Ras-associated autoimmune leukoproliferative disorder (RALD) is a rare, nonmalignant condition characterized by monocytosis, lymphoproliferation, and autoimmunity, driven by KRAS or NRAS variants. Immune thrombotic thrombocytopenic purpura (iTTP) results from autoantibodies against ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13).

Can RALD co-occur with iTTP, and how can it be diagnosed?

A patient presenting with neutropenia, monocytosis, and thrombocytopenia was initially diagnosed with chronic myelomonocytic leukemia. She later developed splenomegaly, lymphadenopathy, and iTTP. Reevaluation identified a somatic KRAS G12A variant in peripheral blood, prompting a diagnosis of RALD. Flow cytometry demonstrated immunophenotypic changes involving B cells, T cells, and monocytes. The patient had four ADAMTS13 relapses, responsive to rituximab.

This case highlights co-occurrence of RALD and iTTP, extending the spectrum of Ras-associated autoimmune cytopenias.

Sexual function can be negatively affected in individuals with congenital bleeding disorders (CBDs). Patient-reported outcome measures can provide insight into patients' experiences and help address sexual function and sexual satisfaction in clinical care.

This study evaluates the measurement properties of a selection of PROMIS Sexual Function and Satisfaction (PROMIS SexFS) measures in adults with CBDs and describes the outcomes.

In this cross-sectional multicenter study, men with hemophilia and women with hemophilia or von Willebrand disease were invited to participate. Six screener items, 12 measures from the PROMIS SexFS, and disease-specific items on sexual function and satisfaction were completed. Reliability was evaluated using standard error of T-scores. Internal consistency was evaluated using item-total correlation. Known-group validity was examined by testing predefined hypotheses. Feasibility was evaluated using percentage of lowest and highest scores, and relevance was evaluated qualitatively. Lastly, PROMIS T-scores were compared with reference data from the Dutch general population using independent samples t-test.

Data from 231 patients (mean age 44 years, range 18-81 years; 54% male) were collected. For all measures, >78% met the reliability criterion. Internal consistency and feasibility were sufficient, and known-group validity was supported. Compared with reference data, patients reported greater orgasm pleasure (d = 0.23) and more interest in sexual activity (d = 0.19). Males reported better erectile function (d = 0.26), while females reported more vaginal discomfort with sexual activity (d = 0.48).

The Dutch PROMIS SexFS measures showed sufficient reliability and validity for assessing sexual function and satisfaction in individuals with CBDs. It can inform research and support clinical discussions.

Frailty predicts poor outcomes in older adults with cardiovascular disease (CVD) and is closely related to neuromuscular dysfunction. Lower limb surface electromyography (sEMG) during walking may capture frailty-related motor alterations, but its characteristics and discriminative value in older adults with CVD remain unclear. This study aimed to compare lower limb sEMG features between frail and nonfrail older adults with CVD and evaluate their ability to identify frailty.

This case-control study included 150 older adults with CVD (75 frail, 75 nonfrail; 80 men, 70 women). Frailty was defined using the Fried frailty phenotype. Wireless sEMG signals were recorded bilaterally from the rectus femoris, semitendinosus, tibialis anterior and medial gastrocnemius during a standardized 10-m walk test. Time-domain parameters, frequency-domain parameters, symmetry indices, contribution ratios and activation-sequence rank were compared with false-discovery-rate correction. Binary logistic regression and receiver operating characteristic (ROC) analysis were used to identify factors independently associated with frailty and evaluate discriminative performance.

Frail participants were older (76.04 ± 7.57 vs. 68.55 ± 6.09 years), more frequently exposed to polypharmacy (93.33% vs 70.67%), required longer to complete the 10-m walk test (13.34 ± 3.23 vs. 9.44 ± 1.21 s) and had lower Tinetti Performance-Oriented Mobility Assessment (POMA) scores (21.51 ± 4.27 vs. 27.59 ± 0.92; all p < 0.001). The frail group showed higher median integrated EMG (IEMG) of the left semitendinosus (534.4 [451.3, 680.7] vs. 455.5 [384.5, 542.0] μV·s, FDR-adjusted p = 0.0084) and higher activation-sequence rank of the left rectus femoris (4.333 [3.000, 5.667] vs. 3.333 [2.333, 4.333], FDR-adjusted p = 0.0404). In the frequency domain, median frequency (MF) was higher in the right rectus femoris, bilateral tibialis anterior and right medial gastrocnemius, whereas mean power frequency (MPF) was higher in six muscles (all FDR-adjusted p < 0.05). In multivariable analysis, MF of the right rectus femoris (OR = 1.067, 95% CI 1.003-1.135, p = 0.038), MF of the right medial gastrocnemius (OR = 1.054, 95% CI 1.009-1.102, p = 0.019), activation-sequence rank of the right tibialis anterior (OR = 0.640, 95% CI 0.448-0.914, p = 0.014), age (OR = 1.128, 95% CI 1.044-1.218, p = 0.002) and Tinetti POMA score (OR = 0.784, 95% CI 0.669-0.918, p = 0.003) were independently associated with frailty. The sEMG + age model achieved an area under the curve (AUC) of 0.8418 (sensitivity = 0.8933; specificity = 0.6400), approaching the full model including Tinetti POMA score (AUC = 0.8740; sensitivity = 0.9200; specificity = 0.7067).

Lower limb sEMG features during walking were independently associated with frailty in older adults with CVD. The simplified sEMG + age model showed good discriminative performance and may provide candidate objective markers to complement conventional frailty assessment.

Cerebrovascular endothelial function can be assessed by measuring the shear-mediated dilation or cerebrovascular reactivity (CVR) of the internal carotid artery (ICA) in response to transient hypercapnia (30 s). ICA CVR is blunted with aging; however, it is not known whether age-related reductions in ICA CVR are influenced by antioxidant-responsive mechanisms. The purpose of this study was to determine whether infusion of the antioxidant, ascorbic acid (AA) restores ICA CVR in middle-aged and older (MA/O) adults. We also examined the effect of AA on middle cerebral artery (MCA) CVR to sustained (3-min) hypercapnia. We hypothesized that MA/O adults would exhibit lower cerebrovascular function compared to young (Y) adults, and that infusion of AA would improve cerebrovascular function in MA/O adults, whereas infusion of saline (SAL) would not. The primary analytic sample included nine Y adults (25 ± 2 years) and nineteen (65 ± 6 years) MA/O adults, with analyzable data varying by outcome. ICA CVR was measured using high-resolution duplex ultrasound, and MCA CVR was measured using transcranial Doppler ultrasound. AA infusion improved ICA CVR and MCA CVR in MA/O adults but had no effect in Y adults. These findings suggest that age-related impairments in cerebrovascular function may be partly attributable to mechanisms responsive to acute, supraphysiological AA administration.

Cardiovascular reserve represents the integrated physiological capacity of the cardiovascular system to maintain tissue perfusion during increasing physiological stress. Although reserve has long been recognized conceptually, its direct assessment remains challenging. No universally accepted definition or gold-standard measure of cardiovascular reserve currently exists. Nevertheless, if cardiovascular reserve can be estimated reliably, reserve-based monitoring could permit earlier recognition of impending circulatory deterioration before conventional physiological indicators become abnormal. Among the reserve-monitoring technologies currently under investigation, the Compensatory Reserve Metric (CRM) and the Cardiovascular Reserve Index (CVRI) represent two distinct approaches to estimating remaining cardiovascular reserve. This review examines the physiological basis of reserve-based monitoring, critically evaluates the available experimental and clinical evidence supporting CRM and CVRI, assesses their strengths and limitations and outlines priorities for future research and potential clinical applications. CRM has demonstrated strong performance in experimental haemorrhage models and remains the most extensively studied reserve-monitoring technology in low output conditions. Although evidence supporting CVRI is more limited, findings from cardiopulmonary exercise testing, haemorrhage and heat stress suggest that it may reflect progressive depletion of cardiovascular reserve across diverse forms of circulatory and physiological stress. Although seemingly promising, current evidence remains limited by small clinical cohorts, heterogeneous study designs and limited independent validation.

To examine the mediating role of cardiac self-efficacy in the relationship between patient empowerment and medication adherence among patients with coronary artery disease (CAD) and to identify which empowerment sub-dimensions are most prominent.

A cross-sectional correlational study.

A convenience sample of adults attending a cardiology clinic completed validated versions of the Coronary Artery Disease Empowerment Scale (CADES), Cardiac Self-Efficacy Scale and Morisky Medication Adherence Scale. Data were analysed using Spearman's correlations, ordinal logistic regression and path analysis with bootstrap mediation testing.

Positive correlations were found among empowerment, self-efficacy and adherence. Regression analysis showed that cardiac self-efficacy predicted adherence, while empowerment did not directly predict adherence. Path analysis confirmed that self-efficacy mediates the empowerment-adherence relationship. The self-determination subscale of empowerment was the strongest predictor of self-efficacy, whereas personal competence was not significant.

Patient empowerment enhances medication adherence indirectly by building cardiac self-efficacy, primarily through fostering patient autonomy rather than merely providing knowledge.

Nurse-led strategies should target cardiac self-efficacy. Motivational interviewing and autonomy-supportive interventions may be more effective than traditional education.

What problem did the study address? The study addressed the gap in understanding the nurse-led interventions that translate patient empowerment into actual medication adherence behaviours. What were the main findings? Self-efficacy acts as the essential bridge between empowerment and adherence and this bridge is built most effectively through self-determination rather than personal competence. Where and on whom will the research have an impact? These results will impact clinical nurses, nurse educators and healthcare professionals involved in cardiac care by highlighting that nurse-led counselling strategies and autonomy-supportive interventions may be more effective for improving medication.

We adhered to the STROBE guidelines.

No Patient or Public Contribution.

Cardiovascular diseases (CVDs) are a leading global cause of mortality and disease burden, closely associated with the remodeling of myocardial energy metabolism. Acylcarnitines (Acs) are key intermediates in the carnitine shuttle and fatty acid β-oxidation (FAO) processes. They play a critical role in transporting long-chain fatty acids across the mitochondrial membrane, maintaining the intracellular acyl-CoA/CoA balance, and buffering metabolic flux. Recent metabolomics studies have demonstrated significant abnormalities in acylcarnitine profiles across various cardiac diseases, including coronary artery disease, ischemia-reperfusion injury, heart failure, diabetic cardiomyopathy, and arrhythmias. These abnormalities are closely correlated with disease severity, metabolic disturbances, and poor clinical prognosis. Mechanistically, the pathological accumulation of long-chain acylcarnitines triggers lipotoxicity, exacerbates mitochondrial oxidative stress, and impairs calcium homeostasis, which collectively drive inflammation and cardiomyocyte apoptosis. This review systematically summarizes the physiological roles of the carnitine shuttle, explores the underlying mechanisms of acylcarnitine-induced cardiac injury, and highlights their translational potential as promising diagnostic biomarkers and novel therapeutic targets for cardiovascular metabolic interventions.

Patients with acute myocardial infarction are found to have layered plaque in the culprit lesion site during optical coherence tomography, indicating that these patients have experienced recurrent thrombotic events locally. Whether inflammation factors are associated with this phenomenon remains unknown.

A total of 125 patients with acute myocardial infarction who underwent coronary angiography followed by optical coherence tomography were prospectively enrolled. 17 patients were excluded due to various reasons. Peripheral blood samples were collected from all patients, and blood samples from the culprit vessel were collected during thrombus aspiration in a subset. All optical coherence tomography images of the culprit vessels were analyzed as well as quantitative coronary angiography. The mRNA expression of IL-1β, IL-4, IL-8, IL-10, IL-18, ELANE, MPO in monocytes of both peripheral and culprit lesion blood samples were analyzed.

Of the 108 eligible patients, 56 (51.9%) had layered plaque at the site of the culprit lesion. Clinical characteristics and quantitative coronary angiography showed no significant difference between the layered plaque and non-layered plaque groups. Layered plaque group had greater mean lipid arc (304.23° [284.52, 330.80] vs 288.16° [256.00, 311.00], p=0.047). Peripheral blood samples revealed no difference in any inflammatory factors expression, however, higher mRNA expression level of IL-1β in culprit lesion blood was observed in layered plaque group, with a mean difference of 1.81 (95% BCa CI [0.66, 3.10], p =0.023). Firth's penalized likelihood logistic regression analysis showed that mRNA expression level of IL-1β was significantly associated with layered plaque (OR, 1.78, 95% CI, 1.16-3.29, p=0.005) after adjusting for age and sex. ROC analysis demonstrated that IL-1β yielded an AUC of 0.781 (95% CI: 0.637-0.924) for predicting layered plaque.

IL-1β was expressed more in the culprit vessel in patients whose culprit lesion showed layered plaque, proving that local IL-1β is associated with layered plaque.

Chronic limb-threatening ischemia (CLTI), a severe manifestation of peripheral artery disease, is particularly prevalent among patients receiving maintenance hemodialysis (HD) and is associated with poor limb and survival outcomes. Low-density lipoprotein (LDL) apheresis, including Rheocarna, is used as adjunctive therapy for refractory CLTI; however, intraprocedural hypotension remains a major limitation, especially when combined with HD. We examined the effects of dialyzer membrane type and extracorporeal circuit sequence on hemodynamic stability during concomitant therapy. This case series comprised two patients with CLTI receiving maintenance HD. Each patient underwent four treatment sessions representing the four configurations defined by two dialyzer membranes (polysulfone [PS] and AN69) and two circuit sequences (Rheocarna → dialyzer vs. dialyzer → Rheocarna). Hemodynamic parameters, including systolic blood pressure, relative blood volume change (ΔBV), and peripheral microvascular perfusion assessed by laser Doppler flowmetry (ΔLDF), were assessed during each treatment session. In both cases, the Rheocarna → AN69 configuration showed the smallest early decrease in systolic blood pressure and the most favorable early ΔBV pattern among the four sessions. Toe ΔLDF was preserved or increased with this configuration. The other three configurations were associated with larger early decreases in systolic blood pressure in one or both patients, including a decrease to below 90 mmHg in Case B. These findings suggest that dialyzer membrane type and circuit sequence may influence intraprocedural hemodynamic stability during concomitant Rheocarna therapy and HD. Among the tested configurations, Rheocarna → AN69 showed better hemodynamic tolerance and preservation of peripheral perfusion. These hypothesis-generating findings warrant further evaluation in larger prospective studies.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide; however, effective clinical therapies that achieve myocardial regeneration are still lacking, underscoring the urgent need for novel therapeutic strategies. In this study, we identified an RNA-binding protein Ptbp1, a key component of RNA metabolism, as a critical regulator of cardiomyocyte proliferation via the formation of biomolecular condensates. We found that Ptbp1 exhibits granule-like structures in cardiomyocyte nuclei during fetal to early postnatal stages. These Ptbp1 foci are phase-separated liquid droplets formed via its multivalent RNA binding domains. Functional analyses revealed that Ptbp1 is essential for cardiomyocyte proliferation in neonatal mouse primary culture assays. Furthermore, proximity labeling using a primary antibody-based approach combined with RIP-seq in highly purified cardiomyocyte populations demonstrated that these condensates are enriched with multiple proliferation-associated factors. Our findings identify a novel phase-separated condensate in cardiomyocytes and provide a new potential therapeutic target for cardiac regeneration.