Free hemoglobin's release into CSF from blood breakdown is a primary instigator of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Early clearance of subarachnoid blood with intrathecal (IT) fibrinolytics has shown potential to decrease incidence of DCI. However, the dosage of fibrinolytic needed is not known. We investigated the ability of low dose tissue plasminogen activator (tPA) to rapidly remove subarachnoid clot.

We performed a single center retrospective review of aSAH patients who received IT tPA. Dosing consistent with the CLEAR III trial for IVH was utilized-tPA (1 mg) administered every 8 h via an external ventricular drain (EVD) for up to three doses. CT imaging was obtained before initiation and after the final dose. Subarachnoid clot was quantified using the Hijdra score on initial and follow-up scans. The IT tPA group was compared to a large retrospective cohort without IT tPA.

Eight aSAH patients received IT tPA treatment for the purpose of increasing blood removal after aSAH. CT imaging indicated that the Hijdra Score had a 70-100% reduction in all patients in the first 4 days with a mean 81.6% reduction compared to 41.3% reduction in a prior natural history cohort, p = 0.001. No ventriculitis or hemorrhagic complications were observed the treatment group. Clinical DCI and radiographic vasospasm was observed in two of the patients.

Low dose IT tPA delivered through an EVD after aSAH is sufficient to rapidly increase CSF blood clearance on CT imaging.

Heart failure with preserved ejection fraction (HFpEF) represents half of all HF diagnoses and is a growing public health concern. Despite therapeutic advancements, HFpEF contributes to substantial health care resource utilization (HCRU) and costs. Characterizing these measures and identifying potential associations in HFpEF is needed.

To characterize the HCRU and costs among the bottom 10th and top 90th percentiles of total health care cost, examine associations of belonging to the 90th percentile, and analyze trends over time.

We conducted a retrospective cohort study using the Merative MarketScan database to examine commercially insured adults diagnosed with HFpEF from 2014 to 2021. HCRU and costs were estimated using a Cox proportional hazards model and Kaplan-Meier sample average techniques, bootstrapping was applied to generate credible intervals. Predictors of high HCRU were identified using a multivariable logistic regression model.

We had 24,071 eligible participants. The HCRU among the 90th percentile possessed an annual incremental average of 13 emergency department/urgent care visits, 3 inpatient admissions, and 30 days in the hospital. Total health care costs of the 90th percentile were $378,880 higher on average than the 10th percentile. Both cohorts experienced the highest HCRU and costs the first month after diagnosis. Credible intervals of total costs from bootstrapping overlapped from 2014 to 2021. Baseline characteristics associated with the 90th percentile included female sex (odds ratio [OR] = 1.13; 95% CI = 1.1-1.2), a Charlson comorbidity index (CCI) score of 2 (OR = 3.28; 95% CI = 3.0-3.6), and a CCI score greater than 2 (OR = 18.81; 95% CI = 16.9-20.9). Comorbidities associated with the 90th percentile included atrial fibrillation (OR = 3.51; 95% CI = 2.8-4.4), loop diuretics (OR = 2.18; 95% CI = 2.0-2.4), angiotensin receptor-neprilysin inhibitor (OR = 1.89; 95% CI = 1.1-3.2), and sodium-glucose cotransporter-2 inhibitors (OR = 4.48; 95% CI = 3.0-6.7). Comorbidities associated with the 10th percentile included diabetes (OR = 0.53; 95% CI = 0.4-0.7), hypertension (OR = 0.71; 95% CI = 0.6-0.8), and chronic kidney disease (OR = 0.63; 95% CI = 0.4-0.9). Interactions indicating multiple comorbidities were significant.

Significant differences in HCRU exist between high- and low-cost patients with HFpEF. However, both groups experienced their highest utilization the first month after diagnosis. Total costs remained consistent from 2014 to 2022. Strategies to reduce the risk of HFpEF onset are essential for lowering health care expenditures. Future research is needed to examine the impact of access to newer therapies.

Chronic hypertension affects 1%-5% of pregnancies, increasing women's risks of adverse pregnancy outcomes and life-long cardiovascular disease risk. Therefore, care management during pregnancy includes close monitoring of blood pressure and medication. Healthy dietary and physical activity behaviors have proven beneficial effects on blood pressure outside and during pregnancy. However, little is known about the best way to support women with chronic hypertension during pregnancy to adopt such behaviors, which could improve pregnancy outcomes, as well as future cardiovascular health.

This study aims to develop and optimize a digital lifestyle intervention-the DAPHNY (Diet and Activity for Pregnancy Hypertension) app-with those who have experienced chronic hypertension during pregnancy.

Guided by the person-based approach to intervention development, a review of literature and continuous expert input, including from patient and public representatives, informed the planning stage. This was followed by focus groups with maternity health professionals (n=23) and think-aloud interviews with women who had experience of chronic hypertension during pregnancy (n=11). A content analysis, underpinned by theoretical modeling using the capability opportunity motivation-behavior model, informed 3 logic models to visualize modifications for meaningful engagement with an intervention and sustained behavior change. The intervention was modified iteratively, leading to a first version of the digital intervention that was tested by women (n=10) to further optimize acceptability and engagement. App use data and user engagement patterns were captured.

An evidence-based, theoretically informed lifestyle app, named DAPHNY, was developed. Key features included in logic models and implemented into a first version of the app comprised supportive messaging to acknowledge challenges of hypertensive pregnancy, goal setting and progress reports for feedback on behaviors, information about health consequences to shape knowledge, credible source endorsement, and a reward or recognition system to acknowledge effort had been made. Engagement with the DAPHNY app during user testing demonstrated variability across users, with a mean of 13 (SD 6.84) sessions per participant. Session duration was variable, with a median of 36 seconds (range: 5 seconds to 5 minutes, 20 seconds). Action-based pages, including recording blood pressure (40 sessions) and step count (39 sessions), were accessed more frequently than informational pages, which required a deeper level of app engagement.

Development of the DAPHNY app, underpinned by an established behavioral framework for developing digital interventions, provided new data insights about how to support women with chronic hypertension to engage in healthy behaviors, a currently overlooked aspect of blood pressure management. Future iterations should focus on increasing engagement and supporting implementation through streamlined content and integration with existing health systems and self-monitoring data. Rigorous, larger-scale studies including comprehensive process evaluation would determine potential clinical effectiveness, implementation strategies, and impact for women and health care professionals.

Antiplatelet drug (APD) therapy is the cornerstone for the prevention of atherosclerotic cardiovascular disease. The main APDs are aspirin and thienopyridines, particularly clopidogrel. These drugs may induce hypersensitivity reactions (HSRs). The most common reported reactions to these drugs are cutaneous, such as exanthemas associated with thienopyridine and urticaria/angioedema by aspirin, which can also induce respiratory symptoms. APDs other than aspirin, particularly ticlopidine, can also cause hematologic reactions consisting mainly of isolated thrombocytopenia, agranulocytosis, and leukopenia. Immune-mediated reactions to aspirin are very rare. Few data suggest the usefulness of skin testing in patients with cutaneous reactions to APDs other than aspirin, particularly clopidogrel. Therefore, the drug provocation test is the gold standard for diagnosing hypersensitivity to APDs. Low-dose aspirin challenge (i.e., up to 150-180 mg) and aspirin desensitization have emerged as effective and safe approaches in patients with suspected or confirmed aspirin hypersensitivity who require aspirin therapy. Both, a short course of oral glucocorticoids without interruption of clopidogrel treatment and desensitization, appears to be effective and safe options in patients with cutaneous HSRs to clopidogrel. This position paper provides data and recommendations regarding the characteristics of HSRs to APDs and related diagnostic procedures in order to make them as safe and effective as possible. Management and treatment options, including desensitization protocols, are also provided.

Monitoring lifestyle habits and physiological metrics are essential for improving cardiovascular outcomes and supporting recovery after acute cardiac events. Sleep is acknowledged as a core component of cardiovascular health and a predictive tool of adverse outcomes following acute myocardial infarction (AMI).

The present study aimed to assess sleep metrics and explore the links between sleep patterns, heart rate variability (HRV) parameters, and traditional cardiovascular risk factors in patients with AMI.

Sixty male patients with AMI (56.77 ± 8.24 years) participated in this study. Cardiac autonomic function was assessed with short-term HRV analysis during the second week post-AMI. Physical activity level was assessed using accelerometers. Sleep quality and quantity were evaluated objectively using a wrist-worn accelerometer and subjectively by the Pittsburgh Sleep Quality Index. Chronotype was evaluated with the Horne and Otsberg questionnaire.

Twenty post-AMI patients (33.3%) tended to experience poor sleep quality, with a sleep efficiency inferior to 85%. Thirty patients (50%) experienced short sleep duration, 16 (26.7%) had a healthy sleep duration (7-8 h), and 14 (23.3%) slept more than 8 h. Multiple regression analysis revealed that patients with healthy sleep quality and quantity exhibited higher HRV parameters, both in time and frequency domain values (p < 0.05). Low physical activity level was observed in patients with long sleep duration (p = 0.005) and evening chronotype (p = 0.022).

Patients who spent more time performing moderate to vigorous physical activity tended to exhibit good sleep health and increased parasympathetic activity which are considered cardioprotective after AMI.

PACTR202208834230748.

The introduction of non-vitamin K antagonist oral anticoagulant (NOAC) into clinical use heralds a new age for anticoagulation therapy in patients with atrial fibrillation (AF).However,anticoagulation-related bleeding is currently a major challenge in the anticoagulation process.Assessing the risk of anticoagulation-related bleeding is an important part for the management of patients with AF.Clinical risk factor scores have moderate ability to predict the risk of anticoagulation-related bleeding.To improve the anticoagulation safety of NOACs,additional clinical and biological markers and genetic polymorphisms should be considered to enhance the predictive capability for anticoagulation-related bleeding.This review summarizes the challenges in the management of anticoagulation therapy,with emphases on the bleeding risk scores,biomarkers,clinical indicators,and genetic loci currently used to guide the risk assessment of anticoagulation-related bleeding in AF patients.This review is expected to provide research insights and reference frameworks for predicting and evaluating the bleeding risk associated with NOACs.

Objective To identify disulfidptosis-related gene(DRG)in acute myocardial infarction(AMI)by bioinformatics,analyze the molecular pattern of DRGs in AMI,and construct a DRGs-related prediction model.Methods AMI-related datasets were downloaded from the Gene Expression Omnibus database,and DRGs with differential expression were screened in AMI.CIBERSORT method was used to analyze the immune infiltration.Based on the differentially expressed DRGs,the AMI patients were classified into distinct subtypes via consensus clustering,followed by immune infiltration analysis,differential expression analysis,gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis,and gene set variation analysis.Weighted gene co-expression network analysis(WGCNA)was then performed to construct subtype-associated modules and identify hub genes.Finally,least absolute shrinkage and selection operator,random forest,and support vector machine-recursive feature elimination were used to screen feature genes to construct a DRGs-related prediction model.The model's diagnostic efficacy was evaluated by nomogram and receiver operating characteristic(ROC)curve analysis,followed by external validation.Results Nine differentially expressed DRGs were identified between AMI patients and controls.Based on the expression levels of these nine DRGs,AMI patients were divided into two DRGs subtypes,C1 and C2.Increased infiltration of monocytes,M0 macrophages,and neutrophils was observed in AMI patients and C1 subtype(all P<0.05),indicating a close correlation between DRGs and immune cells.There were 257 differentially expressed genes between the C1 and C2 subtypes,which were related to biological processes such as myeloid leukocyte activation and positive regulation of cytokines.Fcγ receptor-mediated phagocytosis and NOD-like receptor signaling pathway activity were enhanced in C1 subtype.WGCNA analysis suggested that the brown module exhibited the strongest correlation with DRG subtypes(r=0.67),from which 23 differentially expressed genes were identified.The feature genes screened by three machine learning methods were interpolated to obtain a DRGs-related prediction model consisting of three genes(AQP9,F5 and PYGL).Nomogram and ROC curves(AUC_train=0.891,AUC_test=0.840)showed good diagnostic efficacy.Conclusions DRGs were closely related to the occurrence and progression of AMI.The DRGs-related prediction model consisting of AQP9,F5 and PYGL may provide targets for the diagnosis and personalized treatment of AMI.

Congenital hyperinsulinism (CHI) is a rare but significant cause of persistent neonatal hypoglycemia. While Central Venous Catheters (CVCs) are a known major risk factor for thrombosis in neonates, the evidence linking CHI, catheter use, and thrombotic risk remains limited. This study investigates the prevalence of thrombosis in CHI patients and explores potential contributing factors, such as CVC insertion and infection.

A retrospective cohort study was conducted on 67 patients under 14 years of age who were diagnosed with CHI and treated at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, between 2014 and 2024. Clinical, genetic, and imaging data were analyzed, and associations between thrombosis and risk factors were assessed using univariable analysis.

Of the 67 patients with CHI, 53.7% were female, with a median age at CHI diagnosis of 3 weeks. Genetic analysis revealed ABCC8 mutations as the most frequently identified genetic variant (58.2%). CVCs were used in 61 cases (91.0%), with thrombosis developing in 18.0% of those with CVCs, mostly affecting the vena cava and portal vein. All thrombosis cases were treated with enoxaparin; 63.6% of patients experienced mild, transient complications, including elevated liver enzymes, prolonged partial thromboplastin time (PTT), and thrombocytopenia. A statistically significant association was found between infection and thrombosis (p = 0.001), but no significant correlation was found between specific genetic mutations and thrombosis risk (p > 0.05).

These findings underscore the importance of recognizing thrombosis as a potential complication in patients with CHI undergoing CVC placement. Although most cases were successfully managed, early screening and preventive strategies should be considered to minimize thrombotic complications. Future research should focus on optimizing thromboprophylaxis and evaluating additional contributing factors to refine management strategies and improve patient outcomes.

Aging has a profound impact on the pathophysiology of ischemic stroke and the effectiveness of therapeutic interventions. This study aims to evaluate the therapeutic efficacy of programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) in modulating immune responses and neurovascular repair following ischemic stroke, with a focus on age-dependent differences.

Young and aged mice were subjected to middle cerebral artery occlusion (MCAO) followed by PD-L1 mAb treatment. RNA sequencing, immunofluorescence, and molecular analyses were employed to assess immune modulation, blood-brain barrier (BBB) integrity, and functional recovery.

RNA sequencing revealed significant differential gene expression in ischemic brain tissues, with CD274 (PD-L1) prominently upregulated among immune checkpoint-related genes in young mice. Immunofluorescence confirmed PD-L1 expression in microglia/macrophages, with significantly higher upregulation in young mice. PD-L1 mAb treatment showed superior efficacy in young mice, significantly reducing infarct volume, enhancing neurological recovery, and preserving BBB integrity through greater upregulation of tight junction proteins such as ZO-1, Claudin-5, and Occludin compared to aged mice. It also more effectively reduced neuroinflammation, apoptosis, and pro-inflammatory cytokines (TNF-α, IL-1β), eliciting stronger spleen responses in young mice. These findings underscore the age-dependent advantages of PD-L1-targeted therapies for ischemic stroke recovery.

PD-L1 plays a critical role in ischemic stroke recovery, with PD-L1 mAb treatment demonstrating age-dependent therapeutic efficacy by enhancing BBB integrity, reducing neuroinflammation and apoptosis, and modulating peripheral immune responses.

Carotid artery stenosis increases the risk of ischemic stroke, with carotid endarterectomy (CEA) and carotid artery stenting (CAS) as primary interventions. Age-related vascular changes may contribute to complications. This study aimed to evaluate the impact of age-related vascular changes on postoperative complications and procedural outcomes.

A retrospective cohort of 470 patients who underwent CAS or CEA from January 2020 to November 2021 was analyzed. Demographics, anatomical characteristics, and postoperative complications were assessed. Correlation, regression analyses, and machine learning models were applied to identify predictors of adverse outcomes.

Postoperative complications occurred in 64.9% of CAS and 75.2% of CEA patients. Older age correlated with larger CCA diameter, shorter clavicle-to-bifurcation distance, and increased tortuosity of both CCA and ICA. Several age-related anatomical changes were significantly linked to higher complication rates in both procedures. In CAS, key predictors included symptomatic stenosis, aortic arch variation, CCA ostial lesions, and CCA diameter (p < 0.05). A logistic regression model predicted CAS complications effectively (AUC = 0.82).

This study highlights significant age-related changes in carotid artery anatomy and their impact on postoperative complications. These findings underscore the importance of considering age-related vascular remodeling to enhance patient selection and optimize surgical outcomes.