Evaluating Appropriateness and Diagnostic Stewardship Opportunities of Multiplex Polymerase Chain Reaction Gastrointestinal Testing Within a Hospital System

Objective: This single-center, retrospective, observational cohort study evaluates the appropriateness of the BioFire® FilmArray® Gastrointestinal (GI) multiplex PCR panel testing at a community-teaching hospital. Methods: All adult, hospitalized patients at Prisma Health Richland Hospital with a documented GI multiplex PCR panel from 1 April 2015 through 28 February 2018 were included in the analysis. Inappropriate use of the GI panel was defined as a test obtained without documented diarrhea, greater than 2 days of hospitalization, redundant use with other diagnostic tests (e.g. PCR), or laxative use in the preceding 48 h. Antibiotic use and host variables were compared between groups with positive and negative results. Results: During the study period, 442 GI panels were obtained, among which 268 (61%) were deemed inappropriate. Primary reasons for inappropriate testing were lack of documented diarrhea ( = 92), greater than 2 days of hospitalization ( = 116), having a duplicate PCR test ordered ( = 118), or laxative use in the 48 h before testing ( = 36). A total of 141 (32%) GI panels were positive. The most frequently identified pathogens were (51.1%,  = 72), Enteropathogenic (17.7%,  = 25), and Norovirus GI/GII (12.1%,  = 17). Patients with negative GI panel results were initiated on antibiotics significantly less frequently than those with positive GI panels (62.5% 80.2%,  \u3c 0.00001). Conclusion: Stewardship opportunities exist to optimize the diagnostic application of the GI multiplex PCR panel

Anti-myeloma efficacy of CAR-iNKT is enhanced with a long-acting IL-7, rhIL-7-hyFc

Multiple myeloma (MM), a malignancy of mature plasma cells, remains incurable. B-cell maturation antigen (BCMA) is the lead protein target for chimeric antigen receptor (CAR) therapy because of its high expression in most MM, with limited expression in other cell types, resulting in favorable on-target, off tumor toxicity. The response rate to autologous BCMA CAR-T therapy is high; however, it is not curative and is associated with risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Outcomes in patients treated with BCMA CAR-T cells (CAR-Ts) may improve with allogeneic CAR T-cell therapy, which offer higher cell fitness and reduced time to treatment. However, to prevent the risk of graft-versus-host disease (GVHD), allogenic BCMA CAR-Ts require genetic deletion of the T-cell receptor (TCR), which has potential for unexpected functional or phenotype changes. Invariant natural killer T cells (iNKTs) have an invariant TCR that does not cause GVHD and, as a result, can be used in an allogeneic setting without the need for TCR gene editing. We demonstrate significant anti-myeloma activity of BCMA CAR-iNKTs in a xenograft mouse model of myeloma. We found that a long-acting interleukin-7 (IL-7), rhIL-7-hyFc, significantly prolonged survival and reduced tumor burden in BCMA CAR-iNKT-treated mice in both primary and re-challenge settings. Furthermore, in CRS in vitro assays, CAR-iNKTs induced less IL-6 than CAR-Ts, suggesting a reduced likelihood of CAR-iNKT therapy to induce CRS in patients. These data suggest that BCMA CAR-iNKTs are potentially a safer, effective alternative to BCMA CAR-Ts and that BCMA CAR-iNKT efficacy is further potentiated with rhIL-7-hyFc

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol

INTRODUCTION: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months\u27 closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. METHODS AND ANALYSIS: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. ETHICS AND DISSEMINATION: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications

Evaluation of severe acute respiratory syndrome coronavirus 2 monoclonal antibodies in high-risk solid organ transplant recipients across three major coronavirus disease 2019 variant waves.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to impact immunocompromised populations including solid organ transplant recipients (SOTRs). Monoclonal antibodies (mAbs) have shown effectiveness in reducing COVID-19-related hospitalizations and emergency department (ED) visits in SOTRs at different time frames in the COVID-19 pandemic; however, less data exist on the impact of mAbs for SOTRs across variant waves and with the advent of available COVID-19 vaccines. METHODS: This retrospective study included SOTR outpatients who tested positive for SARS-CoV-2 and received mAbs from December 2020 to February 2022 (n = 233); using in-house sequencing of clinical samples, we monitored the emergence of Alpha, Delta, and Omicron variants. The primary outcome was a composite of 29-day COVID-19-related hospitalizations and ED visits. Prespecified secondary outcomes included individual components of the primary endpoint; for patients requiring hospitalization post-mAb administration, we describe their inpatient treatment. RESULTS: A low percentage of SOTRs treated with mAb required hospitalization or an ED visit (14.6% overall); this did not differ across COVID-19 variants (p = .152). Hospitalization and ED visits did not significantly differ between abdominal and cardiothoracic SOTRs. For hospitalized patients, the majority received treatment with corticosteroids and few required intensive care unit (ICU) care. CONCLUSION: Among SOTR outpatients with mild or moderate COVID-19 symptoms, early administration of mAb minimizes the need for hospital care. For patients requiring hospitalization, corticosteroids were common but patients experienced low rates of oxygen supplementation and ICU care. Use of mAbs in SOTRs should be considered early in the disease when therapy is available