Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer.

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan−Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4−16.7] vs. 21.03 [95% CI: 14.7−24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26−8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72−19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

Hospitalization and survival of solid organ transplant recipients with coronavirus disease 2019: A propensity matched cohort study.

BACKGROUND: Solid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment. METHODS: In this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients. RESULTS: The study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04-2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46-0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72-2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53-1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36-1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64-2.08, P = 0.64). CONCLUSIONS: Hospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study.

Carboxyhemoglobinemia in Critically Ill Coronavirus Disease 2019 Patients.

Carboxyhemoglobinemia is a common but a serious disorder, defined as an increase in carboxyhemoglobin level. Unfortunately, there are few data on carboxyhemoglobinemia in coronavirus disease 2019 (COVID-19) patients. Therefore, our study aimed to evaluate the incidence and etiologies of carboxyhemoglobinemia in COVID-19 patients and determine any association between carboxyhemoglobinemia and novel coronavirus infection. A retrospective chart review was performed at an academic medical center for all inpatient COVID-19 cases with either single or serial carboxyhemoglobin (COHb) levels from March 2020 through August 2020.Our study demonstrates that carboxyhemoglobinemia in COVID-19 patients is due to sepsis, hemolysis, and cytokine storm, triggered by the novel coronavirus infection sequela and is not directly from the virulence of novel coronavirus. Given the coexisting illnesses in critically ill COVID-19 patients, it is impossible to establish if coronavirus virulence was the culprit of elevated COHb levels. Moreover, our study found a high incidence of carboxyhemoglobinemia in critically ill COVID-19 patients. The oxygen saturation measured by pulse oximetry can be inaccurate and unreliable; however, our study could not demonstrate any uniform results on the discrepancy between oxygen saturation measured by pulse oximetry and arterial blood gas. In this study, COHb levels were measured using a CO-oximeter. Therefore, we recommend monitoring the COHb level routinely in critically ill COVID-19 patients to allow more effective and prompt treatment.

Continuous Glucose Monitoring in Critically Ill Patients With COVID-19: Results of an Emergent Pilot Study.

BACKGROUND: Amidst the coronavirus disease 2019 (COVID-19) pandemic, continuous glucose monitoring (CGM) has emerged as an alternative for inpatient point-of-care blood glucose (POC-BG) monitoring. We performed a feasibility pilot study using CGM in critically ill patients with COVID-19 in the intensive care unit (ICU). METHODS: Single-center, retrospective study of glucose monitoring in critically ill patients with COVID-19 on insulin therapy using Medtronic Guardian Connect and Dexcom G6 CGM systems. Primary outcomes were feasibility and accuracy for trending POC-BG. Secondary outcomes included reliability and nurse acceptance. Sensor glucose (SG) was used for trends between POC-BG with nursing guidance to reduce POC-BG frequency from one to two hours to four hours when the SG was in the target range. Mean absolute relative difference (MARD), Clarke error grids analysis (EGA), and Bland-Altman (B&A) plots were calculated for accuracy of paired SG and POC-BG measurements. RESULTS: CGM devices were placed on 11 patients: Medtronic (n = 6) and Dexcom G6 (n = 5). Both systems were feasible and reliable with good nurse acceptance. To determine accuracy, 437 paired SG and POC-BG readings were analyzed. For Medtronic, the MARD was 13.1% with 100% of readings in zones A and B on Clarke EGA. For Dexcom, MARD was 11.1% with 98% of readings in zones A and B. B&A plots had a mean bias of -17.76 mg/dL (Medtronic) and -1.94 mg/dL (Dexcom), with wide 95% limits of agreement. CONCLUSIONS: During the COVID-19 pandemic, CGM is feasible in critically ill patients and has acceptable accuracy to identify trends and guide intermittent blood glucose monitoring with insulin therapy.