Misra, Anisha

Abstract Background The multiplex gastrointestinal pathogen panel (GIP) is a convenient and quick diagnostic test for determining the infectious etiology of diarrhea. It identifies several of the most common pathogens associated with gastroenteritis. However, it is expensive, and test results may not impact care, given that several of the pathogens in the panel are managed expectantly. We describe our experience with a diagnostic stewardship initiative to resolve the overuse of this testing method. Methods We performed a pre/post study of GIPs ordered for inpatients 18 years old and older from December 19, 2018, to December 18, 2020, at Mayo Clinic hospital in Rochester, Minnesota. GIP orders for inpatients were limited to the first 72 hours of hospitalization starting December 19, 2019. Orders after 72 hours were encouraged to be changed to Clostridioides difficile NAAT testing or sent to an infectious disease provider to override on a case-by-case basis. Our hospitals used BioFire® FilmArray® Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City, Utah). Results A total of 2,641 GIPs were performed during the study period. There were 1,568 GIPs (3.3/100 hospitalizations) in the pre-intervention period compared to 1,073 (2.6/100 hospitalizations) post-intervention, representing a drop of 21.2%. The most common pathogen detected was C. difficile (toxin A/B) (48.8%, n=402), followed by norovirus (17.5%, n=144). The overall test positivity rate was 27.9% (n=736). The test positivity rate decreased 1.8% from 28.6% (n=448) to 26.8% (n=288) after the restriction (p=0.33). The proportion of C. difficile among all pathogens detected increased from 48.5% to 49.7% (p=0.67). Table 1. Pre- and Post-Intervention Test Positivity Rate of Specific Pathogens in GIP Conclusion Our study showed that restricting the ordering of GIP to the first 72 hours of hospitalization and directing providers to standalone C. difficile NAAT testing resulted in a reduction of GIPs performed. There were marginal changes in the test positivity rate of GIP. A limitation of our study is that the timing of post-intervention coincided with the COVID-19 pandemic, which had unpredictable effects on hospital practice and patient admissions. Ideally, future quality improvement projects should increase the test positivity of pathogens other than C. difficile while lowering the GIP use in diagnosing C. difficile colitis. Disclosures John C. O'Horo, Sr., MD, MPH, Bates College and Elsevier Inc (Consultant)

Abstract Background Capnocytopha ga is a gram-negative, facultative anaerobe. Human infection is rare but can lead to devastating outcomes. Capnocytophaga canimorsus can cause sepsis following an animal bite, whereas human-oral–associated Capnocytophaga infections were reported in immunocompromised patients. Current data on these infections are not robust. Our goal is to provide a contemporary description of a unique characteristic of Capnocytophaga infections. Methods We performed a retrospective review of all patients with Capnocytophaga infection from January 2010 to August 2020 at 3 main hospitals of Mayo Clinic in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. We collected baseline demographic data, clinical characteristics, microbiological data, and outcomes of C. canimorsus and human-oral–associated Capnocytophaga infection. Results Among 82 patients with Capnocytophaga infection, 46 patients (56.0%) had bacteremia. The most common species identified in this group was C. sputigena (57.9%), followed by C. canimorsus (34.8%). Patients with human-oral–associated Capnocytophaga bacteremia were often immunocompromised, presented with neutropenic fever, and had worse 6-month all-cause mortality compared to C. canimorsus bacteremia (36.4% vs 6.2%, P = .03). They also had a higher β-lactamase production rate (36.4% vs 0.0%, P = .02). Among patients without bacteremia, the main clinical syndrome was polymicrobial head and neck infections (47.2%). Conclusions Human-oral–associated Capnocytophaga bacteremia occurs primarily in immunocompromised patients, particularly those with hematologic malignancy. In contrast, C. canimorsus bacteremia is more likely to present with community-onset infection related to zoonotic exposure. Human-oral–associated Capnocytophaga infection without bacteremia is frequently isolated in polymicrobial infection; this phenomenon’s significance is yet to be fully understood.

A cure for HIV would require eliminating cells that contain the virus in a latent form from the body. Current antiretroviral medications are unable to rid the body of latently infected cells. Here, we show that a combination of investigational agents—ixazomib plus venetoclax—which reactivate latent virus and predispose infected cells to apoptosis may reduce latent virus in a T cell model, but at the expense of nonspecific toxicity in primary cells.

Abstract Purpose: TNF-related apoptosis inducing ligand (TRAIL) expression by immune cells contributes to antitumor immunity. A naturally occurring splice variant of TRAIL, called TRAILshort, antagonizes TRAIL-dependent cell killing. It is unknown whether tumor cells express TRAILshort and if it impacts antitumor immunity. Experimental Design: We used an unbiased informatics approach to identify TRAILshort expression in primary human cancers, and validated those results with IHC and ISH. TRAILshort-specific mAbs were used to determine the effect of TRAILshort on tumor cell sensitivity to TRAIL, and to immune effector cell dependent killing of autologous primary tumors. Results: As many as 40% of primary human tumors express TRAILshort by both RNA sequencing and IHC analysis. By ISH, TRAILshort expression is present in tumor cells and not bystander cells. TRAILshort inhibition enhances cancer cell lines sensitivity to TRAIL-dependent killing both in vitro and in immunodeficient xenograft mouse models. Immune effector cells isolated from patients with B-cell malignancies killed more autologous tumor cells in the presence compared with the absence of TRAILshort antibody (P < 0.05). Conclusions: These results identify TRAILshort in primary human malignancies, and suggest that TRAILshort blockade can augment the effector function of autologous immune effector cells. See related commentary by de Miguel and Pardo, p. 5546