BACKGROUND Acquired hemophilia A (AHA) is a rare but potentially life-threatening condition caused by autoantibodies against factor VIII. It often presents in older adults and its presentation can range from isolated lab abnormality of prolonged activated partial thromboplastin time (aPTT) without bleeding to mild bleeding or spontaneous vs disproportionate life-threatening bleeding. Delayed diagnosis is frequent due to the rarity of the condition and propensity to attribute bleeding to other common causes, such as falls. CASE REPORT A 92-year-old woman with recurrent ground-level falls presented with severe right lower extremity pain of several weeks' duration. She was not on any anticoagulant or anti-platelet agent. Computed tomography angiography demonstrated bilateral lower extremity intramuscular hematomas. She had 2 prior admissions for falls within 6 months, including a fall leading to intramuscular hematoma, which was conservatively managed without evaluation of coagulopathy. During current admission, prolonged aPTT prompted further workup, revealing low factor VIII activity of 5% and a high factor VIII inhibitor titer of 15.6 Bethesda Units, establishing the diagnosis of acquired hemophilia A. Bleeding control required sequential bypassing agents, corticosteroids, rituximab, cyclophosphamide, and eventually emicizumab. CONCLUSIONS This case highlights how recurrent or disproportionate intramuscular hematomas following even minor trauma, such as a ground-level fall, in the absence of risk factors such as anticoagulant use, may prompt evaluation for underlying coagulopathy such as AHA. Basic coagulation testing including prothrombin time and aPTT can help screen patients who warrant additional coagulopathy evaluation. Timely diagnosis is critical to avoid life-threatening bleeding complications.

Epilepsy, a prevalent chronic neurological disorder, has significant neurobiological, cognitive, psychological, and social implications. The American Heart Association (AHA) introduced Life's Essential 8 as a key metric for assessing cardiovascular health. This study aims to investigate the association between Life's Essential 8 and epilepsy prevalence, offering population-level evidence on the potential clinical and public health relevance of cardiovascular health in individuals with epilepsy. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018. A cross-sectional design was used, and logistic regression models, subgroup analyses were utilized to assess the association between LE8 and the prevalence of epilepsy. Restricted cubic splines were utilized to examine the nonlinear correlations. A total of 9408 participants were included in the study. After adjusting for potential confounding factors, LE8 showed a significant inverse association with the odds of epilepsy (odds ratio = 0.98, 95% confidence interval [CI]: 0.96-0.99). Restricted cubic spline analysis revealed a linear relationship between LE8 and the odds of epilepsy (P for nonlinearity = .658). Further analysis indicated that the diet score was significantly inversely associated with the odds of epilepsy (odds ratio = 0.99, 95% CI: 0.98-0.99). Subgroup analysis showed no significant interaction between confounding factors and LE8 on the odds of epilepsy (all interaction P values > .05). Higher LE8 scores were independently associated with lower odds of epilepsy. Despite the modest effect size, these findings suggest potential clinical and public health implications, highlighting the importance of promoting cardiovascular health behaviors, particularly dietary improvements, in relation to epilepsy prevalence.

The 2026 ACC/AHA Multisociety Guideline marks a major shift in dyslipidemia management, extending the traditional LDL-C-centered approach to include non-HDL-C, ApoB, lipoprotein(a), triglyceride-rich lipoproteins, inherited lipid disorders, and severe hypertriglyceridemia. The introduction of PREVENT-ASCVD, the renewed use of explicit lipid targets, and the structured integration of risk enhancers and coronary artery calcium support a more individualized approach to cardiovascular prevention. This review critically examines the guideline's main innovations, with particular attention to the distinction between recommendations supported by cardiovascular outcome evidence and those relying mainly on observational data, surrogate endpoints, or extrapolation. It also compares the US framework with the 2025 ESC/EAS Focused Update, highlighting growing agreement on LDL-C goals but persistent differences in risk estimation, imaging, biomarkers, and treatment pathways. Finally, we discuss unresolved issues involving implementation, adherence, access, cost, health equity, inclisiran outcomes, and emerging lipoprotein(a)-lowering therapies. The guideline's impact will depend on translating greater precision into timely, feasible, and equitable care.

Background/Aims: Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and is a risk factor for stroke. Our previous studies demonstrated that adipocyte-derived exosomes (Ad-EXs) mediate adipose-brain communication. This study investigated the effects of hyperglycemic subcutaneous and visceral Ad-EXs on brain microvascular endothelial cell (BMEC) dysfunction during ischemic injury. Hypothesis: Hyperglycemic Ad-EXs exacerbate stroke injury via inducing oxidative stress and lipid peroxidation in BMECs. Methods: EXs were isolated from primary human subcutaneous and visceral adipocytes cultured in normal glucose (NG): NG-S-Ad-EXs and NG-V-Ad-EXs, or high-glucose (HG, 25 mM) media: HG-S-Ad-EXs and HG-V-Ad-EXs by ultracentrifugation and characterized by a nanoparticle tracking analysis system. PKH26-labeled Ad-EXs were used to evaluate uptake mechanisms in human BMECs (HBMECs). Functional effects were assessed in hypoxia/reoxygenation (H/R)-injured HBMECs treated with different Ad-EXs. Oxidative stress and lipid peroxidation markers (NOX2/4, MDA, 4-HNE, and GPX4) were analyzed. Results: HG increased Ad-EX release from both adipocyte depots. HG-derived Ad-EXs increased HBMEC cytotoxicity and permeability while reducing angiogenesis after H/R injury. Mechanistically, HG-Ad-EXs promoted oxidative stress through increased NOX2/4 and lipid peroxidation via elevated MDA/4-HNE and reduced GPX4 expression. Conclusions: Hyperglycemic Ad-EX triggered oxidative stress via NOX2/4 and lipid peroxidation via MDA/4HNE/GPX4, leading to impaired HBMEC functioning, which was exacerbated in the H/R injury condition.

Glycosaminoglycans (GAGs) are structurally diverse polysaccharides that regulate inflammation, coagulation, and cellular homeostasis through highly specific sulfation patterns and interactions with cationic proteins. Among GAG derivatives, 2-O, 3-O desulfated heparin (ODSH) is a chemically modified heparin derivative characterized by markedly reduced anticoagulant activity yet preserved affinity for key inflammatory mediators. This review summarizes current knowledge on ODSH structure-function relationships, molecular mechanisms, and therapeutic applications across inflammatory, vascular, and immune-mediated diseases. ODSH modulates several convergent pathogenic processes, including HMGB1-RAGE/TLR4 signaling, neutrophil elastase-mediated tissue injury, PF4-dependent platelet activation, selectin-mediated adhesion, and thrombin-induced endothelial permeability. These actions arise from both direct molecular interactions and indirect sequestration of extracellular mediators, collectively associated with reduced cytokine release, enhanced endothelial barrier stability, and attenuation of inflammation-coagulation crosstalk. Preclinical studies report protective effects in acute lung injury, cystic fibrosis, ischemia-reperfusion injury, traumatic brain injury, thrombocytopenia, and metastatic cancer. Some pilot clinical observations in acute myeloid leukemia and septic peritonitis have reported favorable biological effects. Despite multimodal activity, limitations include incomplete pharmacokinetic characterization, limited comparative studies with other desulfated heparins, and the need for dose-response and safety evaluation in human trials. Overall, available evidence suggests that ODSH may have therapeutic relevance in diseases characterized by excessive inflammation, endothelial dysfunction, and dysregulated host responses. This review integrates current evidence to guide future mechanistic and translational investigation into ODSH and related low-anticoagulant heparin derivatives.

Heart failure with preserved ejection fraction (HFpEF) predominantly affects older individuals with multiple comorbidities. Although mitochondrial dysfunction appears to be a major contributor to diastolic dysfunction, the mechanisms underlying it during HFpEF remain unclear. We used a clinically relevant two-hit HFpEF model in aged mice to investigate remodeling of cardiomyocyte mitochondrial proteins and to determine whether mitochondrial dysfunction reflects impaired biogenesis or defective mitochondrial proteostasis. HFpEF was induced in aged (15-month-old) male and female mice using a high-fat diet combined with chronic nitric oxide synthase inhibition (L-NAME). This model recapitulated key features of human HFpEF, including preserved ejection fraction with diastolic dysfunction and impaired cardiac reserve in both sexes. Consistent with impaired energy reserve, mitochondrial respiratory capacity measured by high-resolution respirometry (Oroboros) was significantly reduced in left ventricular muscle fibers. To examine cardiomyocyte-intrinsic mechanisms, mitochondria were isolated from cardiomyocytes using Langendorff perfusion and analyzed by proteomics and pathway enrichment analysis. Proteomic profiling revealed broad suppression of mitochondrial proteins that support oxidative metabolism and organelle maintenance, including those involved in oxidative phosphorylation, carbohydrate metabolism, and the TCA cycle. In contrast, key regulators of mitochondrial biogenesis were preserved. Notably, mitochondrial chaperones and proteases for protein quality control were reduced, leading to increased accumulation of ubiquitinated mitochondrial proteins and impaired mitochondrial proteostasis. Together, these findings indicate that mitochondrial dysfunction in a 3-hit HFpEF model is characterized by reduced respiratory capacity and impaired mitochondrial proteostasis, rather than defective biogenesis, suggesting that impaired mitochondrial protein quality control may contribute to reduced cardiac reserve in HFpEF.

This review aims to summarize migraine attack triggers and understand variance across lifestyles, religions, and regions.

Statins, ezetimibe, and PCSK9 inhibitors have enabled LDL-cholesterol to be lowered to levels previously thought very hard to achieve. However, even after achieving low levels, some patients continued to have cardiovascular events, a phenomenon known as residual cardiovascular risk. This phenomenon indicates the complexity of atherosclerosis, not limited to a simple LDL-driven process. Vascular inflammation persists even in the presence of well-controlled lipids and is largely mediated by the NLRP3-interleukin-1β-interleukin-6 signaling pathway, which has been shown to be a viable therapeutic target in the CANTOS, COLCOT, and LoDoCo2 trials. Triglyceride-rich lipoproteins and remnant cholesterol accumulate in the arterial intima and drive atherogenesis independent of LDL-C, with icosapent ethyl showing meaningful cardiovascular benefit in the REDUCE-IT trial. Apolipoprotein B reflects the true number of circulating atherogenic particles that LDL-C alone fails to identify, especially in patients with metabolic disease. Lipoprotein(a) is an inherited risk factor that statins barely affect, and it carries a well-established association with myocardial infarction, stroke, and aortic stenosis; RNA-based therapies targeting it are now in late-stage trials. The 2026 ACC/AHA Dyslipidemia Guideline now carries a Class I recommendation for universal Lp(a) measurement at least once in all adults. Impaired HDL function, insulin resistance, and a prothrombotic environment provide further risk. GLP-1 receptor agonists and SGLT2 inhibitors have emerged as important contributors to residual cardiovascular risk reduction in patients with metabolic dysfunction, showing consistent cardiovascular benefit on top of their background of statin therapy, with mechanisms that extend far beyond glycemic control. Coronary imaging, such as coronary calcium scoring and coronary CT angiography, can identify high-risk plaque features that persist despite aggressive lipid-lowering. Taken together, these findings make the case that LDL-C treatment is important but incomplete. A more comprehensive approach is required to meaningfully reduce the residual risk, one that considers apoB, remnant cholesterol, inflammation, lipoprotein(a), and metabolic risk.

A patient with relapsed acquired hemophilia A (AHA), who previously failed multiple lines of immunosuppressive therapy (IST) including autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy received teclistamab, a bispecific monoclonal antibody engaging autologous CD3-positive T cells with the B cell maturation antigen (BCMA) on plasma cells and mature B cells. Teclistamab was well tolerated without clinically significant adverse events, except for hypogammaglobulinemia. Prompt and durable remission was observed that lasted for more than one year post treatment. This is the first case of refractory AHA successfully treated with teclistamab, providing a proof-of-concept of plasma cell-directed bispecific antibodies, supporting its further evaluation.

There has been an increase in studies using Aha! ratings to explore insight in creative problem solving. Aha! moments are often assumed to serve as a marker for insight-meaning that solutions are achieved via restructuring. However, similar to metacognitive paradigms that collect FOKs (Feelings of Knowing) or JOLs (Judgments of Learning) and JOUs (Judgments of Understanding) to track monitoring of memory, learning, and comprehension processes, Aha! ratings may be better considered as "Judgments of Aha!" or JOAs derived from an inferential process based on a variety of cues. Only some of these may directly reflect underlying problem-solving processes. Using a set of spatial object-move puzzles, this study explored JOAs and how they may vary (or fail to vary) with initial fixation, correct solution, and individual differences in growth mindset. Instead of JOAs being highest for solutions where an initial representation needed to be revised, they were highest for solutions where solvers made a correct first move. This suggests that Aha! experiences are more closely tied to achieving correct solutions than to restructuring processes. Individuals with a stronger growth mindset were more likely to associate these initially correct solutions with Aha! experiences.

The 2026 ACC/AHA Multisociety Dyslipidemia Management Guideline emphasizes the clinical utility of coronary artery calcium (CAC) and recommends integrating incidental CAC from non-ECG-gated chest CT into cardiovascular risk-stratification workflows; nevertheless, such incidental findings remain substantially underutilized in routine clinical practice. Many young-to-middle-aged patients present with acute myocardial infarction as their index cardiovascular event, even though prior chest CT could identify CAC that would trigger statin-based primary prevention. This single-center retrospective observational study enrolled 976 patients undergoing invasive coronary angiography (CAG) who had non-ECG-gated chest CT within the preceding 1 year (2020-2025) to assess cross-sectional associations between incidental CAC burden and angiographic coronary stenosis. CAC burden was categorized as Grade 0-3 using the validated Shemesh ordinal scoring system, with 79.2% of participants being CAC-positive. CAC positivity and obstructive CAD prevalence increased progressively with age. CAC positivity was associated with higher conditional odds of obstructive CAD among younger individuals, while this conditional risk signal was attenuated in older adults. CAC grade showed a step-wise positive correlation with stenosis severity. Following adjustment for age, sex, hypertension, diabetes mellitus, dyslipidemia, and smoking status, CAC was identified by multivariate regression as the strongest independent predictor of obstructive CAD (OR = 11.732, 95% CI: 7.700-17.875, p < 0.001). Among CAD patients, CAC-negative subjects had higher diabetes prevalence, in keeping with the propensity for non-calcified vulnerable plaques in diabetic individuals. Incidental CAC on routine chest CT represents a robust age-modulated biomarker for obstructive CAD, and considerable primary-prevention opportunities are missed in Chinese patients referred for CAG. Opportunistic age-stratified CAC screening assisted by artificial intelligence may improve real-world cardiovascular primary prevention.