Faculty Bibliography

Urinary tract infections (UTIs) are the second most prevalent bacterial infections and uropathogenic Escherichia coli (UPEC) stands among the primary causative agents of UTIs. The usage of antibiotics is the routine therapy being used in various countries to treat UTIs but becoming ineffective because of increasing antibiotic resistance among UPEC strains. Thus, there must be the development of some alternative treatment strategies such as vaccine development against UPEC. In the following study, pan-genomics along with reverse vaccinology approaches is used under the framework of bioinformatics for the identification of core putative vaccine candidates, employing 307 UPEC genomes (complete and draft), available publicly. A total of nine T-cell epitopes (derived from B-cells) of both MHC classes (I and II), were prioritized among three potential protein candidates. These epitopes were then docked together by using linkers (GPGPG and AAY) and an adjuvant (Cholera Toxin B) to form a poly-valent vaccine construct. The chimeric vaccine construct was undergone by molecular modelling, further refinement and energy minimization. We predicted positive results of the vaccine construct in immune simulations with significantly high levels of immune cells. The protein-protein docking analysis of vaccine construct with toll-like receptors predicted efficient binding, which was further validated by molecular dynamics simulation of vaccine construct with TLR-2 and TLR-4 at 120 ns, resulting in stable complexes' conformation throughout the simulation run. Overall, the vaccine construct demonstrated positive antigenic response. In future, this chimeric vaccine construct or the identified epitopes could be experimentally validated for the development of UPEC vaccines against UTIs.Communicated by Ramaswamy H. Sarma.

Despite higher chronic disease prevalence, minoritized populations live in highly walkable neighborhoods in US cities more frequently than non-minoritized populations. We investigated whether city-level racial residential segregation (RRS) was associated with city-level walkability, stratified by population density, possibly explaining this counterintuitive association. RRS for Black-White and Latino-White segregation in large US cities was calculated using the Index of Dissimilarity (ID), and walkability was measured using WalkScore. Median walkability increased across increasing quartiles of population density, as expected. Higher ID was associated with higher walkability; associations varied in strength across strata of population density. RRS undergirds the observed association between walkability and minoritized populations, especially in higher population density cities.

The 2022 mpox outbreak in New York City posed challenges to rapidly scaling up treatment capacity. We describe a telehealth treatment model launched during this outbreak that facilitated healthcare provider treatment capacity, and was able to adhere to a Centers for Disease Control and Prevention (CDC)-sponsored expanded access investigational new drug (EA-IND) protocol for tecovirimat. Sixty-nine patients were evaluated and prescribed tecovirimat for mpox through telehealth visits at NYC Health + Hospitals/Bellevue and NYU Langone Health from June to August 2022. Thirty-two (46.4%) were previously diagnosed with HIV. Forty-four (63.8%) reported full recovery, with the remainder lost to follow-up. Most patients (n = 60, 87.0%) attended at least one follow-up visit (either in person or through telehealth) after starting treatment. We observed favorable treatment outcomes, with no serious adverse events, hospitalizations, or deaths related to mpox. While equitable access to telehealth remains a limitation that needs to be addressed, this telehealth model enabled a rapid scale-up of tecovirimat prescription during the mpox outbreak, and should be considered as an important tool used to respond to future infectious disease outbreaks.

OBJECTIVE/UNASSIGNED:, the gene encoding the anti-inflammatory IL-1 receptor antagonist (IL-1Ra), on the cytokine release syndrome and mortality. METHODS/UNASSIGNED:gene were assessed for association with laboratory markers of the cytokine release syndrome (CRS) and mortality. RESULTS/UNASSIGNED:rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 - 1.00); 0.052), with the most pronounced effect observed between the ages of 55-74 [5.5% vs. 18.4%, p<0.001]. CONCLUSION/UNASSIGNED:modulates the COVID-19 cytokine release syndrome via endogenous " anti-inflammatory" mechanisms. SIGNIFICANCE STATEMENT/UNASSIGNED:merits further evaluation in severe SARS-CoV-2 infection.

BACKGROUND:Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) was approved by the U.S. Food and Drug Administration in December 2021. This initial phase of implementation represents a prime opportunity to ensure equitable LAI-PrEP provision to communities often underrepresented in PrEP care before disparities in access and uptake emerge. Herein, we describe the EquiPrEP Project which utilizes an equity-oriented implementation science framework to optimize LAI-PrEP rollout in an urban safety-net clinic in New York City. METHODS:The primary objectives of this project are to: (1) increase LAI-PrEP initiation overall; (2) increase uptake among groups disproportionately impacted by the HIV epidemic; (3) preserve high PrEP retention while expanding use; and (4) identify barriers and facilitators to LAI-PrEP use. EquiPrEP will enroll 210 PrEP-eligible participants into LAI-PrEP care with planned follow-up for one year. We will recruit from the following priority populations: Black and/or Latine men who have sex with men, Black and/or Latine cisgender women, and transgender women and nonbinary individuals. To evaluate implementation of LAI-PrEP, we will utilize equity-focused iterations of the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR), in addition to longitudinal surveys and qualitative interviews. DISCUSSION:Novel LAI-PrEP formulations carry tremendous potential to revolutionize the field of HIV prevention. Implementation strategies rooted in equity are needed to ensure that marginalized populations have access to LAI-PrEP and to address the structural factors that hinder initiation and retention in care.

Marcucci M, Painter TW, Conen D, et al; POISE-3 Trial Investigators and Study Groups. Hypotension-avoidance versus hypertension-avoidance strategies in noncardiac surgery: an international randomized controlled trial. Ann Intern Med. 2023;176:605-614. 37094336.

BACKGROUND:Language concordance between health care practitioners and patients have recently been shown to lower the risk of adverse health events. Continuity of care also been shown to have the same impact. OBJECTIVE:The purpose of this paper is to examine the relative effectiveness of both continuity of care and language concordance as alternative or complementary interventions to improve health outcomes of people with limited English proficiency. DESIGN:A multivariable logistic regression model using rehospitalization as the dependent variable was built. The variable of interest was created to compare language concordance and continuity of care. PARTICIPANTS:The final sample included 22,103 patients from the New York City area between 2010 and 2015 who were non-English-speaking and admitted to their home health site following hospital discharge. MEASURES:The odds ratio (OR) average marginal effect (AME) of each included variable was calculated for model analysis. RESULTS:When compared with low continuity of care and high language concordance, high continuity of care and high language concordance significantly decreased readmissions (OR=0.71, 95% CI: 0.62-0.80, P<0.001, AME=-4.95%), along with high continuity of care and low language concordance (OR=0.80, 95% CI: 0.74-0.86, P<0.001, AME=-3.26%). Low continuity of care and high language concordance did not significantly impact readmissions (OR=1.04, 95% CI: 0.86-1.26, P=0.672, AME=0.64%). CONCLUSION:In the US home health system, enhancing continuity of care for those with language barriers may be helpful to address disparities and reduce hospital readmission rates.

RATIONALE:Video visits became more widely available during the coronavirus disease (COVID-19) pandemic. However, the ongoing role and value of video visits in care delivery and how these may have changed over time are not well understood. AIMS AND OBJECTIVES:Compare the relative complexity of in-person versus video visits during the COVID-19 pandemic and describe the complexity of video visits over time. METHODS:We used billing data for in-person and video revisits from non-behavioural health specialities with the most video visit utilisation (≥50th percentile) at a large, urban, public healthcare system from 1 January 2021 to 31 March 2022. We used current procedural terminology (CPT) codes as a proxy for information gathering and decision-making complexity and time spent on an encounter. We compared the distribution of CPT codes 99211-99215 between in-person and video visits using Fisher's exact tests. We used Spearman correlation to test for trends between proportions of CPT codes over time for video visits. RESULTS:Ten specialities (adult primary care, paediatrics, adult dermatology, bariatric surgery, paediatric endocrinology, obstetrics and gynaecologist, adult haematology/oncology, paediatric allergy/immunology, paediatric gastroenterology, and paediatric pulmonology) met inclusion criteria. For each speciality, proportions of each CPT code for in-person visits and for video visits varied significantly, and patterns of variation differed by speciality. For example, in adult primary care, video visits had smaller proportions of moderate/high complexity visits (99214 and 99215) and greater proportions of lower complexity visits (99211-99213) compared with in-person visits (p < 0.001), but in paediatric endocrinology, the opposite was seen (p < 0.001). Trends in CPT codes over time for video visits in each speciality were also mixed. CONCLUSION:In-person and video visits had differing proportions of complexity codes (typically skewing towards lower complexity for video visits). The complexity of video visits changed over time in many specialities. Observed patterns for both phenomena varied by speciality.

Colorectal signet ring cell carcinoma is a rare type of colon cancer. Early diagnosis remains challenging because of nonspecific colonoscopy findings, such as diffuse circumferential thickening, stricture, and ulcerations, and the potential absence of typical pathological features in the initial biopsy sample. In this article, we report a 41-year-old man with ulcerating rectosigmoid stricture in the rectosigmoid colon with inconclusive histology. Subsequently, the patient developed small bowel obstruction and was diagnosed with stage 4 colorectal signet ring cell carcinoma with peritoneal carcinomatosis.