The Association Between Illness Severity Scores and In-hospital Mortality After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: The purpose of this study was to examine the association with in-hospital mortality of 8 illness severity scores in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In a retrospective cohort study, we investigated the association with in-hospital mortality of admission Hunt and Hess (HH) score, Fisher grade, severity of illness and risk of mortality scores, and serial Glasgow coma scale (GCS) score in patients with aSAH. We also explored the changes in GCS between admission and discharge using a multivariate model adjusting for age, clinical vasospasm, and external ventricular drain status. RESULTS: Data from 480 patients with aSAH, of which 383 (79.8%) aneurysms were in the anterior circulation, were included in analysis. Patients were female (n=340, 70.8%) with a median age of 56 (interquartile range: 48 to 66) years. The majority (n=332, 69.2%) had admission HH score 3 to 5, Fisher grade 3 to 4 (n=437, 91%), median severity of illness 3 (range: 1 to 4), median risk of mortality 3 (range: 1 to 4), and median admission GCS of 13 (interquartile range: 7 to 15). Overall, 406 (84.6%) patients received an external ventricular drain, 469 (97.7%) underwent aneurysm repair, and 60 died (12.5%). Compared with admission HH score, GCS 24 hours after admission (area under the curve: 0.84, 95% confidence interval [CI]: 0.79-0.88) and 24 hours after aneurysm repair (area under the curve: 0.87, 95% CI: 0.82-0.90) were more likely to be associated with in-hospital mortality. Among those who died, the greatest decline in GCS was noted between 24 hours after aneurysm repair and discharge (-3.38 points, 95% CI: -4.17, -2.58). CONCLUSIONS: Compared with admission HH score, GCS 24 hours after admission (or 24 h after aneurysm repair) is more likely to be associated with in-hospital mortality after aSAH.

Associations Between Transcranial Doppler Vasospasm and Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study.

OBJECTIVE: The objective is to examine the relationship between transcranial Doppler cerebral vasospasm (TCD-vasospasm), and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In a retrospective cohort study, using univariate and multivariate analysis, we examined the association between TCD-vasospasm (defined as Lindegaard ratio >3) and patient's ability to ambulate without assistance, the need for tracheostomy and gastrostomy tube placement, and the likelihood of being discharged home from the hospital. RESULTS: We studied 346 patients with aSAH; median age 55 years (Interquartile range IQR 46,64), median Hunt and Hess 3 [IQR 1-5]. Overall, 68.6% (n=238) had TCD-vasospasm, and 28% (n=97) had delayed cerebral ischemia. At hospital discharge, 54.3% (n=188) were able to walk without assistance, 5.8% (n=20) had received a tracheostomy, and 12% (n=42) had received a gastrostomy tube. Fifty-three percent (n=183) were discharged directly from the hospital to their home. TCD-vasospasm was not associated with ambulation without assistance at discharge (adjusted odds ratio, aOR 0.54, 95% 0.19,1.45), tracheostomy placement (aOR 2.04, 95% 0.23,18.43), gastrostomy tube placement (aOR 0.95, 95% CI 0.28,3.26), discharge to home (aOR 0.36, 95% CI 0.11,1.23). CONCLUSION: This single-center retrospective study finds that TCD-vasospasm is not associated with clinical outcomes such as ambulation without assistance, discharge to home from the hospital, tracheostomy, and gastrostomy feeding tube placement. Routine screening for cerebral vasospasm and its impact on vasospasm diagnostic and therapeutic interventions and their associations with improved clinical outcomes warrant an evaluation in large, prospective, case-controlled, multi-center studies.

EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma.

PURPOSE: Enhancer of zeste homologue 2 (EZH2), a component of the chromatin modification protein complex, is upregulated in pancreatic ductal adenocarcinoma (PDAC), whereas loss of p53 and its downstream target, p21(waf1/cip1), is also observed frequently. We sought to investigate the role of the p53-p21(waf1/cip1) pathway in relation to EZH2-mediated inhibition of PDAC. METHODS: The PANC-1 cell line was utilized in chromatin immunoprecipitation, gene profiling, Western blot, cell invasion, cell proliferation, and tumor xenograft assays. RESULTS: Western blot analysis with antibodies that recognize both wild-type and mutant p53 did not show any alterations in band intensity; however, antibody that detects only mutant p53 showed a band of significantly lesser intensity with EZH2 knockdown. Western blot analysis further revealed a significant upregulation of p21(waf1/cip1). Gene expression profile analysis indicated significantly enhanced transcripts of transcriptional inducers of p21(waf1/cip1), with downregulation of mutant p53 transcript, corroborating the Western blot analysis. PANC-1 cells expressing EZH2-short hairpin RNA displayed markedly attenuated growth in SCID mice. CONCLUSION: Downregulation of mutant p53 with concomitant enhanced expression of p21(waf1/cip1) and its transcriptional trans-activators may contribute toward EZH2-mediated suppression of PDAC.