Introduction: Achieving both endoscopic and histological remission in ulcerative colitis (UC) is associated with improved clinical outcomes. There is a growing need for noninvasive methods to assess both remission states. This study investigates the utility of serum leucine-rich alpha-2 glycoprotein (LRG) as a biomarker for monitoring endoscopic and histological remission in patients with UC. Methods: Patients with UC who underwent colonoscopy from July 2020 to September 2021 at multiple centers in Japan were included to compare the accuracy of C-reactive protein (CRP) and LRG in detecting endoscopic and histological remission. Receiver operating characteristic curve analyses were performed and area under the curve (AUC) values were compared. Results: A total of 412 patients were identified. The median values of CRP and LRG were 0.07 mg/dL and 12.2 μg/mL, respectively. Endoscopic remission, as defined as Mayo endoscopic sub-score of 0 or 1, was observed in 188 patients, and histological remission, as defined as Geboes score <3.1, was observed in 156 patients. The AUC values for CRP and LRG for detecting endoscopic remission were 0.68 and 0.76, respectively, and the AUC values for CRP and LRG for detecting histological remission were 0.70 and 0.76, respectively. In both cases, the AUC for LRG was significantly higher than that of CRP (p < 0.0001). The optimal cutoff value of LRG for detecting histological remission was 13.4 μg/mL, with a sensitivity of 82% and a specificity of 58%. Conclusion: LRG is superior to CRP in detecting both endoscopic and histological remission in patients with UC.

ObjectivesWe aimed to identify independent factors for intraoperative endoscopic lens cloudiness during gastric and colorectal endoscopic submucosal dissections, investigate the effectiveness of Cleastay, an endoscope anti-fog solution, and examine factors associated with severe submucosal fat deposition.MethodsA total of 220 patients who underwent gastric or colorectal endoscopic submucosal dissections in two institutions between January 2022 and October 2023 were included. Significant factors related to cloudiness were determined using univariate and multivariate analyses. Patient background and tumor characteristics related to severe submucosal fat deposition were investigated, and the degree of intraoperative endoscopic lens cloudiness and outcomes were compared between the Cleash and Cleastay groups.ResultsIn the multivariate analysis, factors increasing lens cloudiness included long procedure time (odds ratio [OR], 17.51; 95% confidence interval [CI], 1.52-202.08), stomach (vs. colon; OR, 5.08; 95% CI, 1.99-12.96), and severe submucosal fat deposition (OR, 12.19; 95% CI, 5.02-29.60). Conversely, the use of Cleastay (vs. Cleash; OR, 0.066; 95% CI, 0.021-0.21) was identified as a factor reducing cloudiness. Location analysis revealed that severe submucosal fat deposition was more common in the upper stomach and right colon.ConclusionsIt was suggested that Cleastay is more useful for endoscopic submucosal dissection of the upper stomach and right colon, where severe submucosal fat deposition is expected.

BACKGROUND:Food-Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE-mediated food allergy that causes gastrointestinal symptoms, though its anatomical origin and pathogenesis remain unclear. Abdominal distention is common in adult FPIES, but symptoms vary among patients. This study aimed to establish objective criteria for assessing abdominal distention and to clarify the pathophysiology and anatomical origin of FPIES. METHODS:This study targeted 26 adult FPIES patients. Abdominal distention was broken down into eight factors, and an evaluation algorithm was developed based on items with high positivity rates. Clinical characteristics, blood, and imaging analyses were performed before and after OFC (oral food challenge) to investigate the pathophysiology. RESULTS:Among 14 adult FPIES patients who underwent OFC, seven showed positive results. The latency period was 1.5 h, with the most frequent symptoms being abdominal distention (100%), abdominal pain, and nausea (71.4%). All patients received treatment with intravenous extracellular fluid infusion and ondansetron, which resulted in reduced symptom duration. In an evaluation of blood test data, there were no specific serological markers of FPIES, except in the severe case. Image analysis with computed tomography revealed significant dilation and edema of the small intestine during the FPIES event, suggesting that dilation of the small intestine is associated with adult FPIES. CONCLUSION:These results are expected to aid in the early and appropriate diagnosis of FPIES based on medical interviews, blood test data, and imaging findings when adult patients present to medical institutions with severe acute gastroenteritis symptoms.

AIM:C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC).METHODS:A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score.RESULTS:Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin-bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313-5.107; log-rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin-bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively.CONCLUSIONS:CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy.

BACKGROUND:Adult food-protein-induced enterocolitis syndrome (FPIES) has recently been recognized, and there are no international diagnostic criteria for this disease. Differentiating adult FPIES from immediate-type food allergy reactions and providing specific treatment for each in an emergency are important, but methods have not been developed. OBJECTIVE:To develop a diagnostic scoring system for adult FPIES by comparing it with an immediate-type food allergy (IgE-mediated food allergy [IgE-FA]). METHODS:This retrospective cohort study of food-avoidant adults based on diagnostic criteria for adult FPIES was conducted through telephone interviews. We compared the clinical profiles of the patients with FPIES and IgE-FA. Adult FPIES-associated factors were extracted using multivariate analysis, and a diagnostic scoring system was developed based on odds ratios. RESULTS:A total of 48 (16.7%) of 288 adults with food allergies were diagnosed with FPIES; of these, 240 (83.3%) had IgE-FA. Seafood was the most common cause of FPIES in adults (68.8%). Multivariate analysis identified an age of onset older than 26 years, more than 10 episodes, a longer latency period, cold sweat, abdominal distention, and vomiting as adult FPIES-associated factors. An adult FPIES diagnostic scoring system was developed using odds ratios with a high area under the curve (0.978), 100% sensitivity, and 87.0% specificity. CONCLUSION:Clinical profiles and an adult FPIES diagnostic scoring system were developed for the first time. This scoring system can be useful in differentiating adult FPIES and IgE-FA when treating food-related acute reactions.

Eosinophilic gastritis (EoG) is a chronic inflammatory disease of the stomach. Patients with the persistent form, which accounts for 65% of patients, rarely have spontaneous remission and have a decline in quality of life (Yamamoto et al, JACIP2022). Reports about transcriptomic analysis of EoG include Caldwell et al. (JACI 2014) and Shoda et al. (JACIP 2017), but more in-depth analysis of the specificity of the syndrome is needed, as well as examinations of changes due to diet and other treatments.

AIM:Portal vein thrombosis (PVT) is one of the common complications of liver cirrhosis. Although anticoagulation contributes to thrombus resolution and is considered the first-choice treatment, its impact on patients' prognosis is still controversial. This study aimed to clarify the benefit of anticoagulation on mortality, liver function, and the incidence of liver cirrhosis-related complications in cirrhotic PVT patients.METHODS:We conducted a multicenter retrospective review in which we included 78 eligible patients with PVT out of 439. After propensity score matching, 21 cirrhotic PVT patients were included in each one of the untreated control and anticoagulation groups.RESULTS:Overall survival was significantly improved in the anticoagulation group compared with the control group (p = 0.041), along with PVT size reduction (53.3% vs. 108.2%, p = 0.009). At the time of CT follow-up, the anticoagulation group showed a lower ALBI score (p = 0.037) and its prevalence of massive ascites was significantly lower (p = 0.043) compared with the control group. The incidence of overt encephalopathy was also lower in the anticoagulation group (p = 0.041). The cumulative incidence of bleeding events did not differ significantly between the two groups.CONCLUSIONS:Anticoagulation improves the survival of patients with cirrhotic PVT. Preserved liver function and reduced risks of cirrhosis-related complications under the treatment may have contributed to a better prognosis. Given its efficacy and safety, anticoagulation is worth initiating in patients with PVT.

CRISPR-mediated mutagenesis of TP53 in HCT-116 cells

Eosinophilic enteritis (EoN) is associated with an eosinophilic infiltrate confined to the small intestine, but treatment options other than diet and corticosteroid therapy are scarce. There is only one report of the use of dupilumab for eosinophilic gastrointestinal disease, involving three pediatric patients. We report a case of successful induction of remission with dupilumab in a 53 year-old female patient with steroid-dependent EoN. The patient presented to the emergency room with uncontrollable abdominal pain and CT revealed a thickened ileal wall and small amount of ascites. Despite no abnormalities on endoscopy, histological examination revealed numerous eosinophilic infiltrates (> 100/HPF) and degranulation in the ileal lamina propria, diagnosing the patient with EoN. The patient achieved clinical remission with prednisolone, but EoN relapsed during tapering. Long-term steroid therapy was inappropriate due to mandibular osteomyelitis and osteoporosis, and she was switched to 9 mg budesonide, an intestine-soluble topical steroid without effect. Dupilumab administration resulted in resolution of abdominal pain, and remission was maintained after discontinuation of budesonide. Histological remission was confirmed 2 months after dupilumab administration. This is the first report of remission induced and maintained with dupilumab in an adult patient with EoN.

Background: Adults with food-protein-induced enterocolitis syndrome (FPIES) often develop severe abdominal symptoms after eating seafood. However, no investigation of a food elimination strategy for adult FPIES patients has been performed to date. Methods: We conducted a retrospective cohort study of seafood-avoidant adults by telephone interview, based on the diagnostic criteria for adult FPIES reported by Gonzalez et al. We compared the clinical profiles, abdominal symptoms, and causative seafoods between FPIES and immediate-type food allergy (IgE-mediated FA) patients. We also profiled the detailed intake-status of seafoods in adult FPIES patients. Results: Twenty-two (18.8 %) of 117 adults with seafood-allergy were diagnosed with FPIES. Compared with the IgE-mediated FA patients, FPIES patients had an older age of onset, more pre-existing gastrointestinal and atopic diseases, more episodes, longer latency and duration of symptoms, more nausea, abdominal distention, and severe abdominal pain, and more frequent vomiting and diarrhea. In particular, abdominal distention-reflecting intestinal edema and luminal fluid retention-may be the most distinctive characteristic symptom in adult FPIES (p < 0.001). Bivalves, especially oysters, were the most common cause of FPIES. Strikingly, intake-status profiling revealed that many FPIES patients can safely ingest an average of 92.6 % of seafood species other than the causative species. Conclusions: There are many differentiators between FPIES and IgE-mediated FA, which may reflect differences in the underlying immunological mechanisms. Although seafood FPIES is unlikely to induce tolerance, many patients can ingest a wide variety of seafood species after a long period from onset. (c) 2023 Japanese Society of Allergology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Food protein-induced enterocolitis syndrome (FPIES) is increasingly found in adults. FPIES requires different treatment from immediate-type food allergy (FA) in emergency medicine. However, no comparison of the clinical presentations of these diseases has been reported.Objective: To compare the clinical presentations and causative crustaceans of adult FPIES and FA using a standardized questionnaire and to thereby lay the groundwork for establishing an algorithm that distinguishes those diseases.Methods: We conducted a retrospective cohort study of crustacean-avoidant adults by telephone interview based on the previously reported diagnostic criteria for adult FPIES to compare the clinical features and crustacean intake status between FPIES and FA.Results: Of 73 adult patients with crustacean allergy, 8 (11%) were diagnosed with having FPIES and 53 (73%) FA. Compared with the patients with FA, those with FPIES had a longer latency period (P < .01), more episodes (P = .02), longer duration of symptoms (P = .04), more frequent abdominal distention (P = .02), and severe colic pain (P =.02). Half of the patients with FPIES experienced fear of death during an episode. Panulirus japonicus (Japanese spiny lobster) and Homarus weber (lobster) were significantly common FPIES-causing foods. A statistically significant 62.5% of patients with FPIES were able to ingest some type of crustacean.Conclusion: FPIES and FA can be clearly differentiated by the abdominal symptoms, latency period, and duration of episodes. Furthermore, some patients with FPIES do not necessarily need to avoid all crustaceans. Our findings lay the groundwork for establishing an algorithm that distinguishes FPIES from FA in adults.(c) 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Gastrointestinal involvement is a rare manifestation of systemic amyloidosis, and few reports have been published on localized amyloidosis of the colon. Only one case report has been published on the long-term prognosis of localized colorectal amyloidosis, and there are no previous reports on localized colorectal ATTR amyloidosis. Here, we report an 80-year-old male with localized colorectal wild-type ATTR amyloidosis who presented with edematous mucosa with vascular changes throughout the colon. He did not exhibit any symptoms or endoscopic exacerbation for 8 years after diagnosis. However, after 8 years, he developed early stage colorectal cancer and cytomegalovirus-associated ulcer. He was treated with endoscopic submucosal dissection, which was relatively challenging due to his hemorrhagic condition and poor elevation of the submucosa caused by amyloid deposits. Since the tumor was completely resected, he will undergo regular follow-up. Our review of 20 previous cases of localized colorectal amyloidosis revealed its clinical features and long-term prognosis. Specifically, ours is the second case of a diffuse pan-colon type of colorectal localized amyloidosis, which may lead to various complications, such as colorectal cancer, over a long period of time, and thus, regular follow-up is necessary.

BACKGROUND AND AIMS:Ulcerative colitis [UC] is a chronic inflammatory disease of the colon with frequent relapses. Telomere shortening in intestinal epithelial cells has been reported in severe or longstanding cases. However, its influence on UC pathogenesis remains unelucidated. To this end, we evaluated telomere shortening using a long-term organoid inflammation model that we had originally established.METHODS:A UC model using human colon organoids was established to assess telomere changes chronologically. MST-312 was used for the telomerase inhibition assay. The potential of telomerase activators as a novel UC treatment was evaluated with an in vitro model, including microarray analysis, and histological changes were assessed using xenotransplantation into mouse colonic mucosa.RESULTS:Our UC model reproduced telomere shortening in vitro, which was induced by the continuous suppression of telomerase activity via P53. MST-312-based analysis revealed that telomere shortening was involved in the pathogenesis of UC. Madecassoside [MD] improved the telomere length of the UC model and UC patient-derived organoids, which further promoted cell proliferation in vitro and improved the graft take-rate of xenotransplantation. Moreover, histological analysis revealed that MD induced normal crypt structure with abundant goblet cells.CONCLUSIONS:This study is the first to reveal the mechanism and importance of telomere shortening in the pathogenesis of UC. MD could be a novel candidate for UC treatment beyond endoscopic mucosal healing.