Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640

Genetic polymorphisms in DNA repair and damage response genes and late normal tissue complications of radiotherapy for breast cancer

Breast-conserving surgery followed by radiotherapy is effective in reducing recurrence; however, telangiectasia and fibrosis can occur as late skin side effects. As radiotherapy acts through producing DNA damage, we investigated whether genetic variation in DNA repair and damage response confers increased susceptibility to develop late normal skin complications. Breast cancer patients who received radiotherapy after breast-conserving surgery were examined for late complications of radiotherapy after a median follow-up time of 51 months. Polymorphisms in genes involved in DNA repair (APEX1, XRCC1, XRCC2, XRCC3, XPD) and damage response (TP53, P21) were determined. Associations between telangiectasia and genotypes were assessed among 409 patients, using multivariate logistic regression. A total of 131 patients presented with telangiectasia and 28 patients with fibrosis. Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia. The odds ratios (OR) were 1.66 (95% confidence interval (CI): 1.02–2.72) for 72Pro carriers and 1.95 (95% CI: 1.13–3.35) for PIN3 A2 allele carriers compared with non-carriers. The TP53 haplotype containing both variant alleles was associated with almost a two-fold increase in risk (OR 1.97, 95% CI: 1.11–3.52) for telangiectasia. Variants in the TP53 gene may therefore modify the risk of late skin toxicity after radiotherapy

Bridging thrombolysis in atrial fibrillation stroke is associated with increased hemorrhagic complications without improved outcomes

BACKGROUND: Atrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT. METHODS: This international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into four groups based on comorbid AF and IVT exposure. Baseline patient characteristics, complications, and outcomes were reported and compared. RESULTS: 6461 patients underwent MT for LVO. 2311 (35.8%) patients had comorbid AF. In non-AF patients, bridging therapy improved the odds of good 90 day functional outcomes (adjusted OR (aOR) 1.29, 95% CI 1.03 to 1.60, p=0.025) and did not increase hemorrhagic complications. In AF patients, bridging therapy led to significant increases in symptomatic intracranial hemorrhage and parenchymal hematoma type 2 (aOR 1.66, 1.07 to 2.57, p=0.024) without any benefit in 90 day functional outcomes. Similar findings were noted in a separate propensity score analysis. CONCLUSION: In this large thrombectomy registry, AF patients exposed to IVT before MT had increased hemorrhagic complications without improved functional outcomes, in contrast with non-AF patients. Prospective trials are warranted to assess whether AF patients represent a subgroup of LVO patients who may benefit from a direct to thrombectomy approach at thrombectomy capable centers

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T&gt;G and c.3113G&gt;A, CHEK2c.349A&gt;G, c.538C&gt;T, c.715G&gt;A, c.1036C&gt;T, c.1312G&gt;T, and c.1343T&gt;G and ATM c.7271T&gt;G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G&gt;A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T&gt;G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A&gt;G OR 2.26 (95% CI 1.29 to 3.95), c.1036C&gt;T OR 5.06 (95% CI 1.09 to 23.5) and c.538C&gt;T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T&gt;G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G&gt;T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.</p

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in the Early and Extended Window

Importance: Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct. Objective: To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5. Design, setting, and participants: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid artery or M1 segment of the middle cerebral artery from January 1, 2016, to December 31, 2020. Patients were followed up for 90 days after intervention. The ASPECTS is a 10-point scoring system based on the extent of early ischemic changes on the baseline noncontrasted computed tomography scan, with a score of 10 indicating normal and a score of 0 indicating ischemic changes in all of the regions included in the score. Exposure: All patients underwent MT in one of the included centers. Main outcomes and measures: A multivariable regression model was used to assess factors associated with a favorable 90-day outcome (modified Rankin Scale score of 0-2), including interaction terms between an ASPECTS of 2 to 5 and receiving MT in the extended window (6-24 hours from symptom onset). Results: A total of 2345 patients who underwent MT were included (1175 women [50.1%]; median age, 72 years [IQR, 60-80 years]; 2132 patients [90.9%] had an ASPECTS of ≥6, and 213 patients [9.1%] had an ASPECTS of 2-5). At 90 days, 47 of the 213 patients (22.1%) with an ASPECTS of 2 to 5 had a modified Rankin Scale score of 0 to 2 (25.6% [45 of 176] of patients who underwent successful recanalization [modified Thrombolysis in Cerebral Ischemia score ≥2B] vs 5.4% [2 of 37] of patients who underwent unsuccessful recanalization; P = .007). Having a low ASPECTS (odds ratio, 0.60; 95% CI, 0.38-0.85; P = .002) and presenting in the extended window (odds ratio, 0.69; 95% CI, 0.55-0.88; P = .001) were associated with worse 90-day outcome after controlling for potential confounders, without significant interaction between these 2 factors (P = .64). Conclusions and relevance: In this cohort study, more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT. A favorable outcome was nearly 5 times more likely for patients with low ASPECTS who had successful recanalization. The association of a low ASPECTS with 90-day outcomes did not differ for patients presenting in the early vs extended MT window

Increased utilization of cervical disk arthroplasty in university hospitals with regional variation and socioeconomic discrepancies.

OBJECTIVE: Treatment of cervical radiculopathy with disk arthroplasty has been approved by the U.S. Food and Drug Administration since 2007. Recently, a significant increase in clinical data including mid- and long-term follow-up has become available, demonstrating the superiority of disk arthroplasty compared with anterior discectomy and fusion. The aim of this project is to assess the nationwide use of cervical disk arthroplasty. METHODS: The University Healthcare Consortium database was accessed for all elective cases of patients treated for cervical radiculopathy caused by disk herniation (International Classification of Diseases [ICD] 722.0) from the fourth quarter of 2012 to the third quarter of 2015. Within this 3-year window, temporal and socioeconomic trends in the use of cervical disk replacement for this diagnosis were assessed. RESULTS: Three thousand four hundred forty-six cases were identified. A minority of cases (10.7%) were treated with disk arthroplasty. Median hospital charges were comparable for cervical disk replacement ($15,606) and anterior cervical fusion ($15,080). However, utilization was seen to increase by nearly 70% during the timeframe assessed. Disk arthroplasty was performed in 8% of patients in 2012 to 2013, compared with 13% of cases in 2015. Disk replacement use was more common for self-paying patients, patients with private insurance, and patients with military-based insurance. There was widespread variation in the use of cervical disk replacement between regions, with a nadir in northeastern states (8%) and a peak in western states (20%). CONCLUSION: Over a short, 3 -year period there has been an increase in the treatment of symptomatic cervical radiculopathy with disk arthroplasty. The authors predict a further increase in cervical disk arthroplasty in upcoming years

Penetrating Spinal Cord Injury in civilians: analysis of a national database

BACKGROUND: Spinal trauma is common in polytrauma; spinal cord injury (SCI) is present in a subset of these patients. Penetrating SCI has been studied in the military; however, civilian SCI is less studied. Civilian injury pathophysiology varies given the generally lower velocity of the projectiles. We sought to investigate civilian penetrating SCI in the United States. METHODS: We queried the National Inpatient Sample for data regarding penetrating spinal cord injury from the past 10 years (2006-2015). The National Inpatient Sample includes data of 20% of discharged patients from U.S. hospitals. We analyzed trends of penetrating SCI regarding its diagnosis, demographics, surgical management, length of stay, and hospital costs. RESULTS: In the past 10 years the incidence of penetrating SCI in all SCI patients has remained stable with a mean of 5.5% (range 4.3%-6.6%). Of the patients with penetrating SCI, only 17% of them underwent a surgical procedure, compared with 55% for nonpenetrating SCI. Patients with penetrating SCI had a longer length of stay (average 23 days) compared with nonpenetrating SCI (15 days). Hospital charges were higher for penetrating SCI: $230,186 compared with$192,022 for closed SCI. Males patients were more affected by penetrating SCI, as well as black and Hispanic populations compared with whites. CONCLUSIONS: Penetrating SCI represents 5.5% of all SCI patients. Men, blacks, and Hispanics are disproportionally more affected by penetrating SCI. Patients with penetrating SCI have fewer surgical interventions, but their overall length of stay and hospital costs are greater compared with nonpenetrating SCI