Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:Rates of obesity are rising in patients with inflammatory bowel disease [IBD]. We conducted a US population-based study to determine the effects of obesity on outcomes in hospitalised patients with IBD. METHODS:We searched the Nationwide Readmissions Database 2016-2017 to identify all adult patients hospitalised for IBD, using ICD-10 codes. We compared obese (body mass index [BMI] ≥ 30) vs non-obese [BMI < 30] patients with IBD to evaluate the independent effects of obesity on readmission, mortality, and other hospital outcomes. Multivariate regression and propensity matching were performed. RESULTS:We identified 143 190 patients with IBD, of whom 9.1% were obese. Obesity was independently associated with higher all-cause readmission at 30 days {18% vs 13% (adjusted odds ratio [aOR] 1.16, p = 0.005)} and 90 days (29% vs 21% [aOR 1.27, p < 0.0001]), as compared with non-obese patients, with similar findings upon a propensity-matched sensitivity analysis. Obese and non-obese patients had similar risks of mortality on index admission [0.24% vs 0.31%, p = 0.18] and readmission [1.5% vs 1.8% p = 0.3]. Obese patients had longer [5.3 vs 4.9 days] and more expensive [USD12,195 vs USD11,154] hospitalisations on index admission. Obesity did not affect the risk of intestinal surgery or bowel obstruction. Compared with index admissions, readmissions were characterised by increased mortality [6-fold], health care use, and bowel obstruction [3-fold] [all p < 0.0001]. CONCLUSIONS:Obesity in IBD appears to be associated with increased early readmission, characterised by a higher burden, despite the introduction of weight-based therapeutics. Prevention of obesity should be a focus in the treatment of IBD to decrease readmission and health care burden.

OBJECTIVE:Estimate the seroprevalence of SARS-CoV-2 antibodies among New York City Health and Hospitals (NYC H+H) healthcare workers during the first wave of the COVID-19 pandemic, and describe demographic and occupational factors associated with SARS-CoV-2 antibodies among healthcare workers. DESIGN:Descriptive, observational, cross-sectional study using a convenience sample of data from SARS-CoV-2 serological tests accompanied by a demographic and occupational survey administered to healthcare workers. SETTING:A large, urban public healthcare system in NYC. PARTICIPANTS:Participants were employed by NYC H+H and either completed serological testing at NYC H+H between 30 April 2020 and 30 June 2020, or completed SARS-CoV-2 antibody testing outside of NYC H+H and were able to self-report results from the same time period. PRIMARY OUTCOME MEASURE:SARS-CoV-2 serostatus, stratified by key demographic and occupational characteristics reported through the demographic and occupational survey. RESULTS:Seven hundred and twenty-seven survey respondents were included in analysis. Participants had a mean age of 46 years (SD=12.19) and 543 (75%) were women. Two hundred and fourteen (29%) participants tested positive or reported testing positive for the presence of SARS-CoV-2 antibodies (IgG+). Characteristics associated with positive SARS-CoV-2 serostatus were Black race (25% IgG +vs 15% IgG-, p=0.001), having someone in the household with COVID-19 symptoms (49% IgG +vs 21% IgG-, p<0.001), or having a confirmed COVID-19 case in the household (25% IgG +vs 5% IgG-, p<0.001). Characteristics associated with negative SARS-CoV-2 serostatus included working on a COVID-19 patient floor (27% IgG +vs 36% IgG-, p=0.02), working in the intensive care unit (20% IgG +vs 28% IgG-, p=0.03), being employed in a clinical occupation (64% IgG +vs 78% IgG-, p<0.001) or having close contact with a patient with COVID-19 (51% IgG +vs 62% IgG-, p=0.03). CONCLUSIONS:Results underscore the significance that community factors and inequities might have on SARS-CoV-2 exposure for healthcare workers.

Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR=29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in anti-viral immunity.

BACKGROUND:Older adults with HIV (OAH) experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps due to chronic inflammation. Cell-free mitochondrial DNA (cfmtDNA) released from cells undergoing necrosis-mediated cell death potentially acts as both a mediator and marker of inflammatory dysregulation. We hypothesized that urinary cfmtDNA would be associated with frailty, body composition and fall history in OAH. METHODS:OAH completed frailty testing, a psychosocial survey, body composition assessment, and measurement of urine cfmtDNA and urine albumin:creatinine in this cross-sectional study. Urine cfmtDNA was measured by qPCR and normalized to urinary creatinine. RESULTS:Across 150 participants, the mean age was 61 years (SD 6 years), half identified as Black, one-third were female, and 93% had HIV-1 viral load <200 copies/ml. Two-thirds met criteria for a pre-frail or frail state. Those with unintentional weight loss had higher urine cfmtDNA concentrations (p=0.03). Higher urine cfmtDNA was inversely associated with skeletal muscle index (SMI) (β =-0.19, p<0.01) and fat mass index (FMI) (β =-0.08, p=0.02) in separate multiple linear regression models adjusted for age, sex, and presence of moderate-severe albuminuria. CONCLUSIONS:In this cross-sectional study of OAH, higher levels of urine cfmtDNA were more common in subjects with less robust physical condition, including unintentional weight loss and less height-scaled body mass of fat and muscle. These findings suggest urine cfmtDNA may reflect pathophysiologic aging processes in OAH, predisposing them to geriatric syndromes. Longitudinal investigation of urine cfmtDNA as a biomarker of geriatric syndromes is warranted.

PURPOSE:Residency programs face overwhelming numbers of residency applications, limiting holistic review. Artificial intelligence techniques have been proposed to address this challenge but have not been created. Here, a multidisciplinary team sought to develop and validate a machine learning (ML)-based decision support tool (DST) for residency applicant screening and review. METHOD:Categorical applicant data from the 2018, 2019, and 2020 residency application cycles (n = 8,243 applicants) at one large internal medicine residency program were downloaded from the Electronic Residency Application Service and linked to the outcome measure: interview invitation by human reviewers (n = 1,235 invites). An ML model using gradient boosting was designed using training data (80% of applicants) with over 60 applicant features (e.g., demographics, experiences, academic metrics). Model performance was validated on held-out data (20% of applicants). Sensitivity analysis was conducted without United States Medical Licensing Examination (USMLE) scores. An interactive DST incorporating the ML model was designed and deployed that provided applicant- and cohort-level visualizations. RESULTS:The ML model areas under the receiver operating characteristic and precision recall curves were 0.95 and 0.76, respectively; these changed to 0.94 and 0.72, respectively, with removal of USMLE scores. Applicants' medical school information was an important driver of predictions-which had face validity based on the local selection process-but numerous predictors contributed. Program directors used the DST in the 2021 application cycle to select 20 applicants for interview that had been initially screened out during human review. CONCLUSIONS:The authors developed and validated an ML algorithm for predicting residency interview offers from numerous application elements with high performance-even when USMLE scores were removed. Model deployment in a DST highlighted its potential for screening candidates and helped quantify and mitigate biases existing in the selection process. Further work will incorporate unstructured textual data through natural language processing methods.

Background As tumor genomes are shaped by their interaction with the immune system, a phenomenon known as immunoediting, it is critical to understand how immunotherapies impact this process. Checkpoint inhibitors directly influence T cells responding to neoantigens, as such, these therapies drastically affect the genomes of surviving tumor clones. Similar to the concept of immune camouflage, observed in infectious diseases, where genomes of pathogens evolve in a way to avoid immune detection, we hypothesized that tumor clones surviving checkpoint inhibition therapy harbor mutations more prone to immune avoidance. Methods We analyzed a cohort of nivolumab-treated melanoma patients (n=41) for which tumor samples were collected from the same site prior (Pre samples) and during (On samples) nivolumab therapy.1 The immunogenic and tolerance potential of mutations from the Pre and On samples were evaluated with the Ancer neoantigen screening platform,2 which includes the EpiMatrix algorithm to identify HLA-I and HLA-II neoepitopes and the JanusMatrix algorithm to evaluate neoepitopes homology with self. Prior work with JanusMatrix showed epitopes highly homologous to self can be inhibitory.3 Matching Pre and On therapy samples were compared to identify mutations deleted (unique to the Pre samples), maintained (found in both the Pre and On samples), and induced while on therapy (unique to the On samples). Results Mutations from the On therapy samples had a lower immunogenic potential than mutations found in the Pre therapy samples (figure 1A, Mann-Whitney test, p=0.0001). After further distinguishing mutations deleted, maintained, and induced while on therapy, we observed that newly induced mutations had a significantly lower immunogenic potential compared to other mutations (Kruskal-Wallis test, p<0.0001). In addition, newly induced mutations were more homologous to self than other mutations (figure 1B, Kruskal-Wallis test, p<0.0001), indicating a greater likelihood for these new mutations to be tolerated by the immune system. In summary, we showed that mutations generated after nivolumab therapy are less immunogenic and more tolerated than mutations found prior to therapy. Abstract 313 Figure 1 Immunogenicity (A) and tolerance (B) potentials of mutations found in matching melanoma tumor samples collected before (Pre) and during (On) nivolumab therapy. Conclusions Our Ancer analysis suggests that nivolumab therapy affects the immunogenicity and tolerance profiles of newly generated mutations in a manner that is consistent with the concepts of immunoediting and immune camouflaging. Mutations induced after therapy appear less immunogenic and more self-like, illustrating a potential mechanism tumors employ to avoid immune surveillance. Furthermore, our approach highlights in silico tools can distinguish effector from tolerance inducing neoepitopes, a critical feature for designing novel neoantigen-based precision immunotherapies

BACKGROUND:With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in BMI among ART-experienced, virologically suppressed PLWH. METHODS:ART-experienced, virologically suppressed PLWH ≥18 years of age in the OPERA cohort were included for analysis if prescribed a new regimen containing one of the following core agents: dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017. Multivariable linear regression was used to assess the association between regimen and mean changes in BMI at 6, 12, and 24 months after switch. RESULTS:(RPV) at 24 months following switch, but gains were observed with every regimen. In adjusted analyses, compared to DTG, only bDRV was associated with a smaller increase in BMI at all time points, while EVG/c and RAL were associated with smaller increases in BMI at 6 months only. Overall, results were consistent in analyses stratified by baseline BMI category. CONCLUSION/CONCLUSIONS:BMI increases were relatively small but followed an upward trend over time in this cohort of treatment-experienced, suppressed PLWH. Gains were attenuated with a longer period of follow-up. BMI gains did not differ by regimens, except for bDRV regimens which were consistently associated with smaller BMI increases than DTG.

The purpose of this consensus paper was to convene leaders and scholars from eight Expert Panels of the American Academy of Nursing and provide recommendations to advance nursing's roles and responsibility to ensure universal access to palliative care. Part I of this consensus paper herein provides the rationale and background to support the policy, education, research, and clinical practice recommendations put forward in Part II. On behalf of the Academy, the evidence-based recommendations will guide nurses, policy makers, government representatives, professional associations, and interdisciplinary and community partners to integrate palliative nursing services across health and social care settings. The consensus paper's 43 authors represent eight countries (Australia, Canada, England, Kenya, Lebanon, Liberia, South Africa, United States of America) and extensive international health experience, thus providing a global context for the subject matter. The authors recommend greater investments in palliative nursing education and nurse-led research, nurse engagement in policy making, enhanced intersectoral partnerships with nursing, and an increased profile and visibility of palliative nurses worldwide. By enacting these recommendations, nurses working in all settings can assume leading roles in delivering high-quality palliative care globally, particularly for minoritized, marginalized, and other at-risk populations.