Faculty Bibliography

PURPOSE OF REVIEW/UNASSIGNED:Dysphagia is a common medical condition among the geriatric population that can significantly impact a patient's quality of life. The manifestations, diagnosis, and treatment of esophageal dysphagia differ greatly based on the underlying etiology, especially in older individuals who may have accompanying complex medical comorbidities. This review explores the intricacies of esophageal dysphagia in the older population and how they are managed. RECENT FINDINGS/UNASSIGNED:Novel modalities, like the functional luminal imaging probe (FLIP) and timed barium esophagram (TBE), are now woven into our diagnostic schemas for esophageal dysphagia. Studies have also looked at the safety profile of available therapeutic interventions for older individuals. There are newer, less invasive treatment options, including radiofrequency application (RFA) and transoral incisionless fundoplication (TIF) for GERD management, that may benefit the geriatric population. SUMMARY/UNASSIGNED:In this review, we discuss the most likely etiologies of esophageal dysphagia in the elderly population. We then explore a diagnostic schema and highlight treatment choices based on diagnosis. Our review specifically explores the risks and benefits of management options in more medically complex geriatric patients.

BACKGROUND AND AIMS/OBJECTIVE:PredictSURE IBD is a prognostic blood test that classifies newly diagnosed, treatment-naïve Inflammatory Bowel Disease (IBD) patients into 'IBDhi' (high-risk) or 'IBDlo' (low-risk) groups (risk of future aggressive disease). We evaluated this assay in a multinational cohort and explored the effect of concomitant corticosteroids on its discrimination. METHODS:One hundred thirty-six (71 Ulcerative colitis [UC], 65 Crohn's Disease [CD]) and 41 (15 UC, 26 CD) patients with active IBD were 'unexposed' and 'exposed', respectively, to corticosteroids at baseline blood sampling. The number of treatment escalations, time to first escalation, and need for repeated escalations were compared between the biomarker subgroups. Another 20 patients (13 UC, 7 CD) were longitudinally sampled over 6 weeks after commencing corticosteroids. RESULTS:In corticosteroids-naïve UC and CD patients, all bowel surgeries (n = 6) and multiple therapy escalations (n = 10) occurred in IBDhi patients. IBDhi UC patients required significantly more treatment escalations, had a shorter time to first escalation, and a greater need for multiple escalations than IBDlo patients. No statistically significant differences were observed among CD patients. In corticosteroid-exposed patients, 66.6% of 'misclassifications' were IBDlo patients who required escalations. Among corticosteroid-treated patients with longitudinal sampling, 81.3% of those classified as IBDhi before steroids switched to IBDlo during therapy. CONCLUSIONS:No significant differences in treatment escalations were observed between biomarker-defined subgroups in CD. However, IBDhi UC patients required significantly earlier and more frequent therapy escalations, highlighting the need to further investigate PredictSURE IBD in UC. Notably, the discrimination ability of the biomarker was unreliable in patients receiving corticosteroid therapy.

BACKGROUND:Hepatitis delta virus (HDV) requires hepatitis B virus (HBV) surface antigen to enter hepatocytes. Although HBV/HDV coinfection is the most severe form of viral hepatitis, disease progression and liver-related data are limited. AIMS/OBJECTIVE:To evaluate the characteristics of studies reporting HDV outcomes and the incidence of liver-related events among individuals with HDV. METHODS:We searched online databases from 1 January 2000 to 14 December 2022 and congress proceedings from 2021 to 2022. Randomised controlled trials (RCTs), non-randomised interventional studies and observational studies reporting incidence of cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant (LT) and liver-related death in ≥ 20 adults with active HDV infection were included. Study/participant characteristics, cumulative incidence and incidence rates were extracted. RESULTS:Data were extracted from 32 unique studies in 47 publications. While most (n = 19; 59%) studies included < 100 individuals, five included ≥ 200. Most were retrospective cohort (n = 19; 59%), and the remainder were prospective cohort (n = 5), non-randomised interventional (n = 3), RCT (n = 3) or registry/database studies (n = 2). Outcomes reported by the largest numbers of studies were hepatic decompensation (n = 21) and HCC (n = 20); the least reported was cirrhosis (n = 9). Heterogeneity existed in participant populations, with variability in baseline markers of liver disease severity. Consequently, a wide range of cumulative incidence values was observed (cirrhosis, 0%-63%; hepatic decompensation, 0%-52%; HCC, 0%-19%; LT, 2%-43%; liver-related death, 0%-19%; composite endpoint, 3%-74%). CONCLUSIONS:The number of studies describing the incidence of liver-related outcomes among people with HDV remains limited. Quantifying incidence of liver-related events can improve our understanding of disease progression and inform potential treatment strategies. TRIAL REGISTRATION/BACKGROUND:PROSPERO registration ID: CRD42023386845.

OBJECTIVES/OBJECTIVE:Post-colonoscopy colorectal cancer (PCCRC) represents an important real-world colonoscopy quality indicator. Using a national database, we evaluated predictors of PCCRC in fecal immunochemical test (FIT)-positive individuals, determined the PCCRC 3-year rate (PCCRC-3y), and performed a root cause analysis (RCA). METHODS:This retrospective cohort study evaluated FIT-positive patients who underwent colonoscopy from January 2015 to July 2022. Data was collected from the Veterans Affairs (VA) national database. PCCRC was defined as CRC detected ≥6 months after colonoscopy. CRC was identified using SNOMED codes and the VA Cancer Registry. The World Endoscopy Organization methodology was used to perform the RCA and calculate the PCCRC-3y rate. RESULTS:We identified 132 PCCRCs among 52,167 FIT-positive individuals. The PCCRC-3y rate was 6.4% (95% CI, 5.0-7.7%). PCCRC locations were proximal colon (43.2%), distal colon (34.8%), and rectum (22%). Root causes were likely new CRC (17.4%), missed lesions with adequate (31.2%) or inadequate (9.8%) examination, incomplete polyp resection (22%), and detected but unresected lesions (19.7%). 16.7% of patients with PCCRC had poor bowel preparation on index colonoscopy. The cecal intubation rate was 88.6% and rectal retroflexion rate was 84.5%. In 14.4% of cases, recommended surveillance intervals did not adhere to established guidelines. Independent predictors of PCCRC were ages 70-79 (HR 7.86; 95% CI, 1.08-57.39), age ≥80 (HR 10.18; 95% CI, 1.06-97.98), tubulovillous adenoma (HR 3.98; 95% CI, 2.52-6.29), and adenoma with high-grade dysplasia (HR 10.15; 95% CI, 5.91-17.42). CONCLUSIONS:Among FIT-positive individuals, the PCCRC-3y rate was 6.4%, with missed lesions and incomplete resection as key contributors. These findings provide useful information on quality metrics in FIT-based CRC screening programs.

BACKGROUND AND AIMS/OBJECTIVE:receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In this post hoc analysis, induction and maintenance efficacy of etrasimod 2 mg vs placebo were assessed by baseline Mayo endoscopic subscore (ES) in ELEVATE UC 52 and ELEVATE UC 12. METHODS:Moderate and severe endoscopic disease were defined as a centrally-read ES of 2 and 3, respectively. Efficacy endpoints were evaluated at Weeks 12 (pooled population) and 52 (ELEVATE UC 52). Subgroup analyses were stratified by baseline modified Mayo score (4-6 vs 7-9) and prior biologic/Janus kinase inhibitor exposure. RESULTS:Overall, 235 patients with moderate and 292 with severe endoscopic disease received etrasimod; 112 and 148 patients, respectively, received placebo. At both time points, significantly greater proportions of patients receiving etrasimod compared with placebo achieved clinical remission in the moderate (Week 12: 38.3% vs 17.9%; Week 52: 36.5% vs 14.3%; both P < .001) and severe (Week 12: 18.2% vs 6.1%; Week 52: 29.4% vs 3.4%; both P < .001) endoscopic disease subgroups. Similar efficacy was observed at Weeks 12 and 52 for most endpoints. The proportion of etrasimod-treated patients with severe endoscopic disease achieving endpoints was generally numerically higher at Week 52 vs Week 12, relative to placebo. Subgroup analysis findings were generally similar. CONCLUSIONS:Etrasimod demonstrated significant induction and maintenance efficacy over placebo in both moderate and severe endoscopic disease. Response to etrasimod in patients with severe endoscopic disease may continue to improve beyond 12-week induction therapy (ClinicalTrials.gov: NCT03945188; NCT03996369).

In Escherichia coli, ribose-5-phosphate (R5P) biosynthesis occurs via two distinct pathways: an oxidative branch of the pentose phosphate pathway (PPP) originating from glucose-6-phosphate, and a reversed non-oxidative branch originating from fructose-6-phosphate, which relies on transaldolases TalA and TalB. Remarkably, we found that disrupting the oxidative PPP branch by deleting the zwf gene significantly increased bacterial susceptibility to killing by a variety of antibiotics. Surprisingly, additional mutations in the talA and talB genes further enhanced bacterial sensitivity to oxidative stress and antibiotic-mediated killing though they had little impact on the minimal inhibitory concentrations (MICs). The hypersensitivity observed in the zwf talAB mutant could be fully reversed by the processes that either utilize R5P or limited its accumulation. Specifically, activating the purine biosynthetic regulon or inhibiting nucleoside catabolism via deoB gene inactivation, which blocks the conversion of ribose-1-phosphate to R5P, restored bacterial tolerance. Furthermore, enhancing the biosynthesis of cell wall component ADP-heptose from sedoheptulose-7-phosphate suppressed antibiotic killing of the zwf talAB mutant. Biochemical analysis confirmed a direct link between elevated intracellular R5P levels and increased bacterial susceptibility to antibiotics-induced killing. These findings suggest that targeting the PPP could be a promising strategy for developing new therapeutic approaches aimed at potentiating clinically relevant antibiotics.IMPORTANCERecent studies have revealed the crucial role of bacterial cell's metabolic status in its susceptibility to the lethal action of antibacterial drugs. However, there is still no clear understanding of which key metabolic nodes are optimal targets to improve the effectiveness of bacterial infection treatment. Our study establishes that the disruption of the canonical pentose phosphate pathway induces one-way anabolic synthesis of pentose phosphates (aPPP) in E. coli cells, increasing the killing efficiency of various antibiotics. It is also demonstrated that the activation of ribose-5-phosphate utilization processes restores bacterial tolerance to antibiotics. We consider the synthesis of ribose-5-phosphate to be one of the determining factors of bacterial cell stress resistance. Understanding bacterial metabolic pathways, particularly the aPPP's role in antibiotic sensitivity, offers insights for developing novel adjuvant therapeutic strategies to enhance antibiotic potency.

Corticosteroids are one of the most frequently prescribed medications for the management of inflammatory bowel disease. While corticosteroids have a critical role for select cases for induction of remission, there is a notable risk of over-use and miss-use of corticosteroids. This narrative review updates the evolving use of corticosteroids in the management of inflammatory bowel disease. The review focuses on the appropriate use, route of administration and duration for the use of corticosteroids. Additionally, this review summarizes the side effects, use of steroids in special populations (e.g. geriatrics, pregnancy, underrepresented minorities), and their use in the peri-operative setting.

BACKGROUND AND AIMS/OBJECTIVE:Endoscopic full-thickness resection (EFTR) is an established, safe technique for the resection of appendiceal orifice (AO) neoplasms. Post-EFTR appendicitis is a recognised adverse event. There are no systematic reviews and a paucity of literature which has assessed outcomes especially with respect to delayed appendicitis, mucocele, or fistula formation. We aimed to evaluate efficacy of EFTR for AO lesions. PATIENTS AND METHODS/METHODS:Consecutive AO lesions referred for consideration of EFTR were prospectively studied. Multiple data points were recorded including technical success, EFTR histopathological data, adverse events, and follow-up surveillance data by colonoscopy. Surveillance CT was performed due to concern of potential mucocele from the obstructed remnant appendix. RESULTS:Over a 4 year period to July 2023, 37 AO lesions were referred to a tertiary center for consideration of EFTR. EFTR was attempted in 35 (95%) lesions. Most lesions were small [median size 10mm, interquartile range (IQR) 10-15mm], Paris 0-IIa morphology (n=32, 91%) with serrated histopathology (n=17, 49%). R0 resection was achieved in most EFTR cases (n=30/35, 86%). Adverse events included appendicitis (n=4, 11%) and delayed bleeding (n=2, 6%). At 6-month (IQR 4-6 months) surveillance colonoscopy, there was 1 (3%) case of residual lesion. This was successfully treated endoscopically, confirmed on a second surveillance colonoscopy. There was one case of appendicitis of the remnant at 7 months. At surveillance CT abdomen/pelvis (median 15 months, IQR 7-37 months), 2/17 (12%) fistulas were identified. Both of these patients had presumed adhesions due to abdominal surgery prior to EFTR. CONCLUSIONS:In conclusion, EFTR is an effective technique for the curative resection of select, small (<15mm) Paris 0-IIa AO lesions. Appendicitis is a relatively common adverse event but often managed conservatively. The long-term significance post-EFTR fistulas remains unclear. Caution should be exercised when considering EFTR in a patient with prior regional surgery.

Widespread hyperalgesia, characterized by pain sensitivity beyond the primary pain site, is a common yet under-characterized feature across chronic pain conditions, including chronic pancreatitis (CP). In this exploratory study, we identified a candidate neural biosignature of widespread hyperalgesia using high-density electroencephalography (EEG) in patients with chronic low back pain (cLBP). Specifically, stimulus-evoked delta, theta, and alpha oscillatory activity in the bilateral medial orbitofrontal cortex (mOFC) differentiated cLBP patients with widespread hyperalgesia from healthy controls. To examine cross-condition generalizability and advance predictive biomarker development for CP, we applied this mOFC-derived EEG biosignature to an independent cohort of patients with CP. The biosignature distinguished CP patients with widespread hyperalgesia and predicted individual treatment responses to peripherally targeted endoscopic therapy. These preliminary findings provide early support for a shared cortical signature of central sensitization across pain conditions and offer translational potential for developing EEG-based predictive tools for treatment response in CP.