VA Northeast Ohio Healthcare System

A spinal cord injury can compromise trunk stability and autonomic functions leading to poor blood pressure regulation and hindering daily activities. Implanted multichannel motor system neuroprostheses can stabilize the trunk by electrically activating the peripheral nerves to contract the paralyzed lumbar spine and hip extensor muscles. This case report presents novel observations of improved blood pressure regulation for a 59-yr-old female patient with a spinal cord injury C5 American Spinal Injury Association Impairment Scale (AIS-A) while utilizing an implanted neuroprosthesis. The participant experienced immediate relief from common symptoms of hypotension (lightheadedness, blurred vision, and occasional syncope) when using the implanted neuroprosthesis to contract paraspinal, gluteal, and hamstrings muscles to complete activities of daily living. During laboratory assessments, stable increases in blood pressure were recorded when using the neuroprosthesis for seated trunk stabilization. These observations demonstrate that neuroprostheses targeting the peripheral nerves of the lumbar spine and pelvic musculature have the potential to aid in blood pressure regulation and relieve hypotensive symptoms during orthostasis. These findings provide support for the use of an implanted neuroprosthesis on acute blood pressure regulation and the potential to address important systemic health-related issues following spinal cord injury.

This article provides a focused update to the clinical practice guideline on the treatment and management of patients with coronavirus disease 2019 (COVID-19), developed by the Infectious Diseases Society of America. The guideline panel presents a recommendation on the use of abatacept in hospitalized adults with severe or critical COVID-19. The recommendation is based on evidence derived from a systematic literature review and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

Electroretinography (ERG) provides a noninvasive functional measure of multiple cell types of the outer retina. We conducted an ERG-based screen of 530 single-gene knockout mouse strains generated as part of the International Mouse Phenotyping Consortium, representing 2.5% of all protein-coding genes, to identify genetic variants affecting retinal function. We identified 30 strains with significantly altered ERG amplitudes. Two of the genes identified, Cfap418 and Syne2, have been previously reported with outer retinal dysfunction, thereby serving as internal controls that validate our screening protocol. Of the remaining 28 genes newly associated with altered retinal function, the majority lacked a contemporaneous histopathology correlate, highlighting the importance of ERG in early detection of functional abnormalities. A rare homozygous missense variant in FCHSD2, the human orthologue of one of the 28 genes identified, was found in a patient presenting with retinal degeneration that lacked a molecular diagnosis. This report represents a useful resource for future investigations into the molecular mechanisms driving inherited retinal diseases and demonstrates the power of large-scale ERG screening in identifying novel genetic determinants of retinal function.

Telehealth can facilitate improving antibiotic use and related antimicrobial stewardship activities in facilities underserved by infectious diseases (IDs) expertise. We describe implementation of the Department of Veterans Affairs (VA) videoconference antimicrobial stewardship team (VAST) to connect multidisciplinary teams from rural VA medical centers (VAMCs) with geographically distant ID experts. We implemented VASTs at 10 rural VAMCs from September 2021 to February 2024. VASTs consisted of regular meetings between rural VAMCs and an off-site ID expert who met by videoconference to discuss clinical cases, emphasizing recommendations for antibiotic prescribing. The VA Corporate Data Warehouse was used to collect information on patient medical encounter information. Interviews with healthcare professionals and surveys assessed perceptions of and experiences with VASTs. VASTs completed 624 clinical encounters on 531 unique patients. Half (53%) of the encounters required >20 minutes. The most frequently discussed infections were respiratory tract (35%), skin and soft tissue (19%), and genitourinary (17%). Of the 73 (53% of 138 contacted) professionals who responded to the survey, >90% perceived VASTs as improving the quality of veteran care and agreed that recommendations were timely. All 24 interviewees identified VASTs as meeting an important need at the rural site and that the virtual system facilitated collaboration. These findings indicate successful implementation of a telehealth program to disseminate ID and antimicrobial stewardship expertise to rural VAMCs. This is a strong model augmenting antimicrobial stewardship in other healthcare systems.

Pseudomonas aeruginosa is a major gram-negative pathogen responsible for a variety of infections and possessing an array of both intrinsic and acquired resistance mechanisms, including β-lactamases, like the chromosomal Pseudomonas-derived cephalosporinase (PDC). β-Lactams are the most widely prescribed class of antibiotics in the United States, and antipseudomonal cephalosporins (including cefepime) are important therapies (alone or combined with β-lactamase inhibitors) for P. aeruginosa infections. Taniborbactam is a novel, bicyclic boronate β-lactamase inhibitor with activity against all β-lactamase classes and is being developed in combination with cefepime. PDC-88 is an R2-loop deletion variant conferring resistance to cefepime and ceftazidime and elevating ceftolozane/tazobactam minimum inhibitory concentration (MIC). Herein, we elucidated PDC-88 resistance mechanisms and compared inhibition by taniborbactam and avibactam. In an isogenic background, PDC-88 increased cefepime MICs by 16-fold compared to PDC-3. In vitro, compared to PDC-3, PDC-88 had 8.3-fold higher catalytic efficiency for cefepime achieved by decreasing KM 12.8-fold and decreasing kcat 1.6-fold. This is supported by our crystallographic observation that the PDC-88 deletion enlarged the active site in the vicinity of the R2-loop, likely better accommodating cefepime. Taniborbactam and avibactam restored cefepime activity by inhibiting PDC-88. Compared to avibactam, taniborbactam had 4.1- and 9-fold lower Ki app values for PDC-3 and PDC-88, respectively, with higher kon (k2/K) and similar koff for both enzymes. Structurally, taniborbactam positioned very similarly in the PDC-3 and PDC-88 active sites, interacting with many nearby residues. Based upon these data, cefepime-taniborbactam may represent an important alternative to ceftazidime-avibactam and ceftolozane-tazobactam for P. aeruginosa infections.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a quality improvement project to improve screening rates for diabetic kidney disease at a Veterans Affairs health system in Northeast Ohio.

Research site mentorship has a positive impact on study enrollment. The VA Cooperative Studies Program's (CSP) Network of Dedicated Enrollment Sites (NODES) utilized an existing site mentorship model to onboard 13 new expansion sites. We describe the successes, challenges, and lessons learned during the development and implementation of this model in this paper. NODES established a "Site Mentorship/Expansion Workgroup (SWG)" in October 2020 to plan and guide the consortium on providing mentorship and services to other clinical research networks, non-Node CSP study sites, and NODES expansion sites. In 2021, the SWG developed a 12-month implementation plan to onboard 13 new sites by pairing original Node (mentor) sites with expansion Node (mentee) sites. Mentors offered prompt guidance and solutions to mentees on site-level challenges by working with them closely. Implementation of the plan occurred from February 2022 through September 2023. Data from the implementation of this mentorship plan demonstrated a 32.7% increase (from 54.8% in 2022 to 87.5% in 2023) in the expansion sites' achievement of their Objectives & Key Results (OKRs). From October 2020-September 2021, prior to mentorship assignments, the original sites (mentors) achieved an average of 88% of their OKRs and attained an average of 86.7% and 80.9% of those OKRs in October-September of 2022 and 2023 respectively during the mentorship implementation phase. The results demonstrate that developing and implementing a research site mentorship model to facilitate onboarding and performance of research sites into an established network was feasible and contributed to the success of those sites.

ABSTRACT Type 2 diabetes affects more than 30 million people in the US, and a major complication is kidney disease. During the analysis of lipotoxicity in diabetic kidney disease, global fatty acid transport protein-2 (FATP2) gene deletion was noted to markedly reduce plasma glucose in db/db mice due to sustained insulin secretion. To identify the mechanism, we observed that islet FATP2 expression was restricted to α-cells, and α-cell FATP2 was functional. Direct evidence of FATP2KO-induced α-cell-mediated GLP-1 secretion included increased GLP-1-positive α-cell mass in FATP2KO db/db mice, small molecule FATP2 inhibitor enhancement of GLP-1 secretion in αTC1-6 cells and human islets, and exendin[9-39]-inhibitable insulin secretion in FATP2 inhibitor-treated human islets. FATP2-dependent enteroendocrine GLP-1 secretion was excluded by demonstration of similar glucose tolerance and plasma GLP-1 concentrations in db/db FATP2KO mice following oral versus intraperitoneal glucose loading, non-overlapping FATP2 and preproglucagon mRNA expression, and lack of FATP2/GLP-1 co-immunolocalization in intestine. We conclude that FATP2 deletion or inhibition exerts glucose-lowering effects through α-cell-mediated GLP-1 secretion and paracrine β-cell insulin release. Graphical abstract

Abstract Background Respiratory tract infections (RTI) cause high morbidity and mortality among nursing home (NH) residents, yet their etiology and frequency remain understudied. We implemented multiplex respiratory panel (MRP) testing to describe RTI epidemiology in NH residents to inform efforts to reduce respiratory virus transmission in NH. Figure 1 Flow diagram and multiplex respiratory panel testing results of SNF residents in NH-PHRN, February–April, 2024. Methods The Nursing Home Public Health Response Network (8 academic sites and 22 affiliated NHs) is conducting RTI surveillance with MRP testing. Staff collect nasal swab (NS) specimens and clinical data from symptomatic residents with suspected RTI. Specimens are collected within 72 hours of symptom onset and tested with the Roche ePlex Respiratory Pathogen Panel 2 (17 viral and bacterial pathogens, Figure 1) in a central laboratory. We describe MRP results, symptoms, and characteristics of residents tested during February–April 2024. We compared symptoms between NH residents with and without viral detection on MRP with Chi-Squared and Fisher Exact tests. Figure 2 Multiplex respiratory pathogen testing results among 81 enrolled residents in 19 nursing homes in NH-PHRN, February – April 2024, United States. *One resident tested positive for both Human Rhinovirus/Enterovirus and Coronavirus. **Influenza A subtype was H3 for all four specimens. Results Of 106 symptomatic residents with suspected RTI, 81 (72%) were tested (Figure 1). MRP detected ≥1 virus in 36/81 (44%) specimens; SARS-CoV-2 was the most common (14%), followed by seasonal coronavirus (12%) (Figure 2). Among residents tested, cough (78%), runny nose (43%), and sore throat (31%) were the most common symptoms. Sore throat was more common among residents with viral detection (53% vs. 13%; P=0.0001) (Figure 3). Of 75 tested residents with demographic and clinical data, median age was 80 (range 53–90), 59% were female, 19% were Black, 68% were long stay ( >100 days), and 99% had received a COVID-19 vaccine. Among 52 tested residents with treatment and outcome data, 14 (27%) received antibacterials, 11 (21%) were hospitalized, and 3 (6%) died. Of 25/52 residents with viral detection on MRP and complete treatment and outcome data, 4 (16%) received antibacterials, 6 (24%) were hospitalized (SARS-CoV-2 = 3, seasonal coronavirus = 2, Influenza A = 1) and none died. Figure 3 Frequency and percentage of symptoms and other clinical characteristics among 81 residents who underwent multiplex respiratory pathogen specimen collection in 19 nursing homes in NH-PHRN, February – April 2024, United States. We used Chi-Square and Fisher Exact tests to compare the type and frequency of symptoms among residents who had multiplex tests with and without pathogens detected. One asymptomatic resident who had no pathogen detected was tested due to leukocytosis. *Comparison P=0.04. **Comparison P=0.01. ***Comparison P=0.0001. Conclusion MRP testing identified a virus in almost half of tested NH residents with suspected RTI at the end of the viral respiratory season. Ongoing surveillance will help describe the burden and clinical relevance of viral respiratory pathogens in NH residents and identify areas of improvement for respiratory virus infection prevention. Disclosures Yasin Abul, MD, Moderna: Grant/Research Support|Moderna, Abt, CDC: Grant/Research Support David Canaday, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Jon P. Furuno, PhD, Merck & Co., Inc: Grant/Research Support Stefan Gravenstein, MD, MPH, CDC: Advisor/Consultant|CDC: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|Genentech: Honoraria|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Honoraria|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Advisor/Consultant Lona Mody, MD, MS, Nanovibronix: Grant/Research Support Morgan Katz, MD, MHS, Ageless Innovation: Advisor/Consultant

BackgroundRoutine screening of all exposed extra-genital sites for sexually transmitted infections (STIs), specifically Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT), is recommended for individuals at high risk, including some men who have sex with men (MSM) and individuals receiving Pre-Exposure Prophylaxis (PrEP). However, there are a number of barriers to screening including privacy and provider availability. While self-collected extra-genital STI samples have the potential to mitigate some of these barriers, this approach has not yet achieved widespread use. This study evaluates the implementation of self-collection of extra-genital STI tests at the VA Northeast Ohio Healthcare System (VANEOHS), assesses acceptability and measures impact on testing rates.MethodsThe study included people with HIV (PWH) and patients on PrEP at the VANEOHS’s infectious diseases clinic and covered 10 Ohio counties. Patients chose between self- and provider-collection. We followed GC and CT rectal and pharyngeal testing frequency and test completion rates and characterized reasons for unsuccessful completion. We also compared extra-genital GC/CT testing rates before and after the availability of self-collection. Finally, we deployed an anonymous survey to assess acceptability of self-collection and ease of use. We used descriptive statistics to report completion rates, survey findings and changes in rates of testing over time.ResultsOf the 276 tests ordered for self-collection for 95 unique veterans, 82 pharyngeal and 60 rectal GC/CT rectal tests were successfully completed and interpreted in the first 8 months of the study (Table 1). The testing rate increased from 8 tests/month to 15 tests/month for pharyngeal GC/CT and from 6 tests/month to 10 tests/month for rectal GC/CT (Figure 1). Of the survey respondents who performed self-collection, 11 of 17 were satisfied or very satisfied with self-collection and most found it easy or very easy to swab their own rectum (9/12) and throat (13/14) (Table 2).ConclusionSelf-sample collection for extra-genital testing is feasible in a large healthcare network. It is highly desired by patients and has the potential to improve access and improve STI screening rates.DisclosuresAll Authors: No reported disclosures