PAD patients.

We performed a systematic review of MEDLINE (via PubMed) and EMBASE from inception to January 2026 and a meta-analysis of observational studies reporting risk of NOAF in PAD patients. For studies using the ankle-brachial index (ABI), we stratified results according to ABI <1.0 or >1.4.

We included 7 studies with 763,919 patients (56,207 with PAD) and 26,064 NOAF events. The pooled analysis showed an association between PAD and NOAF (HR: 1.34; 95% CI: 1.18-1.50, I² = 85%). PAD defined by low ABI<1.0 was associated with NOAF (HR: 1.18; 95% CI: 1.09-1.28; P < 0.001, I² = 37%) while ABI>1.4 did not reach statistical significance (HR: 1.14; 95% CI: 0.99-1.32; P = 0.07, I² = 33%). PAD defined using International Classification of Diseases-Ninth Revision or clinical history (ie, clinically overt PAD) showed the strongest association with NOAF (HR: 1.40; 95% CI: 1.19-1.66; P < 0.001, I² = 81%). The certainty of the evidence according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was low.

Data from observational studies suggest that PAD may be associated with a 34% increased risk of NOAF. In patients diagnosed with PAD (ie, low ABI), proactive management of common atherosclerotic risk factors may be considered to potentially reduce the risk of NOAF.

Spatiotemporally patterned alveolar ridge resorption after tooth extraction compromises subsequent implant placement and esthetic rehabilitation. This challenge is aggravated in diabetes, where chronic inflammation and excessive osteoclast activity drive the extraction socket into an early resorption-dominant remodeling state, exacerbating ridge atrophy. Inspired by the ordered collagen-mineral hierarchy of socket bone, we engineered an aligned, scale-like nanotopographic scaffold (AT) to provide interfacial mechanical cues for regulating pathological remodeling. Transcriptomic profiling revealed broad suppression of osteoclast differentiation-associated programs and attenuation of NF-κB signaling in the AT group. AT further induced pronounced alignment-dependent cell spreading and cytoskeletal remodeling. These effects were accompanied by YAP activation and restraint of IKKα-p100/p52 non-canonical NF-κB signaling, leading to downregulation of key osteoclast regulators and effectors and impaired osteoclast fusion and maturation. In an ob/ob diabetic mouse tooth extraction model, AT rapidly mitigated early excessive resorption, promoted collagen matrix deposition and tissue remodeling, and enhanced alveolar ridge preservation. Collectively, these findings demonstrate that biomimetic aligned nanotopographic interfaces can reprogram diabetes-exacerbated resorption-dominant remodeling via interfacial mechanoregulation, thereby providing a biomaterial strategy for alveolar ridge preservation in high-resorption pathological settings.

This study systematically evaluates the association between trace metal exposure and hypertension risk, explores dose-response patterns, and investigates underlying molecular mechanisms. A systematic review was conducted according to PRISMA guidelines, including 39 high-quality observational studies retrieved from PubMed, Web of Science, Embase, and the Cochrane Library. Meta-analysis results showed a significant positive association between blood lead exposure and hypertension (OR = 1.16, 95% CI: 1.02-1.31) as well as gestational hypertension (OR = 1.56, 95% CI: 1.21-2.02). Conversely, blood manganese demonstrated a potential protective effect, showing a monotonically declining linear trend with hypertension risk and a significantly reduced risk of gestational hypertension (OR = 0.40, 95% CI: 0.25-0.65). Dose-response analysis based on restricted cubic splines revealed nonlinear patterns: blood cadmium exhibited a U-shaped dose-response relationship (P non-linear = 0.005) with risk rising markedly above 3.5 µg/L, and dietary zinc showed a J-shaped curve (P non-linear = 0.004) peaking around 22 mg/day. Urinary biomarkers (cadmium, lead, arsenic, zinc, vanadium, and cobalt) generally showed stronger associations with hypertension than blood biomarkers. However, for several metals - including vanadium, cobalt, chromium, and nickel - the available evidence was limited to one to three studies, and the corresponding risk estimates should therefore be interpreted with caution and require confirmation in future larger-scale studies. Bioinformatics analysis highlighted that trace metal exposure may promote hypertension through mechanisms such as oxidative stress, inflammatory responses (e.g., TNF signaling), and disruption of the AGE-RAGE pathway. The findings suggest that lead exhibits threshold-free linear toxicity, while manganese may have a protective effect. Pregnant women were identified as a particularly sensitive population to environmental metal exposure. This study provides epidemiological evidence and explores molecular mechanisms, supporting preventive strategies for environmentally induced hypertension. The image summary is shown in the Graphical Abstract.

Recommendations on anticoagulation in patients with short bowel syndrome (SBS) following acute mesenteric ischaemia (AMI) or complicated by catheter-related thrombosis (CRT), are limited. Guidance is specifically lacking on antithrombotic drug selection, dosing, treatment duration and monitoring. Moreover, current recommendations do not account for the potentially impaired drug absorption in patients with SBS. This multidisciplinary position paper aims to develop a practical management guide for antithrombotic therapy in patients with SBS following AMI, as well as CRT.

Nineteen intestinal failure experts, coagulation specialists, and clinical pharmacists completed a three-round Delphi voting procedure on 52 initial statements regarding antithrombotic drug and dose selection, duration and monitoring of treatment and testing for underlying diseases in case of AMI.

After three voting rounds, 46 statements were retained with good agreement (i.e., >80%) for 38 of them, moderate agreement (i.e., >70-80%) for two statements, and low agreement (i.e., ≤70%) for the remaining six.

While robust evidence is lacking regarding antithrombotic therapy in patients with SBS, consensus was reached on the majority of statements. More research in this field is required, particularly on oral drug absorption in SBS, development of alternative oral drug formulations, treatment strategies following arterial mesenteric stenting and direct oral anticoagulant (DOAC) dosing for secondary prophylaxis of CRT in SBS.

Observational studies have shown that air pollution may affect functional outcome following ischemic stroke. Our study aimed to explore the relationship between genetically predicted specific air pollutants and poststroke functional outcomes using the Mendelian randomization (MR) methodology. The instrumental variables for air pollution (nitrogen oxide [NOx], nitrogen dioxide [NO2], PM2.5, PM2.5-10, and PM10) were derived from whole-genome association study data of individuals of European descent. Summary data for functional outcomes after ischemic stroke were sourced from the Ischemic Stroke Genetics Functional Outcome Network. Primary analysis employed the "IVW" method for 2-sample MR. In sensitivity analysis, Cochran Q test, inverse variance-weighted (IVW) method, and MR-Egger method were used for heterogeneity assessment. In the horizontal pleiotropy analysis, we utilized the MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) test. Finally, the robustness of the results is ensured. Gene prediction suggested no association between several air pollutants and functional outcome after ischemic stroke (PM2.5 [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.26-2.95; P = .825], NOx [OR, 0.77; 95% CI: 0.27-2.21; P = .629], NO2 [OR 1.73; 95% CI: 0.61-4.90; P = .304], PM2.5-10 [OR 2.48; 95% CI: 0.28-22.12; P = .416], and PM10 [OR 2.54; 95% CI: 0.41-15.87; P = .319]). The supplementary MR methods confirmed similar results. Further analysis, not adjusted for stroke severity, supports these findings. Air pollutants (NOx, NO2, PM2.5, PM2.5-10 and PM10) may not have an impact on functional outcome after ischemic stroke.

Patients with diabetes constitute a substantial proportion of those with acute myocardial infarction (AMI) and exhibit distinct pathophysiological characteristics. However, existing guideline-recommended traditional and generic risk prediction models show limited performance in this specific population. Based on the China Acute Myocardial Infarction (CAMI) registry, 6,091 diabetic patients with AMI were enrolled and randomly divided into training and test sets (8:2). A comprehensive set of 62 multidimensional candidate features was extracted, and three feature selection strategies were applied to develop 12 machine learning models across six algorithm categories. All models underwent hyperparameter tuning via five-fold cross-validation in the training set, with the optimal combination selected according to the area under the receiver operating characteristic curve (AUROC). Two post-hoc ensemble strategies-stacking and probability averaging-were then employed to explore various combinations of top-performing models from different algorithm categories. Across six algorithm categories, the predictive models developed using 11 features selected by Elastic Net had the optimal performance. After evaluating various fusion strategies, the ensembled GLM + TabNet model was ultimately selected as the CAMI-DM model 2.0, achieving an AUROC of 0.875 in the test set. To balance the predictive performance and model simplicity, the CAMI-DM model 1.0 adopted a linear framework and was developed using five features from consensus feature selection Strategy, with an AUROC of 0.821 in the test set. Comparative analyses revealed that the CAMI-DM 2.0 outperformed CAMI-DM 1.0 in terms of discrimination, accuracy, calibration, and clinical net benefit. Furthermore, CAMI-DM 1.0, with its simplified structure, still outperformed the GRACE score in the overall predictive performance and generalizability. This study focused on the specific population of AMI patients with diabetes, and for the first time developed two dedicated models to predict in-hospital mortality risk.

BACKGROUND Top-of-the-basilar syndrome (TOBS) is a rare but clinically heterogeneous posterior circulation disorder characterized by acute ischemia affecting 2 or more territories supplied by the distal basilar artery, including the thalami, midbrain, occipital lobes, medial temporal lobes, and cerebellum. Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is an established treatment for eligible patients with TOBS, and reports of transient coma induced during rt-PA infusion remain exceedingly scarce. CASE REPORT A 77-year-old man with non-valvular atrial fibrillation and hypertension presented with transient visual hallucinations-initially diagnosed as a transient ischemic attack. Emergency head and neck computed tomography angiography revealed severe stenosis-occlusion of the left posterior cerebral artery P1 segment. Within 12 hours, he developed dysarthria and right hemiparesis, prompting intravenous thrombolysis with rt-PA (0.9 mg/kg). Fifty minutes after infusion, he experienced abrupt, self-limiting loss of consciousness, without evidence of intracranial hemorrhage on emergent computed tomography. Subsequent magnetic resonance imaging confirmed incomplete TOBS, showing acute infarcts in bilateral thalami, left hippocampus, and right cerebellar hemisphere. Magnetic resoance angiography demonstrated resolution of the prior P1 stenosis but new suspicious narrowing in the distal P2 segment. CONCLUSIONS This case suggests that the clinical symptoms of cardiogenic TOBS change rapidly and are diverse. This diversity can occur before and during intravenous thrombolytic therapy. If neurological deterioration occurs during the use of thrombolytic agents, it is necessary to promptly identify whether it is stroke progression or hemorrhagic transformation.