Touro Infirmary Foundation

PurposeAnti-PD-1 therapy provides clinical benefit in 40–50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.MethodsClinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune microenvironment to predict disease control with monotherapy PD-1 inhibitors (pembrolizumab and nivolumab). The performance of the biomarker was internally validated using out-of-bag methods.ResultsThe biomarker significantly predicted disease control (65% in predicted non-progressors vs. 17% in predicted progressors, p < 0.001) and was significantly correlated with overall survival (OS; p = 0.004). In addition, the biomarker outperformed PD-L1 IHC across numerous metrics including sensitivity (0.79 vs 0.64, respectively; p = 0.005) and specificity (0.70 vs 0.61, respectively; p = 0.009).ConclusionThis novel assay uses tumor immune microenvironment expression data to predict disease control and OS with high sensitivity and specificity in patients with RM-HNSCC treated with anti-PD-1 monotherapy.

Justificación: La criobiopsia pulmonar transbronquial (TBLC) se ha propuesto como un método menos invasivo para obtener un diagnóstico tisular en pacientes con enfermedad pulmonar intersticial (EPI). El rendimiento diagnóstico de la TBLC en comparación con la biopsia pulmonar quirúrgica (SLB) sigue siendo incierto. Objetivos: Este estudio tuvo como objetivo determinar la precisión diagnóstica de la biopsia pulmonar transbronquial (TBLB) con fórceps y de la TBLC en comparación con la SLB para realizar el diagnóstico final con base en una discusión multidisciplinaria (MDD). Métodos: Los pacientes incluidos en el estudio se sometieron a TBLB y TBLC secuenciales, seguidas inmediatamente de SLB. Los casos, anonimizados y sin información sobre el método de biopsia, fueron revisados por un patólogo, quien trabajó a ciegas con respecto a dicha información, y luego discutidos en una conferencia multidisciplinaria. Resultados: Principales: Entre agosto de 2013 y octubre de 2017 se reclutaron 16 pacientes. La concordancia primaria entre TBLC y SLB para el diagnóstico final de MDD fue de 68.75%, con una kappa de Cohen de 0.6 (IC 95%: 0.39, 0.81). La concordancia primaria y la kappa de Cohen de la TBLC frente a la SLB para el diagnóstico final de MDD fueron mucho menores (50%, 0.21 [IC 95%: 0, 0.42] y 18.75%, 0.08 [IC 95%: -0.03, 0.19], respectivamente). La TBLC se asoció con hemorragia leve (hemorragia de grado 1, que requirió aspiración) en 56.2% de los pacientes. Conclusiones: En los pacientes con EPI de tipo incierto según con los datos clínicos y radiográficos, quienes requieren la toma de muestra de tejido para obtener un diagnóstico específico, la TBLC mostró una correlación moderada con la SLB al realizar el diagnóstico con la guía de una MDD. La TBLB mostró mala concordancia con los diagnósticos de la MDD, tanto mediante TBLC como por SLB.

BackgroundIt is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts.MethodsIn the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6 or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials.ResultsFrom 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0–2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively.ConclusionsIn a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results.Clinical trial registrationNCT02446587

Background and Purpose- Timely access to endovascular thrombectomy (EVT) centers is vital for best acute ischemic stroke outcomes. Methods- US stroke-treating centers were mapped utilizing geo-mapping and stratified into non-EVT or EVT if they reported ≥1 acute ischemic stroke thrombectomy code in 2017 to Center for Medicare and Medicaid Services. Direct EVT-access, defined as the population with the closest facility being an EVT-center, was calculated from validated trauma-models adapted for stroke. Current 15- and 30-minute access were described nationwide and at state-level with emphasis on 4 states (TX, NY, CA, IL). Two optimization models were utilized. Model-A used a greedy algorithm to capture the largest population with direct access when flipping 10% and 20% non-EVT to EVT-centers to maximize access. Model-B used bypassing methodology to directly transport patients to the nearest EVT centers if the drive-time difference from the geo-centroid to hospital was within 15 minutes from the geo-centroid to the closest non-EVT center. Results- Of 1941 stroke-centers, 713 (37%) were EVT. Approximately 61 million (19.8%) Americans have direct EVT access within 15 minutes while 95 million (30.9%) within 30 minutes. There were 65 (43%) EVT centers in TX with 22% of the population currently within 15-minute access. Flipping 10% hospitals with top population density improved access to 30.8%, while bypassing resulted in 45.5% having direct access to EVT centers. Similar results were found in NY (current, 20.9%; flipping, 34.7%; bypassing, 50.4%), CA (current, 25.5%; flipping, 37.3%; bypassing, 53.9%), and IL (current, 15.3%; flipping, 21.9%; bypassing, 34.6%). Nationwide, the current direct access within 15 minutes of 19.8% increased by 7.5% by flipping the top 10% non-EVT to EVT-capable in all states. Bypassing non-EVT centers by 15 minutes resulted in a 16.7% gain in coverage. Conclusions- EVT-access within 15 minutes is limited to less than one-fifth of the US population. Optimization methodologies that increase EVT centers or bypass non-EVT to the closest EVT center both showed enhanced access. Results varied by states based on the population size and density. However, bypass showed more potential for maximizing direct EVT-access. National and state efforts should focus on identifying gaps and tailoring solutions to improve EVT-access.

We conducted a prospective serial laboratory cohort study to assess the correlation of factor VIII (FVIII) levels in response to thrombolysis in patients with large vessel occlusion (LVO) and acute ischemic stroke (AIS). Patients with AIS with anterior circulation LVO were eligible for enrollment if treated within 4.5 hours from last seen normal with intravenous tissue plasminogen activator (tPA). Patients (n = 29) had a mean age of 71 years and median National Institute of Health Stroke Scale of 14. Baseline pre-tPA FVIII was not significantly correlated with clot burden score (−0.147, P = .447) or vessel recanalization (−0.133, P = .499). Median FVIII decreased significantly from baseline to 6 hours post-tPA (282% to 161%, P = .002), but delta in FVIII level did not correlate with vessel recanalization (0.013, P = .948). There was no difference between median FVIII level at baseline and 90 days post-AIS. FVIII level decreased significantly after tPA, but baseline FVIII level and early change in FVIII level were not significant predictors of clot burden, vessel recanalization after thrombolysis, or symptomatic hemorrhage.

Point-of-care testing (POCT) is a commonly used technology that hastens the time to laboratory results in emergency departments (ED). We evaluated an ED-based POCT program on ED length of stay (LOS) and time to care, coupled with qualitative interviews of local ED stakeholders. We conducted a mixed-methods study (2012-2016) to examine the impact of POCT in a single, community ED. The quantiative analysis involved an observational before-after study comparing time to laboratory test result (POC troponin or POC chemistry) and ED LOS after implementation of POCT, using a propensity-weighted interrupted time series analysis (ITSA). A complementary qualitative analysis involved five semistructured interviews with staff using grounded theory on the benefits and challenges to ED POCT. A total of 47,399 ED visits were included in the study (24,705 in the preintervention period and 22,694 in the postintervention period). After POCT implementation, overall laboratory testing increased marginally from 61% to 62%. Central laboratory troponin and chemistry declined by>50% and was replaced by POCT. Prior to POCT implementation, time to troponin and chemistry had declined steadily due to other improvements in laboratory efficiency. After POCT implementation, there was an immediate 20-minute further decline (p<0.001) in both time to troponin and time to chemistry results using the propensity-weighted comparisons. However, the declining trend observed prior to POCT implementation did not continue at the same rate after implementation. Similarly, prior to POCT implementation, ED LOS declined due to other quality improvements. After POCT implementation, LOS continued declined at a similar rate. Because of this prior trend, the ITSA did not show a significant decline in LOS attributable to POCT. Common benefits of POCT perceived by staff in qualitative interviews included improved quality of care (64%) and reductions in time to test results (44%). Common challenges included concerns over POCT accuracy (32%) and technical barriers (29%). In the study ED, implementation of POCT was associated with a reduction in time to test result for both troponin and chemistry. Local staff felt that faster time to test result improved quality of care; however, concerns were raised with POCT accuracy.