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 US but not in resource limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFA) can be used in this setting. Methods Frozen urine specimens were submitted to MiraVista diagnostics for antigen testing from three 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 352 subjects were enrolled, including 66 cases (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (71%),46 had disseminated and 20 had pulmonary histoplasmosis. Four were mild, 42 moderate, and 20 severe. LFA and EIA were highly concordant (kappa 0.84). Sensitivity and specificity of the LFA were 78.8% and 99.3% respectively. LFA sensitivity was higher in proven cases (93.2%), patient 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 patient with moderate/severe disease, and 96.8% in those with galactomannan levels > 1.8 ng/mL. Cross reactivity was noted with other endemic mycoses. Conclusion The MVista Histoplasma LFA meets the need for accurate rapid diagnosis of histoplasmosis in resource limited countries, especially in patient with high disease burden, potentially reducing morbidity and mortality.
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.
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.
Background The SARS-CoV-2 pandemic has caused over 400,000 deaths worldwide thus far, and poses therapeutic challenges for millions of patients. There is currently no treatment for SARS-CoV-2 infection approved by the United States Food and Drug Administration. Multiple agents have been used off-label to treat SARS-CoV-2 infection based on small observational cohorts and in vitro data. Here we present the experience of a large academic medical center in treating SARS-CoV-2 infection. Methods We performed a retrospective cohort study of patients admitted for greater than 24 hours with a nasopharyngeal, oropharyngeal, and/or bronchoalveolar lavage sample positive for SARS-CoV-2 by polymerase chain reaction (PCR). Demographic data, comorbidities, clinical data, and treatment data were collected from the electronic medical record. Off-label therapies were used at the discretion of the treating providers guided by regularly updated treatment guidelines assembled by infectious diseases physicians and antimicrobial stewardship pharmacists. The primary outcome assessed was in-hospital mortality. Secondary outcomes included admission to the intensive care unit (ICU), endotracheal intubation, initiation of vasopressors, and drug-related adverse events. Results Data collection was completed for 448 patients admitted between March 18, 2020 and May 8, 2020. All-cause in-hospital mortality was 13.4% (60/448) during this time. Mortality rates increased with age, up to 45% for patients over 80 years old. Male sex, hypertension, chronic pulmonary disease, end-stage renal disease, chronic liver disease were also risk factors for increased mortality. QTc interval prolongation occurred significantly more frequently in patients who received hydroxychloroquine (HCQ) with or without azithromycin(AZM) than those who did not (HCQ 6%, HCQ+AZM 7.8% vs all other patients, 0%, p< .0001). Review of treatment trends showed close adherence to the treatment recommendations at that time (Figure 1). Patient Characteristics Admission Laboratory Data by Disease Severity QTc Prolongation Conclusion SARS-CoV-2 infection is associated with significant inpatient mortality, and use of off-label treatments was associated with significant drug-related adverse events. Treatment regimens changed rapidly, and providers adhered closely to institutional guidelines as they evolved. Treatment Trends by Week QTC pre/post Treatment by Hydroxychloroquine Use vs. No Hydroxychloroquine Use Disclosures Samir Gupta, MD, Gilead Sciences (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)ViiV (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)
Figure 2 Kaplan-Meier curves for Progression-Free Survival stratified by HIV status Conclusions In this matched cohort study, PLWH and metastatic NSCLC had similar toxicity profiles and clinical outcomes to HIV-counterparts receiving ICI supporting their use in PLWH and their inclusion in clinical trials. Larger
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