Patients presenting to the emergency department (ED) with transient ischemic attack (TIA) or stroke, as well as admitted patients who develop stroke symptoms in acute nonstroke units, are commonly transferred to stroke units, where trained interdisciplinary teams provide comprehensive assessments and discharge planning. However, the lack of integrated interdisciplinary stroke assessments in the ED and acute nonstroke unit care settings has contributed to inefficient patient flow and capacity pressure, prolonged hospital length of stay (LOS), and delayed discharge. Prior models have emphasized rapid outpatient TIA or stroke prevention clinics and ED observation pathways; these approaches have largely focused on expedited medical diagnosis and treatment, with limited attention to coordinated interdisciplinary functional assessment and discharge planning to facilitate early discharge, especially from the ED and nonstroke units, reduce readmissions, and support rehabilitation.

This protocol outlines the implementation and prospective evaluation of the MOTIVE (Mobile Transient Ischemic Attack and Stroke With Adaptive Workflow) team, an interdisciplinary mobile service operational within the ED and inpatient nonstroke units at Health Sciences North, a regional stroke center in Northeastern Ontario. The service aims to deliver prompt medical and functional assessments to facilitate early decision-making and discharge planning. The objectives are to (1) reduce avoidable ED admissions for patients with TIA and minor stroke, (2) decrease hospital LOS, (3) maintain patient safety as measured by 30-day readmission rates, and (4) enhance patient and caregiver experience.

This single-center, prospective, uncontrolled, before-and-after quality improvement study will use control charts to evaluate temporal changes in outcomes. The MOTIVE project will follow the Institute for Healthcare Improvement Model for Improvement and will be reported in accordance with the SQUIRE (Standards for Quality Improvement Reporting Excellence) 2.0 guidelines. The preimplementation period (fiscal year 2022) will serve as the baseline period. The postimplementation evaluation will cover 12 months following the full implementation of the MOTIVE team, with iterative refinement guided by Plan-Do-Study-Act cycles.

This is a study protocol; therefore, the results are not yet available. Planned analyses will include run charts and control charts to evaluate temporal trends, alongside preimplementation and postimplementation comparisons. Outcomes will comprise primary measures (ED-to-inpatient admission rate, acute LOS, and avoided bed-day costs), process measures (time to interdisciplinary assessment, magnetic resonance imaging wait time, and proportion of patients triaged within 24 h), and balancing measures (30-day readmission, outpatient therapy services wait time, stroke prevention clinic referral volume and wait time, and patient and caregiver experience).

This innovative MOTIVE model is anticipated to improve stroke care efficiency, patient outcomes, and patient and caregiver experience through timely interdisciplinary assessments and support earlier discharge for select patients. The findings of this study will inform the feasibility and scalability of this model in similar health care contexts.

OSF Registries osf.io/2jybu; https://osf.io/2jybu.

DERR1-10.2196/93315.

Pediatric psoriasis may result in significant cumulative life course impairment, and there is comparatively less evidence available than for adult psoriasis.

The aim of this study is to provide an update on the management of pediatric psoriasis, integrating recent immunogenetic and therapeutic advances. It highlights challenges, including clinical heterogeneity, complex differential diagnosis, and limited treatment options, especially in Brazil.

A narrative review was conducted, including studies published in English, Portuguese, and Spanish between 2009 and 2025, retrieved from the United States National Library of Medicine (PubMed), Cochrane Library, and Scientific Electronic Library Online (SciELO). The following descriptors were used: "psoriasis", "child health", "pediatrics", "therapeutics", "comorbidity", and "T-lymphocyte antigen differentiation".

Pediatric psoriasis most commonly presents as chronic plaque. Differential diagnoses are broad and include atopic dermatitis and autoimmune diseases. Data about comorbidities, particularly cardiovascular risk, are controversial. Although severe cases are less frequent, they are associated with a substantial impact on quality of life. Conventional therapies include topical corticosteroids, phototherapy, and non-targeted systemic agents such as acitretin, methotrexate, and cyclosporine. Biologic therapies have been approved for pediatric use and demonstrate safety profiles and superior efficacy compared to conventional treatments.

Scarcity of pediatric psoriasis guidelines.

Despite advances in understanding adult psoriasis, evidence in pediatric populations remains limited, especially in Brazil. Expanding knowledge in pediatric psoriasis is essential to improve diagnosis, optimize treatment strategies, and increase access to innovative therapies, thereby reducing inflammatory burden and cumulative life course impairment.

Deep vein thrombosis (DVT) is a significant global health issue, often associated with a high symptom burden and reduced quality of life, especially after discharge. Traditional symptom management models are typically passive, clinician-centered, and lack real-time monitoring and feedback, which can lead to delayed interventions and poor patient engagement. While mobile health (mHealth) interventions offer a promising alternative, they require rigorous usability testing to ensure both efficacy and adoption.

This study aimed to design and develop Tpro (developed by the Department of Vascular Surgery, Peking Union Medical College Hospital), a patient-reported outcome (PRO)-based mobile app for patients with DVT. Using an iterative convergent mixed methods design, the app seeks to enable proactive symptom monitoring, health education, clinician-patient interaction, and peer support, thereby optimizing its usability, functionality, and alignment with patient needs.

The development followed an iterative convergent mixed methods design, comprising predevelopment and iterative optimization phases. Initial functions were informed by qualitative interviews with 14 patients with DVT. Over 4 iterative cycles, qualitative feedback and quantitative usability data (including task completion rates and User Interface Usability Questionnaire [UIUQ] scores) were concurrently collected, analyzed, and integrated via joint displays to guide refinements in content, interface, and system architecture until usability benchmarks were met.

The final Tpro app encompasses 4 core modules, including gamified symptom reporting, multimodal health education, clinician-patient communication, and a peer support community. Iterative testing identified and resolved key usability issues. The final prototype demonstrated high usability, achieving an excellent UIUQ score (mean 89, SD 13) and a task completion rate of 92% (12/13), indicating high user acceptance and operational reliability.

Applying the iterative convergent mixed methods approach enabled the systematic and user-centered development of Tpro. This methodology effectively integrated diverse stakeholder feedback into a functional and engaging patient-reported outcome-based app, ready for subsequent efficacy trials. This approach offers a replicable model for developing digital health tools in complex clinical contexts.

Background and objectives Cerebral venous thrombosis (CVT) is an uncommon cause of stroke, with limited multicentre data from India. This study describes the clinical profile, risk factors, management, and outcomes of CVT from ICMR-NINE Hospital-Based Stroke Registry Programme. Methods A cross-sectional analysis of CVT cases reported from 30 hospitals across India (January 2020-December 2022) was conducted. Sociodemographic, clinical, imaging, treatment, and outcome data were analysed. Functional outcome was assessed using the modified Rankin Scale (mRS). Multivariable logistic regression identified predictors of 3-month mortality. Results Among 34,792 registered stroke cases, 575 (1.6%) had CVT. Mean age was 37.5 years, with 72.4% (n= 416) aged 18-44 years, and 60% (n=345) were male. Headache (n=468, 81.4%), motor impairment (n=285, 49.6%), and seizures (n=259 ,45%) were the common presentations. Haemorrhagic infarction (n=177, 30.8%) was the predominant parenchymal imaging finding, with multiple sinus involvement in 62.4% (n=339). Anaemia (n=186, 32.6%), alcohol use (n=174, 30.9%), and hyperhomocysteinemia (n=152, 26.6%) were the leading risk factors. At 3 months, 74.8% (n=430) achieved good outcomes (mRS 0-2), (n=60) 10.4% remained with some disability, and 9.2% (n=53) died. Mortality was independently associated with age ≥45 years [Odds ration (OR) 12.11 to 18.32 depending on age group], impaired consciousness [OR =2.41, 95% confidence interval (CI): 1.03-5.67; P=0.044], dysphagia at onset (OR =3.36, 95% CI: 1.48-7.65, P=0.004), and delayed arrival at hospital between 12-24 h after symptom onset (OR =4.25, 95% CI: 1.08-16.74, P=0.038). Interpretation and conclusions In India, CVT-related stroke predominantly affects young males. Anaemia, alcohol use, and hyperhomocysteinemia are the major risk factors. Older age, delayed hospital presentation between 12-24 h, impaired consciousness, and dysphagia at onset, predict higher mortality.

Venous leg ulcers (VLUs) are prevalent hard-to-heal (chronic) wounds that decrease quality of life due to pain, reduced function and economic burden. One advanced therapy or cellular, acellular and matrix-like product (CAMP) which serves as a protective barrier for the management of acute and hard-to-heal wounds is a hypothermically stored amniotic membrane (HSAM). The objective of this study was to assess the clinical effectiveness and safety of HSAM plus standard of care (SoC) compared to SoC alone for the management of challenging and complex VLUs.

This prospective, multicentre, randomised controlled trial (RCT) evaluated patients over 24 weeks after a four-week run-in period. Endpoints included: frequency of wound closure of cohorts stratified by wound duration (>6 and >24 months); and intent-to-treat (ITT) population wound improvements of >60% area, >50% depth and >75% volume reduction.

The experimental cohort comprised 206 patients (randomised 1:1 to HSAM+SoC or SoC alone). Patient baseline demographics and wound characteristics were comparable between groups. The HSAM+SoC group demonstrated significantly higher rates of wound closure at weeks 12 and 16 (p<0.05) across both wound duration strata. In the ITT population, the HSAM+SoC group achieved significantly greater incidences of reduction in wound area (p=0.036), depth (p<0.001) and volume (p=0.034) compared to SoC alone.

In this study, HSAM+SoC was shown to be effective in the most challenging and complex VLUs, with increased wound closure rates compared to SoC alone when stratified by wound duration. These findings, alongside diabetic foot ulcer RCT results, provide compelling evidence for the significant clinical benefit of HSAM for hard-to-heal wounds.

Collagen is a key component of the extracellular matrix, providing structural integrity and supporting tissue remodelling. Its biodegradability, biocompatibility and resistance to degradation make it ideal for biomedical applications, such as wound healing, tissue engineering and surgical adhesives. Collagen also plays a vital role in wound healing by supporting clot formation, attracting growth factors and promoting tissue regeneration. The aim of this study was to use the technique of tropocollagen injections and evaluate its effect on wound healing.

In this pilot study, patients with hard-to-heal (chronic) granulating venous leg ulcers (VLUs), which were not infected or cancerous, underwent the procedure with tropocollagen injection to wound edges (at 1cm intervals), every second week for two months (the tropocollagen group). Patients were followed up every week over the two months and assessed for the percentage of wound that had re-epithelialised. Patients' pain levels were also noted using the Numerical Rating Scale (NRS). The same number of patients were treated as per those receiving the tropocollagen injections (debridement and same wound dressings but without the injections) to act as control.

A total of 20 patients were randomly allocated to the two groups (10 in the tropocollagen group and 10 in the control group). The tropocollagen group demonstrated a higher rate of relative wound re-epithelialisation by day 30. On day 60, the tropocollagen group exhibited a significantly higher degree of wound re-epithelialisation compared with the control group (p<0.01). In three patients in the tropocollagen group, complete re-epithelialisation was observed at the end of the study period. Moreover, mean pain levels measured with NRS during dressing changes were only slightly higher in the tropocollagen group than in the control group (4.0 versus 3.0, respectively; p=0.03), yet significantly lower during rest (mean 2.0 versus 3.5±1.0, respectively; p=0.01).

The findings of this small study indicate that tropocollagen injections have a high potential to accelerate the re-epithelialisation of hard-to-heal VLUs that do not respond to other treatment methods. It is an effective method that can be used in outpatient settings, as an alternative to skin grafting.

Leflunomide (LEF) shows promising effect in Takayasu arteritis (TAK), but evidence from randomized controlled trials is lacking. This study aims to investigate the efficacy and safety of LEF versus placebo combined with prednisone for the treatment of TAK.

This is a multicenter, randomized, double-blind, placebo-controlled trial at six sites across China, conducting from December 22, 2016, to November 4, 2022. A total of 116 eligible patients were recruited and randomized 1:1 to receive LEF (20 mg/d, p.o.) or matched placebo for 24 weeks, with all patients having initial prednisone of 0.6 mg/kg/d and following a taper starting at week 4. By week 24, patients in the LEF group who did not achieve clinical remission discontinued the study; all other patients (both LEF and placebo groups) received LEF (20 mg/d) from week 25 to week 52. The primary outcome was clinical remission at week 24. Secondary outcomes were time-to-clinical remission, mean prednisone dose at week 24, clinical remission in those who switched to LEF from week 25, disease recurrence and time-to-recurrence, imaging changes, and safety.

Fifty-four and 57, 45 and 48 patients were included in LEF and placebo group of modified intention-to-treat (mITT) and per-protocol set (PPS). In mITT set, clinical remission was achieved in 44/54 (81.5%) LEF- and 45/57 (78.9%) placebo-treated patients (risk difference: 2.6, 95%CI: -12.5, 17.2) at week 24. The same trend was observed in the sensitivity analyses. Post hoc analyses indicated greater risk differences (LEF minus placebo) in the female subgroup, ≤ 40 years subgroup, refractory subgroup, systemic symptoms subgroup, imaging type II subgroup and in those achieving the composite endpoint of both clinical remission and stable/improved imaging. At week 24, LEF group had a lower mean prednisone dose (mean difference: -2.1, [-4.3, 0.1] mg/d). Adverse events were observed in 13 (24.5%) LEF- and 22 (39.3%) placebo-treated patients. Serious adverse events were reported in six LEF- and four placebo-treated patients. One death was reported in placebo group.

Although the primary endpoint was not met, our results still provide evidence supporting LEF as a potential alternative treatment option for TAK.

ClinicalTrials.gov identifier NCT02981979.

PCSK5 (proprotein convertase subtilisin/kexin 5) is essential for heart development. However, its role in myocardial infarction (MI) remains unexplored. In this study, we found that the plasma levels of PCSK5 were elevated in MI patients and exhibited potential in predicting cardiac function improvement. PCSK5 expression was upregulated in cardiac endothelial cells (ECs) of MI patients. Pcsk5 deficiency in ECs impaired angiogenesis and cardiac recovery post-MI, and delayed tissue repair following hindlimb ischemic injury in male mice. In contrast, the endothelial-specific Pcsk5 delivery enhanced angiogenesis and cardiac function post-MI. Mechanistically, PCSK5 directly cleaved VEGFA, activating its signaling and promoting angiogenic activity. The residues Arg158 and Asn164 of PCSK5 were crucial for its function. Semaglutide increased vascular densities and cardiac function post-MI, partially through EC-derived Pcsk5 in male mice. This study identified PCSK5 as a pro-angiogenic factor secreted by ECs, with the potential to become a therapeutic target for ischemic diseases.

Elevated serum ferritin levels predict adverse outcomes in many autoimmune diseases. However, its clinical significance in Takayasu arteritis (TAK) is not clear. This study aimed to evaluate the predictive value of serum ferritin for major adverse cardiovascular events (MACEs) in TAK.

A two-center retrospective cohort study was conducted. A total of 189 treatment-naïve TAK patients who underwent serum ferritin testing at baseline were consecutively enrolled and followed longitudinally. The association between serum ferritin levels and adverse events was assessed using survival analyses.

Thirty-seven patients (19.6%) experienced MACEs during a median follow-up of 34.00 (20.00-55.00) months. Using the cut-off value of 68.6 μg/L, patients with high serum ferritin levels exhibited significantly higher MACE rates at 12, 36, 60, and 96 months compared to those with low levels (χ2 = 8.59, P = 0.003; χ2 = 15.23, P < 0.001; χ2 = 11.48, P < 0.001; χ2 = 12.63, P < 0.001, respectively). Serum ferritin was an independent predictor of MACEs in TAK at 96 months, both when analyzed as a continuous variable (HR: 1.003, 95% CI: 1.001-1.006, P = 0.007) and as a categorical variable (HR: 2.609, 95% CI: 1.280-5.320, P = 0.008). Furthermore, the predictive value of serum ferritin remained consistent across most subgroups, except among male patients (P for interaction = 0.018, P > 0.05), smokers (P for interaction = 0.027, P > 0.05) and patients receiving glucocorticoids (P for interaction = 0.033, P > 0.05).

Elevated serum ferritin is an independent predictor of MACEs in TAK. Patients with increased baseline serum ferritin levels should undergo close monitoring and may benefit from intensified therapeutic interventions due to their higher risk of adverse events. Key Points • Elevated Serum ferritin is associated with poorer prognosis in Takayasu arteritis. • Serum ferritin is an independent prognostic biomarker in Takayasu arteritis. • The predictive value of serum ferritin is consistent across most subgroups.

To provide an overview of diagnostic tests for Stage B heart failure (SBHF), synthesizing evidence from guidelines and clinical studies.

Advances in diagnostic technologies have expanded the ability to identify subclinical myocardial remodelling and early myocardial injury before symptom onset. We highlight the central role of transthoracic echocardiography as the cornerstone diagnostic modality for detecting subclinical myocardial remodelling and dysfunction, including the use of speckle tracking echocardiography. In parallel, circulating biomarkers, especially natriuretic peptides and high-sensitivity cardiac troponins, can play important roles in the detection and risk stratification of SBHF. Additional diagnostic approaches, including electrocardiography, chest X-ray, cardiac magnetic resonance imaging, cardiac computed tomography, nuclear imaging, and exercise stress testing, are reviewed for their adjunctive roles in selected clinical contexts. Emerging applications of artificial intelligence are explored as promising strategies to increase the diagnostic precision, scalability, and early detection of SBHF in clinical practice. SBHF - representing a subclinical phase of HF characterized by structural cardiac abnormalities, functional impairment, or persistently abnormal cardiac biomarkers in individuals - has historically been difficult to recognize in the community. Advances in imaging, biomarkers, and AI may improve the feasibility of detecting this entity, creating a crucial window for intervention, because timely risk stratification and preventive strategies during SBHF may attenuate progression to symptomatic HF and reduce its long-term clinical and economic burden.