Masayuki Saruta’s research while affiliated with Jikei University School of Medicine and other places

Disruption of intestinal epithelial integrity and increased permeability is central to the pathogenesis of ulcerative colitis (UC). In this study, we identified 3-aminobenzoic acid (3-ABA), a dietary component abundant in azuki beans, soybeans and chickpeas as a regulator of epithelial permeability and inflammation in the colon. Screening 119 gut microbial metabolites revealed the ability of 4-ABA, a structural isomer of 3-ABA, to enhance barrier function in Caco2 cells. Further analysis of structural isomers identified 3-ABA as the most effective, significantly increasing transepithelial electrical resistance and reducing epithelial permeability. Using liquid chromatography-mass spectrometry, 3-ABA was detected in dietary beans and human fecal samples. Fecal 3-ABA levels were significantly lower in UC patients compared to healthy individuals. Metagenomic and functional prediction analyses revealed dysbiosis in UC patients, characterized by an enrichment of bacterial genes involved in ABA degradation. Gene expression analysis of 3-ABA-stimulated Caco2 cells demonstrated upregulation of tight junction molecules, such as CLDN1 and TJP1, enhancing epithelial barrier integrity. In a dextran sodium sulfate-induced colitis mouse model, rectal 3-ABA administration ameliorated colitis by enhancing epithelial barrier function and reducing inflammation. These findings highlight 3-ABA’s potential as a dietary therapeutic agent for UC, offering a novel strategy to enhance intestinal integrity and mitigate inflammation.

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Endoscopic ultrasound-guided pelvic abscess drainage (EUS-PAD) has emerged as a viable alternative to percutaneous drainage (PCD). However, reports of this method are limited to procedures associated with transrectal access. We herein present the first case of successful transvaginal EUS-PAD in a 22-year-old female who developed a pelvic abscess after undergoing a cesarean section. An ultrasound endoscope was inserted transvaginally to visualize the abscess. Puncture and dilation were performed and a 7 Fr endoscopic nasobiliary drainage (ENBD) tube was put in place. The patient showed a rapid improvement after the procedure and was discharged without any complications. This case report highlights the efficacy and safety of transvaginal EUS-PAD as a viable option for performing pelvic abscess drainage.

Background The global QUASAR studies demonstrated efficacy and safety of guselkumab (GUS), a dual-acting interleukin-23p19 subunit inhibitor, as induction and maintenance therapy in participants (pts) with moderately to severely active ulcerative colitis (UC).1-3 We report a subgroup analysis in East Asian pts. Methods The QUASAR Ph 2b/3 clinical development programme for GUS in UC (NCT04033445) included adults with moderately to severely active UC (induction baseline modified Mayo score ≥5 to ≤9) with inadequate response/intolerance to conventional and/or advanced UC therapy. Two placebo (PBO)-controlled, 12-week studies evaluated intravenous (IV) GUS induction therapy: a Phase (Ph) 2b dose-ranging study (GUS 200 mg or 400 mg every 4 weeks [q4w]) and a Ph3 confirmatory study (GUS 200 mg q4w) (Figure 1). Pts from either study who were in clinical response at induction Week (W) 12 were re-randomised (1:1:1) at start of the maintenance study to subcutaneous (SC) GUS 200 mg q4w, GUS 100 mg q8w, or PBO. Primary endpoints were clinical response (Ph2b) or clinical remission (Ph3) at induction W12 and clinical remission at maintenance W44. This subgroup analysis included pts from QUASAR study sites located in East Asia (China, Japan, Korea, and Taiwan). Results This analysis included 71 (Ph2b: China, n=11; Japan, n=36; Korea, n=18; Taiwan, n=6) and 135 (Ph3: China, n=61; Japan, n=58; Korea, n=13; Taiwan, n=3) East Asian pts from the induction studies and 106 East Asian pts (China, n=34; Japan, n=52; Korea, n=13; Taiwan, n=7) who responded to IV GUS induction and participated in the maintenance study. At induction W12, higher proportions of pts in the IV GUS cohorts achieved clinical response and clinical remission relative to PBO pts (Figure 2A). At maintenance W44, higher proportions of pts achieved clinical remission and other meaningful clinical, patient-reported outcome, and endoscopic endpoints, including endoscopic normalisation, with both SC GUS maintenance dose regimens compared with PBO (Figure 2B). Safety results were consistent with the overall population. Frequencies of pts with treatment-emergent adverse events (TEAEs) were generally consistent with rates reported in the overall global population in the maintenance study through W44. No cases of death, active tuberculosis, opportunistic infections, or anaphylactic or serum sickness-like reactions were reported. Conclusion Efficacy of GUS as IV induction and SC maintenance therapy in the subgroup of East Asian pts from QUASAR was consistent with that observed in the global study population. The safety profile of GUS was also favourable and consistent with previous reports. This study was supported by Janssen Scientific Affairs, LLC. References 1.Peyrin-Biroulet L, Allegretti JR, Rubin DT, et al. Gastroenterology. 2023;165(6):1443-1457. 2.Allegretti JR, Peyrin-Biroulet L, Feagan BG, et al. Gastroenterology. 2023;164(6):S-1572. 3.Rubin DT, Allegretti JR, Panés J, et al. Gastroenterology. 2024;166(5 Suppl.): S-180.

Background Data from the real-world GALOCEAN study showed that ~70% of patients have moderately active Ulcerative Colitis (UC).1 A post hoc analysis of the SELECTION study (NCT02914522) found that patients with moderately active UC were more likely to have sustained responses to filgotinib (FIL) than those with severely active UC.2 We report outcomes for patients with moderate (MOD) versus severe (SEV) UC by Mayo endoscopic subscores (ES) in a post hoc analysis of SELECTION. Methods In the phase 2b/3, double-blind, placebo-controlled SELECTION study, 659 patients (18–75 years old) with moderately to severely active UC were randomized (2:2:1) at week 0 (W0) to daily oral FIL 200 mg (FIL200) or 100 mg, or placebo (PBO) for 11 weeks in Induction Study A (biologic [bio]-naive) or B (bio-experienced [bio-exp]).3 Patients with a clinical response at week 10 (W10) were re-randomized (2:1) to FIL or PBO maintenance treatment until week 58 (W58). MOD vs SEV active UC subgroups were defined as a Mayo ES of 2 or 3, respectively. Proportions of patients achieving efficacy endpoints (see Figure footnotes) were compared between subgroups for FIL200 and PBO. Results At W0, mean Mayo Clinic Scores (SD) for MOD versus SEV in bio-naive were 7.8 (1.1) versus 9.2 (1.1); for bio-exp, 7.9 (1.3) versus 9.6 (1.2). The proportion of patients with CRP ≥3mg/L was lower for MOD versus SEV (41% [46/112] vs 66% [88/133]). In the bio-naive, MOD subgroup, fewer patients had UC duration ≥7 years versus the SEV subgroup (35% vs 44%); the bio-exp MOD subgroup had a greater proportion of females versus the SEV subgroup (64% vs 37%). At W10 and W58, significantly greater achievement rates were observed for patients taking FIL200 versus PBO for most outcomes in both UC activity subgroups (greater for MOD than SEV), and for bio-naive and bio-exp patients (Figures 1 and 2). Achievement rates at W10 were greatest for FIL200-treated, bio-naive MOD patients (e.g. ES response for MOD vs SEV: 46% vs 24%). By W58, differences between severity subgroups were less pronounced in bio-naive patients (e.g. ES response: 59% vs 46%); differences between bio-exp subgroups were maintained. Conclusion These data show that patients with moderate or severe UC treated with FIL200 have improvements in efficacy outcomes and quality of life versus PBO; W10 outcomes were generally more favourable and sustained for the MOD subgroup, especially in bio-naive patients. Between-subgroup differences for bio-naive patients became less pronounced over time because response rates increased in the SEV subgroup up to W58. Analyses of the response dynamics for patients with moderate and severe UC activity by ES (and other definitions of UC severity) are ongoing. References 1.Löwenberg M et al. United European Gastroenterol J 2024;12 Suppl 2:406–7. 2.Schreiber S et al. United European Gastroenterol J 2024; doi:10.1002/ueg2.12686. 3.Feagan BG et al. Lancet 2021;397:2372–84.

Frailty and fractures are closely associated with adverse clinical outcomes. This retrospective study investigated the prognostic impact of frailty, prevalent fractures, and the coexistence of both in patients with cirrhosis. Frailty was defined according to the Fried frailty phenotype criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Prevalent fractures were assessed using questionnaires and lateral thoracolumbar spine radiographs. Cumulative survival rates were compared between the frailty and non-frailty groups, fracture and non-fracture groups, and all four groups stratified by the presence or absence of frailty and/or prevalent fractures. Among 189 patients with cirrhosis, 70 (37.0%) and 74 (39.2%) had frailty and prevalent fractures, respectively. The median observation period was 64.4 (38.6–71.7) months, during which 50 (26.5%) liver disease-related deaths occurred. Multivariate analysis identified frailty and prevalent fractures as significant independent prognostic factors in the overall cohort (p < 0.001 and p = 0.003, respectively). The cumulative survival rates were lower in the frailty or fracture groups than in the non-frailty or non-fracture groups, respectively, in the overall cohort and in patients with compensated and decompensated cirrhosis. Patients with both frailty and prevalent fractures showed the lowest cumulative survival rates, whereas those without these comorbidities showed the highest cumulative survival rates among the four stratified groups. Frailty and prevalent fractures were independently associated with mortality in patients with cirrhosis. Additionally, the coexistence of both comorbidities worsened the prognosis.