Abstract This study focuses on the concordance of different data sources (e.g. World Health Organization, Centers for Disease
Control and Prevention etc.) used for reporting of country wise confirmed COVID-19 infection cases and death rates. It discusses
how to estimate related covariates in order to predict COVID-19 confirmed cases and death rates when reporting systems are
questionable. It attempts to explain why the pattern of early outbreak of COVID-19 is different from the stabilized portion of the
outbreak curve, and examines a long tail nature of its slowing down effect. It also examines the role of temperature, pH level,
and humidity in slowing down the spread of COVID-19, and a particular vaccine that many South Asian countries use to protect
children from tuberculosis. To illustrate these ideas, the study focuses on China, Italy, Spain, France, South Korea, and the United
States, and reveals the policies for varying trends of confirmed cases and death rates of COVID-19. Keywords BCG vaccine; Concordance; Confirmed cases; COVID-19; Death rate
Purpose Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non-small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions. Results We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%. Conclusion In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.
The application of artificial intelligence (AI) in diagnosing and managing ocular disease has gained popularity as research highlights the utilization of AI to improve personalized medicine and healthcare outcomes. The objective of this study is to describe current optometric perspectives of AI in eye care.Members of the American Academy of Optometry were sent an electronic invitation to complete a 17-item survey. Survey items assessed perceived advantages and concerns regarding AI using a 5-point Likert scale ranging from "strongly agree" to "strongly disagree."A total of 400 optometrists completed the survey. The mean number of years since optometry school completion was 25 ± 15.1. Most respondents reported familiarity with AI (66.8%). Though half of optometrists had concerns about the diagnostic accuracy of AI (53.0%), most believed it would improve the practice of optometry (72.0%). Optometrists reported their willingness to incorporate AI into practice increased from 53.3% before the COVID-19 pandemic to 65.5% after onset of the pandemic (p<0.001).In this study, optometrists are optimistic about the use of AI in eye care, and willingness to incorporate AI in clinical practice also increased after the onset of the COVID-19 pandemic.
9037 Background: Among patients with NSCLC and a PD-L1 TPS ≥50%, the response rate to the PD-1 inhibitor pembrolizumab is ~45%. Whether certain subsets of patients with a PD-L1 TPS ≥50% are more likely to benefit from treatment with a PD-1 inhibitor is currently unknown. We compared outcomes among NSCLC patients treated with first-line PD-1 inhibitors and different PD-L1 TPS groupings: 50-74% vs 75-100%. Methods: We retrospectively analyzed patients who received a PD-1 inhibitor as first-line treatment for NSCLC with a PD-L1 TPS of ≥50% from the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Clinicopathologic characteristics and clinical outcomes were compared among patients with a PD-L1 TPS of 50-74% vs 75-100%. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test. Results: 112 patients were identified for inclusion in this study: 39.3% (N = 44) had a PD-L1 TPS of 50-74%, and 60.7% (N = 68) had a TPS of 75-100%. There were no significant differences in smoking history, histology, sex, KRAS or EGFR mutation status, and age between both groups of patients. In the entire cohort, the overall response rate (ORR) was 33.9%, median progression-free survival (mPFS) was 4.2 months (95% CI: 2.8-6.2), median overall survival (mOS) was 20.3 months (95% CI: 17.7-NR). Patients with TPS 75-100% had a significantly higher ORR (13.6% vs 47.1%, P < 0.01), significantly longer mPFS (2.5 mo [95% CI: 1.8-4.5] vs 5.1 mo [95% CI: 3.8-7.4 ], P = 0.02), and higher estimated 12-month OS (76.4% vs 54.4%) compared to patients with TPS 50-74%. Conclusions: In the first-line setting for NSCLC, higher PD-L1 TPS levels of 75-100% is associated with improved clinical outcomes compared to patients with a TPS of 50-74%.
<div>AbstractPurpose:<p>We pursued genomic analysis of an exceptional responder with non–small cell lung cancer (NSCLC) through a multi-platform effort to discover novel oncogenic targets.</p>Experimental Design:<p>In this open-label, single-arm phase II study (NCT01829217), an enriched cohort of patients with advanced NSCLC was treated with the multi-kinase inhibitor sunitinib. The primary endpoint was objective response rate. Tissue was collected for multi-platform genomic analysis of responders, and a candidate oncogene was validated using <i>in vitro</i> models edited by CRISPR-Cas9.</p>Results:<p>Of 13 patients enrolled, 1 patient (8%), a never smoker, had a partial response lasting 33 months. Genomic analysis of the responder identified no oncogenic variant using multi-platform DNA analysis including hotspot allelotyping, massively parallel hybrid-capture next-generation sequencing, and whole-exome sequencing. However, bulk RNA-sequencing (RNA-seq) revealed a novel fusion, <i>TMEM87A–RASGRF1</i>, with high overexpression of the fusion partners. <i>RASGRF1</i> encodes a guanine exchange factor which activates RAS from GDP-RAS to GTP-RAS. Oncogenicity was demonstrated in NIH/3T3 models with intrinsic TMEM87A–RASGRF1 fusion. In addition, activation of MAPK was shown in PC9 models edited to express this fusion, although sensitivity to MAPK inhibition was seen without apparent sensitivity to sunitinib.</p>Conclusions:<p>Sunitinib exhibited limited activity in this enriched cohort of patients with advanced NSCLC. Nonetheless, we find that RNA-seq of exceptional responders represents a potentially underutilized opportunity to identify novel oncogenic targets including oncogenic activation of RASGRF1.</p></div>
<p>Screening with drugs targeting sunitinib related receptor tyrosine kinases (RTK) or MAPK pathway were performed in PC9TMEM87A-RASGRF1 clone 1. Relative viability compared with control (treated with DMSO) was shown. A modest inhibitory effect was seen for gilteritinib without control osimertinib, suggesting the off-target toxic effect of the drug rather than on-target inhibition.</p>
