ObjectivesChronic venous insufficiency (CVI) is a prevalent condition with significant socioeconomic implications. Endovenous radiofrequency ablation (RFA) is a minimally invasive treatment option that has gained widespread acceptance due to its high efficacy and low complication rates. This study aimed to investigate the effectiveness of a novel venous access technique using a subcutaneous side branch of the greater saphenous vein (GSV) and compare it to the conventional direct GSV access technique.MethodsA total of 211 patients (288 legs) with CVI were randomly assigned to either the conventional access group (group 1, 145 legs) or the subcutaneous side branch group (group 2, 143 legs). Patients were assessed for demographic characteristics, venous access success rates, complications, and clinical outcomes. The primary outcomes were venous access success and procedural time, while secondary outcomes included complication rates such as vasospasm, ecchymosis, and thrombophlebitis.ResultsThe mean access time was significantly lower in group 2 (30.8 ± 9.9 seconds) compared to group 1 (46.7 ± 14.9 s) (p < 0.001). Additionally, group 2 required fewer cannulation attempts (1.28 ± 0.5) than group 1 (2.2 ± 0.9) (p < 0.001). Vasospasm occurred less frequently in group 2 (3.1%) than in group 1 (5.2%) (p = 0.005), and group 2 had significantly lower rates of ecchymosis (p = 0.033), thrombophlebitis (p = 0.026), and paresthesia (p = 0.045). No significant differences were observed between the groups regarding thermal skin injury (p = 0.142) or GSV occlusion rates at 3 months.ConclusionsThis study demonstrates that accessing the GSV via a subcutaneous side branch is a feasible and advantageous technique, leading to faster cannulation and reduced complication rates compared to the conventional approach. Further research is warranted to assess this novel technique's long-term outcomes and potential benefits in diverse clinical settings.

Muscle spasticity, a prevalent motor impairment after stroke, substantially diminishes patients' quality of life. Governor Vessel moxibustion (GVM), a significant complementary therapy, shows promise, yet the current evidence remains inadequate. This study aimed to evaluate the efficacy of GVM with routine rehabilitation training in alleviating poststroke spasticity (PSS).

We searched PubMed, Cochrane Library, Embase, Web of Science, four Chinese databases, and clinical trials registry for randomized controlled trials (RCTs) of PSS patients who mainly received GVM treatment alongside conventional rehabilitation. Statistical evaluations were conducted using Review Manager 5.4 and R Studio. For assessing bias in the included studies, the Cochrane risk of bias tool (RoB 2.0) was used to evaluate RCTs.

Eleven studies involving 859 PSS patients were included. Meta-analysis demonstrated that when combined with routine rehabilitation training, GVM effectively alleviated muscle spasticity, as measured by the modified Ashworth scale (MD, -0.65 [95% CI, -0.84 to -0.47], p < 0.01) and the composite spasticity index (MD, -1.82 [95% CI, -2.25 to -1.39], p < 0.01). The treatment time and frequency could potentially be the main contributors to heterogeneity. Results suggested that a treatment regimen consisting of 60-min sessions conducted once-weekly and lasting for at least 8 weeks was the most effective, providing evidence for optimizing clinical application of GVM combined with rehabilitation training in PSS management.

GVM serves as an effective complementary therapy to routine rehabilitation for PSS patients, with generally mild adverse events. However, before formulating evidence-based and definitive recommendations, more rigorously designed and in-depth research is warranted.

Hypertension in adolescents is associated with early cardiovascular risk, yet functional and vascular differences between primary and secondary hypertension remain poorly characterized. This study aims to compare body composition, muscle strength, arterial stiffness, physical activity, and sedentary behavior among adolescents with primary and secondary hypertension compared with normotensive peers.

Adolescents with primary hypertension (n = 35), secondary hypertension (n = 17), and normotensive controls (n = 21) were assessed for anthropometric characteristics, handgrip strength (HGS), hemodynamic and arterial stiffness parameters, physical activity levels, sedentary behavior, and perceived barriers to physical activity. Subgroup analyses were performed in adolescents with primary hypertension according to obesity status.

Adolescents with primary hypertension exhibited significantly higher body mass index and fat-free mass compared with other groups (p < 0.001). Pulse wave velocity was significantly higher in the primary hypertension group (p = 0.041), indicating increased arterial stiffness. Non-dominant HGS percentage was lowest in adolescents with secondary hypertension (p < 0.005). Physical activity levels were similarly low across groups, while weekend sedentary time was higher in the primary hypertension group (p = 0.021). Within the primary hypertension group, obesity status was not associated with differences in HGS, sedentary behavior, or arterial stiffness after adjustment for age, sex, height, and fat-free mass.

Adolescents with primary and secondary hypertension demonstrate distinct functional and vascular profiles early in the disease course. Arterial stiffness and reduced muscular strength highlight early cardiovascular risk, while low physical activity and high sedentary behavior are common across all groups. These findings support the need for early, individualized assessment and lifestyle-based interventions in adolescent hypertension.

Aortic aneurysm and dissection (AAD) are life-threatening conditions characterized by progressive aortic dilation and acute aortic complications. Despite advances in surgical and endovascular management, effective pharmacological strategies to prevent AAD expansion and rupture are still lacking. The pathogenesis of AAD is increasingly understood to be driven by profound cellular heterogeneity within the aortic trilaminar wall, where diverse cell subpopulations contribute differentially to disease progression. This review integrates current evidence on how genetic predispositions, epigenetic modifications, clinical risk factors, and wall shear stress induce cellular heterogeneity, focusing on the pivotal roles of smooth muscle cells, endothelial cells, immune cells, and fibroblasts. We particularly highlight smooth muscle cell heterogeneity, which encompasses both distinct embryonic origins contributing to region-specific susceptibility to AAD, and dynamic phenotypic switching into fibroblast-like, proliferative, macrophage-like, osteochondrogenic, stressed, and adipocyte-like states. These phenotypic transitions, occurring in specific spatiotemporal patterns, critically drive extracellular matrix (ECM) degradation, inflammation, and metabolic reprogramming. Beyond smooth muscle cells, dysfunctional endothelial cells compromise barrier integrity through disruption of tight junctions (TJs), adherens junctions, and focal adhesions, facilitating leukocyte infiltration and procoagulant signaling. Diverse immune cell subsets, including heterogeneous monocytes/macrophages, eosinophils, and lymphoid cells, orchestrate complex inflammatory responses and mediate ECM breakdown. Furthermore, activated fibroblast subpopulations contribute to fibrotic remodeling and maintain close interactions with smooth muscle cells. Advances in single-cell multiomics and lineage-tracing technologies have been pivotal in unraveling the cellular complexity underlying AAD, uncovering novel disease mechanisms and cell-specific therapeutic targets. A comprehensive understanding of cellular heterogeneity, thus, holds the potential to develop precision medicine and offer promising therapeutic intervention for AAD.

Syndrome-specific International Classification of Diseases, 10th Revision (ICD-10) codes have the potential to improve identification of patients for precision therapies, clinical trials, and research, yet their real-world uptake is not well characterized. We evaluated the utilization of syndrome-specific ICD-10 codes at a large academic medical center among patients with pathogenic or likely pathogenic variants in 10 monogenic epilepsy genes with established codes (CDKL5, EHMT1, KCNQ2, MECP2, MED13L, SCN1A, SHANK3, SLC13A5, SLC2A1, SYNGAP1). Patients were identified from an institutional genetic testing database and were included if they had at least one clinical encounter after code implementation or genetic diagnosis. Variants of uncertain significance were manually curated, and Rett and Dravet phenotypes were reviewed for accuracy. Of 83 patients with qualifying variants, 39 met inclusion criteria. Only 56.4% (22/39) were ever assigned a syndrome-specific ICD-10 code, which appeared in 31.1% of encounters and accounted for 14.5% of all documented codes. Uptake varied by syndrome, provider specialty, and encounter type and increased over time. In the Dravet syndrome subgroup (n = 23), generic epilepsy codes were documented more than twice as often as the Dravet-specific code (G40.83). When G40.83 was documented, other epilepsy codes were used less frequently, suggesting it may be treated as a substitute for broader epilepsy codes. These findings demonstrate inconsistent and limited adoption of syndrome-specific ICD-10 codes, highlighting the need for improved coding support and integration of structured genetic data within the electronic health record.

Myocardial fibrosis exemplifies a crucial pathological event in the escalation of heart failure. Natural bioactive agents that can modulate and mitigate myocardial fibrosis hold promising potential as key therapeutic and preventive strategies for managing heart failure. In this study, Ginsenoside Rb1 was found to attenuate myocardial fibrosis and suppress inflammatory responses by downregulating exosomal miRNA-24 expression in the experimental mice models. Primary mouse cardiac fibroblasts (pMCFs) were isolated from neonatal C57BL/6J mice for in vitro assays. For the in vivo investigations, adult C57BL/6J mice were utilized to assess the effects of Rb1 and Ang II on exosome-derived inflammatory pathways. Multiple analytical techniques, including qPCR, Western blotting, nanoparticle tracking analysis (NTA), BrdU staining, and ELISA, were employed to evaluate gene expression, protein levels, exosome characterization, cell proliferation, and cytokine secretion. The obtained results showed that Rb1 prevents Ang II-induced cell death and BrdU-positive cells in the pMCFs. Moreover, we have confirmed that the exosomes derived from pMCF cells have a size range of 80-250 nm, with a peak at 149 nm. RBb-1 prevented the Ang II-exposure-stimulated exosomal mRNA and protein expression of cardiac fibrosis markers (COL1a1, COL3a1, ACTA2, and TGFβ1) in both pMCFs and mice models. Moreover, Rb1 inhibited the inflammatory expression which was confirmed by ELISA. In addition to that, Rb1 impedes the exosomal mRNA expression of miRNA-21 in the mouse model. This study will open up a new insight into the relationship between Rb1 and miRNA-21, which mitigates myocardial fibrosis in the Ang II-induced mouse model.

Increased pulmonary blood flow (IPF) from congenital heart diseases causes pediatric pulmonary hypertension and respiratory distress, yet its impact on postnatal lung maturation remains unknown.

This study aimed to establish a neonatal model of IPF and elucidate the molecular mechanisms underlying impaired lung maturation, thereby identifying potential therapeutic targets.

Neonatal mice underwent surgical creation of an aortocaval fistula to induce IPF. Bulk RNA sequencing compared lung transcriptomes at postnatal day (P)14 (alveolar stage) and P30 (maturity) in IPF vs sham-operated controls. Histological validation was performed, and the effects of immunosuppression (cyclosporine A) were assessed.

IPF generated 2,272 differentially expressed genes vs 943 in controls, revealing the following: 1) shared downregulation of extracellular matrix organization and cell cycle pathways; 2) IPF-specific cell cycle dysregulation (downregulated Birc5/CENPE) and hyperactive immunity (upregulated NLRP3/IL23R) impairing alveolar/capillary development; 3) suppressed circadian (Per2) and neural pathways (Nr1d1) unique to normal maturation. Cyclosporine A treatment mitigated alveolar simplification, attenuated vascular remodeling, and improved alveolar epithelial differentiation.

This study establishes the first neonatal IPF model and identifies actionable therapeutic targets, including immune modulators (NLRP3/IL23R inhibitors), cell cycle regulators (Birc5/CENPE agonists), and neural/circadian mediators (Nr1d1/Per2 activators). These findings provide a roadmap for mitigating IPF-driven lung maldevelopment.

High-sensitivity cardiac troponin (hs-cTn) assays are recommended for the diagnosis of acute myocardial infarction. Here, we characterize the analytical performance of a next-generation hs-cTn assay, Elecsys® Troponin T hs Gen 6 (Roche Diagnostics International).

Surplus lithium-heparin plasma or serum samples from patients or healthy volunteers were run on Cobas® e 801, e 402, and Pro analyzers. Limits of blank (LoB), limits of detection (LoD), and limits of quantitation (LoQ) were determined according to CLSI EP17-A2, with target values of 1.0 and 1.5 ng/L for LoB/LoD and 3.0 ng/L (10% CV) and 1.5 ng/L (20% CV) for LoQ, respectively. Precision was measured, per CLSI EP17-A2, using 3 QC samples (approximately 4, 30, and 220 ng/L), 12 native samples, and 3 reagent lots. Linearity, per CLSI EP06-Ed2, was determined by diluting samples with cardiac troponin T (cTnT) concentration above the measuring range with a low/blank sample. Interference (per Glick) with endogenous and assay components at 5 cTnT concentrations was assessed.

Measured values for LoB, LoD, and LoQ at 10% and 20% CV were 0.1 to 0.7 ng/L, 0.3 to 1.4 ng/L, 1.0 to 2.9 ng/L, and 0.4 to 1.2 ng/L, respectively. Repeatability CVs were 1.0 to 5.8% for mean cTnT concentrations of 2.6 to 9230 ng/L in lithium-heparin plasma. High precision was shown across lots, and linearity was observed across the measuring range (1.5 to 9500 ng/L, all Pearson's r = 1.00). No interferences were observed, specified up to ≤1000 mg/dL hemoglobin, ≤50 mg/dL [≤855 µmol/L] icterus/bilirubin, and ≤1200 ng/mL biotin.

The analytical performance characterization of the assay demonstrated high sensitivity, high precision at the low end and across the measuring range, and resistance to interference.

Cerebral small vessel disease (CSVD) is a common incidental MRI finding in patients with transient ischemic attack (TIA) and stroke and has been linked to cognitive decline. This study investigated the prevalence of CSVD imaging biomarkers in TIA patients and their association with cognitive performance over 3 years.

We included 246 TIA patients from the INSPiRE-TMS study (ClinicalTrials.gov: NCT01586702). CSVD was assessed on baseline 3 T MRI using a composite score (0-4) including white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (PVS). Cognitive performance was evaluated using the Montreal Cognitive Assessment (MoCA) at baseline and annually for 3 years.

At least one CSVD imaging biomarker was present in 58.5% of patients. Lacunes (36.6%) were the most common, followed by PVS (28.1%), WMH (19.5%), and CMBs (17.9%). Higher CSVD-score was independently associated with greater cognitive decline over 3 years (β = -0.52, 95% CI -0.95- -0.08, p = 0.020), along with older age (β = -0.08, 95% CI -0.13 to -0.03, p = 0.001). CMB burden was the strongest predictive component of the CSVD-score (β = 0.42, 95% CI -0.63 to -0.22, p < 0.001). CSVD-score was particularly associated with decline in the memory domain (adjusted β of -0.18, 95% CI -0.32 to -0.04, p = 0.015).

CSVD imaging markers are present in over half of TIA patients and are independently associated with cognitive decline up to 3 years, with the strongest effect on memory. Whether the presence of CMBs is the strongest predictive imaging biomarker of cognitive decline in TIA patients requires confirmation in further studies.