Publications

INTRODUCTION: Unspecified functional bowel disorder (FBD-U) is a Rome IV diagnosis of exclusion and occurs when patients report bowel symptoms but do not meet the criteria for other functional bowel disorders (FBD; irritable bowel syndrome [IBS], functional constipation [FC], functional diarrhea [FDr], or functional bloating). Previous research suggests that FBD-U is as/more common than IBS.

METHODS: One thousand five hundred one patients at a single-center tertiary care center completed an electronic survey. Study questionnaires included Rome IV Diagnostic Questionnaires, anxiety, depression, sleep, health care utilization, and bowel symptom severity measures.

RESULTS: Eight hundred thirteen patients met Rome IV criteria for a FBD and 194 patients (13.1%) met criteria for FBD-U, representing the second most common FBD after IBS. Severity of abdominal pain, constipation, and diarrhea were lower in FBD-U compared with other FBD, whereas health care utilization was similar among the groups. Scores on measures of anxiety, depression, and sleep disturbances were similar in FBD-U compared with FC and FDr but were less severe than IBS. Between 25% and 50% of patients with FBD-U did not meet Rome IV criteria for other FBD due to timing of onset of the target symptom (e.g., constipation for FC, diarrhea for FDr, and abdominal pain for IBS).

DISCUSSION: FBD-U, by Rome IV criteria, is highly prevalent in clinical settings. These patients are not represented in mechanistic studies or clinical trials for not having met Rome IV criteria for other FBD. Making future Rome criteria less stringent would minimize the number fulfilling criteria for FBD-U and maximize the true representation of FBD in clinical trials.

BACKGROUND: Therapeutic drug monitoring (TDM) is a decision-making tool for optimizing the use of certain therapies. In this article, the authors review the role of proactive TDM of biological agents in patients with inflammatory bowel disease (IBD) and other immune-mediated inflammatory diseases (IMID). They also discuss the future of TDM as a component of personalized medicine from the clinical laboratory perspective.

METHODS: This narrative review originated from proceedings of the fifth biannual Challenges in Therapeutic Drug Monitoring seminar and was supplemented by additional literature identified at various stages of critical review.

RESULTS: Proactive TDM aims to achieve adequate concentrations of biological drugs, such that patients attain and maintain an optimal treatment response. Proactive TDM may also have a role in de-escalating anti-tumor necrosis factor therapy in patients in clinical remission and in optimizing infliximab monotherapy as an alternative to combination therapy with an immunomodulator. A major proactive TDM application is in pediatric patients with IBD. Achieving mucosal healing in children with IBD requires that infliximab or adalimumab concentrations are monitored early during induction therapy, with dose modifications guided by the timing (week) of measurement. Recent innovations in biological therapy include international standards for infliximab and adalimumab for the global harmonization of bioactivity and monotest devices with an accuracy equivalent to that of conventional enzyme-linked immunosorbent assays and quicker turnaround times.

CONCLUSIONS: Despite several knowledge gaps regarding proactive TDM of anti-tumor necrosis factor therapy in patients with IMID, growing evidence suggests that it is associated with better outcomes than empiric optimization and/or reactive TDM in IBD. Enhanced pharmacokinetic modeling to predict drug exposure and patient genotyping for the precise application of proactive TDM are considered key elements to optimize biological therapy in the future.

Qian HS, Li WJ, Dang YN, et al. Ten-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with bismuth-containing quadruple therapy. Am J Gastroenterol. 2023;118:627-634. 36729890.

BACKGROUND AND AIM: Recently, there has been an increased focus on the role nutrition and diet play in maintaining health in inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on nutrition/diet in IBD.

METHODS: A systematic search was performed on multiple databases from inception until January 1, 2021, to identify guidelines pertaining to nutrition or diet in IBD. All guidelines were reviewed for disclosure of conflicts of interest (COI) and funding, recommendation quality and strength, external document review, patient representation, and plans for update-as per Institute of Medicine (IOM) standards. In addition, recommendations and their quality were compared between guidelines/societies.​ RESULTS: Seventeen distinct societies and a total of 228 recommendations were included. Not all guidelines provided recommendations on key aspects of diet-such as the role of supplements or the appropriate micro/macro nutrition in IBD. Fifty-nine percent of guidelines reported on COI, 24% underwent external review, and 41% included patient representation. 18.4%, 25.9%, and 55.7% of recommendations were based on high-, moderate-, and low-quality evidence, respectively. 10.5%, 24.6%, and 64.9% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence (p = 0.12) and strong recommendations (p = 0.83) did not significantly differ across societies.

CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of diet/nutrition in IBD. As over 50% of recommendations are based on low-quality evidence, further studies on nutrition/diet in IBD are warranted to improve the overall quality of evidence.

INTRODUCTION: Guidelines endorse pancreatic cancer screening in genetically susceptible individuals. We conducted a prospective, multicenter study to determine yield, harms, and outcomes of pancreatic cancer screening.

METHODS: All high-risk individuals undergoing pancreatic cancer screening at 5 centers from 2020 to 2022 were prospectively enrolled. Pancreas findings were designated as low-risk (fatty or chronic pancreatitis-like changes), intermediate-risk (neuroendocrine tumor [NET] <2 cm or branch-duct intraductal papillary mucinous neoplasm [IPMN]), or high-risk lesions (high-grade pancreatic intraepithelial neoplasia/dysplasia, main-duct IPMN, NET >2 cm, or pancreatic cancer). Harms from screening included adverse events during screening or undergoing low-yield pancreatic surgery. Annual screening was performed using endoscopic ultrasound and or magnetic resonance cholangiopancreatography. Annual screening for new-onset diabetes using fasting blood sugar was also performed ( ClinicalTrials.gov : NCT05006131).

RESULTS: During the study period, 252 patients underwent pancreatic cancer screening. Mean age was 59.9 years, 69% were female, and 79.4% were White. Common indications were BRCA 1/2 (36.9%), familial pancreatic cancer syndrome kindred (31.7%), ataxia telangiectasia mutated (3.5%), Lynch syndrome (6.7%), Peutz-Jeghers (4.3%), and familial atypical multiple mole melanoma (3.5%). Low-risk lesions were noted in 23.4% and intermediate-risk lesions in 31.7%, almost all of which were branch-duct IPMN without worrisome features. High-risk lesions were noted in 2 patients (0.8%), who were diagnosed with pancreas cancer at stages T2N1M0 and T2N1M1. Prediabetes was noted in 18.2% and new-onset diabetes in 1.7%. Abnormal fasting blood sugar was not associated with pancreatic lesions. There were no adverse events from screening tests, and no patient underwent low-yield pancreatic surgery.

DISCUSSION: Pancreatic cancer screening detected high-risk lesions with lower frequency than previously reported. No harms from screening were noted.

BACKGROUND: The optimal timing of esophagogastroduodenoscopy (EGD) and the impact of clinico-demographic factors on hospitalization outcomes in non-variceal upper gastrointestinal bleeding (NVUGIB) remains an area of active research.

AIM: To identify independent predictors of outcomes in patients with NVUGIB, with a particular focus on EGD timing, anticoagulation (AC) status, and demographic features.

METHODS: A retrospective analysis of adult patients with NVUGIB from 2009 to 2014 was performed using validated ICD-9 codes from the National Inpatient Sample database. Patients were stratified by EGD timing relative to hospital admission (≤ 24 h, 24-48 h, 48-72 h, and > 72 h) and then by AC status (yes/no). The primary outcome was all-cause inpatient mortality. Secondary outcomes included healthcare usage.

RESULTS: Of the 1082516 patients admitted for NVUGIB, 553186 (51.1%) underwent EGD. The mean time to EGD was 52.8 h. Early (< 24 h from admission) EGD was associated with significantly decreased mortality, less frequent intensive care unit admission, shorter length of hospital stays, lower hospital costs, and an increased likelihood of discharge to home (all with P < 0.001). AC status was not associated with mortality among patients who underwent early EGD (aOR 0.88, P = 0.193). Male sex (OR 1.30) and Hispanic (OR 1.10) or Asian (aOR 1.38) race were also independent predictors of adverse hospitalization outcomes in NVUGIB.

CONCLUSION: Based on this large, nationwide study, early EGD in NVUGIB is associated with lower mortality and decreased healthcare usage, irrespective of AC status. These findings may help guide clinical management and would benefit from prospective validation.

INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD.

METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement.

RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17-0.64], P < 0.001 and odds ratio per μg/mL: 1.11 [95% confidence interval: 1.05-1.19], P < 0.001).

DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.

Cholestasis due to sepsis is commonly seen in critically ill patients; however, it is often overlooked and poses a challenge in clinical diagnosis and management. In this report, we present a 29-year-old woman who presented to the emergency department with jaundice and symptoms of a urinary tract infection. Initially suspected to be Dubin-Johnson syndrome, sepsis-induced cholestasis was eventually diagnosed after testing. Sepsis should always be considered as part of the differential diagnosis while managing a patient with jaundice. The management of sepsis-induced cholestasis involves treating the underlying infection. In most cases, liver injury improves with the resolution of the infectious process.