Dhawan, Manish

e14591 Background: Combined immune checkpoint inhibitors (ICPI) have revolutionized treatment of solid tumors. Their use can lead to treatment-related adverse events (TRAEs) resulting in hospital admissions, treatment discontinuation and increased morbidity. We aim to evaluate gastrointestinal (GI) TRAEs of different combination ICPI. Methods: A comprehensive search of multiple databases from inception to October 2021 was performed. Phase 2 and 3 trials assessing safety and efficacy of combined ICPI in solid tumors were included. Trials reporting concurrent use of chemotherapy, immunosuppressants, targeted therapy, or sequential ICPI therapy were excluded. Primary outcome was pooled luminal, hepatic and pancreatic TRAEs. A meta-analysis of proportions was done for outcomes using a random-effects model. I2 % was used to assess heterogeneity. Results: Out of 3696 citations screened, 53 trials reporting TRAEs in 6186 patients were included. Data from 41 study arms of 35 trials in nivolumab plus ipilimumab (N+I), 15 study arms of 15 trials in durvalumab plus tremelimumab (D+T), 4 study arms of 3 trials in pembrolizumab plus ipilimumab (P+I). The most common indications for combined ICPI were melanoma (26.4%) and lung cancer (24.5%). Pooled GI TRAE rates from the D+T, P+I and two different dosing combinations of N+I are shown in the table. Conclusions: Our study provides pooled data of TRAEs from different combination ICPI use in solid tumors and demonstrates high incidence of all grades and ≥ 3 GI TRAEs. Combined ICPI related TRAEs should be recognized early, as it may require treatment discontinuation. Further studies are required to assess overall impact of TRAEs on treatment course and outcomes.[Table: see text]

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.