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.

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.

OBJECTIVES/OBJECTIVE:Achalasia is an esophageal motility disorder that impairs quality of life and is often missed (20-50%) on endoscopy. A newly developed computer-aided detection (CAD) software has shown high accuracy for achalasia diagnosis in preclinical settings. However, its benefit in a clinical setting remains unclear. METHODS:Between February and August 2023, 83 endoscopists from 27 centers assessed 50 randomized endoscopic videos (25 achalasia, 25 nonachalasia) without and with CAD. Endoscopists assessed videos without CAD, then with CAD after 2 months. The primary end-point was improvement in sensitivity for nonexperienced endoscopists (no endoscopic experience of achalasia). Sensitivity, specificity, and accuracy with and without CAD were compared using the McNemar test. RESULTS:Sensitivity for diagnosing achalasia increased significantly with CAD, rising from 74.2% (95% confidence interval [CI] 72.2-76.0%) to 91.2% (95% CI 89.9-92.4%) for all readers, showing a difference of 17.1% (95% CI 15.1-19.0%). Specifically, sensitivity improved from 66.9% (95% CI 63.6-70.0%) to 91.9% (95% CI 89.9-93.6%) among nonexperienced endoscopists, resulting in a difference of 25.0% (95% CI 21.7-28.4%), and from 79.5% (95% CI 77.1-81.8%) to 90.8% (95% CI 89.0-92.3%) among experienced endoscopists (endoscopic experience of at least one achalasia case), with a difference of 11.3% (95% CI 8.9-13.6%). Accuracy and specificity improved significantly with CAD assistance, regardless of reader's experience. CONCLUSION/CONCLUSIONS:CAD improves achalasia detection by 17%, confirming preclinical results. The benefit was higher for nonexperienced endoscopists. CAD assistance may lead to prompt and effective treatment, minimizing the risk of false-negative diagnosis in clinical practice. TRIAL REGISTRATION/BACKGROUND:This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (https://www.umin.ac.jp/ctr/) number: UMIN000053047.

PURPOSE OF REVIEW/OBJECTIVE:Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with 44% of deaths occurring in individuals aged 75 years and older. With 78 million adults over 65 years projected by 2035, optimizing CRC screening and surveillance is crucial. This review examines guidelines, risks, and personalized approaches. RECENT FINDINGS/RESULTS:CRC screening reduces incidence by 17-33% and mortality by 11-53%. Colonoscopy lowers mortality by 61% but has a 6.8% complication rate in those aged 75 years and older. The risk of gastrointestinal bleeding is 8.7 per 1,000 for polypectomy, and perforation occurs in 0.6 per 1,000. Frailty indices assess suitability, but surveillance guidelines lack clear discontinuation criteria. Screening should balance risk, complications, and health status. It may be cost-effective up to age 86 years in healthy individuals, but more research is needed to refine surveillance strategies and reduce overtreatment in older adults.

IMPORTANCE/UNASSIGNED:Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population. OBJECTIVE/UNASSIGNED:To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection. EXPOSURES/UNASSIGNED:Participants were required to complete a screening colonoscopy after blood collection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions. RESULTS/UNASSIGNED:The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04369053.

INTRODUCTION/UNASSIGNED:In the general population, right I-sided dysplasia presents a higher risk for colorectal cancer (CRC) and metachronous dysplasia compared to left (L)-sided dysplasia. Given that patients with inflammatory bowel disease (IBD) are at higher risk for dysplasia than the general population, we sought to assess the risk factors as well as the differences in outcomes between patients with R-sided, L-sided, and both R- and L-sided dysplasia. METHODS/UNASSIGNED:A retrospective chart review was performed on patients at NYU Langone Health who had evidence of dysplasia on a colonoscopy between 2011 and 2021. Demographics and pertinent medical history were compiled. Cohorts were based on the dysplasia location (R-sided, L-sided, or R- and L-sided) and the IBD-related outcomes were analyzed. RESULTS/UNASSIGNED:= 0.03). CONCLUSIONS/UNASSIGNED:Patients with UC had a higher risk for L-sided colonic dysplasia compared to patients with CD; however, there were no differences in the progression of dysplasia between those who had R-sided and those who had L-sided dysplasia. Larger studies are needed to assess the risk factors and outcomes related to the laterality of dysplasia and further validate these findings among patients with IBD.