Faculty Bibliography

BACKGROUND:Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms. METHODS:No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life. DISCUSSION/CONCLUSIONS:Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier: NCT05216133; January 18, 2022.

AIM/OBJECTIVE:Primary sclerosing cholangitis (PSC) increases the risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients; however, there is a paucity of literature to suggest PSC alone as an independent risk factor for CRC. We aimed to determine if PSC is an independent risk factor for CRC in a large tertiary care medical center. Optimizing screening intervals is of great importance, given the burden and risks associated with a lifetime of colonoscopy screening. METHODS:This retrospective cohort study consists of patients diagnosed with PSC preceding IBD (PSC-IBD) and PSC-only before January 6, 2023 from a large, tertiary, academic medical center. Patients diagnosed with IBD concurrently or before PSC were excluded to reduce IBD's impact on CRC risk. Demographic data and colonoscopy findings were collected and assessed. RESULTS:Overall, 140 patients from all NYU Langone Health clinical settings were included. Patients with PSC-IBD were more likely to be diagnosed with CRC (23.3% vs. 1.8%, p < 0.01) and either low-grade or uncharacterized dysplasia (16.7% vs. 0.0%, p < 0.01) compared with those with PSC-only. Among PSC-only patients, the estimated CRC risk was significantly elevated compared with that expected of the standard NYU Langone population (SIR 9.2, 95% CI 1.1, 33.2). CONCLUSIONS:Our study revealed a significantly heightened CRC risk in PSC-IBD patients compared with those with PSC-only. Importantly, individuals with PSC-only also face a greater CRC risk compared with the general population. Individuals with PSC-alone may require extended screening and surveillance colonoscopy intervals compared with those with PSC-IBD, yet still require more frequent monitoring than screening guidelines recommend for the general population.

We assessed factors associated with increased risk to loss of follow-up with infectious diseases staff in OPAT patients. Discharge to subacute healthcare facilities is strongly associated with loss to follow-up. We did not identify sociodemographic disparities. Poor communication between OPAT providers and subacute healthcare facilities remains a serious issue.

Teclistamab, a B-cell maturation antigen (BCMA)- and CD3-targeting bispecific antibody, is an effective novel treatment for relapsed/refractory multiple myeloma (R/RMM), but efficacy in patients exposed to BCMA-directed therapies and mechanisms of resistance have yet to be fully delineated. We conducted a real-world retrospective study of commercial teclistamab, capturing both clinical outcomes and immune correlates of treatment response in a cohort of patients (n = 52) with advanced R/RMM. Teclistamab was highly effective with an overall response rate (ORR) of 64%, including an ORR of 50% for patients with prior anti-BCMA therapy. Pretreatment plasma cell BCMA expression levels had no bearing on response. However, comprehensive pretreatment immune profiling identified that effector CD8+ T-cell populations were associated with response to therapy and a regulatory T-cell population associated with nonresponse, indicating a contribution of immune status in outcomes with potential utility as a biomarker signature to guide patient management.

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥ 3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.

Teclistamab (Tec) is a first-in-class BCMA X CD3 bispecific T-cell engager antibody approved for treating multiple myeloma progressing after at least 4 lines of therapy. The objective of this study was to evaluate the rate of cytokine release syndrome (CRS) in patients who were treated with commercial Tec and had prior exposure to other T-cell redirection therapies. A retrospective chart review was performed to identify patients who completed the Tec step-up dosing phase between November 2022 and November 2023. Patients were divided into 2 cohorts based on prior exposure to T-cell redirection therapy (cohort 1: T-cell redirection therapy experienced; cohort 2: T-cell redirection therapy naïve). The primary objective was to compare the differences in the rates of CRS between the two cohorts. Univariate and multivariate logistic regression analyses were performed to assess the association between CRS rates with Tec and prior treatment with T-cell redirection therapy. A total of 72 patients were included in the analysis (27 in cohort 1 and 45 in cohort 2). The CRS rates were significantly lower in cohort 1 (37%, n=10) compared to cohort 2 (80%, n=36; p=0.0004). Based on multivariate logistic regression analysis, patients without prior exposure to T-cell redirection therapy (cohort 2) had about a 4-fold increase in the incidence of CRS (95% CI: 1.40-14.90, p=0.0002) with Tec. In our study, prior exposure to T-cell redirection therapy reduced the risk of CRS with Tec during the step-up dosing phase. This observation will allow for the optimization of CRS prophylactic strategies for Tec.

INTRODUCTION/UNASSIGNED:Patients and clinicians face challenges in participating in video telehealth visits. Patient navigation has been effective in other settings in enhancing patients' engagement with clinical programs. Our objective was to assess whether implementing a telehealth navigator program to support patients and clinicians affected video visit scheduling, video usage, and non-attendance. METHODS/UNASSIGNED:This was a quasi-experimental quality improvement project using difference-in-differences. We included data from 17 adult primary care sites at a large, urban public healthcare system from October 1, 2021 to October 31, 2022. Six sites received telehealth navigators and 11 sites were used as comparators. Navigators contacted patients (by phone) with upcoming video visits to assess and address potential barriers to successful video visit completion. They also provided on-site support to patients and clinicians regarding telehealth visits and usage of an electronic patient portal. The primary outcomes were difference-in-differences for the proportion of telehealth visits scheduled and, separately, completed as video visits and non-attendance for visits scheduled as video visits. RESULTS/UNASSIGNED:There were 65 488 and 71 504 scheduled telehealth appointments at intervention and non-intervention sites, respectively. The adjusted difference-in-differences for the proportion of telehealth visits scheduled as video was -9.1% [95% confidence interval -26.1%, 8.0%], the proportion of telehealth visits completed as video visits 1.3% [-4.9%, 7.4%], and non-attendance for visits scheduled as video visits -3.7% [-6.0%, -1.4%]. CONCLUSIONS/UNASSIGNED:Sites with telehealth navigators had comparatively lower video visit non-attendance but did not have comparatively different video visit scheduling or completion rates. Despite this, navigators' on-the-ground presence can help identify opportunities for improvements in care design.

PURPOSE OF REVIEW/OBJECTIVE:Hypertension results in significant morbidity, mortality, and healthcare expenditures. Fortunately, it is largely preventable and treatable by implementing dietary interventions, though these remain underutilized. Here, we aim to explore the role of healthy dietary patterns in hypertension management and describe approaches for busy clinicians to address nutrition effectively and efficiently with patients. RECENT FINDINGS/RESULTS:DASH, Mediterranean, vegetarian, and vegan diets that include minimally processed, plant-based foods as core elements have consistently shown positive effects on hypertension. Recommendations that distill the most healthful components of these diets can significantly impact patient outcomes. Clinicians can harness evidence-based dietary assessment and counseling tools to implement and support behavioral changes, even during brief office visits. Healthful plant-based dietary patterns can often effectively prevent and treat hypertension. Clinicians may help improve patient outcomes by discussing evidence-based nutrition with their patients. Future work to promote infrastructural change that supports incorporating evidence-based nutrition into medical education, clinical care, and society at large can support these efforts.

BACKGROUND/UNASSIGNED:Fecal calprotectin (FC) is a reliable predictor of active bowel inflammation in postoperative Crohn's disease (CD), but cutoffs vary between studies. Recent guidelines recommend a cutoff of <50 ug/g to avoid routine endoscopy in patients at low pretest probability for CD recurrence. We evaluated the performance of this threshold in a real-world CD cohort after ileocolic resection (ICR). METHODS/UNASSIGNED:-test and Fisher's exact test were utilized for statistical analysis. All postoperative FCs were matched to closest colonoscopy within 1 year to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS/UNASSIGNED: = .005). Median time to first endoscopic recurrence in FC ≥ 50 ug/g was 145 days. There were 39 matched pairs of FC and colonoscopy. At an FC cutoff of 50 ug/g, calculated sensitivity was 90% and NPV was 93%, whereas specificity and PPV were 48% and 38%, respectively. CONCLUSIONS/UNASSIGNED:In this real-world cohort, FC < 50 ug/g is a useful cutoff to exclude endoscopic recurrence in a post-ICR CD population that is at low pretest probability of recurrence.