Faculty Bibliography

PURPOSE:Sustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma. The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We hypothesized that dietary factors affect the microbiome (abundance of butyrate-producing bacteria or stool butyrate concentration) and may be associated with multiple myeloma outcomes. EXPERIMENTAL DESIGN:We examined the relationship of dietary factors (via a food frequency questionnaire), stool metabolites (via gas chromatography-mass spectrometry), and the stool microbiome (via 16S sequencing - α-diversity and relative abundance of butyrate-producing bacteria) with sustained MRD negativity (via flow cytometry at two timepoints 1 year apart) in myeloma patients on lenalidomide maintenance. The Healthy Eating Index 2015 score and flavonoid nutrient values were calculated from the food frequency questionnaire. The Wilcoxon rank sum test was used to evaluate associations with two-sided P < 0.05 considered significant. RESULTS:At 3 months, higher stool butyrate concentration (P = 0.037), butyrate producers (P = 0.025), and α-diversity (P = 0.0035) were associated with sustained MRD negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (P = 0.009) and sustained MRD negativity (P = 0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins P = 0.01, flavones P = 0.01, and flavanols P = 0.02). CONCLUSIONS:This is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production, and sustained MRD negativity in multiple myeloma, providing rationale to evaluate a prospective dietary intervention.

BACKGROUND:Patients with ulcerative colitis may require colectomy for severe disease unresponsive or refractory to pharmacological therapy. Managing ulcerative colitis is complicated as there are many factors at play, including patient optimization and treatment; the guidance varies on the ideal perioperative use of corticosteroids, immunomodulators, biologics, and small molecule agents. OBJECTIVE:A systematic literature review was performed to describe the current status of perioperative management of ulcerative colitis. DATA SOURCES/METHODS:PubMed and Cochrane databases were used. STUDY SELECTION/METHODS:Studies between January 2000 and January 2022, in any language, were included. Articles regarding pediatric or endoscopic management were excluded. INTERVENTIONS/METHODS:Perioperative management of ulcerative colitis was included. MAIN OUTCOME MEASURES/METHODS:Successful management, including reducing surgical complication rates, was measured. RESULTS:A total of 121 studies were included in this review, including 23 meta-analyses or systematic reviews, 25 reviews, and 51 cohort studies. LIMITATIONS/CONCLUSIONS:Qualitative review including all study types. The varied nature of study types precludes quantitative comparison. CONCLUSION/CONCLUSIONS:Indications for colectomy in UC include severe disease unresponsive to medical treatment and colitis-associated neoplasia. Urgent colectomy has a higher mortality rate than elective colectomy. Corticosteroids are associated with postsurgical infectious complications and should be stopped or weaned before surgery. Biologics are not associated with adverse postoperative effects and do not necessarily need to be stopped preoperatively. Additionally, the clinician must assess individuals' comorbidities, nutrition status, and risk of venous thromboembolism. Nutritional imbalance should be corrected, ideally at preoperative period. Postoperatively, corticosteroids can be tapered based on the length of preoperative corticosteroid use.

Background Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits. Methods and Results We conducted a retrospective cohort study within a large, multi-site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered <80% over 6 months. We assessed the association between copayment and nonadherence using multivariable logistic regression, and nonbinarized proportion of days covered using multivariable Poisson regression, adjusting for demographic, clinical, and neighborhood-level covariates. A total of 921 patients met inclusion criteria, with 192 (20.8%) having $0 copayment, 228 (24.8%) with $0.01 to $10 copayment, 206 (22.4%) with $10.01 to $100, and 295 (32.0%) with >$100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (P<0.001). After multivariable adjustment, odds of nonadherence were significantly higher for copayment of $10.01 to $100 (odds ratio [OR], 1.93 [95% CI, 1.15-3.27], P=0.01) or >$100 (OR, 2.58 [95% CI, 1.63-4.18], P<0.001), as compared with $0 copayment. Similar associations were seen when assessing proportion of days covered as a proportion. Conclusions We found higher rates of not filling ARNI prescriptions among patients with higher copayments, which persisted after multivariable adjustment. Our findings support future studies to assess whether reducing copayments can increase adherence to ARNI and improve outcomes for heart failure.

BACKGROUND:Current guidelines suggest antibiotics prophylaxis is not necessary for patients with orthopedic prosthetics undergoing gastrointestinal endoscopy. Clinical evidence to support this recommendation is lacking. AIMS/OBJECTIVE:To analyze the association between inpatient gastrointestinal endoscopy and prosthetic joint infection (PJI) in patients with a recent arthroplasty. METHODS:We included patients admitted from July to October of each calendar year (index admissions) who had an arthroplasty in the same calendar year prior to the index admission. We followed the occurrence of PJI for 60 days after the index admission. Only admissions from July to October were chosen as index admissions, and the follow-up period was limited to 60 days because the database structure prohibits the analysis of events in different calendar years. We compared the rate of 60-day PJI between those who had gastrointestinal endoscopy on index admissions to those who had not. We excluded patients aged less than 18 years, who died on index admission, or had any infection in the same calendar year before or during the index admission. RESULTS:Of 1,831,218 patients with arthroplasty, 88,345 met the inclusion criteria, out of which 5,855 had gastrointestinal endoscopy. The rate of 60-day PJI in those who had endoscopy was 0.23%, and in those who had not was 0.52% (P < 0.001). EGD without excision (adjusted odds ratio [95% confidence interval]: 0.20 [0.03-1.42], P = 0.107), EGD with excision (0.58 [0.21-1.60], P = 0.295), colonoscopy without excision (0.43 [0.11-1.72], P = 0.233), colonoscopy with excision (0.31 [0.04-2.21], P = 0.241), and PEG/PEJ (0.38 [0.05-2.71], P = 0.337) were not associated with risk of 60-day PJI. We found no PJI cases in patients underwent esophageal dilation, ERCP, and EUS with FNA. CONCLUSIONS:Gastrointestinal endoscopy in hospitalized patients with a recent previous arthroplasty is not associated with an increased risk of 60-day prosthetic joint infection.

BACKGROUND:Endoscopic balloon dilation (EBD) has emerged as an alternative intervention to manage Crohn's disease (CD) strictures. We determined the cost-effectiveness of EBD versus resection surgery for patients with short (< 4-5 cm) primary or secondary/anastomotic small or large bowel strictures. METHODS:A microsimulation state-transition model analyzed the benefits and risks of EBD and resection surgery for patients with primary or anastomotic CD strictures. Our primary outcome was quality-adjusted life years (QALYs) over ten years, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (2021 $US) and incremental cost-effectiveness ratios (ICER) were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty. RESULTS:The EBD strategy cost $19,822 and resulted in 6.18 QALYs while the surgery strategy cost $41,358 and resulted in 6.37 QALYs. Surgery had an ICER of $113,332 per QALY, making EBD a cost-effective strategy. The median number of EBDs was 5 in the EBD strategy and 0 in the surgery strategy. The median number of surgeries was 2 in the surgery strategy and 1 in the EBD strategy. Of individuals who initially received EBD, 50.4% underwent subsequent surgery. One-way sensitivity analyses showed that the probabilities of requiring repeated interventions, surgery mortality (< 0.7%), and quality of life after interventions were the most influential model parameters. Probabilistic sensitivity analyses favored EBD in 50.9% of iterations. CONCLUSIONS:EBD is a cost-effective strategy for managing CD strictures. Differences in patient risk and quality of life after intervention impact cost-effectiveness. Intervention decisions should consider cost-effectiveness, patient risks, and quality of life.

Background. HIV-associated wasting (i.e., progressive, involuntary weight loss with both fat and lean tissue loss; HIVAW) is an under-appreciated AIDS-defining illness; the 2012-2018 period prevalence was reported as 18% in a recent claims study in the United States. We aimed to assess the association between incident HIVAW/ low weight and all-cause mortality in the era of modern combination antiretroviral therapy (ART). Methods. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, PWH without (a) any prior HIVAW/low weight, (b) malignancy within 3 years, and (c) opportunistic infection within 1 year who were active in care between 2016 and 2020 were followed through death, loss to follow-up, or study end (31OCT2021). HIVAW/low weight included a wasting or low BMI/underweight diagnosis (ICD codes, title search) or BMI < 20 kg/m2. Hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-dependent incident HIVAW/low weight (exposure) and all-cause mortality (outcome) were estimated with extended Cox regression models. The adjusted model included age at baseline, race, ethnicity, and time-dependent covariates (log10 viral load, Veterans Aging Cohort Study [VACS] Mortality Index score). Viral load and VACS score were included as surrogate markers for ART use and comorbidities, respectively. Linear and quadratic terms of continuous variables were included. Results. Of 67,119 PWH without prior HIVAW/low weight in OPERA, 62,314 (93%) PWH had non-missing covariate data and were included in the models; baseline characteristics did not differ between the full and model study populations (Table 1). Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of incident HIVAW/low weight and 1,354 (2%) deaths. In the adjusted model, PWH who experienced incident HIVAW/low weight had a significantly increased risk of death over follow-up than those who did not experience HIVAW/low weight (HR: 1.96; 95% CI: 1.68, 2.27) (Table 2). Conclusion. In this analysis of 62,314 PWH in care, incident HIVAW/low weight was associated with twice the risk for all-cause mortality in the modern ART era. Particular attention needs to be paid to HIVAW/low weight among PWH to restore health and potentially reduce the risk of death

BACKGROUND/UNASSIGNED:Nonadherence to antihypertensive medications remains a persistent problem that leads to preventable morbidity and mortality. Behavioral economic strategies represent a novel way to improve antihypertensive medication adherence, but remain largely untested especially in vulnerable populations which stand to benefit the most. The Behavioral Economics Trial To Enhance Regulation of Blood Pressure (BETTER-BP) was designed in this context, to test whether a digitally-enabled incentive lottery improves antihypertensive adherence and reduces systolic blood pressure (SBP). DESIGN/UNASSIGNED:BETTER-BP is a pragmatic randomized trial conducted within 3 safety-net clinics in New York City: Bellevue Hospital Center, Gouveneur Hospital Center, and NYU Family Health Centers - Park Slope. The trial will randomize 435 patients with poorly controlled hypertension and poor adherence (<80% days adherent) in a 2:1 ratio (intervention:control) to receive either an incentive lottery versus passive monitoring. The incentive lottery is delivered via short messaging service (SMS) text messages that are delivered based on (1) antihypertensive adherence tracked via a wireless electronic monitoring device, paired with (2) a probability of lottery winning with variable incentives and a regret component for nonadherence. The study intervention lasts for 6 months, and ambulatory systolic blood pressure (SBP) will be measured at both 6 and 12 months to evaluate immediate and durable lottery effects. CONCLUSIONS/UNASSIGNED:BETTER-BP will generate knowledge about whether an incentive lottery is effective in vulnerable populations to improve antihypertensive medication adherence. If successful, this could lead to the implementation of this novel strategy on a larger scale to improve outcomes.

Background. In-vitro neutralizing antibody (Ab) titers correlated with ~250 IU/ mL Spike Ig Ab level for the Delta COVID-19 variant, establishing the 2021 French and Swiss cutoff for booster guidance. In a New York City healthcare clinic where those guidelines were adopted, we aimed to quantify vaccination responses in HIV + and HIV- individuals to assess the utility of quantifying antibodies to guide booster timing. Methods. Adults who were fully vaccinated against SARS-CoV-2 virus (i.e., 2 Pfizer, 2 Moderna or 1 J&J vaccine) were included if >1 Roche SARS-CoV-2 Semi-Quant Spike Ig Ab test was performed >21 days after vaccination and before any booster (through 03DEC2021). Vaccine response was assessed at the first Ab test and considered adequate (>250 IU/mL) or inadequate (low: >=51 to <=250 IU/ mL; no response: < 51 IU/mL). The rate of Ab decline was estimated with linear regression, using all sequential Ab tests over the first 6 months between vaccination and boosting. Analyses were stratified by vaccine type, HIV status and CD4 count in HIV+ ( >200 cells/muL cutoff). Results. Out of 1979 patients, 869 completed their primary vaccinations, of whom 825 (95%) had >=1 eligible Ab test (HIV+: 512; HIV-: 313; Table). Overall, 83% had an adequate immune response to vaccination (Pfizer: 82%, Moderna: 94%, J&J: 51%), with similar findings regardless of HIV status and CD4 count (Figure 1). In those with >=2 Ab tests within six months between vaccination and boosting, Ab levels declined at a rate of 91 IU/mL per month (95% CI: -138, -44). While some variation was observed, rates of Ab decay were generally consistent across vaccine, HIV status and CD4 count strata (Figure 2). Only 1/7 breakthrough COVID-19 infections occurred post booster (6 days later Conclusion. In the pre-omicron era, primary COVID immunization with a mRNA vaccine generally yielded adequate Ab responses, although inadequate responses were observed in 19% of Pfizer, 6% of Moderna, and 49% of J&J vaccine recipients. Ab levels decreased at an average rate of 91 IU/mL per month after primary immunization. Variability in vaccine responses and Ab declines show the utility of measuring spike Ig Ab levels rather than using empiric time frames for booster guidance. Omicron-specific quantitative IgG neutralization levels must be established to inform preventative care