• A composite conductive hydrogel loaded with alginate/gelatin microspheres with micro-environmentally induced smart temporal regulation for acute myocardial infarction treatment.
    1 week ago
    Designing a temporal regulation system for responsive stem cell delivery that simultaneously addresses micro-environmental improvement in the infarcted area and electromechanical coupling compensation through synergistic stem cell therapy continues to pose substantial research challenges. We present a micro-environmentally induced smart temporal regulation composite conductive hydrogel for myocardial infarction therapy. Adipose derived stem cells (ADSC) were seeded on alginate (Alg)/gelatin (GT) composite microspheres (Alg/GT), which were encapsulated into reactive oxygen species (ROS) responsive conductive hydrogels (HGB) based on hyaluronic acid functionalized with phenylboronic acid (HA-PBA), dopamine-modified GT (GT-DA), and borate-functionalized polyaniline (BPA). Alg/GT microspheres exhibit excellent carrying capacity for ADSC and promoting ADSC paracrine effects. Besides the smart controlled release properties, the optimised hydrogel (HGB3) possesses a variety of functional properties including injectability, appropriate mechanical strength and electrical conductivity, anti-inflammatory and antioxidant properties. Together, these properties contribute to micro-environmental enhancement and electromechanical coupling restoration in the infarcted myocardial region. When the composite system was injected into the infarcted myocardifm, it achieved benign remodeling of the infarcted myocardium through regulation of inflammation, inhibition of fibrosis and promotion of vascular regeneration. This micro-environmentally induced smart temporal regulation composite conductive hydrogel system offers a novel therapeutic strategy for the management of acute myocardial infarction.
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  • Reference intervals for aCL and anti-β2GPI IgAGM antibodies in a large health-inspection population: a foundational study for combined-isotype assay interpretation.
    1 week ago
    Combined-isotype anticardiolipin (aCL) and anti-β2-glycoprotein I (anti-β2GPI) immunoglobulin A, G and M (IgAGM) assays are used in current laboratory practice, but their disease relevance and clinical interpretation remain incompletely defined. This study aimed to establish 99th-percentile reference intervals for aCL IgAGM and anti-β2GPI IgAGM in a large general healthy population and to provide a basis for future disease-oriented evaluation.

    A total of 7846 eligible individuals who underwent health inspection were included in the analysis. Plasma aCL IgAGM and anti-β2GPI IgAGM were measured by ELISA. A physiologically normal reference subgroup was defined by excluding predefined laboratory abnormalities at the retained index visit (n=989). Retrospective contextual analyses were also performed in systemic lupus erythematosus (SLE) and coronary heart disease (CHD) populations with historical IgAGM results.

    Among 7846 individuals (5170 male and 2676 female; age 15-90 years), the 99th percentiles were 35.4 relative units (RU)/mL for aCL and 51.7 RU/mL for anti-β2GPI. In the physiologically normal reference subgroup, the corresponding values were 23.33 RU/mL and 46.25 RU/mL. Sex differences were significant for both antibodies in the overall population and in the physiologically normal subgroup, and aCL showed age-related increases at the upper tail. In retrospective analyses, SLE showed higher proportions above all four cut-offs than CHD, with significance for anti-β2GPI at both the general health participant cut-off (11.4% vs 4.5%, p=0.0425) and the physiologically normal cut-off (12.3% vs 4.5%, p=0.0200). Exploratory analyses linked antibody levels to triglyceride-related profiles.

    Assay-specific 99th-percentile reference intervals for aCL IgAGM and anti-β2GPI IgAGM were established in a large health-inspection population and a physiologically normal reference subgroup. These findings provide a practical interpretive framework for combined-isotype assays and support future disease-oriented evaluation.
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  • Impact of cardiometabolic comorbidities on clinical characteristics, prescription patterns and retention rate of first b/tsDMARD treatment in 5299 European real-world patients with psoriatic arthritis.
    1 week ago
    To investigate associations between cardiometabolic comorbidities and clinical characteristics, prescription patterns and retention of first biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) in patients with psoriatic arthritis (PsA).

    Patients with PsA initiating a first b/tsDMARD treatment in 2015 or later were identified in eight European rheumatology registries. Patients with information on five cardiometabolic comorbidities (obesity, dyslipidaemia, diabetes, hypertension, ischaemic heart disease) at treatment start (baseline) were included. All analyses were conducted according to patients' comorbidity burden (count: 0/1/≥2) and status (presence/absence of each comorbidity). Patient characteristics and prescription patterns were described. Twelve-month treatment retention rates were estimated and compared using Kaplan-Meier plots, log-rank tests and multivariable Cox regression analyses.

    Among 5299 patients, 36% had at least one cardiometabolic comorbidity. Patients with comorbidity were older, had higher disease activity and more disability. Regardless of comorbidity, most patients were prescribed a tumour necrosis factor inhibitor (76%). The use of interleukin-17 inhibitors increased with comorbidity burden (0/1/≥2 comorbidities: 13%/18%/19%), whereas Janus kinase inhibitor use declined (2.3%/1.6%/0.8%). Retention rates were marginally lower with higher comorbidity burden (80%/76%/78%) (log-rank, p=0.036) and obesity (absent 79% vs present 77%) (log-rank, p=0.04). The risk of treatment withdrawal was only marginally higher in patients with higher comorbidity burden (one comorbidity: HR 1.19; 95% CI 1.02 to 1.40; ≥2 comorbidities: HR 1.18; 0.98 to 1.42).

    Patients with cardiometabolic comorbidities had higher disease activity at treatment initiation of the first b/tsDMARD. Prescription patterns varied with comorbidity burden. Cardiometabolic comorbidity burden, especially obesity, was associated with marginally lower treatment retention.
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  • The association between weight-adjusted waist circumference index and risks of cardiovascular and all-cause mortality: a retrospective analysis based on the NHANES database.
    1 week ago
    Nowadays, obesity has become a public health issue. Weight-adjusted waist circumference index (WWI) is gaining attention as a new obesity indicator. Evidence regarding the association between WWI and all-cause mortality and cardiovascular mortality among the general adult population in the United States remains limited.

    This retrospective cohort study analyzed 3,081 U.S. adults from the 1999-2018 NHANES database. Weighted Cox regression, trend chi-square test, Kaplan-Meier analysis, and comprehensive predictive performance assessments were used to explore the association between WWI and all-cause/cardiovascular mortality, and validate WWI's predictive value versus BMI/waist circumference/body weight. Subgroup and interaction analyses were also performed.

    WWI was positively associated with all-cause (Model 3 HR = 1.944, p < 0.001) and cardiovascular mortality (Model 3 HR = 1.854, p = 0.013), with a significant linear upward trend in mortality risks with increasing WWI quartiles (all p < 0.001). WWI had higher AUC than traditional indices, with significant DeLong test differences, stable long-term predictive performance, and superior net benefit in clinically relevant DCA threshold ranges.

    This study demonstrates a significant association between WWI and all-cause mortality and cardiovascular mortality among the general adult population in the United States, Our findings suggest that older people, women, low-income and low-educated people, smokers have higher WWI, and people with high WWI also have higher prevalence of hypertension and diabetes, Integrating WWI into clinical risk assessment may help identify high-risk populations and guide targeted interventions to reduce mortality risk.
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  • Acute Kidney Injury and Risk of Adverse Neurocognitive Outcomes: A Systematic Review and Meta-Analysis.
    1 week ago
    Chronic kidney disease is a recognized risk factor for adverse neurocognitive outcomes, but the effect of acute kidney injury (AKI) on brain health remains less well defined. We conducted a systematic review and meta-analysis to evaluate associations between AKI and subsequent risk of stroke, delirium, and dementia.

    Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until April 2025. Studies were included if they reported quantitative estimates with measures of precision for the association between AKI and delirium, stroke, or dementia in adult populations. Two reviewers independently screened and extracted data, and study quality was assessed using standardized criteria. Study characteristics, participant demographics, and adjusted effect estimates (hazard ratios [HRs] or odds ratios [ORs]) with 95% CIs were extracted. Pooled HRs and ORs with 95% CIs were calculated using random-effects models. Heterogeneity was evaluated with the χ2 test and I2 statistic, and sources of heterogeneity were explored through prespecified subgroup analyses and meta-regression.

    We identified 49 studies comprising 11,253,825 participants with 1,279,145 events. Individuals with AKI were at increased risk of stroke (pooled adjusted HR 1.35, 95% CI 1.20-1.52), delirium (pooled adjusted OR 1.76; 1.42-2.17), and dementia (pooled adjusted HR 1.64, 1.41-1.89). A gradient of risk across increasing AKI stages was demonstrated for stroke (stage 1: HR 1.11; 1.00-1.23; combined stages 2 and 3: HR 1.57; 1.35-1.81). AKI was also associated with higher in-hospital and 90-day mortality poststroke (pooled HR 2.13, 1.56-2.90, and 4.81, 2.55-9.08, respectively) and with 90-day disability (pooled adjusted OR 1.47, 1.22-1.76). Associations between AKI and all outcomes were directionally consistent across sensitivity analyses and pooled propensity score-matched studies.

    In this systematic review and meta-analysis, AKI was consistently associated with increased short-term and long-term neurocognitive risk, including stroke, delirium, and dementia. These findings suggest that AKI may identify individuals vulnerable to both acute and chronic brain injury. Further studies are needed to clarify mechanisms linking AKI to brain injury and to identify strategies to mitigate neurocognitive risk in this high-risk population.
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  • Clearance of Early Complement Protein From CSF After Aneurysmal Subarachnoid Hemorrhage and Influence on Neurologic Outcome.
    1 week ago
    Aneurysmal subarachnoid hemorrhage (aSAH) triggers a robust inflammatory response, which has been associated with brain injury and poor outcome. The complement system is an integral part of the innate immune system activated after acute brain injury. The early complement proteins C1q and C3 have roles in glial-neuronal interactions and synaptic pruning. The objective of this study was to determine whether changes in CSF complement proteins over time after aSAH are associated with neurologic outcome.

    We performed an exploratory retrospective case-control study investigating the association of CSF levels and clearance of C1q and C3 with outcome in patients with aSAH and compared with controls with normal CSF. Clearance was defined as the percent change of complement protein levels between 2 time points corresponding to peaks of early (<72 hours) and delayed (5-7 days) brain injury after aSAH. The primary endpoint was functional outcome, assessed by Glasgow Outcome Scale (GOS; range 1-5 with higher scores denoting better outcome), at the time of discharge. Good functional outcome was defined as GOS 4-5. Complement protein clearance was adjusted by baseline differences, and receiver operating characteristic analysis was performed.

    Early after aSAH, there was a robust increase in C1q (median 89.10 vs 6.42 ng/mL, p < 0.0001) and C3 (78.00 vs 8.72 µg/mL, p = 0.0001) in CSF of 20 patients with aSAH compared with 11 controls. Between early and late time points, both C1q (97.38 vs 47.85 ng/mL, p = 0.0326) and C3 (85.23 vs 23.10 µg/mL, p = 0.0004) decreased in those with good outcome. Percent clearance of C3 from CSF was larger in those with good vs poor neurologic outcome (median 74.85% vs 11.43% reduction over time, p = 0.0159). C3 clearance, particularly when adjusted by baseline Glasgow coma scale on admission, was a highly sensitive and specific marker of neurologic outcome after aSAH (area under curve = 0.990, 95% confidence interval 0.958-1.000, sensitivity 90.9%, specificity 100.0%).

    Increased CSF clearance of C3 within the first week after aSAH appears to be associated with improved neurologic outcome. Future strategies to promote clearance of inflammatory mediators such as early complement proteins from CSF may, therefore, improve outcomes after aSAH.
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  • Effectiveness of a Telehealth Intervention on Functional Status, Anxiety, Depression, and Rehospitalization Among Older Adults Undergoing Coronary Artery Bypass Grafting: Randomized Controlled Trial.
    1 week ago
    Telehealth has shown promise in enhancing care transitions and physical health outcomes in patients with cardiovascular disease. However, limited studies have explored its effect on functional status, psychological health, and rehospitalization, specifically in older patients undergoing coronary artery bypass grafting (CABG).

    This study aimed to evaluate the effectiveness of a telehealth intervention in improving functional status, reducing anxiety and depression, and decreasing rehospitalization rates compared with usual care among older patients undergoing CABG.

    The study was a 2-arm parallel randomized controlled trial. This was conducted in 2 phases. Phase 1 was conducted in the cardiac surgical units at a university hospital in Bangkok, Thailand. Phase 2 involved following up with the participant at home 30 and 90 days after discharge. A total of 84 older adults undergoing CABG were randomly assigned to either the control group (n=42), which received usual care (discharge planning), or the intervention group (n=42), which received a telehealth intervention based on the transitional care model in addition to usual care. The telehealth intervention included home monitoring via the "Zip Heart" app and scheduled video consultations. The primary outcome was functional status, measured using the Thai version of the Enforced Social Dependency Scale. Secondary outcomes included anxiety and depression, assessed using the Thai Hospital Anxiety and Depression Scale, and rates of rehospitalization. Data were collected at baseline, 30, and 90 days after discharge. Analyses were conducted using an intention-to-treat approach, with missing outcome data handled using multiple imputation. Two-way repeated-measures ANOVA was used to evaluate group, time, and group-by-time interaction effects.

    A total of 84 participants were randomized and included in the intention-to-treat analysis (intervention group, n=42; control group, n=42). At baseline, there were no statistically significant differences between the two groups. Significant group-by-time interactions were observed for functional status scores (F2,164=32.09, ηp²=.28; P<.001), anxiety (F2, 164=20.22, ηp²=.2; P<.001), and depression (F2,164=16.81, ηp²=.17; P<.001). The intervention group demonstrated significantly greater improvements in functional status and greater reductions in anxiety and depression at both 30 and 90 days after discharge compared to the control group (all P<.001). Additionally, rehospitalization rates were significantly lower in the intervention group at 30 days (Z=2.77; P=.006) and between 31 and 90 days post discharge (Z=2.31; P=.02).

    The Telehealth intervention is effective in improving functional and psychological outcomes and reducing rehospitalization rates among older patients undergoing CABG. Integrating telehealth into usual care can support recovery and enhance continuity of care.
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  • Effects of deconstructed Tai Chi step training combined with conventional rehabilitation on lower limb function in brunnstrom stage III stroke patients: A randomized controlled trial.
    1 week ago
    To evaluate whether a deconstructed Tai Chi stepping protocol adapted for patients with Brunnstrom Stage III stroke, when combined with conventional rehabilitation, improves lower limb motor function, walking ability, and joint mobility compared with conventional rehabilitation plus limb synergy training.

    In this assessor-blinded randomized controlled trial, 52 patients with subacute stroke (Brunnstrom Stage III, ≤ 6 months post-stroke) were randomized in a 1:1 ratio to an experimental group (conventional rehabilitation plus adapted Tai Chi stepping training) or a control group (conventional rehabilitation plus limb synergy training). Both interventions were delivered 5 days per week for 8 weeks. Fifty participants completed the study and were included in the final per-protocol analysis (25 per group). Outcomes were assessed at baseline and after intervention. The primary outcomes were the Fugl-Meyer Assessment for Lower Extremity (FMA-LE) and Holden Walking Function Classification. Secondary outcomes were hip, knee, and ankle range of motion (ROM).

    Both groups improved after treatment, with greater improvement observed in the experimental group. FMA-LE scores increased by 5.6 ± 1.5 points in the experimental group and 1.8 ± 0.8 points in the control group (p < 0.001, Cohen's d = 1.32). In addition, 92% (23/25) of participants in the experimental group achieved Holden Grades II-III compared with 60% (15/25) in the control group (p < 0.001). The experimental group also showed larger gains in joint ROM, including hip flexion (+19.9° vs. + 4.2°), knee external rotation (+9.9° vs. + 3.7°), and ankle dorsiflexion (+7.6° vs. + 1.3°) (all p < 0.001).

    Deconstructed Tai Chi stepping training combined with conventional rehabilitation was associated with greater improvement in lower limb motor function, walking ability, and joint mobility than conventional rehabilitation plus limb synergy training in patients with Brunnstrom Stage III stroke. This stage-specific protocol may represent a practical adjunct to stroke rehabilitation, although confirmation in larger trials is still needed.

    International Traditional Medicine Clinical Trial Registry (ITMCTR; a WHO ICTRP Primary Registry), registration number ITMCTR2025000972.
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  • VExUS versus CVP for assessing venous congestion: oasis or mirage?
    1 week ago
    Both venous excess ultrasound (VExUS) and central venous pressure (CVP) can assess venous congestion from different perspectives. CVP provides continuous and simple monitoring of the risk of congestion and is easily repeatable in patients with a central venous catheter. In contrast, VExUS offers an intermittent, organ-level evaluation of established congestion and may help identify the venous waterfall phenomenon. Furthermore, assessment of pulmonary congestion should not be overlooked.
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