Mohamed, Islam

Background: Liver transplantation (LT) remains the definitive treatment for end-stage liver disease; however, post-LT outcomes may differ depending on underlying disease etiology. Our study aimed to compare post-LT outcomes between alcoholic and non-alcoholic steatohepatitis (NASH)-related liver transplant recipients in the United States. Methods: A retrospective cohort study was conducted using the TriNetX Research Network. Adult liver transplant recipients (≥18 years) were categorized into two mutually exclusive cohorts: alcoholic liver disease and NASH-related liver disease. Propensity score matching (1:1) was performed to balance baseline characteristics. Clinical outcomes were assessed. Comparative analyses included risk ratios, risk differences, odds ratios, Kaplan–Meier survival analysis, and hazard ratios with log-rank testing. Results: Compared with NASH recipients, alcoholic LT recipients had a significantly higher risk of rejection (14.5% vs. 12.1%; RR 1.195, 95% CI 1.076–1.327; p = 0.001) and hepatic encephalopathy (14.3% vs. 8.3%; RR 1.720, 95% CI 1.526–1.938; p < 0.001). Acute kidney injury was also more frequent in the alcoholic cohort (47.3% vs. 43.6%; RR 1.084, 95% CI 1.036–1.133; p < 0.001). In contrast, sepsis (15.6% vs. 18.0%; RR 0.869, 95% CI 0.794–0.952; p = 0.003) and CKD (46.1% vs. 51.1%; RR 0.901, 95% CI 0.863–0.939; p < 0.001) occurred less frequently in alcoholic LT patients. No significant differences were observed for liver transplant failure or ascites. Kaplan–Meier analyses demonstrated significantly lower rejection-free survival (HR 1.241, p < 0.001), higher hepatic encephalopathy (HR 1.808, p < 0.001), increased AKI risk (HR 1.150, p < 0.001) and higher all-cause mortality in the alcoholic cohort (HR 1.106, p = 0.031). Conclusions: In this large real-world matched cohort study, alcoholic LT recipients demonstrated higher risks of complications and all-cause mortality compared with NASH LT recipients.

Antibody–drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring.

Abstract Background We aimed to describe the real-world durability of clinical and endoscopic outcomes of upadacitinib (UPA) in ulcerative colitis (UC). Methods We retrospectively analyzed an ongoing multi-center cohort of UC patients(pts) in the United States who were started on UPA for active disease. Primary outcome was clinical remission at 1yr assessed by partial Mayo score(pMS)(resolution of all UC related symptoms and physician global assessment). Secondary outcomes assessed at various timepoints, including after re-escalation, included clinical response(&gt;50%reduction in symptoms utilizing the pMS), endoscopic response (Mayo endoscopic score≤1or absence of erosions/ulcerations) and histological remission(defined as normal or chronic inactive). Durable secondary outcomes achieved at both 6months and at 1yr and beyond were also assessed. Descriptive statistics were performed. Adverse events(AEs) investigated included cardiovascular events and herpes zoster (HZ). Results 416pts were included(Table 1) with median values for age at initiation of36.00yrs(range27-48), disease duration7.00yrs(range3-14)and follow-up 993days(IQR,672-1103), with206(49.52%)with follow-up at 1yr or beyond. Of these, 66.1%had extensive colitis. Induction duration was8wks in 86.5%and16wks in 4.8 %(20/416). Most received an induction dose of45mg(97.1%)and maintenance dose of30mg(85.8%). Among the evaluable population at1yr and beyond, 62.5%(45/80)were in clinical remission, 75.9%(22/29)in endoscopic response with58.6%(17/29) in remission and66.6%(20/30)in histological remission. At 6months, clinical remission was51.6%(42/93), endoscopic response was 75%(24/32) of which43.75%(14/32)were in remission and histologic remission was seen in 40.8%(20/49).Durable secondary outcomes of clinical remission were seen in 71.4%(30/42), endoscopic improvement in 45.8%(11/24), and histologic remission in35%(7/20). Re-escalation to 45mg occurred in 35pts, of which48.6%(17/35)were re-escalated due to incomplete induction clinical response with all achieving response(11 in remission). The rest(18/35)were re-escalated for clinical relapse after initial remission where72.2%(13/18)were able to recapture remission. After re-escalation,54.3%(19/35)continued on 45mg daily. AEs were reported in12.7%with HZ in 7pts(2.1%). One pt aged53yrs had an episode of TIA after 1yr on UPA at 15mg, without pre-existing cardiovascular risk factors and UPA use is ongoing at the same dose. There were no reported episodes of worsening of pre-existing cardiovascular disease or DVT/PE. Conclusion UPA is durably effective and safe in a real-world clinical setting with re-escalation to 45mg capturing response in a majority of the pts. Ongoing recruitment will provide further evidence on long term effectiveness and safety. Conflict of interest: Ms. Huang, Katherine: No conflict of interest Chandnani, Arun: No conflict of interest Samaan, Sami: None Tan, Tingyi: I have no conflict of interests to declare. Ramesh, Prajith Raj: None Conlon, Caroline: No conflict of interest Klein, Jeremy: None Reddy, Nikhil: No conflict of interest Ayoub, Malek: None Cervantes Limon, Gabriela: none Myers, Melissa: None Bucaram, Martha: No conflict of interest Lieto, Stephen: No conflict of interest Scalzo, Nicholas: No conflict of interest Cohen, Benjamin: Abbvie - consulting and speaking ALPCO - consulting J & J Innovative Medicine - consulting Takeda - consulting and speaking Emmes Biopharma Services LLC - DSMB Pfizer - consulting Mohamed, Islam: nothing to declare Ciorba, Matthew: Advisory Board: Janssen, AbbVie, Pfizer, Geneoscopy Consulting: Janssen, AbbVie, Pfizer, Geneoscopy Grant contracts: Janssen, Pfizer, Incyte Shukla, Richa: Speakers bureau - Abbvie and Lilly Wright, Michael: None Xu, An Tao: No conflict of interest Chowla, Navreet: No conflict of interest Ogholikhan, Sina: Abbvie Medical Director Kujawski, Michelle: Abbvie Scientific Director Dulaney, David: Speaker bureau - Regeneron Speaker bureau - Sanofi Speaker bureau - Takeda Speaker bureau - Eli Lilly Fenster, Marc: none Benson, Caroline: No conflict of interest Alhobayb, Tamara: No conflict of interest Berinstein, Jeffrey: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.

Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC). Study Question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC? Data Sources: MEDLINE, Embase, Scopus, and Cochrane databases. Study Design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis. Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66–2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39–2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34–2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53–2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60–2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11–2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86–1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86–0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36–0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)]. Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy with the ability to induce weight loss, improve insulin sensitivity and reduce hepatic steatosis. We aim to compare the efficacy of different IF regimens for MASLD management. A systematic review and network meta-analysis of randomized controlled trials investigating different IF regimens for MASLD. PubMed, EMBASE, WOS, SCOPUS and Cochrane Central Register of Controlled Trials were searched until 10 April 2023. Analysis was performed using R software with the meta and netmeta packages. Mean difference (MD) was used to pool continuous outcomes with 95% confidence intervals (CIs). Our meta-analysis was registered in PROSPERO (CRD42023418467). Our meta-analysis included eight randomized controlled trials with a total of 635 participants. The 5 : 2 diet significantly improved liver stiffness (MD, −0.32; 95% CI, −0.55 to −0.09; P < 0.01). Time-restricted feeding significantly improved liver steatosis (controlled attenuation parameter score) (MD, −39.83; 95% CI, −64.78 to −14.87; P < 0.01). No significant changes were observed in asparate aminotransferase, gamma-glutamyl transpeptidase, low-density lipoproteins cholesterol, total cholesterol, triglyceride levels, basal metabolic index, blood pressure, Homeostatic Model Assessment of Insulin Resistance, fasting blood sugar, lean body mass or waist circumference across all IF regimens. However, alternate-day fasting showed positive results in anthropometric measures, including significant improvements in lean body mass, waist circumference, fat mass and weight reduction (P < 0.05). IF regimens showed various positive effects on clinical outcomes in MASLD patients; however, these effects were not consistent. Therefore, a patient-tailored IF regimen should be considered.