Immunologic changes in the hematoma of patients with intracerebral hemorrhage (ICH) and the contribution of these changes to prognosis are unknown. We collected the blood samples and hematoma fluid from 35 patients with acute ICH (<30 hours from symptom onset) and 55 age-matched healthy controls. Using flow cytometry and ELISA, we found that the percentages of granulocytes, regulatory T cells, helper T (Th) 17 cells, and dendritic cells were higher in the peripheral blood of patients with ICH than in healthy controls, whereas the percentages of lymphocytes, M1-like macrophages, and M2-like macrophages were lower. Levels of IL-6, IL-17, IL-23, TNF-α, IL-4, IL-10, and TGF-β were higher in the peripheral blood of patients with ICH. The absolute counts of white blood cells, lymphocytes, monocytes, and granulocytes in the hematoma tended to be greater at 12-30 hours than they were within 12 hours after ICH, but the percentage of Th cells decreased in peripheral blood.Increased levels of IL-10 in the serum and hematoma, and a reduction in M1-like macrophages in hematoma were independently associated with favorable outcome on day 90. These results indicate that immunocytes present in the hematoma may participate in the acute-phase inflammatory response after ICH. K E Y W O R D Shematoma, immune changes, intracerebral hemorrhage, outcome, patients | 2775 JIANG et Al.
BackgroundWe aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High‐risk patients with Acute Non‐disabling Cerebrovascular Events) trial.Methods and ResultsIn total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow‐up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89–3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98–3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke (P=0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results.ConclusionsConcurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack.
Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.
Background and Purpose— The role of dual-antiplatelet therapy with clopidogrel plus aspirin has been demonstrated to substantially decrease the risk of recurrent stroke among patients with minor stroke and transient ischemic attack. We aimed to determine whether the efficacy of clopidogrel-aspirin therapy among patients with minor stroke / transient ischemic attack was influenced by the stratification of CYP2C19 genotype and body mass index (BMI). Methods— CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with either LoFA of *2 or *3. Low/normal weight and overweight/obesity was defined as BMI <25 and ≥25 kg/m 2 , respectively. Primary outcome was defined as stroke recurrence at 3 months. Results— In a total of 2933 patients, there were 1726 (58.8%) LoFA carriers and 1275 (43.5%) patients with overweight/obesity (BMI ≥25 kg/m 2 ). Stratified analyses by LoFA carrying status and BMI, hazard ratios (hazard ratios 95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.90 (0.60–1.36), 0.87 (0.56–1.35), 0.65 (0.39–1.09), and 0.40 (0.22–0.71) among subgroups of LoFA carriers with overweight/obesity, LoFA carriers with low/normal weight, LoFA noncarriers with overweight/obesity, and LoFA noncarriers with low/normal weight, respectively, with P =0.049 for interaction. Conclusions— Efficacy of clopidogrel-aspirin therapy in reducing the risk of stroke recurrence is not present in CYP2C19 LoFA noncarriers with overweight/obesity. Our study suggests that BMI significantly influences the correlation between CYP2C19 genotype and efficacy of clopidogrel-aspirin therapy. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00979589.
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