Poor Functional Outcome Research Articles

Effect of post-stroke cognitive impairment and dementia on stroke recurrence and functional outcomes: A systematic review and meta-analysis.

Post-stroke cognitive impairment (PSCI) and dementia may have a significant impact on stroke recurrence and long-term functional outcomes of patients. To investigate the potential link between PSCI and dementia, and stroke recurrence, mortality, and poor functional outcomes of stroke survivors. A systematic search across Medline, Google Scholar, and Science Direct databases was done for studies that evaluated the association of PSCI and dementia with long-term stroke outcomes. The results were expressed as pooled hazard ratios (HR) with 95% confidence intervals (CI), and heterogeneity was assessed using the I2 statistic and the Chi-square test. Subgroup analyses were performed based on the sample size, geographical location, follow-up, and type of dementia/cognitive impairment. Study quality was evaluated using the Newcastle Ottawa Scale (NOS). The meta-analysis included thirteen studies. Of them, ten studies (n = 4036) reported a significant association between PSCI and stroke recurrence, with a pooled HR of 1.33 (95% CI: 1.14-1.55, I2 = 84.6%). Subgroup analysis revealed a statistically significant association between PSCI and stroke recurrence across various subrgoups. Four studies (n = 1944) demonstrated that patients with PSCI had a higher risk of poor functional outcome, with a pooled HR of 1.68 (95% CI: 1.16-2.05, I2 = 80.0%). However, the multivariate analysis did not detect a significant association between PSCI and stroke mortality, with a pooled HR of 1.50 (95% CI: 0.94-2.40, I2 = 45.9%). The study showed that PSCI was associated with 33% increased stroke recurrence and 68% higher rate of poor functional outcome. Our findings underscore the adverse impact of PSCI on stroke recurrence and functional outcomes, emphasizing the importance of early detection and targeted interventions to mitigate the cognitive impairment burden in stroke survivors.

Depressive and negative symptoms in the early and established stages of schizophrenia: integrating structural brain alterations, cognitive performance, and plasma interleukin-6 levels

BackgroundDepressive and negative symptoms are related to poor functional outcomes in schizophrenia. Cognitive deficits, reduced brain cortical thickness (CT) and volumes as well as inflammation may contribute to depressive and negative symptoms, but pharmacological treatment and disease progression may confound the associations. MethodsWe evaluated whether higher plasma IL-6 levels would be associated with more severe negative or depressive symptoms in schizophrenia and explored illness stage utilizing Early (BeneMin; n=201, males=72.8%) and Established schizophrenia (iRELATE; n=94, males=67.3%) cohorts. Using Structural Equation Modeling (SEM) in a subsample (iRELATE; n=42; males=69.0%; BeneMin; n=102; males=76.5%) with data on structural brain metrics (CT and volume), general cognitive performance, and plasma IL-6 levels, we assessed the interrelationships between these variables on depressive and negative symptom severity in Early and Established schizophrenia samples combined and Early schizophrenia only. All analyses were adjusted for sex, age, and chlorpromazine equivalent dose. ResultsHigher plasma IL-6 levels were related to more severe depressive symptoms in Early (p<0.05) and negative symptoms in Established schizophrenia (p<0.05). SEM findings in Early and Established schizophrenia samples combined, and Early schizophrenia only showed that the interrelationship between higher plasma IL-6 levels, structural brain metrics, and general cognitive performance did not predict the severity of depressive and negative symptoms (p>0.05). Higher plasma IL-6 levels and lower general cognitive performance were associated with reduced brain metrics (p<0.05). ConclusionOur results indicate that higher plasma IL-6 levels may be differently associated with the severity of depressive and negative symptoms dependent on the illness stage. Future work identifying elevated levels of inflammation in larger samples may allow stratification and personalized intervention by subgroups who are at risk of poor outcomes.

Recent and future advances in intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) is defined by the rupture of a cerebral blood vessel and the entry of blood into the brain parenchyma. With a global incidence of around 3.5 million, ICH accounts for almost 30 % of all new strokes worldwide. It is also the deadliest form of acute stroke and survivors are at risk of poor functional outcome. The pathophysiology of ICH is a dynamic process with key stages occurring at successive times: vessel rupture and initial bleeding; hematoma expansion, mechanical mass effect and secondary brain injury (peri-hematomal edema). While deep perforating vasculopathy and cerebral amyloid angiopathy are responsible for 80 % of ICH, a prompt diagnostic work-up, including advanced imaging is require to exclude a treatable cause. ICH is a neurological emergency and simple therapeutic measures such as blood pressure lowering and anticoagulant reversal should be implemented as early as possible as part of a bundle of care. Although ICH is still devoided of specific treatment, recent advances give hope for a cautious optimism. Therapeutic approaches under the scope are focusing on fighting against hemorrhage expansion, promoting hematoma evacuation by minimally invasive surgery, and reducing secondary brain injury. Among survivors, the global vascular risk is now better established, but optimal secondary prevention is still unclear and is based on an individual benefit-risk balance evaluation.

The clinical value of fibrosis indices for predicting the hemorrhagic transformation in patients with acute ischemic stroke after intravenous thrombolysis

BackgroundThe incidence of stroke in China is approximately 343 per 100,000 people each year, the highest rate worldwide. Hemorrhagic transformation (HT), particularly symptomatic intracerebral hemorrhage (sICH) following acute ischemic stroke (AIS) with or without intravenous thrombolysis (IVT), can lead to rapid neurological deterioration, poor prognosis, and even death. Non-alcoholic fatty liver disease (NAFLD) has been identified as a risk factor for stroke occurrence and associated with poor long-term functional outcomes. Nonetheless, no studies have examined the association between liver fibrosis and HT in AIS patients who underwent IVT.MethodA total of 826 patients with AIS who underwent IVT were included in this study. We calculated nine validated liver fibrosis indices to assess the extent of liver fibrosis. HT was detected by follow-up cranial CT/MRI within 24 h post-IVT and was classified as either hemorrhagic infarction (HI) or parenchymal hematoma (PH). Symptomatic intracranial hemorrhage was defined as a sudden symptomatic neurological deterioration, indicated by an increase in (National Institutes of Health Stroke Scale) NIHSS score of 4 points or more.ResultThe median values of fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aspartate aminotransferase (AST)-platelet ratio index (APRI), Forns index, alanine aminotransferase (ALT)/AST (ARR), AST/ALT ratio-platelet ratio index (AARPRI), fibrosis quotient (FibroQ), and Fibrosis Index were significantly higher, while the fibrosis-5 (FIB-5) was significantly lower in the HT and sICH groups (all P &amp;lt; 0.001). After adjusting for potential confounders, all nine liver fibrosis indices remained associated with HT and sICH. Receiver operating characteristic (ROC) curve analysis revealed that the FibroQ score had the best predictive ability for HT (AUC = 0.707, CI = 0.652–0.762, P &amp;lt; 0.001), while FIB-4 had the best predictive ability for sICH (AUC = 0.802, CI = 0.711–0.892, P &amp;lt; 0.001).ConclusionLiver fibrosis, as validated by FIB-4, mFIB-4, FIB-5, APRI, Forns index, ARR, AARPRI, FibroQ, and Fibrosis Index, was associated with HT and sICH in AIS patients after IVT.

Perfusion-Based Relative Cerebral Blood Volume Is Associated With Functional Dependence in Large-Vessel Occlusion Ischemic Stroke.

Pretreatment computed tomography perfusion parameter relative cerebral blood volume (rCBV) lesion volume has been shown to predict 90-day modified Rankin Scale score in small-core strokes with Alberta Stroke Program Early Computed Tomography Score ≥5, including those with medium-vessel occlusions (mid and distal M2 segment occlusions). Hence, in this study we aim to assess the performance of different rCBV lesion volume thresholds (rCBV <42%, rCBV <38%, and rCBV <34%) with 90-day modified Rankin Scale score including patients with large core (Alberta Stroke Program Early Computed Tomography Score <5) and strictly including only patients with anterior circulation large-vessel occlusion. In this retrospective evaluation of our prospectively collected database, inclusion criteria were (1) Computed tomographic angiography confirmed anterior circulation large-vessel occlusion from September 1, 2017, to October 1, 2023; and (2) diagnostic computed tomography perfusion. Student t test, Mann-Whitney U test, and χ2 test were used in the univariate data analysis. Spearman's rank correlation analysis was used to assess correlations. Outcome measure was dichotomized into good functional outcome (90-day modified Rankin Scale score, 0-2) and poor functional outcome (90-day modified Rankin Scale score, 3-6) for logistic regression and receiver operating characteristic analysis. P≤0.05 was considered significant. In total, 229 patients met our inclusion criteria. The majority of the patients (n=161) in our cohort had M1 occlusion. All the rCBV thresholds were significantly higher in patients with poor 90-day functional outcomes and were independently associated with the outcome. Spearman's rank correlation analysis revealed a slightly stronger correlation of rCBV <42% (ρ=0.27, P<0.001), as compared with rCBV <38% (ρ=0.25, P<0.001) and rCBV <34% (ρ=0.24, P<0.001) with functional outcome. Receiver operating characteristic analysis revealed that rCBV <42% (area under the curve, 0.67 [95% CI, 0.60-0.74]; P<0.001) performed marginally better than rCBV <38% (area under the curve, 0.66 [95% CI, 0.59-0.73]; P<0.001), and rCBV <34% (area under the curve, 0.65 [95% CI, 0.58-0.72]; P<0.001). All the rCBV thresholds were independently associated with poor 90-day functional outcome; however, the rCBV <42% marginally outperformed rCBV <38% and rCBV <34% lesion volumes.

Acute hyperglycemia is associated with intraventricular extension among patients with spontaneous intracerebral hemorrhage

ObjectiveAcute hyperglycemia following intracerebral hemorrhage (ICH) is associated with poor functional outcomes and may result from a neuroendocrine stress response. Given the proximity of neuroendocrine structures to the cerebral ventricles, we tested the hypothesis that intraventricular hemorrhage (IVH) is associated with hyperglycemia. Materials and methodsA post-hoc analysis of the ICH Deferoxamine (i-DEF) trial was conducted to determine predictors of IVH. Variables with significant differences (p < 0.1) in univariable tests between patients with and without IVH were entered into a logistic regression model along with age, sex, diabetes, hyperglycemia (admission glucose ≥140 mg/dL), and baseline intraparenchymal hemorrhage (IPH) volume. This model was then applied to an independent cohort of consecutive non-traumatic ICH patients admitted to a single referral center (2007 to 2018). ResultsAmong 294 patients in the i-DEF cohort with mean age 60 ± 12 years (IVH in 41 %), hyperglycemia (aOR 1.90, 95 % CI [1.06–3.38]), smoking history (aOR 1.90, 95 % CI [1.11–3.27]), and non-lobar ICH location (aOR 3.38, 95 % CI [1.49–7.69]) were independently associated with IVH. In the independent cohort consisting of 856 patients with mean age 71 ± 12 years (IVH in 37 %), hyperglycemia (aOR 2.23, 95 % CI [1.55–3.20]), non-lobar ICH location (aOR 2.50, 95 % CI [1.75–3.59]), and IPH volume (aOR 1.02, 95 % CI [1.01–1.02]) were associated with IVH. ConclusionsHyperglycemia is associated with IVH and may be a peripheral marker for the inflammatory response to hemorrhage within the ventricles. Further translational studies are needed to elucidate the pathophysiological basis for this phenomenon.

Mediation Analysis of Serum Fibroblast Growth Factor 20 and Poor Prognosis After Ischemic Stroke.

We aimed to examine the relationship between serum FGF20 (fibroblast growth factor 20) levels and stroke prognosis in a multicenter cohort study. Patients with ischemic stroke/transient ischemic attack were prospectively recruited from 5 participating centers and followed up at 3 months and 1 year. FGF20 levels were measured using the ELISA method. The primary outcome was poor stroke functional outcome (modified Rankin Scale score of 3-6), and secondary outcomes included death and composite vascular events. Multivariable logistic regression analysis or Cox proportional hazards regression analysis was employed to estimate the relationship between FGF20 and study outcomes. Mediation analysis was conducted to examine the mediating effects of traditional risk factors on the association between FGF20 and stroke outcomes. A total of 1011 patients with ischemic stroke were included in the study. After adjusting for potential confounding factors, an elevated serum FGF20 level was associated with a reduced risk of the poor outcome and death. Multivariable adjusted spline regression analysis demonstrated a linear correlation between serum FGF20 levels and the stroke outcomes. The incorporation of FGF20 alongside conventional risk factors marginally enhanced the reclassification of adverse outcomes. Renal function and white blood cell count partially mediated the relationship between FGF20 and the prognosis of ischemic stroke. Elevated FGF20 level is associated with decreased risks of adverse outcomes after ischemic stroke, which was partially mediated by renal function and white blood cells with a modest amount, indicating that serum FGF20 might serve as a promising biomarker for predicting stroke prognosis. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100051104.

Severe traumatic brain injury temporally affects cerebral blood flow, endothelial cell phenotype, and cilia.

Previous clinical work suggested that altered cerebral blood flow (CBF) in severe traumatic brain injury (sTBI) correlates with poor executive function and clinical outcome. However, the molecular consequences of altered CBF on endothelial cells (ECs) and their blood flow-sensor organelle called cilia are not known. We performed laser speckle contrast imaging, single cell isolation, and single cell RNA sequencing (scRNAseq) after sTBI in a closed skull, linear impact mouse model. Validation of select ciliary target protein changes was performed using flow cytometry. Additionally, in vitro experiments modeled the post-injury hypoxic environment to evaluate the effect on cilia protein ARL13B in human brain microvascular ECs. We detected immediate reductions in CBF that were sustained for at least 100 minutes in both impacted and non-impacted sides of the brain. Our scRNAseq data detected heterogeneity in the brain cortex-derived EC cluster and demonstrated that two of five unique EC sub-clusters changed their relative proportions post-sTBI. Consistent with flow changes, we identified multiple genes associated with the fluid shear stress pathway that were significantly differentially expressed in brain ECs post-injury. Also, ECs displayed activation of ischemic pathway as early as day 1 post-injury, and enrichment of hypoxia pathway at day 7 and 28 post- injury. Arl13b ciliary gene expression was lost on day 1 in ECs cluster and remained lost for the entire course of the injury. We validated the loss of cilia protein ARL13B specifically from brain ECs as early as day 1 post-injury and detected the protein in the peripheral blood of the injured mice. We also determined that hypoxia could induce loss of ARL13B protein from cultured ECs. In severe TBI, blood flow is disrupted in both impacted and non-impacted regions of the brain, creating a hypoxic environment that may influence ciliary gene and protein expression on ECs.

Prehospital blood pressure lowering in patients with ischemic stroke: A systematic review and meta-analysis of randomized controlled trials.

Whether prehospital blood pressure control improves outcomes among patients with acute ischemic stroke is uncertain. This systematic review and meta-analysis aimed to evaluate the effect of prehospital blood pressure reduction treatment in patients with ischemic stroke. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials that compared prehospital blood pressure reduction treatment with usual treatment or no treatment in patients with stroke. The primary outcome was functional outcome, assessed with the distribution of modified Rankin Scale (mRS) at 90 days, while secondary outcome was mortality at 90 days. Of 428 studies reviewed, three were appropriate for analysis, totaling 3878 patients. In patients with ischemic stroke, prehospital blood pressure reduction treatment was associated with higher mRS scores at 90 days (common odds ratio (OR) for worse mRS, OR: 1.27, 95% confidence interval (CI): 1.08-1.49) and increased risk of mortality at 90 days (OR: 1.28, 95% CI: 1.02-1.61) compared with the usual treatment. In patients with ischemic stroke, prehospital blood pressure reduction treatment was associated with a higher likelihood of poor functional outcome and an elevated risk of mortality.

Predicting poor functional outcomes for patients with large computed tomography perfusion core infarctions treated with endovascular thrombectomy.

Stroke patients with large core infarctions benefit from endovascular intervention, though only approximately 20% are functionally independent at 90 days. We studied prognostic factors for patients presenting with a large computed tomography perfusion (CTP) core. Retrospective analysis from a health system stroke registry, including consecutive thrombectomy patients treated within 24 hours from August 2020-December 2022 with an anterior circulation large vessel occlusion and CTP core infarct ≥50 milliliters. Logistic regression was used to determine independent predictors of 90-day modified Rankin Scale (mRS) score 4-6. The prognostic ability of previously reported scales was also assessed. In 118 included patients, with mean age 64.3 ± 14.1 years, poor functional outcomes were present in 66 subjects (55.9%). The multivariable regression analysis demonstrated that higher presenting National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.23, p = 0.014), elevated glucose (OR 1.02, 95% CI 1.01-1.03, p = 0.002), absence of treatment with intravenous thrombolysis (OR 4.01, 95% CI 1.35-11.95, p = 0.013), and poor revascularization (OR 4.76, 95% CI 1.24-18.37, p = 0.023) were independently associated with primary outcome. The Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS) predicted 90-day mRS 4-6 (per 25-point increase, OR 1.22, 95% CI 1.10-1.34, p<0.001) and mRS 5-6 (per 25-point increase, OR 1.21, 95% CI 1.10-1.33, p<0.001). Nineteen of 20 (95%) patients with CLEOS ≥ 675 had 90-day mRS scores of 4-6, while 10 of 12 (83.3%) with CLEOS ≥ 725 had 90-day mRS scores of 5-6. We report prognostic factors that can risk stratify thrombectomy patients with large CTP core infarctions.

Comparison of functional outcome after intracerebral hemorrhage in patients with or without end stage renal disease on hemodialysis: a propensity-score matched study

BackgroundEnd stage renal disease (ESRD) requiring hemodialysis (HD) increases mortality among patients with intracerebral hemorrhage (ICH). The aim of this study is to investigate the clinical characteristics and outcome of ICH patients with ESRD on HD versus propensity-score matched controls.MethodsThis is a single center retrospective study. Consecutive ICH admissions at the University of California, Irvine Medical Center from January 1, 2018 to July 31, 2022 were analyzed.ResultsAmong 347 ICH admissions that met inclusion criteria, 24 patients (6.92%) had ESRD on HD. Compared to patients without ESRD, patients with ESRD on HD had significantly higher rate of diabetes mellitus (79.2% vs. 36.8%, p < 0.01) and in-hospital mortality (25% vs. 7.43%, p < 0.01). There were no significant differences in demographics, other comorbidities, clinical characteristics, good (mRS score 0–3) or poor (mRS score 4–5) functional outcomes, rate of comfort care and the time to comfort care decision between the 2 groups. After propensity score matching, the ESRD group had a significantly higher in-hospital mortality rate (27.3% vs. 8%, p = 0.012) and a lower rate of obesity (9.1% vs. 34.1%, p = 0.02). Among patients who died during admission, ESRD on HD status did not inadvertently influence end-of-life care decisions. Univariate logistic regression and area under curve analysis showed that ICH score ≥ 3 was a predictor of increased mortality in both ESRD and non-ESRD groups.ConclusionsICH patients with ESRD on HD had significantly higher in-hospital mortality and lower rate of obesity than propensity score matched controls, suggesting a survival benefit from obesity. ICH score ≥ 3 is an independent predictor for poor outcomes in both ESRD and non-ESRD groups.

The California collaborative network to promote data driven care and improve outcomes in early psychosis (EPI-CAL) project: rationale, background, design and methodology

BackgroundA prolonged first episode of psychosis (FEP) without adequate treatment is a predictor of poor clinical, functional, and health outcomes and significant economic burden. Team-based “coordinated specialty care” (CSC) for early psychosis (EP) has established effectiveness in promoting clinical and functional recovery. However, California’s CSC program implementation has been unsystematic and could benefit from standardizing its processes and data collection infrastructure. To address this, we established a consortium of EP clinics across the state via a Learning Health Care Network (LHCN) framework to develop the Early Psychosis Intervention Network of California (EPI-CAL). EPI-CAL’s LHCN developed a core battery of evidence-based measures for service users and family members and linked them together using a unique data collection and visualization application, Beehive.Methods and objectivesEPI-CAL’s LHCN collects, visualizes, and aggregates data at the individual and clinic level for EP programs across California via Beehive. Beehive was designed to: (1) collect outcomes data from service users receiving care at EP programs and their support persons, (2) provide the data to providers on a secure web-based dashboard to support measurement-based care, and (3) allow data to be used for program or research analysis. We will (1) determine the feasibility of implementing an LHCN across a diverse, decentralized network of early psychosis programs, (2) determine if the implementation of an LHCN increases the delivery of measurement-based care, and (3) determine if the implementation of measurement-based care is associated with significant improvements in key service user outcomes. EPI-CAL’s network will contribute data to the Early Psychosis Intervention Network (EPINET) program.DiscussionThe current study aims to establish an LHCN of EP clinics in California that implements harmonized data collection using Beehive and assesses the feasibility of establishing such a network. Our goal is for this harmonized data collection approach to be used to inform decisions and develop learning opportunities for service users, staff, and administrators, and to improve outcomes for service users and their supporters in CSC care. Further, the data will enable programs and research teams to examine what elements of care lead to program success and improved treatment outcomes for service users.Clinical trials registrationwww.ClinicalTrials.gov, identifier NCT04007510; registered 07/05/2019.

Investigating the Overaction of the Inferior Oblique Muscle and Associated Vertical Strabismus: Indications, Timing, and Methods of Surgical Intervention

Treatment of the vertical strabismus due to the overaction of the inferior oblique extraocular muscle usually requires surgical intervention. In addition to the cosmetic issues, the main indications for surgical treatment of the inferior oblique overaction are the presence of cyclotropia and torsional diplopia. Most procedures target the weakening of the inferior oblique muscle; however, there is the risk of some intraoperative and postoperative complications, including highly invasive procedures, difficulty of technical implementation because of the need for manipulations in inaccessible locations of the globe near the optic nerve, macular area, and large vessels, long duration of the surgery, inability to determine the dosage of the outcomes of the surgery, and poor functional outcomes. Most complications are absent in the procedure of anterior transposition in which the neuro-fibrovascular bundle serves as the axis of rotation of the inferior oblique muscle. This technique changes the inferior oblique muscle’s action field and increases treatment effectiveness. Despite the advantages of this technique, its application is still limited because of the lack of methods for controlling the amount of anterior transposition to treat inferior oblique overaction, particularly of small degrees.

Pre-existing dementia is associated with 2-3 folds risk for in-hospital mortality and complications after intracerebral hemorrhage stroke.

Pre-existing dementia was related to poor functional outcome after intracerebral hemorrhage (ICH), and its commonly underlying pathologies were considered as cerebral amyloid angiopathy. But the impact of pre-existing dementia on in-hospital mortality in Chinese ICH patients has not been well characterized. To investigate the association between pre-existing dementia and in-hospital mortality after ICH. Data were extracted from the China Stroke Center Alliance database. Information about the existence of prior to stroke dementia was obtained from next of kin informants and registered in clinical charts. Patients' characteristics, in-hospital mortality, home discharge and complications were compared between ICH patients with and without pre-existing dementia. Out of the 72,318 ICH patients, we identified 328 patients with pre-existing dementia. Patients with pre-existing dementia were more likely to experience greater stroke severity as measured by the National Institute of Health Stroke Scale and Glasgow Coma Scale. In the adjusted models, the presence of pre-existing dementia was associated with an increased risk of in-hospital mortality (OR 2.31, 95% CI 1.12-4.77), more frequent in-hospital complications of pulmonary embolism (OR 5.41, 95% CI 1.16-25.14), pneumonia (OR 1.58, 95% CI 1.08-2.33), urinary tract infection (OR 2.37, 95% CI 1.21-4.64), gastrointestinal bleeding (OR 2.39, 95% CI 1.27-4.49) and lower home discharge (OR 0.59, 95% CI 0.38∼0.93). ICH patients with pre-existing dementia are more likely to suffer from greater stroke severity, poorer outcomes and lower home discharge. Future studies should evaluate the value of intensive risk factor control among individuals with pre-existing dementia for stroke prevention.

Genetic associations between physical activity levels and functional outcome after ischemic stroke: Insights from Mendelian randomization

ObjectiveThe genetic relationship between daily physical activity (PA) levels and functional outcome after ischemic stroke remains unclear. This study aimed to investigate the genetic associations of PA on functional outcome after ischemic stroke using Mendelian randomization (MR). MethodsWe conducted two-sample MR analyses using genome-wide association studies (GWASs). This included data on light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) from the UK Biobank, and functional outcome after ischemic stroke from the Genetics of ischemic stroke Functional Outcome (GISCOME). The inverse-variance weighted (IVW) method served as our primary MR analysis approach, supplemented by several sensitivity analyses. ResultsIn univariable Mendelian randomization (UVMR) analysis, MVPA was significantly associated with a reduced risk of poor functional outcome (OR = 0.15, 95 % CI = 0.04–0.56, P < 0.01), whereas LPA had no genetic relationship (OR = 0.37, 95 % CI = 0.002–51.40, P = 0.69). In multivariate Mendelian randomization (MVMR) analysis adjusting for potentially confounding traits including hypertension, type 2 diabetes, and smoking, the overall patterns between MVPA and poststroke outcome remained (OR = 0.23, 95 % CI = 0.07–0.78, P = 0.02). ConclusionMVPA is a protective factor for functional outcome after ischemic stroke. This finding is important for the rehabilitation and functional outcome of stroke patients.

Trajectory clustering of immune cells and its association with clinical outcomes after aneurysmal subarachnoid hemorrhage.

The immune response following aneurysmal subarachnoid hemorrhage (aSAH) can exacerbate secondary brain injury and impact clinical outcomes. As the immune response after aSAH is a dynamic process, we aim to track and characterize immune cell trajectories over time to identify patterns associated with various clinical outcomes. In this retrospective single-center study of patients with aSAH, we analyzed immune cell count trajectories, including neutrophil, monocyte, and lymphocyte counts, collected from day 1 to day 14. These trajectories were classified into four distinct clusters utilizing the k-means longitudinal clustering method. A comprehensive multivariable analysis was performed to explore the associations of these immune cell clusters with various clinical outcomes. These outcomes included a Modified Rankin Scale score (mRS) of 3 to 6, indicative of poor functional outcomes, along with complications including shunt dependency, vasospasm, and secondary cerebral infarction. In this study, 304 patients with aSAH were analyzed. The trajectories of immune cell counts, including neutrophils, monocytes, and lymphocytes, were successfully categorized into four distinct clusters for each immune cell type. Within neutrophil clusters, both persistent neutrophilia and progressive neutrophilia were associated with poor functional outcomes, shunt dependency, and vasospasm, with resolving neutrophilia showing a lesser degree of these associations. Within monocyte clusters, early monocytosis was associated with vasospasm, whereas delayed monocytosis was associated with shunt dependency. Within lymphocyte clusters, both early transient lymphopenia and early prolonged lymphopenia were associated with poor functional outcomes. Our study demonstrates that distinct immune cell trajectories post-aSAH, identified through unsupervised clustering, are significantly associated with specific clinical outcomes. Understanding these dynamic immune responses may provide key insights with potential for future therapeutic strategies.

Sex Modifies the Severity and Outcome of Spontaneous Intracerebral Hemorrhage.

The limited existing evidence on sex differences in the clinical characteristics of patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) comes from small, single-center studies. Here, we performed an individual patient data meta-analysis of 3 randomized clinical trials and 1 multi-ethnic observational study of ICH to investigate the impact of sex on ICH severity and outcome. Inclusion criteria in our study were a neuroimaging-confirmed ICH. We evaluated whether sex was associated with ICH severity (hematoma volume and expansion) and poor functional outcomes (modified Rankin Scale >3) 3 or 6 months after the ICH. A total of 4,812 ICH patients were evaluated (mean age 62, 40% female). Males with ICH were younger, more likely to be smokers and have diabetes, and less likely to be on anticoagulants (all p < 0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR]: 1.63; 95% confidence interval [CI]: [1.39-1.92]; p < 0.001), larger hemorrhages (beta: 0.16 [0.08-0.23]; p < 0.001) and a higher risk of hematoma expansion (OR: 1.43 [1.20-1.71]; p < 0.001). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 24% lower risk of poor outcomes (OR: 0.76 [0.64-0.90]; p = 0.002). Compared to females, males with ICH have larger bleeds and higher risk of hematoma expansion. Despite the larger bleeds and higher risk of hematoma expansion, males with ICH have lower risk of poor outcomes. Our results suggest that the biology and clinical trajectory are different in females and males with ICH, supporting sex-specific research in this condition. ANN NEUROL 2024.

Collagen triple helix repeat-containing 1 protein: an emerging biomarker and its influence on the clinical and sonographic disease severity in Egyptian medicated female rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of synovial joints, with a multifactorial etiology. Collagen triple helix repeat-containing 1 protein (CTHRC1) is a biomarker produced by fibroblast-like synoviocytes, which was shown to be highly expressed in RA patients. The study aimed to measure serum CTHRC1 level in female RA patients currently on medical treatment and its influence on the clinical and sonographic severity of the disease.ResultsThe patients’ mean age was 43.39 ± 8.55 years and median RA disease duration of 5.5 (0.33–20) years. RA patients showed significantly higher serum CTHRC1 level [89.71 ng/ml (53.95–353.45)] in comparison to controls [87.38 ng/ml (44.47–110.3)] (U = 430, P = 0.014). Furthermore, higher serum CTHRC1 levels were recorded in seropositive versus seronegative patients (U = 76, P = 0.022) and in RA patients with severe disease activity compared to those with lower disease activity (H = 9.79, P = 0.007). Furthermore, serum CTHRC1 levels were lower in RA patients receiving biological therapy compared to those receiving conventional therapy; however, this difference did not reach statistical significance.Significant positive correlations were found between CTHRC1 and disease activity, acute-phase reactants, serological markers, functional assessment, fatigue, and erosions detected by ultrasound, while a significant negative correlation was recorded between CTHRC1 and duration of biologic intake (rs = − 0.45, P = 0.036). Furthermore, on multivariate linear regression analysis, serum CTHRC1 was the only significant predictor for higher disease activity (P = 0.028, B = 0.009, 95% CI 0.001 to 0.017).ConclusionRA patients showed higher CTHRC1 serum levels compared to healthy controls, especially those with seropositivity and highly active disease. Furthermore, it was positively associated with poor patient functional outcome, fatigability, and erosive findings by ultrasound, thus suggesting that serum CTHRC1 can be a good predictor for high RA disease activity and possibly severity. Moreover, biological therapy could influence serum CTHRC1 levels in these patients.

Association of Uric Acid, High-Sensitivity C-Reactive Protein, and 90-Day Risk of Poor Function Outcome in Patients with Ischemic Stroke or Transient Ischemic Attacks.

The interaction between inflammatory biomarkers (high-sensitivity C-reactive protein, hsCRP) and antioxidants (uric acid, UA) regarding prognosis after ischemic stroke or transient ischemic attack (TIA) remains inadequately explored. This study aimed to assess (1) the individual and joint effects of hsCRP and UA, and (2) the neuroprotective role of UA in patients with elevated hsCRP levels concerning poor functional outcomes at 90 days. A prospective cohort study was conducted involving 2140 consecutive ischemic stroke or TIA patients with hsCRP and UA levels. The primary outcome was defined as a poor functional outcome, indicated by a modified Rankin Scale (mRS) score of 3-6 at 90 days, with a shift in the mRS score as a secondary outcome. Logistic regression and propensity score (PS) analyses were employed to ensure robustness. Poor functional outcome occurred in 345 (16.1%) patients. Individual effects found that the highest quartiles of hsCRP (adjusted OR = 3.090; 95% CI 2.150-4.442) and UA (adjusted OR = 0.671; 95% CI 0.551-0.883) were associated with increased or decreased risk of poor functional outcome, respectively. Joint effects (adjusted OR = 3.994; 95% CI 2.758-5.640) between hsCRP and UA on the primary outcome were more apparent in patients with high hsCRP levels (hsCRP > 1.60 mg/L) and low UA levels (UA ≤ 291.85 µmol/L). For the patients with high hsCRP levels, patients with low UA levels had a higher risk of primary and secondary outcomes, compared with those with high UA levels, after unadjusted or adjusted for hsCRP. Similar and reliable results were observed in PS-based models. In patients with ischemic stroke or TIA, joint high levels of hsCRP and low UA levels significantly correlate with increased risk of poor functional outcome at 90 days. In addition, high UA levels could reduce the risk of poor functional outcome for patients with high hsCRP levels.

Maternal care is associated with neural and behavioral effects of oxytocin administration during empathic accuracy in schizophrenia and controls

Empathic accuracy, the ability to accurately understand other people’s emotions, is a complex social cognitive skill that is often impaired in schizophrenia and this impairment is associated with poor functional outcomes. Intranasally administered oxytocin, a neuropeptide implicated in social behavior, is thought to improve empathic accuracy for individuals with schizophrenia. However, early experiences related to caregiving may shape the oxytocinergic system and influence individual responses to oxytocin administration. Using a cross-over, double-blind, placebo-controlled design coupled with fMRI, the current study investigated whether administration of oxytocin improves empathic accuracy in schizophrenia compared to a matched placebo, and the moderating role of early maternal care. Results revealed that, compared to controls, individuals with schizophrenia had lower empathic accuracy and recruited a sparser pattern of neural activation to achieve empathic accuracy. Oxytocin administration was not associated with improved empathic accuracy for either group. However, in both groups, individuals reporting higher maternal care demonstrated the greatest improvements in empathic accuracy with oxytocin administration, accompanied by decreased activity in the right dorsolateral prefrontal cortex, a region implicated in selective attention to socioemotional stimuli. Findings highlight the importance of examining individual differences in responses to oxytocin administration and suggest that early social experiences influence later responses to oxytocin administration.