Ritesh Kaushal

Balloon Guide Catheter Improves Revascularization and Clinical Outcomes With the Solitaire Device Analysis of the North American Solitaire Acute Stroke Registry

Background and Purpose— Efficient and timely recanalization is an important goal in acute stroke endovascular therapy. Several studies demonstrated improved recanalization and clinical outcomes with the stent retriever devices compared with the Merci device. The goal of this study was to evaluate the role of the balloon guide catheter (BGC) and recanalization success in a substudy of the North American Solitaire Acute Stroke (NASA) registry. Methods— The investigator-initiated NASA registry recruited 24 clinical sites within North America to submit demographic, clinical, site-adjudicated angiographic, and clinical outcome data on consecutive patients treated with the Solitaire Flow Restoration device. BGC use was at the discretion of the treating physicians. Results— There were 354 patients included in the NASA registry. BGC data were reported in 338 of 354 patients in this subanalysis, of which 149 (44%) had placement of a BGC. Mean age was 67.3±15.2 years, and median National Institutes of Health Stroke Scale score was 18. Patients with BGC had more hypertension (82.4% versus 72.5%; P=0.05), atrial fibrillation (50.3% versus 32.8%; P=0.001), and were more commonly administered tissue plasminogen activator (51.6% versus 38.8%; P=0.02) compared with patients without BGC. Time from symptom onset to groin puncture and number of passes were similar between the 2 groups. Procedure time was shorter in patients with BGC (120±28.5 versus 161±35.6 minutes; P=0.02), and less adjunctive therapy was used in patients with BGC (20% versus 28.6%; P=0.05). Thrombolysis in cerebral infarction 3 reperfusion scores were higher in patients with BGC (53.7% versus 32.5%; P<0.001). Distal emboli and emboli in new territory were similar between the 2 groups. Discharge National Institutes of Health Stroke Scale score (mean, 12±14.5 versus 17.5±16; P=0.002) and good clinical outcome at 3 months were superior in patients with BGC compared with patients without (51.6% versus 35.8%; P=0.02). Multivariate analysis demonstrated that the use of BGC was an independent predictor of good clinical outcome (odds ratio, 2.5; 95% confidence interval, 1.2–4.9). Conclusions— Use of a BGC with the Solitaire Flow Restoration device resulted in superior revascularization results, faster procedure times, decreased need for adjunctive therapy, and improved clinical outcome.

Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans : no evidence of association

Although genomewide scans have identified several potential chromosomal susceptibility regions in several human populations, finding a causative gene for type 2 diabetes has remained elusive. Others have reported a novel gene, calpain-10 (CAPN10), located in a previously identified region on chromosome 2q37.3, as a putative susceptibility gene for type 2 diabetes. Three single-nucleotide polymorphisms (SNPs) (UCSNP43, UCSNP19, and UCSNP63) were shown to be involved in increased risk of the disease among Mexican Americans. We have tested the association of these three SNPs with type 2 diabetes among the Samoans of Polynesia, who have a very high prevalence of the disease. In the U.S. territory of American Samoa, prevalence is 25% and 15% in men and women, respectively, whereas, in the independent nation of Samoa, prevalence is 3% and 5% in men and women, respectively. In our study sample, which consisted of 172 unrelated affected case subjects and 96 control subjects, we failed to detect any association between case subjects and control subjects in allele frequencies, haplotype frequencies, or haplotype combinations of UCSNP43, -19, and -63. Also, our data showed no evidence of linkage, among 201 affected sib pairs, in the region of chromosome 2 that contains these SNPs. Three plausible scenarios could explain these observations. (1) CAPN10 is a susceptibility gene only in particular ethnic groups; (2) our study lacks power to detect the effects of CAPN10 polymorphisms (but our sample size is comparable to that of earlier reports); or (3) the underlying biological mechanism is too complex and requires further research.

North American Solitaire Stent Retriever Acute Stroke registry: post-marketing revascularization and clinical outcome results

Background Limited 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. Methods The 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. Results 354 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). Conclusions The NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results.

Association of Apolipoprotein E4 and Haplotypes of the Apolipoprotein E Gene With Lobar Intracerebral Hemorrhage

Background and Purpose— Conflicting reports in the literature exist with regard to the association of apolipoprotein E (apo E) alleles and lobar intracerebral hemorrhage (ICH). We genotyped 12 single-nucleotide polymorphisms in the 5′ upstream regulatory, exonic, and intronic regions of the apo E gene and performed genotype and haplotype association analyses. Methods— We prospectively enrolled subjects with hemorrhagic stroke and matched them with 2 controls based on age, race, and sex. Each case was reviewed by a physician to determine case status and location of the ICH. Multivariate logistic-regression modeling with backward elimination was used to determine significant risk factors for lobar ICH. Associations at the genotype and haplotype levels and linkage disequilibrium were conducted according to standard statistical methods. Results— Between May 1997 and December 2002, 315 cases of ICH were recruited, of whom 107 were lobar ICH cases matched to 205 controls. No association was found for apo E2, E3, or E4 with nonlobar ICH. Independent, significant risk factors for lobar ICH included apo E4, untreated hypertension, anticoagulant use, a first-degree relative with ICH, and ≤high school education (compared with >high school education). Treated hypercholesterolemia compared with “no history of hypercholesterolemia” was associated with a decreased risk of lobar ICH. Haplotype association analysis demonstrated a significant association of the apo E gene with lobar ICH among whites (P<0.0001) and blacks (P=0.0024). Conclusions— Apo E4 is independently associated with lobar ICH but not nonlobar ICH. Haplotypes of the apo E gene are associated with lobar ICH. Untreated hypertension is a risk factor for lobar ICH.

North American SOLITAIRE Stent-Retriever Acute Stroke Registry: choice of anesthesia and outcomes.

Background and Purpose— Previous work that predated the availability of the safer stent-retriever devices has suggested that general anesthesia (GA) may have a negative impact on outcomes in patients with acute ischemic stroke undergoing endovascular therapy. Methods— We reviewed demographic, clinical, procedural (GA versus local anesthesia [LA], etc), and site-adjudicated angiographic and clinical outcomes data from consecutive patients treated with the Solitaire FR device in the investigator-initiated North American SOLITAIRE Stent-Retriever Acute Stroke (NASA) Registry. The primary outcomes were 90-day modified Rankin Scale, mortality, and symptomatic intracranial hemorrhage. Results— A total of 281 patients from 18 centers were enrolled. GA was used in 69.8% (196/281) of patients. Baseline demographic and procedural factors were comparable between the LA and GA groups, except the former demonstrated longer time-to-groin puncture (395.4±254 versus 337.4±208 min; P=0.04), lower National Institutes of Health Stroke Scale (NIHSS; 16.2±5.8 versus 18.8±6.9; P=0.002), lower balloon-guide catheter usage (22.4% versus 49.2%; P=0.0001), and longer fluoroscopy times (39.5±33 versus 28±22.8 min; P=0.008). Recanalization (thrombolysis in cerebral infarction ≥2b; 72.94% versus 73.6%; P=0.9) and rate of symptomatic intracranial hemorrhage (7.1% versus 11.2%; P=0.4) were similar but modified Rankin Scale ⩽2 was achieved in more LA patients, 52.6% versus 35.6% (odds ratio, 1.4 [1.1–1.8]; P=0.01). In multivariate analysis, hypertension, NIHSS, unsuccessful revascularization, and GA use (odds ratio, 3.3 [1.6–7.1]; P=0.001) were associated with death. When only anterior circulation and elective GA patients were included, there was a persistent difference in good outcomes in favor of LA patients (50.7% versus 35.5%; odds ratio, 1.3 [1.01–1.6]; P=0.04). Conclusions— The NASA Registry has demonstrated that clinical outcomes and survival are significantly better in patients treated with LA, without increased symptomatic intracranial hemorrhage risk. Future trials should prospectively evaluate the effect of GA on outcomes.

Predictors of poor outcome despite recanalization: a multiple regression analysis of the NASA registry

Background Mechanical thrombectomy with stent-retrievers results in higher recanalization rates compared with previous devices. Despite successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b) of 70–83%, good outcomes by 90-day modified Rankin Scale (mRS) score ≤2 are achieved in only 40–55% of patients. We evaluated predictors of poor outcomes (mRS >2) despite successful recanalization (TICI ≥2b) in the North American Solitaire Stent Retriever Acute Stroke (NASA) registry. Methods Logistic regression was used to evaluate baseline characteristics and recanalization outcomes for association with 90-day mRS score of 0–2 (good outcome) vs 3–6 (poor outcome). Univariate tests were carried out for all factors. A multivariable model was developed based on backwards selection from the factors with at least marginal significance (p≤0.10) on univariate analysis with the retention criterion set at p≤0.05. The model was refit to minimize the number of cases excluded because of missing covariate values; the c-statistic was a measure of predictive power. Results Of 354 patients, 256 (72.3%) were recanalized successfully. Based on 234 recanalized patients evaluated for 90-day mRS score, 116 (49.6%) had poor outcomes. Univariate analysis identified an increased risk of poor outcome for age ≥80 years, occlusion site of internal carotid artery (ICA)/basilar artery, National Institute of Health Stroke Scale (NIHSS) score ≥18, history of diabetes mellitus, TICI 2b, use of rescue therapy, not using a balloon-guided catheter or intravenous tissue plasminogen activator (IV t-PA), and >30 min to recanalization (p≤0.05). In multivariable analysis, age ≥80 years, occlusion site ICA/basilar, initial NIHSS score ≥18, diabetes, absence of IV t-PA, ≥3 passes, and use of rescue therapy were significant independent predictors of poor 90-day outcome in a model with good predictive power (c-index=0.80). Conclusions Age, occlusion site, high NIHSS, diabetes, no IV t-PA, ≥3 passes, and use of rescue therapy are associated with poor 90-day outcome despite successful recanalization.

Variants in the HEPSIN gene are associated with prostate cancer in men of European origin

There is considerable evidence that genetic factors are involved in prostate cancer susceptibility. We have studied the association of 11 single nucleotide polymorphisms (SNPs) in the HEPSIN gene (HPN) with prostate cancer in men of European ancestry. HPN is a likely candidate in prostate cancer susceptibility, as it encodes a transmembrane cell surface serum protease, which is overexpressed in prostate cancer; HPN is also located on 19q11–q13.2, where linkage is found with prostate cancer susceptibility. In this case-control association study (590 men with histologically verified prostate cancer and 576 unrelated controls, all of European descent), we find significant allele frequency differences between cases and controls at five SNPs that are located contiguously within the gene. A major 11-locus haplotype is significantly associated, which provides further support that HPN is a potentially important candidate gene involved in prostate cancer susceptibility. Association of one of the SNPs with Gleason score is also suggestive of a plausible role of HPN in tumor aggressiveness.

Influence of Age on Clinical and Revascularization Outcomes in the North American Solitaire Stent-Retriever Acute Stroke Registry

Background and Purpose— The Solitaire With the Intention for Thrombectomy (SWIFT) and thrombectomy revascularization of large vessel occlusions in acute ischemic stroke (TREVO 2) trial results demonstrated improved recanalization rates with mechanical thrombectomy; however, outcomes in the elderly population remain poorly understood. Here, we report the effect of age on clinical and angiographic outcome within the North American Solitaire-FR Stent-Retriever Acute Stroke (NASA) Registry. Methods— The NASA Registry recruited sites to submit data on consecutive patients treated with Solitaire-FR. Influence of age on clinical and angiographic outcomes was assessed by dichotomizing the cohort into ⩽80 and >80 years of age. Results— Three hundred fifty-four patients underwent treatment in 24 centers; 276 patients were ⩽80 years and 78 were >80 years of age. Mean age in the ⩽80 and >80 cohorts was 62.2±13.2 and 85.2±3.8 years, respectively. Of patients >80 years, 27.3% had a 90-day modified Rankin Score ⩽2 versus 45.4% ⩽80 years (P=0.02). Mortality was 43.9% and 27.3% in the >80 and ⩽80 years cohorts, respectively (P=0.01). There was no significant difference in time to revascularization, revascularization success, or symptomatic intracranial hemorrhage between the groups. Multivariate analysis showed age >80 years as an independent predictor of poor clinical outcome and mortality. Within the >80 cohort, National Institutes of Health Stroke Scale (NIHSS), revascularization rate, rescue therapy use, and symptomatic intracranial hemorrhage were independent predictors of mortality. Conclusion— Greater than 80 years of age is predictive of poor clinical outcome and increased mortality compared with younger patients in the NASA registry. However, intravenous tissue-type plasminogen activator use, lower NIHSS, and shorter revascularization time are associated with better outcomes. Further studies are needed to understand the endovascular therapy role in this cohort compared with medical therapy.

Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry

Background and Purpose— Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. Methods— STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. Results— A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab–adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. Conclusions— This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Predictors of Mortality in Acute Ischemic Stroke Intervention Analysis of the North American Solitaire Acute Stroke Registry

Background and Purpose— Failure to recanalize predicts mortality in acute ischemic stroke. In the North American Solitaire Acute Stroke registry, we investigated parameters associated with mortality in successfully recanalized patients. Methods— Logistic regression was used to evaluate baseline characteristics and recanalization parameters for association with 90-day mortality. A multivariable model was developed based on backward selection with retention criteria of P<0.05 from factors with at least marginal significance (P⩽0.10), then refit to minimize the number of excluded cases (missing data). Results— Successfully recanalized patients had lower mortality (25.2% [59/234] versus 46.9% [38/81] P<0.001). There was no difference in symptomatic intracranial hemorrhage between patients with successful versus failed recanalization (9% [21/234] versus 14% [11/79]; P=0.205). However, mortality was significantly higher in patients with symptomatic intracranial hemorrhage (72% [23/32] versus 26% [73/281]; P<0.001). Proximal occlusion (internal carotid artery or vertebrobasilar), initial National Institutes of Health Stroke Scale≥18, use of rescue therapy (P<0.05), and 3+ passes (P<0.10) were associated with mortality in recanalized patients. In the multivariate model with good predictive power (c index=0.72), proximal occlusion, initial National Institutes of Health Stroke Scale≥18, and use of rescue therapy remained significant independent predictors of 90-day mortality. Conclusions— Failure to recanalize and presence of symptomatic intracranial hemorrhage resulted in increased mortality. Despite successful recanalization, proximal occlusion, high National Institutes of Health Stroke Scale, and need for rescue therapy were predictors of mortality.