Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China.

BACKGROUND: Vast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care. METHODS: This study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015-2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3-6 was assessed at 3 and 12 months. Multivariate logistic regression was used. RESULTS: Among 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53-3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38-0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05). CONCLUSIONS: There was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT02470624).

The Neuroprotective Role of MiR-124-3p in a 6-Hydroxydopamine-Induced Cell Model of Parkinson's Disease via the Regulation of ANAX5.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a progressive loss of dopaminergic neurons in the midbrain. Several pathogenetic factors have been involved in the onset and progression of PD, including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Ample evidence indicates that miRNAs could regulate post-transcriptional gene expression and neuronal disease. In this study, we evaluated the effects and mechanism of miR-124-3p on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and SH-SY5Y cells. qRT-PCR results showed that the level of miR-124-3p was downregulated in 6-OHDA-treated PC12 and SH-SY5Y cells, and overexpression of miR-124-3p significantly promoted the cell viability of 6-OHDA-treated PC12 and SH-SY5Y cells, whereas miR-124-3p inhibitor reversed these effects. In addition, PC12 or SH-SY5Y cells were treated with miR-124-3p mimics or inhibitors following 6-OHDA administration, which mediated cell apoptosis and downregulation or upregulation of Caspase-3 activity, respectively. A luciferase reporter assay revealed that annexinA5 (ANXA5) is a direct target gene of miR-124-3p, and miR-124-3p overexpression markedly downregulated the level of ANXA5. Strikingly, further analysis showed that miR-124-3p enhanced the viability of 6-OHDA-treated PC12 or SH-SY5Y cells by targeting ANXA5, which was associated with the stimulation of the ERK pathway. This study revealed that miR-124-3p may play a neuroprotective role in PD; this observation may provide new ideas and therapeutic targets for PD. J. Cell. Biochem. 119: 269-277, 2018. © 2017 Wiley Periodicals, Inc.

Cerebral venous thrombosis caused by spontaneous intracranial hypotension due to spontaneous spinal cerebrospinal fluid leakage in the high cervical region: a case report.

Spontaneous intracranial hypotension (SIH) may lead to cerebral venous thrombosis (CVT). This case report describes the diagnostic and treatment processes used for a patient with CVT caused by SIH due to spontaneous spinal cerebrospinal fluid (CSF) leakage in the high cervical region. Clinical data were collected from a 37-year-old man with an initial symptom of spontaneous posterior cervical pain. The diagnostic and treatment processes of SIH-induced CVT were described. A magnetic resonance imaging (MRI) study showed superior sagittal sinus thrombosis, and a lumbar puncture revealed a low initial CSF pressure of less than 60 mmH2O. The patient underwent anticoagulation and fluid rehydration therapies. No abnormalities were observed in the thoracic MRI scan, but a cervical MRI scan revealed a spontaneous CSF leak. An epidural blood patch with autologous blood was performed, and symptoms completely resolved 3 days after the procedure. This report proposes a diagnostic procedure for detecting rare cases of SIH-induced CVT, thereby preventing future misdiagnoses and delayed treatment. When a patient presenting with CVT in conjunction with intracranial hypotension has no history of trauma or piercing, SIH caused by spontaneous spinal CSF leakage should be considered as a potential cause of secondary low intracranial pressure. For detection of CSF leaks at rare sites, an MRI of the whole spine rather than a localized MRI of the spine needs to be performed to avoid misdiagnosis. An epidural blood patch should be performed as soon as possible as it may shorten the length of hospitalization and improve prognosis.

Effect of weekend versus weekday admission on the mortality of acute ischemic stroke patients in China: an analysis of data from the Chinese acute ischemic stroke treatment outcome registry.

Background: Due to disparities in medical resources in rural and urban areas as well as in different geographic regions in China, the effect of weekend versus weekday admission on the outcomes of acute ischemic stroke (AIS) patients is unknown. Our aim was to investigate whether the outcomes of AIS patients differ according to the day of admission in China. Methods: The data were extracted from the Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR), a multicenter prospective study database of patients diagnosed with AIS. The chi-square test (χ2) and logistic regression were used to assess mortality for weekday and weekend admissions among AIS patients stratified by rural or urban status and geographic region (including the eastern, northeastern, central, and western regions). Results: In total, 9,256 patients were included in this study. Of these patients, 57.2% were classified as urban, and 42.8% were classified as rural. A total of 6,760 (73%) patients were admitted on weekdays, and 2,496 (27%) were admitted on weekends. There was no significant difference in the mortality rate among patients admitted on weekends compared with those admitted on weekdays in urban (7.5% versus 7.4%) or rural areas (8.8% versus 8.1%; p > 0.05). The mortality rate was the highest among patients admitted on weekends and weekdays (11.6% versus 10.3%) in the northeastern area, without statistical significance before and after adjusting for the patients' background characteristics (p > 0.05). In addition, regression analysis revealed that the mortality of patients admitted on weekdays was more likely to be influenced by regional subgroup, hospital level and intravenous thrombolysis than that of patients admitted on weekends. Conclusion: The weekend effect was not observed in the mortality of patients with AIS regardless of rural-urban status or geographic region in China.

Regional Differences in Hospital Costs of Acute Ischemic Stroke in China: Analysis of Data From the Chinese Acute Ischemic Stroke Treatment Outcome Registry.

Background and Purpose: Studies on the regional differences in hospital costs of acute ischemic stroke (AIS) are scarce in China. We aimed to explore the regional differences in hospital costs and identify the determinants of hospital costs in each region. Methods: Data were collected from the Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR), a multicenter prospective study on patients diagnosed with AIS and hospitalized from 2015 to 2017. Univariate and multivariate analyses were undertaken to identify the determinants of hospital costs of AIS. Results: A total of 8,547 patients were included in the study, of whom 3,700 were from the eastern area, 2,534 were from the northeastern area, 1,819 were from the central area, and 494 were from the western area. The median hospital costs presented a significant difference among each region, which were 2175.9, 2175.1, 2477.7, and 2282.4 dollars in each area, respectively. Each region showed a similar hospital cost proportion size order of cost components, which was Western medicine costs, other costs, diagnostic costs, and traditional medicine costs, in descending order. Male sex, diabetes mellitus, severe stroke symptoms, longer length of stay, admission to the intensive care unit, in-hospital complications of hemorrhage, and thrombectomy were independently associated with hospital costs in most regions. Conclusion: Hospital costs in different regions showed a similar proportion size order of components in China. Each region had different determinants of hospital costs, which reflected its current medical conditions and provided potential determinants for increasing medical efficiency according to each region's situation.

Predictors and Prognosis of Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke Patients Without Thrombolysis: Analysis of Data From the Chinese Acute Ischemic Stroke Treatment Outcome Registry.

Background and Purpose: There is limited information on symptomatic intracranial hemorrhage (sICH) in stroke patients without thrombolysis. This study aimed to evaluate the risk factors of sICH and the association between sICH and the prognosis at 3 and 12 months in acute ischemic stroke patients without thrombolysis. Methods: Data originated from the Chinese Acute Ischemic Stroke Treatment Outcome Registry. Univariate analysis and multivariate logistic regression were used to screen the risk factors of sICH. Multivariable logistic regression models were used to assess the association of sICH with poor outcome and all-cause mortality. Results: Totally, 9,484 patients were included, of which 69 (0.73%) had sICH. Atrial fibrillation (odds ratio [OR], 3.682; 95% confidence interval [CI], 1.945-6.971; p < 0.001), history of tumors (OR, 2.956; 95% CI, 1.115-7.593; p = 0.024), and the National Institutes of Health Stroke Scale (NIHSS) score on admission ([6-15: OR, 2.344; 95% CI, 1.365-4.024; p = 0.002] [>15: OR, 4.731; 95% CI, 1.648-13.583; p = 0.004]) were independently associated with sICH. After adjustment of the confounders, patients with sICH had a higher risk of poor outcome (OR, 1.983; 95% CI, 1.117-3.521; p = 0.018) at 3 months and that of all-cause mortality at 3 (OR, 6.135; 95% CI, 2.328-16.169; p < 0.001) and 12 months (OR, 3.720; 95% CI, 1.513-9.148; p = 0.004). Conclusion: sICH occurred in 0.73% of acute ischemic stroke patients without thrombolysis and was associated with a worse prognosis at 3 and 12 months. Atrial fibrillation, history of tumors, and NIHSS score at admission were independent risk factors of sICH.

Neuroprotective effect of FMS-like tyrosine kinase-3 silence on cerebral ischemia/reperfusion injury in a SH-SY5Y cell line.

Neuron damage contributes to ischemic brain injury. Although FMS-like tyrosine kinase-3 (FLT3) plays a critical role in neuron survival, its function and molecular mechanism in cerebral ischemia/reperfusion injury is unclear. In the present study, we exposed SH-SY5Y cells to oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic ischemia/reperfusion injury. We found that FLT3 and MAPK14/p38α expression increased in OGD/R-treated cells. FLT3 silence significantly increased OGD/R-induced SH-SY5Y cell survival, inhibited reactive oxygen species production. Also, we observed that FLT3 silence suppressed OGD/R-induced SH-SY5Y cell apoptosis, apoptosis related protein Bax level and caspase-3 activity was decreased and Bcl-2 expression was increased in FLT3 silence SH-SY5Y cell treated with OGD/R. Furthermore, FLT3 depletion induced MAPK14/p38α inhibition in SH-SY5Y cultures after OGD/R exposure. These findings suggest that MAPK14/p38α overexpression reverses the action of FLT3 silence in OGD/R-induced SH-SY5Y cells. They also provide the first evidence that FLT3 silence has a neuroprotective role in OGD/R-induced SH-SY5Y cell damage. These data provide insight about potential neuroprotective molecular for ischemia/reperfusion injury.