Endovascular Thrombectomy for Mild Strokes: How Low Should We Go? A Multicenter Cohort Study

Background and Purpose:Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion (LVO) and NIHSS ≥6. However, EVT benefit for mild deficits LVOs (NIHSS Methods: A retrospective cohort of patients with anterior circulation LVO and NIHSSoutcome; mRS=0–2 was the secondary. Symptomatic intracerebral hemorrhage (sICH) was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time-last-seen-normal-to-presentation, center, IV-alteplase, ASPECTS, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results: 214 patients (EVT-124, medical management-90) were included from 8 US and Spain centers between January/2012 and March/2017. The groups were similar in age, ASPECTS, IValteplase rate and time-last-seen-normal-to-presentation. There was no difference in mRS=0–1 between EVT and medical management (55.7% versus 54.4%, respectively, aOR=1.3, 95%CI=0.64–2.64, p=0.47). Similar results were seen for mRS=0–2 (63.3% EVT versus 67.8% medical management, aOR=0.9, 95%CI=0.43–1.88, p=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5%EVT, 48.4% medical management; OR=1.17, 95%CI=0.54–2.52, p=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance (p=0.07). sICH rates were higher with thrombectomy (5.8% EVT versus 0% medical management, p=0.02). Conclusions: Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHS

Outcomes of Endovascular Thrombectomy vs Medical Management Alone in Patients With Large Ischemic Cores

Importance The efficacy and safety of endovascular thrombectomy (EVT) in patients with large ischemic cores remains unknown, to our knowledge. Objective To compare outcomes in patients with large ischemic cores treated with EVT and medical management vs medical management alone. Design, Setting, and Participants This prespecified analysis of the Optimizing Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) trial, a prospective cohort study of imaging selection that was conducted in 9 US comprehensive stroke centers, enrolled patients between January 2016 and February 2018, and followed them up for 90 days. Patients with moderate to severe stroke and anterior circulation large-vessel occlusion presenting up to 24 hours from the time they were last known to be well were eligible for the cohort. Of these, patients with large ischemic cores on computed tomography (CT) (Alberta Stroke Program Early CT Score \u3c6) or CT perfusion scanning (a volume with a relative cerebral blood flow \u3c30% of ≥50 cm3) were included in analyses. Exposures Endovascular thrombectomy with medical management (MM) or MM only. Main Outcomes and Measures Functional outcomes at 90 days per modified Rankin scale; safety outcomes (mortality, symptomatic intracerebral hemorrhage, and neurological worsening). Results A total of 105 patients with large ischemic cores on either CT or CT perfusion images were included: 71 with Alberta Stroke Program Early CT Scores of 5 or less (EVT, 37; MM, 34), 74 with cores of 50 cm3 or greater on CT perfusion images (EVT, 39; MM, 35), and 40 who had large cores on both CT and CT perfusion images (EVT, 14; MM, 26). The median (interquartile range) age was 66 (60-75) years; 45 patients (43%) were female. Nineteen of 62 patients (31%) who were treated with EVT achieved functional independence (modified Rankin Scale scores, 0-2) vs 6 of 43 patients (14%) treated with MM only (odds ratio [OR], 3.27 [95% CI, 1.11-9.62]; P = .03). Also, EVT was associated with better functional outcomes (common OR, 2.12 [95% CI, 1.05-4.31]; P = .04), less infarct growth (44 vs 98 mL; P = .006), and smaller final infarct volume (97 vs 190 mL; P = .001) than MM. In the odds of functional independence, there was a 42% reduction per 10-cm3 increase in core volume (adjusted OR, 0.58 [95% CI, 0.39-0.87]; P = .007) and a 40% reduction per hour of treatment delay (adjusted OR, 0.60 [95% CI, 0.36-0.99]; P = .045). Of 10 patients who had EVT with core volumes greater than 100 cm3, none had a favorable outcome. Conclusions and Relevance Although the odds of good outcomes for patients with large cores who receive EVT markedly decline with increasing core size and time to treatment, these data suggest potential benefits. Randomized clinical trials are needed

Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy

Background To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies.Methods Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set.Results Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γ signature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders.Conclusion Our study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM

A meta‐analysis of the global impact of the COVID‐19 pandemic on stroke care & the Houston Experience

Abstract Objective To review the global impact of the COVID‐19 pandemic on stroke care‐metrics and report data from a health system in Houston. Methods We performed a meta‐analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January–June 2019 and January–June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. Results A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1‐5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. Interpretation The COVID‐19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs

ImportanceUniversal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.ObjectiveTo compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.Design, setting, and participantsTwo-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included.InterventionUniversal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline).Main outcomes and measuresICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%.ResultsAmong the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]).Conclusions and relevanceNasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin.Trial registrationClinicalTrials.gov Identifier: NCT03140423