Background: Rehabilitation methods that include anodal transcranial direct current stimulation (atDCS) and extended reality (XR) exercises have been used to enhance neural networks and improve functional performance in stroke patients, but the neuromuscular and neurophysiological mechanisms underlying these improvements are not fully understood. The purpose of this study was to examine the effects of atDCS during XR rehabilitation exercises on cortical, neuromuscular, and clinical outcomes of stroke survivors. Methods: Nineteen chronic stroke survivors were placed into either a transcranial direct current stimulation (tDCS) or a Sham group, without significant (p > 0.73) differences in the baseline levels of disability between groups. The tDCS group received active atDCS and the Sham group received sham atDCS applied on the ipsilesional primary motor cortex (M1) while performing a 10-session XR rehabilitation program. Surface electromyography (EMG) activity was recorded from deltoid and rectus femoris of the paretic limb without and with the application of active/sham atDCS on the M1. Shoulder abduction and hip flexion active maximum joint range of motion (ROM_max), electroencephalography (EEG)-derived brain symmetry index (BSI) and functional/clinical tests were assessed before and after the rehabilitation program. Results: EMG activity was ~ 31% greater during hip flexion of the paretic limb with the application of active atDCS than without atDCS (p=0.04). Paretic hip flexion ROM_max increased by ~ 26%, BSI decreased by ~ 72% (indicating greater brain symmetry) and timed up and go (TUG) functional test improved by ~ 11% from before to after the rehabilitation program for the tDCS group only (p < 0.05). No other significant differences (p > 0.05) were observed. Conclusion: It seems that the application of active atDCS targeted the ipsilesional M1 representation of the quadriceps, which potentiated muscle activation in the paretic rectus femoris during XR exercises and resulted in greater motor recovery in hip flexion movements. The EEG-derived BSI results also indicate that atDCS was effective in reorganizing the ipsilesional hemisphere brain activity after stroke.

A 50-year-old Romanian gentleman presented with fever, myalgia and 30 kg weight loss. He was treated for syphilis after acquiring it 16 years ago. On examination, there was a pansystolic murmur in the axilla, and the patient had an ataxic gait. Blood tests showed raised inflammatory markers. However, standard investigations for infective endocarditis, including multiple blood cultures, serological titres for fastidious organisms and antibody tests were negative. A computed tomography (CT) of the chest, abdomen and pelvis demonstrated hepatosplenomegaly with multiple splenic infarcts. A magnetic resonance imaging (MRI) of the head with contrast showed multiple punctate enhancement in the bilateral hemispheres with leptomeningeal enhancement. Transthoracic echocardiogram demonstrated a large vegetation leading to severe mitral regurgitation. Serum treponemal antibodies were positive; Treponema pallidum particle agglutination (TPPA) was positive at 1 : 1280, and rapid plasma reagin (RPR) 1 : 4 treponemal IgM was negative; lumbar puncture syphilis serology was negative. The patient was treated with an extensive period of intravenous antibiotics, in addition to a prosthetic metallic valve replacement, where unusual ragged calcified valvular tissue was observed. Tertiary syphilis is a difficult diagnosis to confirm, since it can often be indolent and occur in areas of the body where it may go unnoticed. In our case, a diagnosis of probable syphilitic endocarditis was made from a combination of the history, an initial increase in the size of the lesion following antibiotic therapy and observation of likely gumma on the mitral valve during surgery. In such cases, surgery in addition to optimal antimicrobial therapy is necessary for effective treatment. This case adds to the current literature that treatment with penicillin is likely inadequate to prevent late complications.

An active lifestyle can lessen the risk of cardiometabolic conditions and improve overall life quality. To support lifestyle change and help healthcare providers deliver optimal physical activity interventions, we aimed to compare the effectiveness of four different physical activity intervention designs (education, behaviour-change, motivational/goal-setting and multi-component) against usual care/minimal intervention in increasing physical activity among adults with cardiometabolic conditions.

A systematic review and network meta-analysis of randomised controlled trials (RCTs) were conducted. Four databases were searched (January 2000-February 2025).

steps per day, moderate-vigorous physical activity (MVPA) and combined physical activity.

sedentary time, HbA1c, BMI, weight loss, SBP, DBP, cholesterol, LDL-C and HDL-C. Steps per day were analysed via time-course model-based meta-analysis. Bayesian random-effects network meta-analysis estimated mean differences (MD)/standardised mean differences (SMD) and 95% credible intervals (CrIs). Evidence quality was assessed using CINeMA.

Sixty-two trials comprising 8952 participants were included, 51 were analysed in the meta-analysis. Behaviour-change (MD = 3287, 95% CrI 1576 to 4997 steps per day), multi-component (MD = 2939, 95% CrI 1714 to 4164), education (MD = 2054, 95% CrI 369 to 3740) and motivational/goal-setting (MD = 1344, 95% CrI 243 to 2445) interventions were significantly more effective than usual care in increasing steps per day. Overall, combined physical activity interventions excluding minimal interventions and when compared to usual care only, increased steps per day significantly from baseline by 143 (95% CrI 114 to 182; median 18 weeks), with the highest number of steps per day predicted at around 75 weeks from baseline (MD = 738, 95% CrI 581 to 893). Only multi-component interventions were consistently found to significantly increase physical activity across all primary measures-steps per day, MVPA and combined physical activity-compared to usual care or minimal care. In terms of secondary outcomes, motivational (MD = - 0.28%, CrI = - 0.46 to - 0.10%) and multi-component interventions were associated with significant HbA1c reductions (MD = - 0.24%, CrI = - 0.47 to - 0.02%) compared to usual care; no significant effects were found on other secondary outcomes.

Multi-component interventions were most effective at improving physical activity levels among people with cardiometabolic conditions. The crucial next step for patients, clinicians and policymakers is to enhance the understanding of how to tailor and implement these interventions effectively for sustained improvements in long-term physical activity levels.

PROSPERO number CRD42023405306.

Out-of-hospital cardiac arrest (OHCA) has poor survival rates, but extracorporeal cardiopulmonary resuscitation (ECPR) shows promise for selected patients, as a second line of therapy after failure of conventional CPR to obtain return of spontaneous circulation, despite implementation challenges. This study aimed to identify distinct sub-phenotypes among patients with OHCA who undergo ECPR and to investigate their association with clinical outcomes.

This multi-center, retrospective, observational study used the Japanese Association for Acute Medicine OHCA registry from 83 hospitals that performed ECPR among 91 participating centers between June 2014 and December 2020. We included adult patients with OHCA who received ECPR during cardiac arrest. Three-class latent class analysis (LCA) was employed to identify sub-phenotypes based on 15 variables, including pre- and in-hospital factors. Logistic regression analysis was used to assess the association between sub-phenotypes and 30-day survival and neurological outcomes.

A total of 1528 patients were included. The median low-flow time was 47 min (interquartile rage: 38-58 min). The 30-day survival rate for eligible patients was 20.9%. LCA identified three distinct sub-phenotypes: Standard ECPR Group (n = 702), Delayed ECPR Group (n = 457), and Non-shockable Rhythm Group (n = 369). The variables with high discriminative power in the LCA was low-flow time, followed by pre-hospital shock delivery and initial cardiac rhythm. Thirty-day survival rates varied significantly among the sub-phenotypes (p = 0.001): Standard ECPR Group (26.9%), Delayed ECPR Group (17.1%), and Non-shockable Rhythm Group (14.1%). Favorable neurological outcomes at 30 days also differed significantly (p = 0.004), with the Standard ECPR Group showing the highest rate (12.1%). After adjusting for covariates, both the Delayed ECPR Group (adjusted OR: 0.61, 95% CI 0.44-0.82) and Non-shockable Rhythm Group (adjusted OR: 0.47, 95% CI 0.32-0.68) had significantly lower odds of 30-day survival compared to the Standard ECPR Group.

Three clinically meaningful sub-phenotypes were identified using simple pre-hospital and in-hospital factors, with low-flow time emerging as the most critical discriminating factor. The sub-phenotypes showed significant associations with clinical outcomes and provide a practical framework for ECPR patient stratification. These findings suggest that timing optimization may be as important as rhythm characteristics for ECPR patient selection and support the development of sub-phenotype-specific treatment strategies.

Low blood pressure at acute ischemic stroke onset is associated with both short- and long-term adverse outcomes. Studies have shown that YQFM (YiQiFuMai lyophilized injection) can ameliorate neurological deficits in ischemic stroke.However, all of these studies are all small-sample clinical observations lacking rigorous study design for AIS with inappropriate blood pressure.

To describe the design of the YQFM aimed at reducing the disability rate in AIS patients with inappropriate blood pressure.

This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled, superiority trial aimed at evaluating the efficacy and safety of YQFM in reducing the disability rate in patients with acute hypoperfusion stroke within 90 days. We will recruit 480 patients with AIS within 48 h of symptom onset from 24 hospitals, who have large atherosclerosis, systolic pressure ≤ 155 mmHg, and an NIHSS score of 4-18. Eligible patients will be randomly assigned to receive either YQFM or 0.9% NaCl injection once daily for 10 days and will be followed up until the 90th day after stroke onset.The primary outcome will be the proportion of patients with mRS ≤ 2 at 90 days after patient recruitment. Secondary outcomes will include the proportion of early neurological deterioration at 7 days, patient self-reported outcomes and the syndrome score at 10 days, MMSE scale and BI scale at 90 days.During the trial, adverse events will be recorded. These data will be analyzed according to the predetermined statistical analysis plan.

This study is the first randomized controlled double-blind trial to evaluate the efficacy and safety of YQFM in patients with AIS. This trial will provide evidence-based data for YQFM application in AIS with inappropriate blood pressure.

ChiCTR2300074125 was registered on 31 July, 2023. For more information, please visit Clinical Trials.gov at https://www.chictr.org.cn/showproj.html?Proj=200686 .

Cardiofaciocutaneous syndrome (CFCS) is a rare syndromic disorder caused by germline mutations affecting the RAS/MAPK pathway. It is characterized by distinctive craniofacial dysmorphism, congenital heart defects, skin abnormalities, gastrointestinal dysfunction, neurocognitive impairment, and epilepsy. Emerging evidence suggests an association with hypogammaglobulinemia, but a comprehensive characterization of immunological abnormalities in CFCS is lacking.

We conducted a retrospective, multicenter observational study to investigate the immunological phenotype of CFCS. Clinical features, immune-related manifestations, and laboratory parameters were analyzed to delineate the immunological profile of affected individuals.

A total of 56 patients with a confirmed clinical and molecular diagnosis of CFCS were included, with a median age at evaluation of 13 years (range: 1-39 years). Increased susceptibility to infections was reported in 18/56 patients (32%), while autoimmune manifestations were observed in 14/56 patients (25%). Common immunological findings included monocytosis (32%), lymphopenia (21%), and hypogammaglobulinemia, with decreased IgG, IgA, or IgM levels in 21%, 40%, and 35% of patients, respectively. Genotype-phenotype analysis revealed that BRAF mutations were predominantly associated with T-cell lymphopenia, whereas MAP2K1 mutations were linked to monocytosis, reduced naïve and switched-memory B cells, and hypogammaglobulinemia. Immunodeficiency-related treatments, including immunoglobulin replacement therapy, antibiotic prophylaxis, or immunosuppressive therapy, were administered to 6/56 patients (11%).

CFCS is associated with recurrent yet heterogeneous immunological abnormalities, including lymphopenia, hypogammaglobulinemia, and increased infection susceptibility. Given these findings, routine immunological assessment should be considered in CFCS patients to facilitate early detection and appropriate management of immune dysfunction.

Racially minoritized populations in the United States (US), notably African American (AA) and American Indian/Alaska Native (AI/AN), experience disproportionately higher rates of chronic kidney disease (CKD), diabetes, and hypertension compared to their White peers but are understudied. This real-world cohort study examines the standards of CKD care provided to these groups in two US health systems.

Using electronic health record data from the Center for Kidney Disease Research, Education, and Hope (CURE-CKD) Registry (N = 381,011) collected between 2015 and 2020, adjusted binary logistic regression models were used to identify predictors of two CKD care outcomes: 1) prescriptions for CKD-related guideline-directed medical therapy (CKD-GDMT) in the form of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and 2) testing for urine albumin-creatinine/urine protein-creatinine ratio (UACR/UPCR) among adult patients of AA and AI/AN race compared to the reference group (White, non-Hispanic).

AA (62 ± 17 years) and AI/AN (57 ± 18 years) patients with CKD were younger compared to the White, non-Hispanic reference group (68 ± 17 years). Diabetes and hypertension were the most important predictors for increased odds of CKD-GDMT and UACR/UPCR testing. Prevalence of CKD-GDMT was only 46%, 40% and 38% in AA, White, and AI/AN patients, respectively. AA patients were more likely to receive CKD-GDMT prescriptions (OR = 1.20, 95% CI: 1.17-1.23, p < 0.001) and UACR/UPCR testing (OR = 1.34, 95% CI: 1.29-1.38, p < 0.001) compared to White patients. AI/AN were also more likely to receive GDMT (OR = 1.07, 95% CI: 1.00-1.15, p = 0.046) compared to White patients but had lower odds of UACR/UPCR testing (OR = 0.73, 95% CI: 0.67-0.81, p < 0.001). However, the frequency or prescribing of CKD-GDMT and UACR/UPCR testing were suboptimal across all examined racial identity groups. Exploratory machine learning approaches, including logistic regression, lasso regression, and random forest found similar findings.

While there were modest racial differences in the prescription of CKD-GDMT and frequency of UACR/UPCR testing, rates were lower than expected in this high-risk population. Our findings suggest the disproportionate burden of CKD on AA and AI/AN individuals is not solely attributable to the current standards of care delivery. The relatively higher rates of CKD-GDMT for AA patients may be due to clinician recognition of their increased risk for progressing to kidney failure.

Not applicable.

Inflammation plays a key role in the progression of Peripheral arterial disease (PAD). The objective of this research is to explore the possible link between the neutrophil-to-albumin ratio (NPAR) and the occurrence of PAD.

In this cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) 199-2004, data from 5,470 participants were analyzed. The Ankle-brachial index (ABI) was obtained by dividing the mean systolic blood pressure in the ankle by the mean blood pressure in the arm. PAD was characterized by an ABI value of less than 0.9 in either leg. Patients diagnosed with PAD and those without, all of whom had detailed NPAR data from NHANES. Weighted multivariable logistic regression models were used to analyze the relationship between free NPAR and PAD. The nonlinear relationship between NPAR and PAD was investigated using restricted cubic splines. Additionally, subgroup analyses and interaction tests were carried out to provide further understanding.

This study analyzed data from 31,126 NHANES participants (1999-2004), focusing on those aged ≥ 40 years undergoing ABI tests (n = 9,970). After exclusions, the final sample was 5,470 participants, representing 79,363,231 U.S. adults. The weighted prevalence of peripheral artery disease (PAD) was 3.75% (95% CI: 3.20-4.38%). Logistic regression analysis revealed significant associations between higher NPAR levels and increased prevalence of PAD. In the adjusted models, the odds ratios (ORs) for the highest versus the lowest NPAR tertile were significant (OR: 1.18, 95% CI: 1.05-1.33). Restricted cubic spline (RCS) analysis showed a positive correlation between NPAR and PAD prevalence (overall p = 0.005), though the nonlinear effect was not statistically significant (p = 0.504). Stratified analyses indicated significant associations in specific subgroups, such as males (OR: 1.18, 95% CI: 1.10-1.27) and non-diabetics (OR: 1.12, 95% CI: 1.06-1.18), those without CVD (OR: 1.10, 95% CI: 1.04, 1.16), white participants (OR: 1.11, 95% CI: 1.03-1.19), moderate drinkers (OR: 1.14, 95% CI: 1.05-1.25), heavy drinkers (OR:1.19, (95% CI: 1.06-1.33), sedentary individuals (OR:1.10, 95% CI: 1.01-1.19), and former smokers (OR:1.12, 95% CI: 1.04-1.21).

Our study demonstrates a positive correlation between NPAR levels and the prevalence of PAD, implying that elevated NPAR levels are linked to a greater probability of developing PAD. As a cross-sectional study, it cannot establish the temporal sequence of events or causality.

Effective control of blood pressure (BP) is potentially a critical determinant in making a successful recovery from acute ischemic stroke. BP is often elevated after the onset of this critical illness, and it is related to both the severity of the ischemic injury and subsequent changes in cerebral perfusion and collateral blood flow. However, recent studies have challenged longstanding assumptions over the safety and efficacy of BP lowering in being able to reduce the risk of reperfusion injury in acute ischemic stroke. This review synthesizes contemporary evidence and discusses the evolving landscape of BP management in acute ischemic stroke.

Three prehospital ambulance-initiated trials of early BP lowering in patients with undifferentiated stroke have shown neutral or adverse effects, while the results of multiple trials of in-hospital management BP lowering in patients who have received successful reperfusion therapy for acute ischemic stroke due to large-vessel occlusion highlight the risks of over-aggressive treatment. Despite considerable research effort, the optimal BP management strategy in acute ischemic stroke remains uncertain, although avoiding excessive reductions appears critical.

Recent studies have shown that palmitoylation is involved in ischemic stroke(IS). However, the role of palmitoylation in IS has not been systematically investigated. The aim of this study is to explore the causal relationship and mechanism between palmitoylation genes, metabolites, and IS using Mendelian randomization (MR) method. The GWAS data of IS from GISCOME network database, the palmitoylation gene data from eQTLGen database, and the metabolite data from GWAS database were used in this study. Two-sample MR analysis, summary-based Mendelian randomization (SMR) analysis, and mediation analysis were used. Firstly, two-sample MR analysis was used to evaluate the causal relationship between palmitoylation genes and IS. The SMR method was then used to verify the correlation between gene expression and IS. The GSE140275 dataset of GEO database was used to test the expression of palmitoylation genes. Mediation analysis was used to explore the mediating effect between palmitoylation gene expression and metabolites and IS (metabolites are mediators, genes are exposures). The high expression of ZDHHC13 gene is significantly negatively correlated with the risk of IS. ZDHHC13 indirectly affects the occurrence of IS by regulating Mannonate metabolites. Sensitivity and SMR analyses supported our findings, indicating high statistical robustness. Based on the observational results serum data set of IS patients, the expression of ZDHHC13 is decreased after IS. However, ZDHHC13 has a protective effect before the occurrence of ischemic stroke, which MR analysis result is contrary to observational results. This study reveals the role of ZDHHC13 in the progression of IS by regulating Mannonate metabolites and provides potential clinical application prospects for ZDHHC13 as a biomarker or preventive target for early diagnosis and treatment of IS.