Association of blood group O with a recurrent risk for acute lower gastrointestinal bleeding from a multicenter cohort study.

The relationship between blood group and rebleeding in acute lower gastrointestinal bleeding (ALGIB) remains unclear. This study aimed to investigate the association between blood group O and clinical outcomes in patients with ALGIB. The study included 2336 patients with ALGIB whose bleeding source was identified during initial endoscopy (from the CODE BLUE-J Study). The assessed outcomes encompassed rebleeding and other clinical parameters. The rebleeding rates within 30 days in patients with blood group O and those without blood group O were 17.9% and 14.9%, respectively. Similarly, the rates within 1 year were 21.9% for patients with blood group O and 18.2% for those without blood group O. In a multivariate analysis using age, sex, vital signs at presentation, blood test findings, comorbidities, antithrombotic medication, active bleeding, and type of endoscopic treatment as covariates, patients with blood group O exhibited significantly higher risks for rebleeding within 30 days (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.04-1.65; P = 0.024) and 1 year (OR 1.29; 95% CI 1.04-1.61; P = 0.020) compared to those without blood group O. However, the thrombosis and mortality rates did not differ significantly between blood group O and non-O patients. In patients with ALGIB, blood group O has been identified as an independent risk factor for both short- and long-term rebleeding.

A novel prediction tool for mortality in patients with acute lower gastrointestinal bleeding requiring emergency hospitalization: a large multicenter study.

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation.

Ustekinumab Decreases Circulating Th17 Cells in Ulcerative Colitis.

Objective T helper (Th) cells play a central role in the pathogenesis of ulcerative colitis (UC). The present study analyzed the changes in circulating T cells by administration of ustekinumab (UST), an interleukin-12/23p40 antibody. Methods CD4 T cells were isolated from peripheral blood at 0 and 8 weeks after UST treatment, and we analyzed the proportion of CD4 T cells by flow cytometry. Clinical information and laboratory data were obtained at 0, 8, and 16 weeks. Patients We evaluated 13 patients with UC who received UST for the induction of remission between July 2020 and August 2021. Results The median partial Mayo score improved from 4 (1-7) to 0 (0-6) (p<0.001) with UST. Among serological parameters, albumin concentrations, C-reactive protein concentrations, the sedimentation rate, and leucine-rich alpha 2 glycoprotein concentrations showed significant improvement with UST. A flow cytometric analysis of circulating CD4 T cells showed that the percentage of Th17 cells was significantly decreased by UST treatment in all patients (1.85% to 0.98%, p<0.0001). Th1 cells were significantly increased by UST treatment (9.52% to 10.4%, p<0.05), but Th2 and regulatory T cells were not significantly different. The high-Th17 subgroup had a significantly better partial Mayo score than the low-Th17 subgroup at 16 weeks after UST treatment (0 vs. 1, p=0.028). Conclusion Treatment with UST decreases circulating Th17 cells, suggesting that this change may be related to the anti-inflammatory effect of UC.

Characteristics, outcomes, and risk factors of surgery for acute lower gastrointestinal bleeding: nationwide cohort study of 10,342 hematochezia cases.

BACKGROUND: Current evidence on the surgical rate, indication, procedure, risk factors, mortality, and postoperative rebleeding for acute lower gastrointestinal bleeding (ALGIB) is limited. METHODS: We constructed a retrospective cohort of 10,342 patients admitted for acute hematochezia at 49 hospitals (CODE BLUE J-Study) and evaluated clinical data on the surgeries performed. RESULTS: Surgery was performed in 1.3% (136/10342) of the cohort with high rates of colonoscopy (87.7%) and endoscopic hemostasis (26.7%). Indications for surgery included colonic diverticular bleeding (24%), colorectal cancer (22%), and small bowel bleeding (16%). Sixty-four percent of surgeries were for hemostasis for severe refractory bleeding. Postoperative rebleeding rates were 22% in patients with presumptive or obscure preoperative identification of the bleeding source and 12% in those with definitive identification. Thirty-day mortality rates were 1.5% and 0.8% in patients with and without surgery, respectively. Multivariate analysis showed that surgery-related risk factors were transfusion need ≥ 6 units (P < 0.001), in-hospital rebleeding (P < 0.001), small bowel bleeding (P < 0.001), colorectal cancer (P < 0.001), and hemorrhoids (P < 0.001). Endoscopic hemostasis was negatively associated with surgery (P = 0.003). For small bowel bleeding, the surgery rate was significantly lower in patients with endoscopic hemostasis as 2% compared to 12% without endoscopic hemostasis. CONCLUSIONS: Our cohort study elucidated the outcomes and risks of the surgery. Extensive exploration including the small bowel to identify the source of bleeding and endoscopic hemostasis may reduce unnecessary surgery and improve the management of ALGIB.

Disease Flares Following COVID-19 Vaccination in Patients with Inflammatory Bowel Disease.

Objective Flares of inflammatory bowel disease (IBD) can occur infrequently after vaccination for coronavirus disease 2019 (COVID-19), although the details of this phenomenon are poorly understood. To clarify the possibility of an unfavorable response in patients with IBD, we investigated IBD-related symptoms during the COVID-19 vaccination. Methods Between October 2021 and February 2022, we obtained the COVID-19 vaccination status of 411 IBD patients who were being treated at our institution. The disease course of IBD after vaccination was investigated in 188 patients with ulcerative colitis (UC) and 119 patients with Crohn's disease (CD) who had received at least one dose of the vaccine during the clinical remission phase. The baseline characteristics before vaccination were compared between the patients with UC with or without disease flares. Results During the 30-day follow-up period, eight patients with UC (4.3%) and one patient with CD (0.8%) experienced disease flares following vaccination. Disease flares occurred after the first vaccination in six patients and after the second vaccination in three patients. As for the timing of onset of disease flares, eight events (88.9%) occurred within one week of vaccination. Two patients required hospitalization, and one patient with CD required surgery for an intra-abdominal abscess. The baseline characteristics did not significantly differ between patients with UC who experienced flares and those who did not. Conclusion IBD flares following COVID-19 vaccination are rare and vaccination should therefore be recommended for patients with IBD. However, the possibility of disease flares should be considered for approximately one week after each vaccination, especially in patients with UC.

Early feeding reduces length of hospital stay in patients with acute lower gastrointestinal bleeding: A large multicentre cohort study.

AIM: No studies have compared the clinical outcomes of early and delayed feeding in patients with acute lower gastrointestinal bleeding (ALGIB). This study aimed to evaluate the benefits and risks of early feeding in a nationwide cohort of patients with ALGIB in whom haemostasis was achieved. METHODS: We reviewed data for 5910 patients with ALGIB in whom haemostasis was achieved and feeding was resumed within 3 days after colonoscopy at 49 hospitals across Japan (CODE BLUE-J Study). Patients were divided into an early feeding group (≤1 day, n = 3324) and a delayed feeding group (2-3 days, n = 2586). Clinical outcomes were compared between the groups by propensity matching analysis of 1508 pairs. RESULTS: There was no significant difference between the early and delayed feeding groups in the rebleeding rate within 7 days after colonoscopy (9.4% vs. 8.0%; p = 0.196) or in the rebleeding rate within 30 days (11.4% vs. 11.5%; p = 0.909). There was also no significant between-group difference in the need for interventional radiology or surgery or in mortality. However, the median length of hospital stay after colonoscopy was significantly shorter in the early feeding group (5 vs. 7 days; p < 0.001). These results were unchanged when subgroups of presumptive and definitive colonic diverticular bleeding were compared. CONCLUSION: The findings of this nationwide study suggest that early feeding after haemostasis can shorten the hospital stay in patients with ALGIB without increasing the risk of rebleeding.

Weekend Effect on Clinical Outcomes of Acute Lower Gastrointestinal Bleeding: A Large Multicenter Cohort Study in Japan.

INTRODUCTION: Weekend admissions showed increased mortality in several medical conditions. This study aimed to examine the weekend effect on acute lower gastrointestinal bleeding (ALGIB) and its mortality and other outcomes. METHODS: This retrospective cohort study (CODE BLUE-J Study) was conducted at 49 Japanese hospitals between January 2010 and December 2019. In total, 8,120 outpatients with acute hematochezia were enrolled and divided into weekend admissions and weekday admissions groups. Multiple imputation (MI) was used to handle missing values, followed by propensity score matching (PSM) to compare outcomes. The primary outcome was mortality; the secondary outcomes were rebleeding, length of stay (LOS), blood transfusion, thromboembolism, endoscopic treatment, the need for interventional radiology, and the need for surgery. Colonoscopy and computed tomography (CT) management were also evaluated. RESULTS: Before PSM, there was no significant difference in mortality (1.3% vs. 0.9%, p = 0.133) between weekend and weekday admissions. After PSM with MI, 1,976 cases were matched for each admission. Mortality was not significantly different for weekend admissions compared with weekday admissions (odds ratio [OR] 1.437, 95% confidence interval [CI] 0.785-2.630; p = 0.340). No significant difference was found with other secondary outcomes in weekend admissions except for blood transfusion (OR 1.239, 95% CI 1.084-1.417; p = 0.006). Weekend admission had a negative effect on early colonoscopy (OR 0.536, 95% CI 0.471-0.609; p < 0.001). Meanwhile, urgent CT remained significantly higher in weekend admissions (OR 1.466, 95% CI 1.295-1.660; p < 0.001). CONCLUSION: Weekend admissions decrease early colonoscopy and increase urgent CT but do not affect mortality or other outcomes except transfusion.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding - A Multicenter Nationwide Study.

INTRODUCTION: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). METHODS: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. RESULTS: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. CONCLUSIONS: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Ferroptosis in the colon epithelial cells as a therapeutic target for ulcerative colitis.

BACKGROUND: Ferroptosis, a type of programmed cell death triggered by oxidative stress, was suspected to play a role in ulcerative colitis. Indigo naturalis is highly effective against ulcerative colitis, but its mechanism is unclear. This study found that indigo naturalis treatment suppressed ferroptosis. METHODS: We analyzed 770 mRNA expressions of patients with ulcerative colitis. Suppression of ferroptosis by indigo naturalis treatment was shown using a cell death assay. Malondialdehyde levels and reactive oxygen species were analyzed in CaCo-2 cells treated with indigo naturalis. Glutathione metabolism was shown by metabolomic analysis. Extraction of the ingredients indigo naturalis from the rectal mucosa was performed using liquid chromatograph-mass spectrometry. RESULTS: Gene expression profiling showed that indigo naturalis treatment increased antioxidant genes in the mucosa of patients with ulcerative colitis. In vitro analysis showed that nuclear factor erythroid-2-related factor 2-related antioxidant gene expression was upregulated by indigo naturalis. Indigo naturalis treatment rendered cells resistant to ferroptosis. Metabolomic analysis suggested that an increase in reduced glutathione by indigo naturalis. The protein expression of CYP1A1 and GPX4 was increased in the rectum by treatment with indigo naturalis. The main ingredients of indigo naturalis, indirubin and indigo inhibited ferroptosis. Indirubin was detected in the rectal mucosa of patients with ulcerative colitis who were treated with indigo naturalis. CONCLUSIONS: Suppression of ferroptosis by indigo naturalis in the intestinal epithelium could be therapeutic target for ulcerative colitis. The main active ingredient of indigo naturalis may be indirubin.

Multicenter propensity score-matched analysis comparing short versus long cap-assisted colonoscopy for acute hematochezia.

Background and Aim: While short and long attachment caps are available for colonoscopy, it is unclear which type is more appropriate for stigmata of recent hemorrhage (SRH) identification in acute hematochezia. This study aimed to compare the performance of short versus long caps in acute hematochezia diagnoses and outcomes. Methods: We selected 6460 patients who underwent colonoscopy with attachment caps from 10 342 acute hematochezia cases in the CODE BLUE-J study. We performed propensity score matching (PSM) to balance baseline characteristics between short and long cap users. Then, the proportion of definitive or presumptive bleeding etiologies found on the initial colonoscopy and SRH identification rates were compared. We also evaluated rates of blood transfusions, interventional radiology, or surgery, as well as the rate of rebleeding and mortality within 30 days after the initial colonoscopy. Results: A total of 3098 patients with acute hematochezia (1549 short cap and 1549 long cap users) were selected for PSM. The rate of colonic diverticular bleeding (CDB) diagnosis was significantly higher in long cap users (P = 0.006). While the two groups had similar rates of the other bleeding etiologies, the frequency of unknown etiologies was significantly lower in long cap users (P < 0.001). The rate of SRH with active bleeding was significantly higher in long cap users (P < 0.001). Other clinical outcomes did not differ significantly. Conclusion: Compared to that with short caps, long cap-assisted colonoscopy is superior for the diagnosis of acute hematochezia, especially CDB, and the identification of active bleeding.

Long-term Risks of Recurrence After Hospital Discharge for Acute Lower Gastrointestinal Bleeding: A Large Nationwide Cohort Study.

BACKGROUND & AIMS: Currently, large, nationwide, long-term follow-up data on acute lower gastrointestinal bleeding (ALGIB) are scarce. We investigated long-term risks of recurrence after hospital discharge for ALGIB using a large multicenter dataset. METHODS: We retrospectively analyzed 5048 patients who were urgently hospitalized for ALGIB at 49 hospitals across Japan (CODE BLUE-J study). Risk factors for the long-term recurrence of ALGIB were analyzed by using competing risk analysis, treating death without rebleeding as a competing risk. RESULTS: Rebleeding occurred in 1304 patients (25.8%) during a mean follow-up period of 31 months. The cumulative incidences of rebleeding at 1 and 5 years were 15.1% and 25.1%, respectively. The mortality risk was significantly higher in patients with out-of-hospital rebleeding episodes than in those without (hazard ratio, 1.42). Of the 30 factors, multivariate analysis showed that shock index ≥1 (subdistribution hazard ratio [SHR], 1.25), blood transfusion (SHR, 1.26), in-hospital rebleeding (SHR, 1.26), colonic diverticular bleeding (SHR, 2.38), and thienopyridine use (SHR, 1.24) were significantly associated with increased rebleeding risk. Multivariate analysis of colonic diverticular bleeding patients showed that blood transfusion (SHR, 1.20), in-hospital rebleeding (SHR, 1.30), and thienopyridine use (SHR, 1.32) were significantly associated with increased rebleeding risk, whereas endoscopic hemostasis (SHR, 0.83) significantly decreased the risk. CONCLUSIONS: These large, nationwide follow-up data highlighted the importance of endoscopic diagnosis and treatment during hospitalization and the assessment of the need for ongoing thienopyridine use to reduce the risk of out-of-hospital rebleeding. This information also aids in the identification of patients at high risk of rebleeding.

Continuous use of antithrombotic medications during peri-endoscopic submucosal dissection period for colorectal lesions: A propensity score matched study.

BACKGROUND AND AIM: The aim of this study was to elucidate the continuous use of antithrombotic medications during the peri-colorectal endoscopic submucosal dissection (ESD) period. METHODS: This study included 468 patients with colorectal epithelial neoplasms treated by ESD, consisting of 82 under antithrombotic medications and 386 patients without the medications. Among patients taking antithrombotic medications, antithrombotic agents were continued during the peri-ESD period. Clinical characteristics and adverse events were compared after propensity score matching. RESULTS: Before and after propensity score matching, post-colorectal ESD bleeding rate was higher in patients continuing antithrombotic medications (19.5% and 21.6%, respectively) than in those not taking antithrombotic medications (2.9% and 5.4%, respectively). In the Cox regression analysis, continuation of antithrombotic medications was associated with post-ESD bleeding risk (hazard ratio, 3.73; 95% confidence interval, 1.2-11.6; P < 0.05) compared with patients without antithrombotic therapy. All patients who experienced post-ESD bleeding were successfully treated by endoscopic hemostasis procedure or conservative therapy. CONCLUSIONS: Continuation of antithrombotic medications during the peri-colorectal ESD period increases the risk of bleeding. However, the continuation may be acceptable under careful monitoring for post-ESD bleeding.

Outcomes and recurrent bleeding risks of detachable snare and band ligation for colonic diverticular bleeding: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: Ligation therapy, including endoscopic detachable snare ligation (EDSL) and endoscopic band ligation (EBL), has emerged as an endoscopic treatment for colonic diverticular bleeding (CDB); its comparative effectiveness and risk of recurrent bleeding remain unclear, however. Our goal was to compare the outcomes of EDSL and EBL in treating CDB and identify risk factors for recurrent bleeding after ligation therapy. METHODS: We reviewed data of 518 patients with CDB who underwent EDSL (n = 77) or EBL (n = 441) in a multicenter cohort study named the Colonic Diverticular Bleeding Leaders Update Evidence From Multicenter Japanese Study (CODE BLUE-J Study). Outcomes were compared by using propensity score matching. Logistic and Cox regression analyses were performed for recurrent bleeding risk, and a competing risk analysis was used to treat death without recurrent bleeding as a competing risk. RESULTS: No significant differences were found between the 2 groups in terms of initial hemostasis, 30-day recurrent bleeding, interventional radiology or surgery requirements, 30-day mortality, blood transfusion volume, length of hospital stay, and adverse events. Sigmoid colon involvement was an independent risk factor for 30-day recurrent bleeding (odds ratio, 1.87; 95% confidence interval, 1.02-3.40; P = .042). History of acute lower GI bleeding (ALGIB) was a significant long-term recurrent bleeding risk factor on Cox regression analysis. A performance status score of 3/4 and history of ALGIB were long-term recurrent bleeding factors on competing risk regression analysis. CONCLUSIONS: There were no significant differences in outcomes between EDSL and EBL for CDB. After ligation therapy, careful follow-up is required, especially in the treatment of sigmoid diverticular bleeding during admission. History of ALGIB and performance status at admission are important risk factors for long-term recurrent bleeding after discharge.

Nationwide cohort study identifies clinical outcomes of angioectasia in patients with acute hematochezia.

BACKGROUND: While angioectasia is an important cause of acute hematochezia, relevant clinical features remain unclear. This study aims to reveal risk factors, clinical outcomes, and the effectiveness of therapeutic endoscopy for patients with acute hematochezia due to angioectasia. METHODS: This retrospective cohort study was conducted at 49 Japanese hospitals between January 2010 and December 2019, enrolling patients hospitalized for acute hematochezia (CODE BLUE-J study). Baseline factors and clinical outcomes for angioectasia were analyzed. RESULTS: Among 10,342 patients with acute hematochezia, 129 patients (1.2%) were diagnosed with angioectasia by colonoscopy. The following factors were significantly associated with angioectasia: chronic kidney disease, liver disease, female, body mass index < 25, and anticoagulant use. Patients with angioectasia were at a significant increased risk of blood transfusions compared to those without angioectasia (odds ratio [OR] 2.61; 95% confidence interval [CI] 1.69-4.02). Among patients with angioectasia, 36 patients (28%) experienced rebleeding during 1-year follow-up. The 1-year cumulative rebleeding rates were 37.0% in the endoscopic clipping group, 14.3% in the coagulation group, and 32.8% in the conservative management group. Compared to conservative management, coagulation therapy significantly reduced rebleeding risk (P = 0.038), while clipping did not (P = 0.81). Multivariate analysis showed coagulation therapy was an independent factor for reducing rebleeding risk (hazard ratio [HR] 0.40; 95% CI 0.16-0.96). CONCLUSIONS: Our data showed patients with angioectasia had a greater comorbidity burden and needed more blood transfusions in comparison with those without angioectasia. To reduce rebleeding risk, coagulation therapy can be superior for controlling hematochezia secondary to angioectasia.

Timing of colonoscopy in acute lower GI bleeding: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: We aimed to determine the optimal timing of colonoscopy and factors that benefit patients who undergo early colonoscopy for acute lower GI bleeding. METHODS: We identified 10,342 patients with acute hematochezia (CODE BLUE-J study) admitted to 49 hospitals in Japan. Of these, 6270 patients who underwent a colonoscopy within 120 hours were included in this study. The inverse probability of treatment weighting method was used to adjust for baseline characteristics among early (≤24 hours, n = 4133), elective (24-48 hours, n = 1137), and late (48-120 hours, n = 1000) colonoscopy. The average treatment effect was evaluated for outcomes. The primary outcome was 30-day rebleeding rate. RESULTS: The early group had a significantly higher rate of stigmata of recent hemorrhage (SRH) identification and a shorter length of stay than the elective and late groups. However, the 30-day rebleeding rate was significantly higher in the early group than in the elective and late groups. Interventional radiology (IVR) or surgery requirement and 30-day mortality did not significantly differ among groups. The interaction with heterogeneity of effects was observed between early and late colonoscopy and shock index (shock index <1, odds ratio [OR], 2.097; shock index ≥1, OR, 1.095; P for interaction = .038) and performance status (0-2, OR, 2.481; ≥3, OR, .458; P for interaction = .022) for 30-day rebleeding. Early colonoscopy had a significantly lower IVR or surgery requirement in the shock index ≥1 cohort (OR, .267; 95% confidence interval, .099-.721) compared with late colonoscopy. CONCLUSIONS: Early colonoscopy increased the rate of SRH identification and shortened the length of stay but involved an increased risk of rebleeding and did not improve mortality and IVR or surgery requirement. Early colonoscopy particularly benefited patients with a shock index ≥1 or performance status ≥3 at presentation.

[A case of chronic enteropathy associated with SLCO2A1 gene diagnosed by capsule endoscopy and successfully treated by ferric carboxymaltose].

Chronic non-specific multiple ulcers of the small intestine is a disease condition postulated in Japan. It is an uncommon gastrointestinal disease that causes chronic anemia and hypoalbuminemia by causing numerous ulcers without any histopathologically identifiable features. In recent years, it has been revealed that the mutations of SLCO2A1, which codes the prostaglandin transporter protein, are the cause of this disease;it is called the new name "chronic enteropathy associated with SLCO2A1 gene." The ileum, except the terminal ileum, is the most common place making it difficult to identify major lesions. Other than conservative treatments, such as nutrition therapy and iron supplements, no effective treatment has been identified so far. We present a case of chronic non-specific multiple ulcers of the small intestine diagnosed by capsule endoscopy and effectively treated by ferric carboxymaltose. A 48-year-old female had chronic iron deficiency anemia since around the age of 15. Because of severe anemia, the patient had upper and lower endoscopy at the age of 47 to find the source of the bleeding, but it was not detected. Except for the terminal ileum, the capsule endoscopy revealed ring-like ulcers, tape-like ulcers, and oblique ulcer scars in the ileum. Genetic analysis showed a homozygous mutation in intron 7, c.940+1G>A, indicating a definitive diagnosis of non-specific multiple ulcers of the small intestine. Anemia and anemia-related symptoms such as general malaise persisted despite continuous oral administration of iron drugs. Three intravenous injections of ferric carboxymaltose increased hemoglobin and enhanced the symptoms.

One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study.

BACKGROUND/AIMS: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC. METHODS: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences. RESULTS: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment. CONCLUSIONS: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.

The Compositional Structure of the Small Intestinal Microbial Community via Balloon-Assisted Enteroscopy.

INTRODUCTION: An association has been found between human-gut microbiota and various diseases (e.g., metabolic disease) by analyzing fecal or colonic microbiota. Despite the importance of the small intestinal microbiota, sampling difficulties prevent its full analysis. We investigated the composition and metagenomic functions of microbiota along the small intestine and compared them with the microbiota from feces and from other gastrointestinal (GI) sites. METHODS: Mucosal samples from the six GI sites (stomach, duodenum, distal jejunum, proximal ileum, terminal ileum, and rectum) were collected under balloon-assisted enteroscopy. Fecal samples were collected from all participants. The microbial structures and metagenomic functions of the small intestinal mucosal microbiota were compared with those from feces and other GI sites using 16S ribosomal RNA gene sequencing. RESULTS: We analyzed 133 samples from 29 participants. Microbial beta diversity analysis showed that the jejunum and ileum differed significantly from the lower GI tract and the feces (p < 0.001). Jejunal and duodenal microbiotas formed similar clusters. Wide clusters spanning the upper and lower GI tracts were observed with the ileal microbiota, which differed significantly from the jejunal microbiota (p < 0.001). Veillonella and Streptococcus were abundant in the jejunum but less so in the lower GI tract and feces. The metagenomic functions associated with nutrient metabolism differed significantly between the small intestine and the feces. CONCLUSIONS: The fact that the compositional structures of small intestinal microbiota differed from those of fecal and other GI microbiotas reveals that analyzing the small intestinal microbiota is necessary for association studies on metabolic diseases and gut microbiota.

Endoscopic direct clipping versus indirect clipping for colonic diverticular bleeding: A large multicenter cohort study.

BACKGROUND: Direct and indirect clipping treatments are used worldwide to treat colonic diverticular bleeding (CDB), but their effectiveness has not been examined in multicenter studies with more than 100 cases. OBJECTIVE: We sought to determine the short- and long-term effectiveness of direct versus indirect clipping for CDB in a nationwide cohort. METHODS: We studied 1041 patients with CDB who underwent direct clipping (n = 360) or indirect clipping (n = 681) at 49 hospitals across Japan (CODE BLUE-J Study). RESULTS: Multivariate analysis adjusted for age, sex, and important confounding factors revealed that, compared with indirect clipping, direct clipping was independently associated with reduced risk of early rebleeding (<30 days; adjusted odds ratio [AOR] 0.592, p = 0.002), late rebleeding (<1 year; AOR 0.707, p = 0.018), and blood transfusion requirement (AOR 0.741, p = 0.047). No significant difference in initial hemostasis rates was observed between the two groups. Propensity-score matching to balance baseline characteristics also showed significant reductions in the early and late rebleeding rates with direct clipping. In subgroup analysis, direct clipping was associated with significantly lower rates of early and late rebleeding and blood transfusion need in cases of stigmata of recent hemorrhage with non-active bleeding on colonoscopy, right-sided diverticula, and early colonoscopy, but not with active bleeding on colonoscopy, left-sided diverticula, or elective colonoscopy. CONCLUSIONS: Our large nationwide study highlights the use of direct clipping for CDB treatment whenever possible. Differences in bleeding pattern and colonic location can also be considered when deciding which clipping options to use.