Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay: A Multicenter Study.

BACKGROUND: Accurate and timely methods for the diagnosis of histoplasmosis in resource-limited countries are lacking. Histoplasma antigen detection by enzyme immunoassay (EIA) is widely used in the United States (US) but not in resource-limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFAs) can be used in this setting. METHODS: Frozen urine specimens were submitted to MiraVista diagnostics for antigen testing from 3 medical centers in endemic areas of the US. They were blinded and tested for the MVista Histoplasma LFA. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable; pulmonary or disseminated; immunocompetent or immunosuppressed; and mild, moderate, or severe. RESULTS: Three hundred fifty-two subjects were enrolled, including 66 cases (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (71%), and 46 had disseminated and 20 had pulmonary histoplasmosis. Four cases were mild, 42 moderate, and 20 severe. LFA and EIA were highly concordant (κ = 0.84). Sensitivity and specificity of the LFA were 78.8% and 99.3%, respectively. LFA sensitivity was higher in proven cases (93.2%), patients with disseminated (91.3%), moderate (78.6%), and severe disease (80%), and those with galactomannan levels >1.8 ng/mL (97.8%). Specificity was 99.3% in proven cases, 99.3% in patients with moderate or severe disease, and 96.8% in those with galactomannan levels >1.8 ng/mL. Cross-reactivity was noted with other endemic mycoses. CONCLUSIONS: The MVista Histoplasma LFA meets the need for accurate rapid diagnosis of histoplasmosis in resource-limited countries, especially in patients with high disease burden, potentially reducing morbidity and mortality.

Insight into an acute hepatitis A outbreak in Indiana.

Hepatitis A virus (HAV) infection causes an acute enteric hepatitis associated with substantial morbidity and mortality, particularly in older individuals. Incidence of HAV infection is low in the United States, mostly related to consumption of contaminated food. Starting in 2017, Indiana reported a large HAV outbreak. We sought to characterize the risk-exposures, clinical features and outcomes of HAV and examine the differences based on underlying cirrhosis and age. Adults ≥18 years diagnosed with HAV between January 2017 and April 2019 at two large healthcare systems in Indiana were identified. Demographic data, risk-exposures, clinical features, laboratory data and clinical outcomes were collected for analysis. The HAV cohort constituted 264 individuals with mean age of 41-years, 62% male and 94% Caucasian. Risk-exposures identified were illicit drug use (74%), food-borne (15%), person-to-person (11%) and incarceration (11%). Mortality rate was 2%, acute liver failure (ALF) was seen in 4% and acute on chronic liver failure (ACLF) was seen in 30% (6 of 20 with underlying cirrhosis). Admission MELD score was the only factor associated with ALF [OR = 1.17 (1.08-1.2), p < 0.0001], on multivariable logistic regression analysis. Higher proportion of individuals with underlying cirrhosis developed acute kidney injury (AKI) (26% vs. 9%, p = 0.03), ascites (45% vs. 11%, p < 0.0001) and hepatic encephalopathy (35% vs. 4%, p < 0.0001). In conclusion, illicit drug use was the predominant risk-exposure in the current HAV outbreak, which was associated with 2% mortality rate, and those with cirrhosis had worse outcomes (AKI, ascites and HE), of whom 30% developed ACLF.

Single-institution experience of medical students' bacterial colonization during training.

BACKGROUND: Medical students are often potential vectors for resistant bacteria to their entourage. We therefore conducted this study to evaluate the variation of medical students' multiple drug resistant bacterial flora throughout their medical training. METHODS: We performed a cross-sectional study enrolling medical students of the 2016 academic year from the Saint-Joseph University - Faculty of Medicine, Lebanon. RESULTS: The multivariate analysis identified the medical year as the sole factor contributing to the extended spectrum beta-lactamase producing Enterobacteriaceae colonization (OR = 2.33 [1.14-4.77], P = 0.021). DISCUSSION: Lack of hygiene knowledge among medical trainees is not uncommon. Hence, the degree of clinical exposure predicts their risk of contamination from critically ill patients. CONCLUSIONS: Implementing regular and practical training in line with a behavioral modification program would limit the colonization of medical students with resistant germs.