Faculty Bibliography

IMPORTANCE/UNASSIGNED:A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain. OBJECTIVE/UNASSIGNED:To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER)-Adult cohort, which consists of individuals enrolled in and prospectively followed up at 83 sites in 33 US states plus Washington, DC, and Puerto Rico. Data were examined from all participants enrolled between October 29, 2021, and July 5, 2024, who had a qualifying study visit 6 months or more after their initial SARS-CoV-2 infection. EXPOSURE/UNASSIGNED:Self-reported sex (male, female) assigned at birth. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Development of long COVID, measured using a self-reported symptom-based questionnaire and scoring guideline at the first study visit that occurred at least 6 months after infection. Propensity score matching was used to estimate risk ratios (RRs) and risk differences (95% CIs). The full model included demographic and clinical characteristics and social determinants of health, and the reduced model included only age, race, and ethnicity. RESULTS/UNASSIGNED:Among 12 276 participants who had experienced SARS-CoV-2 infection (8969 [73%] female; mean [SD] age at infection, 46 [15] years), female sex was associated with higher risk of long COVID in the primary full (RR, 1.31; 95% CI, 1.06-1.62) and reduced (RR, 1.44; 95% CI, 1.17-1.77) models. This finding was observed across all age groups except 18 to 39 years (RR, 1.04; 95% CI, 0.72-1.49). Female sex was associated with significantly higher overall long COVID risk when the analysis was restricted to nonpregnant participants (RR, 1.50; 95%: CI, 1.27-1.77). Among participants aged 40 to 54 years, the risk ratio was 1.42 (95% CI, 0.99-2.03) in menopausal female participants and 1.45 (95% CI, 1.15-1.83) in nonmenopausal female participants compared with male participants. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this prospective cohort study of the NIH RECOVER-Adult cohort, female sex was associated with an increased risk of long COVID compared with male sex, and this association was age, pregnancy, and menopausal status dependent. These findings highlight the need to identify biological mechanisms contributing to sex specificity to facilitate risk stratification, targeted drug development, and improved management of long COVID.

BACKGROUND:As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS/OBJECTIVE:To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS:We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS:Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION/CONCLUSIONS:Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.

BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

BACKGROUND AND AIMS/UNASSIGNED:In 2013, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) steering group published recommendations to standardize reporting quality in randomized controlled trials (RCTs). We aim to assess adherence to SPIRIT reporting guidelines in RCTs on endoscopic colorectal cancer (CRC) screening and participants' adherence to trial protocols. METHODS/UNASSIGNED:We searched databases for RCTs evaluating flexible sigmoidoscopy or colonoscopy for CRC screening published in English language through September 2023. Each eligible study was evaluated using the 8 core SPIRIT statement areas, totaling 51 points. Each item received 1 point if it met the criteria and 0 points if it did not. Adherence to SPIRIT items was calculated, and participant adherence to RCT protocols was assessed as the proportion of participants screened compared to those invited. RESULTS/UNASSIGNED:Five RCTs, including 4 on flexible sigmoidoscopy and 1 on colonoscopy, were analyzed. Adherence to SPIRIT guidance ranged from 82.4% to 92.2%. The most missed recommendation was item 2b (trial registrations), scored 0 across all studies. Additionally, item 32 (informed consent materials) scored 20%, and items 17a & b (blinding) scored 40% each. In total, 587,572 participants were randomized across the 5 RCTs. Of these, 37% (200,610) underwent CRC screening, with 69.8% (139,983/200,610) adhering to the protocol. The Nordic-European Initiative on Colorectal Cancer (NordICC) trial, employing a unique invitation method, had a lower adherence rate of 42%. Excluding this trial would raise the adherence rate to 74.3% (128,050/172,390). CONCLUSION/UNASSIGNED:The published CRC screening trials have acceptable adherence to the SPIRIT reporting guidelines. However, reporting appended consent form materials and disclosing all WHO trial registration data can be improved.

BACKGROUND:Despite reports indicating that polyps proximal to the splenic flexure have higher rates of metachronous colorectal adenocarcinoma (CRC), the role of adenoma location on surveillance recommendations remains unclear. This study aimed to analyze the association between index polyp location and post-colonoscopy CRC among participants of the Minnesota Colon Cancer Control Study (MCCCS). METHODS:The MCCCS randomized 46,551 patients 50-80 years to usual care, annual, or biennial screening with fecal occult-blood testing (FOBT). Screening was performed between 1976-1992. Positive FOBT was followed by colonoscopy. We analyzed participants whose colonoscopy revealed at least one adenoma. Patients were divided into those with at least one lesion proximal to the splenic flexure and those without. RESULTS:Of 2,295 patients, 815 had proximal adenomas. The majority were men; mean age =62 years at randomization, and 69 years at index polyp. There was a high rate of advanced adenomas: 44% ≥1 polyp ≥1 cm, 35% with villous histology, and 5% high grade dysplasia. At 20 years, 87 patients had a CRC diagnosis, and the estimated cumulative incidence of CRC was 4.3%. Proximal adenomas had a higher risk of developing a post-colonoscopy CRC (SHR=1.63, 95% CI=1.05-2.53, P=0.03), which was attenuated after adjusting for polyp multiplicity in sensitivity analyses (SHR=1.56, 95% CI=0.96-2.53, P=0.07). CONCLUSION/CONCLUSIONS:Although patients with proximal adenomas were found to have higher hazards of post-colonoscopy CRC, adjusting for polyp multiplicity attenuated the strength of association. Further research is warranted to determine whether polyp location should be factored in the determination of appropriate surveillance intervals.

INTRODUCTION/BACKGROUND:Failure to document colonoscopy follow-up needs postpolypectomy can lead to delayed detection of colorectal cancer (CRC). Automating the update of a unified follow-up date in the electronic health record (EHR) may increase the number of patients with guideline-concordant CRC follow-up screening. METHODS:Prospective pre-post design study of an automated rules engine-based tool using colonoscopy pathology results to automate updates to documented CRC screening due dates was performed as an operational initiative, deployed enterprise-wide May 2023. Participants were aged 45-75 years who received a colonoscopy November 2022 to November 2023. Primary outcome measure is rate of updates to screening due dates and proportion with recommended follow-up < 10 years. Multivariable log-binomial regression was performed (relative risk, 95% confidence intervals). RESULTS:Study population included 9,824 standard care and 19,340 intervention patients. Patients had a mean age of 58.6 ± 8.6 years and were 53.4% female, 69.6% non-Hispanic White, 13.5% non-Hispanic Black, 6.5% Asian, and 4.6% Hispanic. Postintervention, 46.7% of follow-up recommendations were updated by the rules engine. The proportion of patients with a 10-year default follow-up frequency significantly decreased (88.7%-42.8%, P < 0.001). The mean follow-up frequency decreased by 1.9 years (9.3-7.4 years, P < 0.001). Overall likelihood of an updated follow-up date significantly increased (relative risk 5.62, 95% confidence intervals: 5.30-5.95, P < 0.001). DISCUSSION/CONCLUSIONS:An automated rules engine-based tool has the potential to increase the accuracy of colonoscopy follow-up dates recorded in patient EHR. The results emphasize the opportunity for more automated and integrated solutions for updating and maintaining EHR health maintenance activities.

BACKGROUND/UNASSIGNED:Colonoscopy remains the predominant diagnostic modality for colorectal cancer (CRC), as the diagnostic performance of tumor markers in alone, particularly in the early stages of the disease, is limited. This study sought to develop a diagnostic model for CRC that integrated various laboratory parameters. METHODS/UNASSIGNED:One hundred patients with CRC were assigned to an experimental group while 114 with benign colorectal diseases and 101 healthy individuals were assigned to a control group. The clinical and laboratory data, including the tumor markers such as carcinoembryonic antigen (CEA), glycan carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 242 (CA242), blood count parameters, blood biochemical parameters, and coagulation parameters, were collected for each participant. Three machine-learning models [multilayered perceptron (MLP), eXtreme Gradient Boosting (XGBoost), and random forest (RF)] were used to construct CRC diagnostic models. The performance of each model was evaluated based on its area under the curve (AUC), sensitivity, and specificity. RESULTS/UNASSIGNED:There are 12 parameters: including CEA, CA19-9, CA242, absolute neutrophil value (NEUT), hemoglobin, the neutrophil/lymphocyte ratio, the platelet/lymphocyte ratio, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, albumin, and prothrombin time, were selected to build the diagnostic model. For the validation set, the RF machine-learning model achieved the highest performance in identifying CRC [AUC: 0.902 (95% confidence interval: 0.812-0.989), accuracy: 0.803, sensitivity: 0.908, specificity: 0.772, positive predictive value: 0.664, negative predictive value: 0.890, and F1 score: 0.763]. The AUC, sensitivity, specificity, and Youden's index for the combined diagnosis of tumor markers CEA, CA19-9, and CA242 were 0.761, 0.486, 0.983, and 0.469, respectively. The RF diagnostic model showed better diagnostic efficacy than the combined diagnosis model of tumor markers CEA, CA19-9 and CA242. CONCLUSIONS/UNASSIGNED:The use of machine learning combined with multiple laboratory parameters effectively improved the diagnostic efficiency of CRC and provided more accurate results for clinical diagnosis.

CRC accounts for approximately a tenth of all cancer cases and deaths in the US. Due to large differences in demographics among the different states, we aim to determine trends in the CRC epidemiology and across different states, age groups, and genders. CRC rates, age-adjusted to the standard US population, were obtained from the GBD 2019 database. Time trends were estimated as annual percentage change (APC). A pairwise comparison was conducted between age- and gender-specific trends using the tests of parallelism and coincidence. Age-specific trends were also assessed in two age subgroups: younger adults aged 15-49 years and older adults aged 50-74 years. We also analyzed the prevalence, incidence, mortality, and DALYs in the US between 1990 and 2019. A total of 5.53 million patients were diagnosed with CRC in the US between 1990 and 2019. Overall, CRC incidence rates have significantly increased in younger adults (11.1 per 100,000 persons) and decreased in older adults (136.8 per 100,000 persons) (AAPC = 1.2 vs. -0.6; AAPC difference = 1.8, p < 0.001). Age-specific trends were neither identical (p < 0.001) nor parallel (p < 0.001), suggesting that CRC incidence rates are different and increasing at a greater rate in younger adults compared to older adults. However, for both men and women (49.4 and 35.2 per 100,000 persons), incidence rates have decreased over the past three decades at the same rate (AAPC = -0.5 vs. -0.5; AAPC difference = 0, p = 0.1). Geographically, the southern states had the highest mortality rates with Mississippi having the highest rate of 20.1 cases per 100,000 population in 2019. Massachusetts, New York, and the District of Colombia had the greatest decreases in mortality over the study period (-42.1%, -41.4%, and -40.9%). Decreased mortality was found in all states except Mississippi, where the mortality of CRC increased over the study period (+1.5%). This research provides crucial insights for policymakers to tailor resource allocation, emphasizing the dynamic nature of CRC burden across states and age groups, ultimately informing targeted strategies for prevention and intervention.

BACKGROUND AND AIMS/UNASSIGNED:Pouchitis is an inflammatory condition affecting the ileal pouch in patients' status after ileal pouch anal anastomosis (IPAA). This affects a significant portion of IPAA patients. Our aim was to study the prevalence of active pouch symptoms among currently treated outpatients with endoscopic pouchitis and understand patients' perspective of disease control and quality of life. METHODS/UNASSIGNED:We cross-sectionally reviewed the medical charts of patients who had undergone pouchoscopy at NYU Langone Health from 2010 to 2022 and recorded demographic, clinical, and endoscopic data. Based on the most recent data in the medical record, we defined active pouch symptoms as 2 or more current clinical symptoms and "endoscopic pouchitis" as "moderate" or "severe" by pouchoscopy. We also administered surveys in March 2023 to 296 patients with an IPAA to understand symptom control, quality of life, and interest in fecal microbiota transplant. RESULTS/UNASSIGNED:We identified 282 unique patients. The median age of patients was 46 (interquartile range 33-59), with 54.3% males. Of these, 37.2% of patients currently had active pouch symptoms, 36.9% had endoscopic pouchitis, and 14.9% met the criteria for both. Of the 296 surveys sent to patients with IPAA, 74 (25%) responded. The median age of respondents was 49.5 (interquartile range 34-62). 59.5% were male. Average treatment satisfaction score (scale of 0-10) was 6.4 and quality of life score was 5.8. A majority (64.9%) expressed interest in fecal microbiota transplant. CONCLUSION/UNASSIGNED:Outpatients with active pouch symptoms or endoscopic pouchitis have high prevalence of active disease and report ongoing symptoms. The results underscore the inadequacy of current treatments and highlight the need for additional therapeutic options.