Penglian Wang

Interrelationship Among Common Medical Complications After Acute Stroke Pneumonia Plays an Important Role

Background and Purpose— Medical complications are common among patients with stroke. However, little is known about the potential interrelationship among them. In the present study, we aimed to investigate the association between common in-hospital medical complications after acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH). Methods— We analyzed patients enrolled in the China National Stroke Registry from 2007 to 2008. The occurrence of 11 common stroke-associated medical complications during acute hospitalization was prospectively registered. Multivariable analysis using generalized estimation equation was performed to assess association between medical complications in AIS and ICH cohort, respectively. Results— A total of 14 702 patients with AIS and 5221 patients with ICH were enrolled. The median age was 65 years (interquartile range, 55–74 years), and 38.1% were female. The median length of hospital stay was 14 days (interquartile range, 10–20 days) for AIS and 18 days (interquartile range, 11–26 days) for ICH. Pneumonia was the most common medical complication after AIS (11.4%) and ICH (16.8%). In the AIS cohort, after adjusting for potential confounders, pneumonia was significantly associated with development of gastrointestinal bleeding (adjusted odds ratio [OR], 8.35; 95% confidence interval [CI], 6.27–11.1; P<0.001), decubitus ulcer (adjusted OR, 5.31; 95% CI, 3.39–8.31; P<0.001), deep vein thrombosis (adjusted OR, 4.27; 95% CI, 2.41–7.59; P<0.001), epileptic seizure (adjusted OR, 3.96; 95% CI, 2.67–5.88; P<0.001), urinary tract infection (adjusted OR, 3.34; 95% CI, 2.73–4.10; P<0.001), atrial fibrillation/flutter (adjusted OR, 3.17; 95% CI, 2.58–3.90; P<0.001), and recurrent stroke (adjusted OR, 2.65; 95% CI, 2.07–3.40; P<0.001). Similar significant association between pneumonia and development of several nonpneumonia medical complications was verified in ICH cohort as well. Conclusions— Pneumonia is closely associated with the development of several nonpneumonia medical complications after AIS and ICH.

Effects of recombinant human relaxin upon proliferation of cardiac fibroblast and synthesis of collagen under high glucose condition

Cardiac fibrosis is a key component of diabetes and involves the proliferation and differentiation of matrixproducing fibroblasts. We determined the influence of high glucose (HG) conditions on cardiac fibroblasts (CF) functions and the effects of recombinant human (rh) relaxin (RLX) in these responses. We cultured neonatal rat CF in either normal glucose (NG) or HG media. The mRNA of procollagen types I and III, and RLX-1 were assessed by real time PCR and procollagen type I C-terminal peptide (PICP) and procollagen type III amino terminal peptide (PIIINP), matrix metalloproteinases 2 (MMP2), MMP9 were assessed by enzyme linked immunosorbent assay. The results are as follows: a) CF proliferation was significantly increased by HG; rhRLX significantly inhibited HG fibroblast proliferation, while it had no marked effect on CF proliferation in NG. b) CF treated with HG significantly increased the production of PICP and PIIINP. rhRLX had no marked effect on production of PICP and PIIINP in NG. rhRLX blocked the HG-induced increases in collagen synthesis, c) The production of MMP2 and MMP9 is significantly increased by HG. rhRLX decreased overproduction of MMP2 and MMP9 in the presence of HG. d) The RLX-1 mRNA expression of HG group was higher than in the NG group. We concluded that rhRLX could inhibit both the proliferation of CF and the synthesis of collagen under the HG condition. HG concentration could stimulate the expression of endogenous RLX.

Rationale and design of a double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of nimodipine in preventing cognitive impairment in ischemic cerebrovascular events (NICE).

BackgroundStroke is the second most common cause of mortality and the leading cause of neurological disability, cognitive impairment and dementia worldwide. Nimodipine is a dihydropyridinic calcium antagonist with a role in neuroprotection, making it a promising therapy for vascular cognitive impairment and dementia.Methods/designThe NICE study is a multicenter, randomized, double-blind, placebo-controlled study being carried out in 23 centers in China. The study population includes patients aged 30–80 who have suffered an ischemic stroke (≤7 days). Participants are randomly allocated to nimodipine (90 mg/d) or placebo (90 mg/d). The primary efficacy is to evaluate the level of mild cognitive impairment following treatment of an ischemic stroke with nimodipine or placebo for 6 months. Safety is being assessed by observing side effects of nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are required in this study to obtain statistical power of 90%. The first patient was recruited in November 2010.DiscussionPrevious studies suggested that nimodipine could improve cognitive function in vascular dementia and Alzheimer’s disease dementia. It is unclear that at which time-point intervention with nimodipine should occur. Therefore, the NICE study is designed to evaluate the benefits and safety of nimodipine, which was adminstered within seven days, in preventing/treating mild cognitive impairment following ischemic stroke.

Role of protein kinase C β2 in relaxin-mediated inhibition of cardiac fibrosis

IntroductionRelaxin is a pleiotropic hormone owing endogenous antifibrosis effect on numerous organs. We demonstrated relaxin’s inhibitive effect on cardiac fibrosis previously.ObjectiveThe aim of this study was to investigate the role of protein kinase C (PKC) β2 in relaxin’s action under high glucose conditions.Methods and resultsCardiac fibroblasts (CFs) were isolated, exposed to high glucose and incubated with recombinant human relaxin (rhRLX). Western blot analysis revealed a relaxin-mediated decrease in total expression and translocation of PKCβ2, showing downregulation of PKCβ2 is involved in relaxin’s action. Blocking PKCβ2 pathway with ruboxistaurin accelerated rhRLX-mediated inhibition in both proliferation of CFs and deposition of collagen.ConclusionIn conclusion, relaxin can inhibit high glucose-associated cardiac fibrosis partly through PKCβ2 pathway. Further work should be done to fully understand intracellular mechanisms of relaxin’s action to accelerate its clinical use.

Risk score to predict gastrointestinal bleeding after acute ischemic stroke

BackgroundGastrointestinal bleeding (GIB) is a common and often serious complication after stroke. Although several risk factors for post-stroke GIB have been identified, no reliable or validated scoring system is currently available to predict GIB after acute stroke in routine clinical practice or clinical trials. In the present study, we aimed to develop and validate a risk model (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB score) to predict in-hospital GIB after acute ischemic stroke.MethodsThe AIS-GIB score was developed from data in the China National Stroke Registry (CNSR). Eligible patients in the CNSR were randomly divided into derivation (60%) and internal validation (40%) cohorts. External validation was performed using data from the prospective Chinese Intracranial Atherosclerosis Study (CICAS). Independent predictors of in-hospital GIB were obtained using multivariable logistic regression in the derivation cohort, and β-coefficients were used to generate point scoring system for the AIS-GIB. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively.ResultsA total of 8,820, 5,882, and 2,938 patients were enrolled in the derivation, internal validation and external validation cohorts. The overall in-hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and external validation cohort, respectively. An 18-point AIS-GIB score was developed from the set of independent predictors of GIB including age, gender, history of hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke dependence, admission National Institutes of Health stroke scale score, Glasgow Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95% CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts. The AIS-GIB score was well calibrated in the derivation (P = 0.42), internal (P = 0.45) and external (P = 0.86) validation cohorts.ConclusionThe AIS-GIB score is a valid clinical grading scale to predict in-hospital GIB after AIS. Further studies on the effect of the AIS-GIB score on reducing GIB and improving outcome after AIS are warranted.

Web-based tool for dynamic functional outcome after acute ischemic stroke and comparison with existing models

BackgroundAcute ischemic stroke (AIS) is one of the leading causes of death and adult disability worldwide. In the present study, we aimed to develop a web-based risk model for predicting dynamic functional status at discharge, 3-month, 6-month, and 1-year after acute ischemic stroke (Dynamic Functional Status after Acute Ischemic Stroke, DFS-AIS).MethodsThe DFS-AIS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Good functional outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at discharge, 3-month, 6-month, and 1-year after AIS, respectively. Independent predictors of each outcome measure were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and plot of observed and predicted risk were used to assess model discrimination and calibration.ResultsA total of 12,026 patients were included and the median age was 67 (interquartile range: 57–75). The proportion of patients with good functional outcome at discharge, 3-month, 6-month, and 1-year after AIS was 67.9%, 66.5%, 66.9% and 66.9%, respectively. Age, gender, medical history of diabetes mellitus, stroke or transient ischemic attack, current smoking and atrial fibrillation, pre-stroke dependence, pre-stroke statins using, admission National Institutes of Health Stroke Scale score, admission blood glucose were identified as independent predictors of functional outcome at different time points after AIS. The DFS-AIS was developed from sets of predictors of mRS ≤ 2 at different time points following AIS. The DFS-AIS demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.837-0.845). Plots of observed versus predicted likelihood showed excellent calibration in the derivation and validation cohorts (all r = 0.99, P < 0.001). When compared to 8 existing models, the DFS-AIS showed significantly better discrimination for good functional outcome and mortality at discharge, 3-month, 6-month, and 1-year after AIS (all P < 0.0001).ConclusionThe DFS-AIS is a valid risk model to predict functional outcome at discharge, 3-month, 6-month, and 1-year after AIS.

Phosphodiesterase 4D polymorphisms associate with the short-term outcome in ischemic stroke

It has been demonstrated that phosphodiesterase 4D (PDE4D) genetic polymorphism is associated with ischemic stroke. However, the association between PDE4D gene and prognosis after ischemic stroke remains unknown. We consecutively enrolled ischemic stroke patients admitted to Beijing Tiantan Hospital from October 2009 to December 2013. Clinical, laboratory and imaging data upon admission were collected. All patients were followed up 3 months after stroke onset. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the associations of genetic polymorphisms with 3-month outcome after ischemic stroke and different subtypes, under various genetic models. A total of 1447 patients were enrolled, and 3-month follow-up data were obtained from 1388 (95.92%). Multivariate regression analysis showed that SNP87 of PDE4D gene was associated with increased risk of unfavorable outcome after total ischemic stroke (OR = 1.47, 95%CI 1.12–1.93), as well as stroke due to large-artery atherosclerosis (OR = 1.49, 95%CI 1.04–2.11) and small-artery occlusion (OR = 1.76, 95%CI 1.05–2.96) under a recessive model. No association between SNP83 genotype and poor outcome was found. Overall, this study demonstrated that the TT genotype of SNP87 in PDE4D was associated with increased risk of poor outcome after total ischemic stroke, large-artery atherosclerosis and small-artery occlusion, in a Chinese population.

In-hospital medical complications associated with stroke recurrence after initial ischemic stroke: A prospective cohort study from the China National Stroke Registry.

Abstract In-hospital medical complications are common and strongly associated with the risk of death and dependency in stroke patients. Whether similar associations extend to stroke recurrence is unclear. We prospectively and systematically investigated whether in-hospital medical complications are associated with recurrent stroke of patients in the China National Stroke Registry (CNSR). We examined patients with initial ischemic stroke enrolled in CNSR between 2007 and 2008. Recurrent stroke at 3, 6, and 12 months post-stroke was used as stroke outcome. Medical complications were associated with stroke outcomes using multivariable logistic regression. Of the 7593 study patients, recurrent stroke occurred in 1115 (14.7%) within 12 months after stroke onset. In-hospital medical complications were independent risk factors for stroke recurrence in patients with initial ischemic stroke at 3 months (adjusted odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.85 to 2.60), 6 months (adjusted OR = 2.04, 95% CI 1.74 to 2.38), and 12 months (adjusted OR = 1.88; 95% CI 1.62 to 2.19) after onset. The persistence of secondary prevention medications in patients with complications was lower than that in patients without complications. Stroke recurrence post-acute ischemic stroke is significantly associated with in-hospital medical complications.