Journal of Stroke and Cerebrovascular Diseases

Background: Circulating endothelial progenitor cells (cEPCs) contribute to vascular repair following an ischemic stroke. The aim of the study was to evaluate the association between cEPCs and functional outcomes in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) who received endovascular therapy (EVT). Methods: Prospective study of patients with LVO-AIS who received EVT. Blood samples were obtained within 24 +- 12 hours and on day 7+-1 from stroke onset. cEPCs were detected using flow cytometry (CD34+/VEGFR2+/CD133+). The primary endpoint was a favourable functional outcome (modified Rankin Scale 0-2) at three months of follow-up. Secondary endpoints include baseline to 24 hours/day 7 changes in the National Institutes of Health Stroke Scale (NIHSS) score and collateral circulation (CC) status. Bivariate and multivariable logistic regression analyses were performed. Results: Included were 90 patients (73.2+-12.7 years, 41.1% women) in 42 of whom (46.7%) cEPCs were detected at 24 hours. On day 7, cEPCs were detected in 27 (43.6%) of 62 patients for which this information was available. Atrial fibrillation, prior anticoagulant treatment and stroke onset-to-door time <6 hours were associated with lower cEPC counts, and intravenous fibrinolysis therapy was associated with a higher cEPC count on day 7. No association was found between cEPCs and functional outcomes at three months. Patients with the highest cEPC count (Q4) at 24 hours had a lower probability of good CC (46.2% vs 77.3%; p=0.031). Conclusion: cEPC count in patients with LVO-AIS who received EVT was not associated with functional outcomes.

Stroke is a leading cause of disability and mortality worldwide, with ischaemic stroke the most prevalent type. Statins, used for cholesterol management, have demonstrated benefits in reducing stroke risk and improving outcomes in preclinical studies. However, the impact of pre-stroke statin use on stroke outcomes remain inconsistent. In this study, we aim to evaluate whether pre-stroke statin use is associated with greater volume of salvaged tissue and improved cerebral collateral perfusion. A retrospective analysis was conducted using data from 281 patients presenting with acute ischemic stroke to the John Hunter Hospital between May 2015 and May 2020. Patients were grouped based on pre-stroke statin use, and clinical variables, including infarct volume and collateral perfusion, were assessed. The primary outcome was salvage volume derived from baseline perfusion lesion volume minus infarct volume at follow-up. Collateral perfusion was measured by the hypoperfusion volume defined by delay time (DT)>6 seconds divided by the hypoperfusion volume defined by DT >2 seconds. Patients on statins at admission were significantly older and had more comorbidities. No significant association was found between pre-stroke statin use and salvage volume or collateral perfusion after adjusting for covariates. Larger initial infarct core was a significant predictor of salvage volume due to larger salvageable tissue volume at baseline. These findings indicate that pre-morbid statin use is not associated with larger salvage volume or improved cerebral collateral perfusion.

Background: Late complications after stroke (LCAS), including cognitive symptoms, impact quality of life and recovery. It is not known if neighborhood-level measures of socioeconomic status (SES) influence LCAS. This study assessed associations between SES measures, including neighborhood income inequality (Gini) and area deprivation index (ADI), and cognitive symptoms after acute ischemic stroke (AIS) in a hospital leveraging active surveillance of LCAS. Methods: This retrospective cohort study included 512 patients hospitalized with AIS at Tufts Medical Center with subsequent follow-up (between zero and three months or between three and twelve months) in the Stroke Clinic from 1/1/2018 - 12/31/2022. Using ZIP code data, patients were characterized as low Gini (low inequality) and high ADI (high deprivation) (Gini <= 0.4302, ADI >= 5) by state medians. These variables were combined, indicating patients who were living in both a low Gini and high ADI neighborhood to evaluate the effects of living in a homogeneously deprived area. There were 206 and 281 patients in the low Gini and high ADI groups respectively. 140 patients lived in a low Gini and high ADI neighborhood. The multivariable logistic analysis assessed the likelihood of cognitive symptoms, adjusting for age, race, ethnicity, sex, NIH Stroke Scale (NIHSS), thrombolysis, active LCAS surveillance, poverty, and ADI-Gini combination. Results: There were no associations between high ADI (OR: 1.03, 95% CI: 0.67 ? 1.57) or low Gini (OR: 1.74, 95% CI: 0.98 ? 3.07) alone and cognitive symptoms after AIS. However, the combined variable demonstrated increased likelihood of cognitive symptoms in the high ADI-low Gini group (OR: 1.82, 95% CI: 1.08 ? 3.06). Conclusions: This study suggests that individuals living in homogeneously deprived neighborhoods report higher likelihood of cognitive symptoms after AIS. Further studies with increased power are needed to investigate the underlying causes of these disparities and to develop interventions to reduce these complications.

INTRODUCTION Severe acute brain injury (stroke, traumatic brain injury or hypoxic-ischemic encephalopathy; SABI) is increasingly recognized as a chronic condition with care and communication needs beyond the initial hospitalization. This study aimed to characterize post-acute care patterns among SABI survivors, focusing on healthcare utilization and outpatient communication. METHODS Data were collected from a prospective cohort of hospitalized SABI patients using surveys, chart reviews, and the ED Information Exchange database. Socioeconomic disadvantage was assessed using the Area Deprivation Index (ADI), and qualitative analysis of outpatient notes examined conversations around palliative care needs and goals-of-care. RESULTS Two-thirds of patients (140/222) survived until discharge, primarily to nursing facilities (39%) or inpatient rehabilitation (38%). Among 109 with one-year follow-up, there were 89 hospitalizations, 104 ED visits, and 28 deaths. Patients from the most disadvantaged neighborhoods had significantly higher odds of rehospitalization or ED use within 30 days (OR 3.37, p=0.036). ADI was not linked to one-year utilization. seen outpatient by primary care (40%), neurology/neurosurgery (57%), and palliative care (1%), but conversations rarely revisited prognosis or goals-of-care. CONCLUSIONS Our findings highlight the need for improved long-term care planning and communication, particularly for socioeconomically disadvantaged survivors of SABI.

Objective: Outcome after surgical hematoma evacuation for intracerebral hemorrhage (ICH) depends on hematoma location. As corticospinal tract (CST) integrity affects motor recovery after stroke, we hypothesized that CST integrity drives heterogeneity in surgical outcomes and investigated this in a secondary analysis of MISTIE-III participants. Methods: Risk of CST injury was categorized into four levels, based on the interaction between the CST, the hematoma, and perihematomal edema (PHE) on automatically segmented stability CT: no risk, PHE infiltration, hematoma infiltration, and complete interruption of the CST. Associations with outcome were tested using multivariable linear regression for motor National Institutes of Health Stroke Scale (NIHSS) at day 180 and ordinal regression for modified Rankin Scale (mRS) at day 365, introducing an interaction term between CST risk and treatment group. Results: Day 180 motor NIHSS was significantly lower for 'no risk' ({beta}:-3.77, [95% confidence interval [CI]: -5.8 to -1.70], p=0.0003) and 'PHE infiltration' ({beta}:-2.3, [95%CI: -3.5 to -1.1]; p=0.0002) vs. 'complete interruption'. Surgery was associated with lower Day 180 motor NIHSS in participants with hematoma infiltration ({beta}:-2.07, [95%CI: -3.8 to -0.4], p=0.016). Compared to complete interruption, 'no risk' (adjusted odds ratio [aOR]:0.27, [95%CI: 0.10 to 0.74], p=0.01) and 'PHE infiltration' (aOR:0.41, [95%CI: 0.23 to 0.74]; p=0.003) were associated with lower odds of unfavorable day 365 mRS. Surgery was associated with lower mRS in participants with no risk (aOR:0.23, [95%CI: 0.05 to 0.97, p=0.045). Interpretation: Increasing CST risk is associated with worse motor recovery (day 180) and disability (day 365). CST risk modifies the effect of the MISTIE-III procedure on motor recovery and disability.

Background: Depression and heart disease frequently co-occur in the aging population and are associated with functional decline and poor health outcomes. Understanding how depressive symptoms relate to different aspects of physical function among adults with heart disease may help identify high-risk subgroups. Objective: To examine the association of depressive symptoms with self-reported and observed physical function measures among participants with heart disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and assess whether associations differ by sex and race?sex groups. Methods: We conducted a cross-sectional analysis using data from REGARDS study second in-home visit (2013?2016). Depressive symptoms were measured with the 10-item Center for Epidemiologic Studies Depression scale (CES D 10), considering scores ?10 as clinically significant. Physical function measures were instrumental activities of daily living (IADL), activities of daily living (ADL), chair stand time (5 repetitions), and gait speed. Linear regression models estimated associations of depressive symptoms with function, adjusting for sociodemographic, health behavior, antidepressant medications, body mass index, and social support. Effect modification by sex and race?sex group was evaluated. Results: Among 3,055 participants, 11.7% had CES D 10 ?10. Compared to CES-D-10 scores <10, CES D 10 ?10 was associated with more limitations in IADL (1.84 points; 95% CI 1.62, 2.06), ADL (0.43 points; 95% CI 0.34, 0.52) and slower chair stand time (0.88 second; 95% CI 0.07, 1.69); associations with gait speed were modest (?0.04 meters/second; 95% CI ?0.08, -0.01). Women had a stronger association between CES-D-10 and ADL (0.49 points; 95% CI 0.35, 0.64) than men (0.33 points; 95% CI 0.21, 0.44; p for interaction = 0.01). Interaction between CES D 10 and race?sex groups was not statistically significant. Conclusions: Among adults with heart disease, clinically significant depressive symptoms were associated with lower physical function, particularly among women.

This cross-sectional study aimed to examine the prevalence of alcohol use and its sociodemographic correlates among adults with cardiovascular disease (CVD). We analyzed data from two large US cohorts: the All of Us Research Program (2017-2023) and the National Health and Nutrition Examination Survey (NHANES, 1999-2016). Both CVD diagnosis and past-year alcohol consumption were self-reported. Risky drinking was defined as exceeding moderate drinking or binge drinking (All of Us), or moderate/heavy drinking (NHANES). Multivariable logistic regression was used to exam associations with sociodemographic and lifestyle factors. Among 32,788 current drinkers with CVD in the All of Us cohort, 15% exceeded moderate drinking thresholds and 26% reported binge drinking. Older age, female sex, and higher socioeconomic status were inversely associated with risky drinking, while smoking was positively associated. In NHANES, moderate drinking rose from 47.3% to 57.2% and heavy drinking from 6.7% to 7.2%. Moderate/heavy drinking was positively associated with age <65 but inversely with age [&ge;]65. Higher education and income were linked to moderate drinking, while current smoking was strongly associated with heavy drinking. These results highlight the need to integrate holistic screening for alcohol use, tobacco use, and social context into routine cardiovascular care.

Brain-derived tau (BD-tau) is an emerging blood-based biomarker for neurodegeneration, yet there are currently limited well validated BD-tau assays available for research and clinical use. To enhance access to this vital biomarker for neurological disorders including traumatic brain injury (TBI), we developed a novel blood-based immunoassay for BD-tau on the ultra-sensitive Quanterix HD-X platform using Single Molecule Array technology. Analytical validation assessed dilution linearity, specificity, precision, detection limits, and spike recovery, each recording robust metrics in agreement with international expert recommendations. The assay demonstrated robust validation metrics, achieving between-run stability of 95% when analyzing aliquots from six independent plasma and serum samples across five analytical runs. It also showed strong dilution linearity when diluted four-fold and achieved over 90% recovery when spiked with cerebrospinal fluid. Next, we evaluated the clinical utility of the assay in cohorts of individuals with traumatic brain injury (TBI), where strong performances were recorded whether using the 2-step or 3-step assay formats ({rho}= 0.94; p < 0.0001). Furthermore, plasma BD-tau distinguished samples from TBI patients based on time from injury and severity (AUC=0.93). Plasma BD-tau differentiated between favorable and unfavorable functional outcomes in the acute-severe group. Our findings underscore the significant potential of the BD-tau assay as a biomarker for TBI in the severe phase.

Background. Capillary refill time is a resuscitation target in septic shock,1-4 but bedside measurement is examiner-dependent. An ICU monitor co-records a photoplethysmogram on the pulse oximeter and intermittent noninvasive blood pressure cuff cycles; if the probe and the cuff share a limb, each cycle is an unplanned vascular occlusion test on the distal microvascular bed. Standard practice places the two on opposite limbs. Objective. To measure how often, in MIMIC-IV-WDB v0.1.0, charted cuff cycles show the photoplethysmographic morphology expected of a same-limb cuff and probe, and to characterize the candidate capillary refill-like signal when that morphology is present. Methods. MIMIC-IV-WDB v0.1.05 was linked to the MIMIC-IV clinical database.6 A pre-registered rule-based detector identified candidate occlusion-reperfusion signatures on the 1-Hz perfusion-index envelope around each charted cuff timestamp. The primary endpoint was the proportion of cuff cycles suitable for analysis that were detector-positive at a 15-second reperfusion threshold, with 95% confidence intervals estimated by resampling patients at a fixed seed. A secondary analysis used a locally hosted multimodal language model (a Gemma-3 derivative on a non-device server) to adjudicate the same signature on perfusion-index plots; no MIMIC-IV-WDB content left the workstation. Results. Of 9,224 charted cuff cycles, 8,909 had a usable pulse-oximeter waveform, and 268 cycles in 15 patients (4.30% of the 6,236 cuff cycles suitable for analysis, 95% CI 2.60 to 6.03) met the primary 15-second threshold. The language model adjudicated the same cycles and called 1,367 of the 8,909 cycles with a usable waveform (15.34%) signature-present, roughly five times the detectors count. Because no laterality ground truth exists, agreement with a single blinded reader served as the comparator rather than accuracy. The two methods were about equally concordant with the reader: precision was 0.25 (95% CI 0.14 to 0.39) for the detector and 0.24 (95% CI 0.10 to 0.35) for the language model, although reweighting to the full population of cycles with a usable waveform lowered the language model to 0.030 (95% CI 0.009 to 0.053). These estimates are reference-limited: a blinded re-read of a 150-card subsample showed only moderate intra-rater reliability (Cohen {kappa} 0.46 to 0.59) with systematic undercalling on the first pass, and rescoring against the corrected re-read roughly doubled precision for both methods. Conclusions. Opportunistic extraction of capillary refill-like signals from archived ICU pulse oximetry is limited in two distinct ways. First, sensor geometry limits how often the signal is recordable: cuff cycles rarely show the morphology expected of a same-limb cuff and probe pair, consistent with opposite-limb placement, so the bottleneck is geometry rather than signal processing. Second, the modest reliability of morphology adjudication limits how well any single flagged cycle can be confirmed: against a blinded reader the detector is a usable screen but a noisy confirmer, the reference is itself only moderately reliable, and the language model is no more concordant despite flagging many more cycles. The minority of cycles in which the morphology appears contain a candidate signal that may merit prospective study under controlled placement with laterality recorded.

Introduction: Early hospital presentation after stroke onset is necessary for rapid assessment and access to time-dependent acute management. This study examined the correlates of late presentation for stroke care among patients recorded at a tertiary hospital in Ondo State, Nigeria. Methods: A retrospective records review was conducted using secondary data from the Stroke Registry of the University of Medical Sciences Teaching Hospital, radiology department records, referral notes, and ambulance records. Records of stroke cases documented within the preceding 24 months were reviewed. Late presentation was defined as hospital presentation more than four hours after symptom onset. Frequencies, chi-square tests, and modified Poisson regression with robust standard errors were used to estimate adjusted prevalence ratios. Results: The analysis included 371 stroke cases. Of these, 317 (85.4%) presented after four hours, and the median time to presentation was 24 hours (interquartile range: 9-72 hours). Late presentation differed significantly by employment status, first-contact route, and pathway complexity at bivariate analysis. After adjustment, non-hospital first contact remained strongly associated with late presentation: patients whose first documented contact was non-hospital-based had almost 3 times the prevalence of delay compared with those whose first contact was hospital-based (adjusted prevalence ratio = 2.89; 95% confidence interval: 2.15-3.90; p < 0.001). Conclusion: Late presentation was pervasive in this tertiary hospital record cohort and was primarily associated with the initial direction of care-seeking. Stroke response interventions should emphasise immediate hospital presentation and strengthen urgent referral from non-hospital first-contact points.

Background: A growing burden of cardiovascular risk factors has raised cardiovascular disease-related mortality in Sub-Saharan Africa (SSA), driving higher prevalence of heart failure with reduced ejection fraction (HFrEF) and its complication with atrial fibrillation (AF). No prospective study has examined AF's clinical impact on HFrEF in SSA. Aim: To determine AF prevalence in HFrEF, describe HFrEF-AF clinical characteristics, and determine AF's impact on mortality. Methods: In this prospective observational study at a tertiary hospital in Johannesburg, 136 HFrEF patients were enrolled and categorised as HFrEF- SR (sinus rhythm) or HFrEF-AF. Baseline clinical characteristics and biochemistry were recorded. Comprehensive echocardiography including left atrial strain by 2D speckle-tracking was performed. Median follow-up was 30.6 months. Results: AF was present in 28 patients (21%). The mean age was 58.7 {+/-} 14.9 years (52.9% male) and differed between groups (p < 0.001). Hypertensive heart disease was the leading cause of HFrEF (36%). Compared with SR, HFrEF-AF patients had poorer health status (KCCQ 27 [16-43] vs 45 [32-60], p < 0.001) and lower left atrial strain (26.2 {+/-} 11.3%, p < 0.001). Guideline-directed medical therapy was suboptimal in the AF group: anticoagulation use was higher than SR (60% vs 9.5%, p < 0.001) but overall inadequate; HFrEF-AF patients received lower median doses of carvedilol (15.6 mg vs 25 mg, p = 0.002) and enalapril (10 mg vs 20 mg, p = 0.004), and fewer received spironolactone (50% vs 75.3%, p = 0.013). Survival was significantly lower in HFrEF-AF (0.41 [0.22-0.61]) versus SR (0.73 [0.61-0.82], p < 0.001). Independent predictors of mortality included prior stroke, lower TAPSE and KCCQ, and higher E/e' and heart rate. Conclusion: AF is common among HFrEF patients in this SSA cohort (though lower than in high-income countries) and associates with worse clinical status, suboptimal therapy, and higher mortality.

Background: Primary aldosteronism (PA) is increasingly recognized as a common cause of hypertension. The 2025 Endocrine Society guideline introduced a simplified diagnostic framework, but its real-world clinical implications remain unclear. Methods: We conducted a multicenter retrospective cohort study of hypertensive patients undergoing PA testing in Taiwan. PA was defined biochemically according to the 2025 Endocrine Society criteria. Multivariable logistic regression identified factors associated with PA diagnosis and aldosterone-targeted therapy. Among patients with suppressed renin (?1 ng/mL/h), restricted cubic splines evaluated the adjusted association between renin and PA probability. Results: Among 18,766 patients undergoing PA testing, 6,760 (36.0%) met diagnostic criteria for PA. PA was associated with older age, female sex, lower potassium, resistant hypertension, and a higher antihypertensive medication burden. Among patients with suppressed renin, lower renin remained significantly associated with higher adjusted PA probability. However, only 39.0% of patients with PA received aldosterone-targeted therapy, including 28.2% who received mineralocorticoid receptor antagonist therapy within 6 months and 9.4% who underwent adrenalectomy during follow-up. Lower renin, higher aldosterone, lower potassium, and resistant hypertension were associated with aldosterone-targeted therapy, while younger patients with fewer comorbidities were more likely to undergo adrenalectomy. Conclusions: Using the updated diagnostic framework, PA was highly prevalent among hypertensive patients undergoing PA testing. Nevertheless, many patients who met these biochemical criteria did not receive aldosterone-targeted therapy in routine care. These findings highlight the potential treatment implications of broader PA recognition and support the development of practical pathways to guide MRA therapy, adrenalectomy referral, and individualized management.

Background Totally endoscopic aortic root (AR) surgery via right anterior minithoracotomy (RAMT) may reduce surgical trauma and accelerate recovery compared with full sternotomy (FS). However, the approach is technically demanding due to limited access and anatomical complexity. This study compares early clinical outcomes and quality of life (QoL) after RAMT versus FS to evaluate the feasibility and safety of the totally endoscopic approach. Methods This single-center, retrospective study included 149 patients underwent AR surgery via RAMT (n=74) or FS (n=75) between January 2021 and March 2026. Patients with aortic dissection, infective endocarditis, redo surgery, concomitant procedures, or arch replacement were excluded. Operative outcomes, postoperative recovery, 30-day and 1-year mortality were analyzed. QoL was assessed using the Short Form-8 (SF-8) questionnaire. Results The median age was 60.0 years, and 79.9% of patients were male. Bentall procedure was performed in 84.6% of patients, 15.4% underwent a David procedure. Compared with FS-AR, RAMT-AR was associated with shorter median operative time (147.0 vs. 178.0 min; p<0.001), lower median chest drainage volume (650.0 vs. 850.0 mL; p<0.001), and shorter median ICU stay (24.0 vs. 25.0 h; p=0.008) and hospital stay (6.0 vs. 8.0 days; p=0.028). Overall, 30-day and 1-year mortality was 0.7%. SF-8 analysis demonstrated significantly higher physical and mental component scores in RAMT-AR patients. Conclusion In specialized centers, totally endoscopic AR surgery via RAMT is a safe and feasible minimally invasive approach associated with favorable early outcomes and a potential benefit in postoperative physical and mental QoL by reducing surgical trauma.

Aims This multicenter study aims to compare outcomes of total aortic arch replacement (TAR) using the frozen elephant trunk (FET) technique in patients with and without heritable thoracic aortic disease (HTAD) and to assess whether HTAD influences postprocedural adverse aortic events (AAEs). Methods From 06/2007 to 05/2024, aortic databases from 13 European centers were screened for HTAD patients undergoing TAR with FET. All consecutive dissection and aneurysm non-HTAD patients from the four core centers served as comparator. The primary outcome was AAE, a composite of diameter progression, distal stent graft induced new entry (dSINE), malperfusion, rupture and pseudoaneurysm at 5 years after FET implantation. Results Of 2739 FET patients, 196 (7.2%) were diagnosed with HTAD. The control group consisted of 867 non-HTAD FET patients. Marfan syndrome was the most common condition (72%), followed by Loeys-Dietz syndrome (11%), vascular Ehlers-Danlos syndrome (5.6%) and Turner syndrome (2.0%). Seventeen (8.8%) patients were diagnosed with ns-HTAD. At 5 years 46 (24%) AAEs occurred in the HTAD group, 169 (20%) in the non-HTAD group (p=0.2). Diameter progression was the most common event (10% vs. 12%; p=0.6), followed by dSINE (5.8% vs. 4.5%; p=0.5), malperfusion (4.2% vs. 3.3%; p=0.5), rupture (2.1% vs. 0.7%; p=0.09) and pseudoaneurysm (0.5% vs. 0.2%; p=0.5). Conclusions The FET technique appears safe and effective for acute and chronic aortic disease in HTAD patients, with outcomes comparable to non-HTAD cases and no increase in graft-related complications, challenging traditional concerns about stent graft use in genetically mediated aortic disease.

Introduction: Stroke care is time-sensitive, yet patients in low-resource settings may reach tertiary services only after passing through multiple formal and informal care options. This study examined documented care-seeking pathways and time to presentation among stroke cases recorded at the University of Medical Sciences Teaching Hospital (UNIMEDTH), Ondo State, Nigeria. Methods: A retrospective hospital record review was conducted using secondary data from the Stroke Registry, radiology department records, referral notes, and ambulance records at UNIMEDTH. The analysis included 371 stroke cases with documented time from symptom onset to UNIMEDTH presentation and reconstructable care pathways. First-contact routes were classified as hospital/biomedical, self/informal or traditional/faith-based care, and the number of documented steps defined pathway complexity before and including tertiary presentation. Frequencies and percentages described pathway patterns; median presentation times were compared using Mann-Whitney U and Kruskal-Wallis tests. Results: The median time to tertiary presentation was 24 hours (interquartile range [IQR] 9-72), and 317 patients (85.4%) presented after four hours. Only 30 patients (8.1%) presented directly to UNIMEDTH; 44 distinct care-pathway sequences were recorded. Hospital-facility first contact was documented for 81 patients (21.8%). It was associated with a median presentation time of 3 hours (IQR 2-6), compared with 48 hours (IQR 24-72) among patients whose initial contact was outside a hospital facility (U = 699.50, p < 0.001). The median time also differed across grouped first-contact categories and pathway complexity levels (both p < 0.001). Conclusion: Non-hospital or multi-step care-seeking pathways commonly preceded tertiary stroke presentations in this setting. The findings indicate that delayed tertiary arrival is partly embedded in the pathway followed after symptom onset. Interventions should combine public recognition of stroke warning signs with urgent referral linkages involving hospitals, patent medicine vendors, traditional and faith-based providers, and emergency transport systems.

Background: In atrial fibrillation (AF), cerebral microbleed (CMB) burden guides anticoagulation decisions, yet AF is itself inconsistently associated with CMBs, a paradox unexplained by frameworks that treat CMBs as a unitary marker of small vessel disease. We hypothesized that the white matter hyperintensity (WMH) context in which CMBs arise modifies their vascular meaning, and that this context-dependence underlies the inconsistent AF-CMB association. Methods: From a multicenter Korean stroke registry, we analyzed 5,735 first-ever ischemic stroke patients imaged at nine centers using susceptibility-weighted MRI. WMH volume and CMB count were extracted by validated deep learning pipelines. Patients were cross-classified by age-adjusted WMH residual (median split) and CMB count (2) into four groups. The AF-CMB association was estimated by multivariable logistic regression within each WMH stratum with formal interaction testing. Spatial CMB distribution was analyzed against the Automated Anatomical Labeling atlas. Results: In the full cohort (mean age 69.5 years; 57.7% male), AF was not associated with CMBs (OR 1.04; 95% CI 0.87-1.25). Stratification yielded divergent estimates: the adjusted AF OR was 1.46 (1.11-1.93; P = 0.007) in the WMH-low stratum and 0.95 (0.73-1.22; P = 0.665) in the WMH-high stratum, with significant interaction (OR 0.56; P < 0.001). The discordant phenotype (low WMH, high CMB; 8.9%) was enriched for AF (28.0%) and showed fronto-temporal cortical predominance with deep structure sparing. AF independently reduced the proportion of deep CMBs (IRR 0.80; P = 0.040). The interaction was preserved across prespecified sensitivity analyses. Conclusions: The AF-CMB association is confined to patients with low WMH burden relative to age and is accompanied by a topographically distinct CMB distribution. Clinical assessment of small vessel disease based on WMH alone may overlook a CMB phenotype linked to AF.

Introduction: To investigate the epidemiological characteristics of chronic kidney diseases (CKD) in China in 2021 and its trends between 1990 and 2021, in the context of significant population growth and lifestyle changes over the past 30 years that have likely influenced the CKD spectrum. Methods: Data on CKD prevalence, mortality, disability-adjusted life-years (DALY), and risk factors were obtained from the Global Burden of Disease Study 2021. The estimated decadal percentage changes were calculated to evaluate changes in trends in prevalence, mortality and disease burden. Results: In 2021, an estimated 118.4 (95% UI 109.4 to 127.5) million people in China were affected by CKD, contributing to 204 230 (95% UI 164 736 to 246 372) deaths and 6.13 (95% UI 5.18 to 7.21) million DALY. Although CKD due to diabetes mellitus and hypertension accounted for less than a quarter of all cases, they were responsible for over 90% of CKD-related deaths. Over the past three decades, CKD mortality and DALY rates have steadily increased, although the prevalence has stabilized in the last decade. Diabetes mellitus type 2 and hypertension have emerged as key drivers of CKD burden in China. Conclusions: The CKD burden in China shows a dual pattern of rising incidence and high mortality from diabetes and hypertension-related chronic kidney disease, alongside persistently high years lived with disability from glomerulonephritis and other causes.

Background: Cardiac surgery using cardiopulmonary bypass uses controlled hypoperfusion which leads to relative organ damage. Acute kidney injury is the most frequent and most important organ failure, in particular in patients with chronic kidney disease. To date, there are no approved drug treatments that could effectively prevent acute kidney injury. SP16, an agonist of the low-density lipoprotein receptor-related protein 1, has been shown to exert both reno- and cardioprotective effects in preclinical trials. Early clinical use of SP16 in phase I trials was safe. Administration of SP16 had beneficial trends on inflammatory response and infarct size in patients with ST-segment elevation myocardial infarction. The primary objective of this phase IIa trial is to demonstrate that injection of SP16 is safe and superior to placebo in preventing cardiac surgery-associated acute kidney injury within 7 days after surgery. Methods: This randomised, double-blinded, placebo-controlled, single centre study evaluates the efficacy and safety of SP16 in 120 high-risk chronic kidney disease patients with disease stadium G2-G3b undergoing cardiac surgery who are randomised into one of two treatment groups in a 1:1 ratio: SP16 (12 mg) or placebo. The study medication is administered via two subcutaneous injections, with the first dose given before surgery, followed by an additional dose after 9 h. Primary endpoints are the incidence of acute kidney injury during 7 days post-surgery and the frequency of adverse events within 72 h after index surgery. Important secondary endpoints include the incidence of major adverse kidney events at day 90 and impact on cardiac function. Safety assessments encompass adverse events, vital signs, electrocardiograms and routine safety laboratory tests. Additional evaluations include pharmacokinetics and immunological biomarkers. Discussion: This single-centre phase IIa trial will assess the incidence of cardiac surgery-associated acute kidney injury, describing the renoprotective potential of SP16 and its safety profile in patients undergoing cardiac surgery.

Background: Mucopolysaccharidosis type IIIB (MPS IIIB) is a devastating neurodegenerative lysosomal storage disorder caused by alpha-N-acetylglucosaminidase (NAGLU) deficiency. There is currently no approved therapy. We report the 3-month outcomes of a novel intracerebroventricular (ICV) gene therapy in a child with MPS IIIB. Methods: In an open-label, single-center, investigator-initiated trial (ChiCTR2600121466), a single dose of RDGT-101 (2.0E14; vg of an AAV9 vector encoding human NAGLU) was administered via ICV infusion. Primary outcomes were safety and tolerability. Secondary outcomes included serum NAGLU activity, urinary heparan sulfate (HS) excretion, and neurocognitive function. Exploratory analyses included hematological parameters. Results: The patient achieved serum NAGLU activity (17.06 nmol/mL/hour) approaching that of healthy controls (17.75 {+/-} 1.37 nmol/mL/hour) by Month 3, accompanied by a 58.4% reduction in urinary HS. Clinically, previously severe hand and toe contractures resolved, allowing for full extension. Neurocognitive improvements were observed, including clear articulation, logical conversation, and sustained eye contact. Hematological analyses revealed normalized red blood cell indices and improved iron utilization. No dose-limiting toxicities, serious adverse events, or clinically significant laboratory abnormalities were observed. Conclusions: A single ICV infusion of RDGT-101 was safe and well-tolerated in this patient with MPS IIIB. Early biochemical correction was accompanied by marked improvements in somatic, neurocognitive, and hematological parameters. These findings support further investigation of ICV AAV9 gene therapy for MPS IIIB.

Abstract Background: Heart Failure is a complex clinical syndrome of growing public health concern in sub-Saharan Africa, yet the data from Sierra Leone are absent. The aim of the study is to characterise the clinical profile, etiological and temporal trends of hospitalised HF patients at Choithrams Memorial Hospital (CMH), Freetown, Sierra Leone, to confirm specific management strategies. Methods: This single-center, retrospective observational cohort study analysed data on HF patients (>18years) admitted at the CMH between January 2021 to 31 December 2025. The clinical definition of HF was based on the Framingham criteria and the European Society of Cardiology (ESC) guidelines , including standard echocardiographic parameters. All variables, including patients demographics, HF. phenotype, aetiology, medical history and hospital outcomes were extracted from the digital record. Non-parameteric tests, multivariable logistic regression to identify variables associated with etiology, Wilcoxon rank-sum test to compare groups and Kruskal-Wallis test to analyse trends over time were utilised. Result: A total of 765 patients were included in the study, with a median age of 53 years (IQR 42-61) and male predominance of 55.3%. Patients with recurrent HF (60.9%) were more common than those with de novo HF (39.1%), were older (54 years vs 53 years), had a higher comorbidity burden (34% vs 4%, p < 0.001), and presented with a cold-wet hemodynamic profile (18.4% vs 8.4%, p < 0.001). HFrEF (61.3%) was the most predominant phenotype, though HFpEF increased with age. Dilated Cardiomyopathy (37.0%), Hypertensive Heart Disease (31.2%) and Valvular Heart Failure (17.1%) were the leading etiologies, while ischemic heart disease (6.3%) was relatively uncommon. A majority of the patients were referred (77.9%), and 50.8% presented with NYHA IV. The strongest independent predictor for HF was hypertensive heart disease [AOR = 17.81; C.I 95%: (3.13-48.76), p <0.001]. An analysis of the trends in etiologies and demographics over the five-year period demonstrated no significant changes (all p-values > 0.05 for age, sex, aetiology, and most comorbidities). Conclusion: HF affects the younger adult population in Sierra Leone and is mainly caused by DCM and HHD. The late case presentations, the high prevalence of recurrent HF, and the associated high burden of comorbidities emphasize an urgent need to develop and implement improved strategies for the prevention, early detection, and long-term management of HF within Sierra Leone's healthcare system.