RESUMO
BACKGROUND: Alkaline phosphatase (ALP) has been implicated to be associated with poor outcome in ischemic stroke patients, yet its role in aneurysmal subarachnoid hemorrhage (aSAH) patients is unknown. The current study aimed to investigate the on-admission and short-term variation trend of ALP levels in aSAH patients as well as its associations with vasospasm, delayed cerebral ischemia (DCI), and outcome after aSAH. METHODS: Between January 2014 and May 2018, all consecutive aSAH patients were prospectively enrolled. Blood samples from patients and 78 healthy individuals were obtained. Baseline information, clinical data, and radiologic data were collected, and serum ALP levels during hospitalization were measured. Patients were followed up for 6 months. RESULTS: One hundred and ninety-six aSAH patients were included. The serum ALP levels in aSAH patients were significantly higher compared to controls (71 vs. 61 U/L, p = 0.0002), yet did not differ significantly between patients with severe (WFNS 4-5) and mild clinical condition (72 vs. 63 U/L, p = 0.3362). However, ALP was significantly higher in patients with severe radiologic status (modified Fisher 3-4) compared to those with mild radiologic status (77 vs. 61.5 U/L, p = 0.0005). A significant correlation emerged between modified Fisher score and ALP level (r = 0.246, p = 0.001). Multivariable analysis found that higher ALP level was associated with angiographic vasospasm (OR 1.019, 95% CI 1.002-1.036, p = 0.026) and DCI-caused clinical deterioration (OR 1.019, 95% CI 1.001-1.037, p = 0.037), while higher WFNS score, modified Fisher score, and ALP level were independently associated with unfavorable outcome (serum ALP level, OR 1.083, 95% CI 1.041-1.127, p < 0.001). Trend analysis of ALP level based on 103 patients' data revealed a significant decrease in ALP level on post-admission day 7-9 (median; on-admission day vs. post-admission day 7-9, 72 vs. 60 U/L, p = 0.0012; post-admission day 3-5 vs. day 7-9, 70 vs. 60 U/L, p = 0.0052) and subsequent increase in ALP level on post-admission day 12-14 (median, 84 U/L, p < 0.0001). Higher ALP levels were observed in patients with unfavorable outcome on on-admission day, post-admission day 3-5, and 12-14 (median; unfavorable vs. favorable; on-admission day, 86 vs. 67 U/L, p = 0.0122; post-admission day 3-5, 80 vs. 64 U/L, p = 0.0044; post-admission day 7-9, 75 vs. 53.5 U/L, p < 0.0001) but not on post-admission day 12-14. CONCLUSIONS: Elevated serum ALP level is associated with vasospasm, DCI-caused clinical deterioration, and functional outcome after aSAH. Further studies are required to examine the potential role of serum ALP as an outcome predictor for aSAH patients.
Assuntos
Fosfatase Alcalina/sangue , Isquemia Encefálica/sangue , Hemorragia Subaracnóidea/sangue , Vasoespasmo Intracraniano/sangue , Idoso , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Angiografia Cerebral , Infarto Cerebral/sangue , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/fisiopatologia , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/epidemiologia , Vasoespasmo Intracraniano/etiologiaRESUMO
Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKß/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1ß. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1ß production. Next, we confirmed that LPS-induced MALAT1 activated IKKß/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1ß through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1ß levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs.
Assuntos
Quinase I-kappa B/genética , Inflamação/genética , MicroRNAs/genética , Microglia/fisiologia , NF-kappa B/genética , RNA Longo não Codificante/genética , Traumatismos da Medula Espinal/genética , Animais , Células Cultivadas , Citocinas/genética , Regulação para Baixo/genética , Interleucina-1beta/genética , Locomoção/genética , Camundongos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética , Traumatismos da Medula Espinal/patologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients' complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH. METHODS: We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People's Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence. RESULTS: Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability. CONCLUSIONS: The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH.
Assuntos
Anemia , Nomogramas , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Anemia/etiologia , Anemia/diagnóstico , Anemia/sangue , Estudos Prospectivos , Idoso , Adulto , Aneurisma Intracraniano/complicaçõesRESUMO
BACKGROUND: This meta-analysis aimed to evaluate the risk of shunt-dependent hydrocephalus among patients with ruptured intracranial aneurysms treated with either coil placement or clipping. METHODS: A systematic literature search of Embase, PubMed, Web of Science, and the Cochrane Library was performed to confirm relevant studies. The scientific literature was screened in accordance with the predetermined inclusion and exclusion criteria. After quality assessment and data extraction from the eligible studies, a meta-analysis was conducted using the STATA 12.0 software (Stata corporation, College Station, Texas, USA). RESULTS: Thirteen studies met all inclusion criteria and were included in the analysis. In total, these studies included 13,751 patients. Of the patients, 8444 of them underwent neurosurgical clipping, and 5307 underwent endovascular coiling. The overall result of a pooled estimate revealed there was no statistically significant risk of shunt dependency difference between the clipping and coiling groups (11.4% vs. 12.0%, respectively; relative risk [RR], 0.92; 95% confidence interval [CI], 0.84-1.01). Six prospective studies (n = 1373) reported shunt-dependent hydrocephalus revealed no significant difference between clipping and coiling (23.3% vs. 20.1%, respectively; RR, 1.12; 95% CI, 0.91-1.38). Seven retrospective studies (n = 12,378) reported shunt-dependent hydrocephalus found statistical significance between the surgical and endovascular treatment groups (10.0% vs. 11.1%, respectively; RR, 0.88; 95% CI, 0.79-0.98). CONCLUSIONS: Microsurgical clipping and endovascular coiling of ruptured cerebral aneurysms are associated with similar incidences of ventricular shunt placement for hydrocephalus. The risk of shunt-dependent hydrocephalus is not higher after coiling than after clipping of ruptured intracranial aneurysms.