scholarly journals BIIB093 (intravenous glibenclamide) for the prevention of severe cerebral edema

2021 ◽  
Vol 12 ◽  
pp. 80
Author(s):  
Daniel W. Griepp ◽  
Jason Lee ◽  
Christina M. Moawad ◽  
Cyrus Davati ◽  
Juliana Runnels ◽  
...  

Background: Vasogenic edema in the setting of acute ischemic stroke can be attributed to the opening of transient receptor potential 4 channels, which are expressed in the setting of injury and regulated by sulfonylurea receptor 1 (SUR1) proteins. Glibenclamide, also known as glyburide, RP-1127, Cirara, and BIIB093, is a second-generation sulfonylurea that binds SUR1 at potassium channels and may significantly reduce cerebral edema following stroke, as evidenced by recent clinical trials. This review provides a comprehensive analysis of clinical considerations of glibenclamide use and current patient outcomes when administered in the setting of acute ischemic stroke to reduce severe edema. Methods: National databases (MEDLINE, EMBASE, Cochrane, and Google scholar databases) were searched to identify studies that reported on the clinical outcomes of glibenclamide administered immediately following acute ischemic stroke. Results: The pharmacological mechanism of glibenclamide was reviewed in depth as well as the known indications and contraindications to receiving treatment. Eight studies were identified as having meaningful clinical outcome data, finding statistically significant differences in glibenclamide treatment groups ranging from matrix metalloproteinase-9 serum levels, midline shift, modified Rankin Scores, National Institute of Health Stroke Score, and mortality endpoints. Conclusion: Studies analyzing the GAMES-Pilot and GAMES-PR trials suggest that glibenclamide has a moderate, however, measurable effect on intermediate biomarkers and clinical endpoints. Meaningful conclusions are limited by the small sample size of patients studied.

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Digvijaya Navalkele ◽  
Chunyan Cai ◽  
Mohammad Rahbar ◽  
Renganayaki Pandurengan ◽  
Tzu-Ching Wu ◽  
...  

Background: Per American Heart Association guidelines, blood pressure (BP) should be < 185/110 to be eligible for intravenous tissue plasminogen activator (tPA). It is shown that door to needle (DTN) time is prolonged in patients who require anti-hypertensive medications prior to thrombolysis in the emergency department (ED). To our knowledge, no studies have focused on pre-hospital BP and its impact on DTN times. We hypothesize that DTN times are longer for patients with higher pre-hospital BP. Methods: We conducted a retrospective review of acute ischemic stroke patients who presented between 1/2010 and 12/2010 to our ED through Emergency Medical Services (EMS) within 3-hrs of symptom onset. Patients were identified from our registry and categorized into two groups: Pre-hospital BP ≥ 185/110 (Pre-hsp HBP) and < 185/110 (Pre-hsp LBP). BP records were abstracted from EMS sheets. Two groups were compared using two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher’s exact test for categorical variables. Results: A total of 107 consecutive patients were identified. Out of these, 75 patients (70%) were treated with tPA. Among the patients who received thrombolysis, 35% had pre-hospital BP ≥ 185/110 (n= 26/75). Greater number of patients required anti-hypertensive medications in ED in high BP group compared to low BP group (Pre-hsp HBP n= 14/26, 54%; Pre-hsp LBP n= 13/49, 27%, p < 0.02). Mean door to needle times were significantly higher in Pre-hsp HBP group. (mean ± SD 87.5± 34.2 Vs. 59.7±18.3, p<0.0001). Analysis of patients only within the Pre-hsp HBP group (n= 26) revealed that DTN times were shorter if patients received pre-hsp BP medications compared to patients in the same group who did not receive pre-hsp BP medication (n= 10 vs 16; mean ± SD 76.5 ± 25.7 Vs. 94.3 ± 37.7, p = 0.20) Conclusion: Higher pre-hospital BP is associated with prolonged DTN times and it stays prolonged if pre-hospital high BP remains untreated. Although the later finding was not statistical significant due to small sample size, pre-hospital blood pressure control could be a potential area for improvement to reduce door to needle times in acute ischemic stroke.


2020 ◽  
Vol 8 (4S) ◽  
pp. 95-103
Author(s):  
K. M. Vakkosov ◽  
D. Yu. Naumov ◽  
N. I. Vodop`yanova ◽  
I. V. Moldavskaya ◽  
V. I. Ganyukov

Aim. Mechanical thrombectomy is standard of care for the treatment of acute ischemic stroke. The objective of this study is to analyze the results of our own experience of endovascular treatment in Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases” Kemerovo.Methods. 12 patients with AIS and underwent mechanical thrombectomy with «Trevo» stent-retriever were included in this analysis. Primary outcomes included 90-day modified Rankin scale (mRS) score, first pass effect (FPE) and recanalization rate (TICI score), the combined incidence of postintervention hemorrhages and mortality at 90 days.Results. Among 12 patients (66.7% male, age 59.5 [57.5; 66.5] years) hypertension were in 100%, 61.5% had an ischemic heart disease, 53.8% was current smoking and atrial fibrillation. Median of the NIHSS scale was 13 points, mRS≥4 was in 75% of patients. In 33.3% was a tandem lesion (internal carotid artery terminus and middle cerebral artery) and 25% required stenting of the carotid artery. Good clinical outcomes (mRS≤2 at 90 days) were achieved in 77.8% (7/9) among surviving patients. The 90-day NIHSS score – 4 [1; 5]. The first pass effect and recanalization rate (TICI Scores 2b-3/3) was achieved in 50% and 91.7% of patients. The combined incidence of postintervention hemorrhages and mortality at 90 days was 33.3% and 25% respectively.Conclusion. Despite the small sample size, stent retriever mechanical thrombectomy in AIS provides satisfactory clinical results.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ashish Kulhari ◽  
Daniel Ro ◽  
Amrinder Singh ◽  
Farah Fourcand ◽  
Gurneel Kaur Dhanesar ◽  
...  

Background: Multiple recent positive endovascular trials have proven mechanical thrombectomy as standard of care for large vessel occlusion (LVO) of the Anterior Circulation (AC). Post-thrombectomy subarachnoid hemorrhage (PT-SAH) is a known complication of this procedure. The aim of this study was to compare the incidence of SAH in proximal (ICA terminus and MCA M1) versus distal (MCA M2 and beyond) LVOs with use of stentrievers. Methods: Retrospective analysis of patients who underwent anterior circulation acute ischemic stroke interventions (AISI) at a community based, university affiliated comprehensive stroke center during a 5 year period (2014-2019) was done. AISI using stentrievers were separated in 2 groups based on location of LVO (Proximal and Distal). Post procedure CT heads were reviewed for SAH in location of stent deployment. Results: 2980 patients presented with acute ischemic stroke during the pre-specified time period. Of those, 2,682 were anterior circulation strokes. Of those, 373 received AISI. Stentrievers were used in 193 patients. Proximal occlusions (ICA terminus and MCA M1) were placed into Group A (n=150). Distal occlusions (MCA M2 and beyond) were placed into Group B (n=43). Group A had 6% SAH (n=9); Group B had 16% SAH (n=7) (p value <0.05). Conclusion: This study reveals an increased incidence of PT-SAH for distal LVOs. Main limitation of the study is the small sample size. Next generation stentrievers with smaller stent size and different design may decrease incidence of PT-SAH. Larger prospective RCTs are warranted to validate these results.


2021 ◽  
pp. 20210414
Author(s):  
Mark Paxton ◽  
Eitan Barbalat ◽  
Nathan Perlis ◽  
Ravi J Menezes ◽  
Mark Gertner ◽  
...  

Objective: Determine the multiparametric magnetic resonance imaging (mpMRI) appearance of the prostate following focal laser ablation (FLA) for PCa and to identify imaging characteristics associated with recurrent disease. Methods: Retrospective analysis of patients who underwent FLA for low-intermediate risk PCa between 2010 and 2014 was performed. Early (median 4 months) and late mpMRI (median 49 months) follow-up were qualitatively assessed for T2-weighted, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) appearances and also compared to corresponding PSA values and biopsy results. Results: 55 cancers were treated in 54 men (mean age 61.0 years). Early mpMRI was performed in 30 (54.5%) patients while late follow-up mpMRI in 42 (84%). Ill-defined scarring with and without atrophy at the treatment site were the most common appearances. In patients with paired MRI and biopsy, one of four patients with clinically significant PCa on biopsy (≥GG2 or≥6 mm GG1) showed hyperenhancement or restricted diffusion at early follow-up. At late follow-up, positive biopsies were seen in 5/8 (63%) cases with hyperenhancement and 5/6 (83%) cases with restricted diffusion at the treatment site. PSA change was not associated with biopsy results at either time point. Conclusion: mpMRI is able to document the morphological and temporal changes following focal therapy. It has limited ability to detect recurrent disease in early months following treatment. Late-term mpMRI is sensitive at identifying patients with recurrent disease. Small sample size is, however, a limitation of the study. Advances in knowledge: Implementing MRI in follow-up after FT may be useful in predicting residual or recurrent PCa and therefore provide reliable outcome data.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
I. A. Mulder ◽  
E. T. van Bavel ◽  
H. E. de Vries ◽  
J. M. Coutinho

AbstractWith the introduction of endovascular thrombectomy (EVT), a new era for treatment of acute ischemic stroke (AIS) has arrived. However, despite the much larger recanalization rate as compared to thrombolysis alone, final outcome remains far from ideal. This raises the question if some of the previously tested neuroprotective drugs warrant re-evaluation, since these compounds were all tested in studies where large-vessel recanalization was rarely achieved in the acute phase. This review provides an overview of compounds tested in clinical AIS trials and gives insight into which of these drugs warrant a re-evaluation as an add-on therapy for AIS in the era of EVT. A literature search was performed using the search terms “ischemic stroke brain” in title/abstract, and additional filters. After exclusion of papers using pre-defined selection criteria, a total of 89 trials were eligible for review which reported on 56 unique compounds. Trial compounds were divided into 6 categories based on their perceived mode of action: systemic haemodynamics, excitotoxicity, neuro-inflammation, blood–brain barrier and vasogenic edema, oxidative and nitrosative stress, neurogenesis/-regeneration and -recovery. Main trial outcomes and safety issues are summarized and promising compounds for re-evaluation are highlighted. Looking at group effect, drugs intervening with oxidative and nitrosative stress and neurogenesis/-regeneration and -recovery appear to have a favourable safety profile and show the most promising results regarding efficacy. Finally, possible theories behind individual and group effects are discussed and recommendation for promising treatment strategies are described.


2018 ◽  
Vol 10 (Suppl 1) ◽  
pp. i45-i49 ◽  
Author(s):  
Osama O Zaidat ◽  
Alicia C Castonguay ◽  
Rishi Gupta ◽  
Chung-Huan J Sun ◽  
Coleman Martin ◽  
...  

BackgroundLimited post-marketing data exist on the use of the Solitaire FR device in clinical practice. The North American Solitaire Stent Retriever Acute Stroke (NASA) registry aimed to assess the real world performance of the Solitaire FR device in contrast with the results from the SWIFT (Solitaire with the Intention for Thrombectomy) and TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) trials.MethodsThe investigator initiated NASA registry recruited North American sites to submit retrospective angiographic and clinical outcome data on consecutive acute ischemic stroke (AIS) patients treated with the Solitaire FR between March 2012 and February 2013. The primary outcome was a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a. Secondary outcomes were 90 day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage.Results354 patients underwent treatment for AIS using the Solitaire FR device in 24 centers. Mean time from onset to groin puncture was 363.4±239 min, mean fluoroscopy time was 32.9±25.7 min, and mean procedure time was 100.9±57.8 min. Recanalization outcome: TIMI ≥2 rate of 83.3% (315/354) and TICI ≥2a rate of 87.5% (310/354) compared with the operator reported TIMI ≥2 rate of 83% in SWIFT and TICI ≥2a rate of 85% in TREVO 2. Clinical outcome: 42% (132/315) of NASA patients demonstrated a 90 day mRS ≤2 compared with 37% (SWIFT) and 40% (TREVO 2). 90 day mortality was 30.2% (95/315) versus 17.2% (SWIFT) and 29% (TREVO 2).ConclusionsThe NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results.


2019 ◽  
Vol 33 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Aaron P Wessell ◽  
Gregory Cannarsa ◽  
Helio Carvalho ◽  
Matthew J Kole ◽  
Pankaj Sharma ◽  
...  

Introduction The Sofia 6-French PLUS catheter is a recently approved aspiration catheter for use in neuro-endovascular procedures. The description of Sofia 6-French PLUS use in acute ischemic stroke is limited. Objective The purpose of this article is to describe our initial experience with the new Sofia 6-French PLUS catheter for treatment of acute ischemic stroke and to report on its safety and efficacy. Methods We performed a retrospective study of 54 thrombectomy cases treated with the Sofia 6-French PLUS catheter. Mean patient age and admission National Institutes of Health Stroke Scale score were 65.30 (1.92) and 15.98 (0.89), respectively. The most common sites of vessel occlusion included the M1 segment (50%) and internal carotid artery (31%). Thrombectomy was performed using the direct aspiration first pass technique and/or aspiration in conjunction with a stent retriever. Results Successful navigation of the Sofia 6-French PLUS catheter to the site of thromboembolus was achieved in 94% of cases. Revascularization was achieved in a total of 47 cases (87%). Mean time from groin access to revascularization was 42.79 (3.23) min. There were no catheter-related complications. Final outcome data was available for 44 patients (81%). Of these patients, 41% achieved a good outcome (modified Rankin scale score of 0–2) at 60–90 day follow-up, 41% had a poor outcome (modified Rankin 3–5) and eight patients died (18%). Conclusions We demonstrate the safe and effective use of the Sofia 6-French PLUS catheter for treatment of acute ischemic stroke. Future studies in the form of a randomized clinical trial or multicenter registry are warranted to further evaluate its comparative safety and efficacy.


2011 ◽  
Vol 165 (6) ◽  
pp. 841-849 ◽  
Author(s):  
Ahmad Hazem ◽  
Mohamed B Elamin ◽  
German Malaga ◽  
Irina Bancos ◽  
Yolanda Prevost ◽  
...  

ContextThe diagnostic accuracy of tests used to diagnose GH deficiency (GHD) in adults is unclear.ObjectiveWe conducted a systematic review and meta-analysis of studies that provided data on the available diagnostic tests.Data sourcesWe searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Sciences, and Scopus) through April 2011.Study selectionReview of reference lists and contact with experts identified additional candidate studies. Reviewers, working independently and in duplicate, determined study eligibility.Data extractionReviewers, working independently and in duplicate, determined the methodological quality of studies and collected descriptive, quality, and outcome data.Data synthesisTwenty-three studies provided diagnostic accuracy data; none provided patient outcome data. Studies had fair methodological quality, used several reference standards, and included over 1100 patients. Several tests based on direct or indirect stimulation of GH release were associated with good diagnostic accuracy, although most were assessed in one or two studies decreasing the strength of inference due to small sample size. Serum levels of GH or IGF1 had low diagnostic accuracy. Pooled sensitivity and specificity of the two most commonly used stimulation tests were found to be 95 and 89% for the insulin tolerance test and 73 and 81% for the GHRH+arginine test respectively. Meta-analytic estimates for accuracy were associated with substantial heterogeneity.ConclusionSeveral tests with reasonable diagnostic accuracy are available for the diagnosis of GHD in adults. The supporting evidence, however, is at high risk of bias (due to heterogeneity, methodological limitations, and imprecision).


Sign in / Sign up

Export Citation Format

Share Document