Citations

Introduction: Prehospital telestroke is increasingly utilized in mobile stroke units and telemedicine-enabled ambulances for acute ischemic stroke (AIS). While the NIHSS remains the standard for telestroke assessment, simpler scales have been validated to help paramedics recognize large vessel occlusion (LVO) strokes but have not been evaluated in a traditional telestroke network. We aimed to determine the accuracy of common LVO scales in a large academic telestroke practice. Methods: This retrospective study included all telestroke consults performed in a large academic telestroke network from 2019 to 2020. Patients were excluded if no NIHSS or vessel imaging was performed. We recorded presenting NIHSS, site of vessel occlusion, and discharge diagnosis. LVO was defined as an acute occlusion of the internal carotid artery and/or M1 middle cerebral artery. The NIHSS was used to calculate 7 LVO scales (RACE, C-STAT, FAST-ED, 3I-SS, PASS, VAN, and G-FAST). Diagnostic performance was assessed by calculating sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy using the established thresholds of each scale. These results were compared to NIHSS at thresholds of 6, 8, and 10. Area under curve (AUC) was calculated using c-statistics by treating scales as continuous variables. Results: A total of 625 patients were included, 373/625 (59.7%) of which were diagnosed with AIS at discharge. LVO was identified in 78/625 (12.5%) patients. VAN was the most sensitive prehospital stroke scale (83.3%), whereas 3I-SS ≥ 4 was the most specific (95.2%). Both the RACE and FAST-ED scales demonstrated superior accuracy and AUC compared to the NIHSS (Table 1). Conclusions: To our knowledge, this is the first study assessing LVO scale accuracy in a large telestroke network. As use of prehospital telestroke grows, this study highlights several scales that may allow for faster prehospital triage decisions without sacrificing accuracy.

Introduction: Telestroke facilitates emergent assessment of patients with suspected acute ischemic stroke (AIS) to identify candidates for acute interventions. The diagnostic accuracy of the telestroke consultation of a large academic hub and spoke telemedicine network has yet to be investigated. The goal of our study is to determine the diagnostic accuracy of the initial telestroke consultation. Methods: This is an IRB-exempt retrospective study including all patients evaluated for cerebral ischemia via video telestroke consultation in a large academic hub and spoke telemedicine network from 2019 to 2020. Detailed chart review was conducted to identify initial suspected diagnosis and final diagnosis. Cerebral ischemia was defined as AIS and transient ischemic attack (TIA). All other diagnoses were defined as stroke mimics. Data was organized into continuous and categorical variables. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, area under the curve (AUC) and likelihood ratio (LR+) for the initial telestroke consultation diagnosis were calculated while using the final diagnosis as the gold standard diagnosis. Results: A total of 1043 patients met inclusion criteria. Final diagnosis of cerebral ischemia was made in 63.5% of all patients (539/1043 with AIS,123/1043 with TIA). Stroke mimic was diagnosed in 36.5% patients (381/1043). The sensitivity and specificity of telestroke evaluation for diagnosis of cerebral ischemia were 97.1% and 81.4%, respectively. PPV was 90.1%, and NPV was 94.2%. Overall diagnostic accuracy was 91.4% with a LR+ of 5.21 and AUC of 0.89. The most common stroke mimics were metabolic encephalopathy (13.7%, 52/381), migraine (10.8%, 41/381) and seizure (10.5%, 40/381). Conclusions: This study highlights the high diagnostic accuracy of telestroke providers to diagnose cerebral ischemia and stroke mimic in a large academic hub and spoke network. Further research is needed to investigate methods to improve our diagnostic accuracy further, as well as explore the application of tele-neurology in the non-stroke setting.

Background. End-stage kidney disease patients with concomitant heart failure (HF) with reduced ejection fraction are often denied kidney transplantation. The aims of this study were to explore factors predictive of suitability for kidney transplant and to assess cardiovascular outcomes in patients with impaired left ventricular ejection fraction (LVEF) after transplant. Methods. We evaluated 109 consecutive adults with LVEF ≤40% at the time of initial kidney transplant evaluation between 2013 and 2018. Posttransplant cardiovascular outcomes were defined as nonfatal myocardial infarction (MI), admission for HF, cardiovascular death, and all-cause mortality. Results. A cardiologist participated in kidney transplant evaluation for 87% of patients and was present at 49% of transplant selection conferences. Twenty-four patients (22%) were denied by a cardiologist for kidney transplant‚ and 59 (54%) were denied by the selection committee, of whom 43 were because of cardiovascular risk. Forty-two (38%) patients were approved for kidney transplant. On univariate analysis, the variables associated with denial for kidney transplant included cardiologist denial, higher cardiac troponin T, prior coronary intervention, cardiovascular event, positive stress study, lower ejection fraction, and lower VO2 max (all P < 0.05). Cardiologist denial was the most significant predictor of denial for kidney transplant in different multivariate models. At a median follow-up of 15 mo, 5 (5%) suffered nonfatal MI, 13 (12%) were hospitalized for HF exacerbation, and 17 (16%) died. Only 22 patients, 52% of those approved, underwent kidney transplant. After kidney transplant, there was 1 death, 1 nonfatal MI, and 3 hospitalizations for HF. Median LVEF improved from 38% before listing to 55% posttransplant. Conclusions. Cardiologist denial was the primary predictor of rejection for kidney transplant. Despite careful selection, prevalence of cardiovascular events and mortality after kidney transplant was 23%. There is need for a structured multidisciplinary approach for patients with impaired LVEF.

AbstractObjectivesThis study aims to analyze the impact of age and sex on botulinum neurotoxin (BoNT‐A) dosing and outcomes in adductor spasmodic dysphonia (AdSD).MethodsA database review of all spasmodic dysphonia patients treated with BoNT from 1989 to 2018 at the Mayo Clinic in Arizona was performed. Only patients who had received ≥4 injections of BoNT‐A for AdSD were included. Patients were divided into two cohorts to analyze age, with an age of first treatment cutoff of 60 years. Patients were divided into male and female cohorts to analyze sex.ResultsThe final analysis included 398 patients. The mean dose of BoNT‐A per treatment was significantly higher in the younger cohort (4.4 vs. 3.9 units, p = 0.048). The mean maximal benefit was similar (72% vs. 70%, p = 0.48); however, the mean length of benefit was significantly shorter in younger patients (3.0 vs. 3.6 months, p < 0.01). The mean BoNT‐A dose was significantly higher in the female cohort (4.2 vs. 3.6 units, p = 0.02). The mean maximal benefit was similar (69% vs. 75%, p = 0.58), as was the mean length of benefit (3.2 vs. 3.5 months, p = 0.11).ConclusionsThis study suggests that age and sex influence BoNT‐A dosing and outcomes in AdSD.

Background and Aims: Efficacy of chimeric antigen receptor (CAR) T cells for treating solid tumors, including HCC, remains a challenge. Nanobodies are emerging building blocks of CAR T cells due to their small size and high expression. Membrane proximal sites have been shown as attractive epitopes of CAR T cells. However, current CAR formats are not tailored toward nanobodies or targeting membrane distal epitopes. Approach and Results: Using hYP7 Fv (membrane proximal) and HN3 VH nanobody (membrane distal) as GPC3 targeting elements, we sought to determine how hinges and transmembrane portions of varying structures and sizes affect CAR T-cell function. We generated multiple permutations of CAR T cells containing CD8, CD28, IgG4, and Fc domains. We show that engineered HN3 CAR T cells can be improved by 2 independent, synergistic changes in the hinge and transmembrane domains. The T cells expressing the HN3 CAR which contains the hinge region of IgG4 and the CD28 transmembrane domain (HN3-IgG4H-CD28TM) exhibited high cytotoxic activity and caused complete HCC tumor eradication in immunodeficient mice. HN3-IgG4H-CD28TM CAR T cells were enriched for cytotoxic-memory CD8+ T cells and NFAT signals, and reduced β catenin levels in HCC cells. Conclusion: Our findings indicate that altering the hinge and transmembrane domains of a nanobody-based CAR targeting a distal GPC3 epitope, in contrast to a membrane proximal epitope, lead to robust T-cell signaling and induce swift and durable eradication of HCC tumors.

ABSTRACT Background Serum cystatin C–based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine–based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. Methods Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. Results There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P &lt; .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P &lt; .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P &lt; .001) and CV events or mortality (HR 1.49, P &lt; .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated. Conclusion eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

Objectives: To date, there are no specific guidelines on antithrombotic therapy (ATT) management, which includes both anticoagulation and antiplatelet medications, for open tracheostomy. The objective of this study was to evaluate whether the use of perioperative antithrombotic medication during open tracheostomy influences the incidence of perioperative or postoperative complications. Methods: A retrospective review was conducted of all patients who underwent open tracheostomies at a tertiary care medical center from January 2015 to December 2019. Charts were reviewed for demographics, comorbidities, indication for tracheostomy, ATT use, operative details, and complications. Results: A total of 217 tracheostomies were evaluated for this study, of which 148 (68.2%) were not on ATT and 69 (31.8%) were on ATT during surgery. No significant difference was observed based on ATT status in perioperative bleeding ( P = .983), postoperative bleeding ( P = .24), or median days to decannulation ( P = .5986). ATT patients were 2.67 times more likely to experience 30-day mortality than those non-ATT patients ( P = .035). There was only one death due to hemorrhage in the ATT group. This was unrelated to the tracheostomy. This compares to 2 hemorrhage-related deaths in those not on ATT. Conclusion: There was no significant difference in perioperative or postoperative bleeding based on ATT use. Patients on ATT were significantly more likely to experience 30-day mortality, however only one death was due to hemorrhage in the ATT group and was unrelated to tracheostomy. Therefore, continued perioperative ATT use appears to be safe when performing open tracheostomy. Level of Evidence: 4

Abstract Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10−8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20–1.30] compared with the other genotypes (OR &lt;1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10−8) and 8q24.23 (rs7005722, P = 2.88 × 10−8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09–1.16) compared with the other genotypes (OR &lt;1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07–1.28) compared with the other genotypes (OR &lt;1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.