Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

BACKGROUND AND AIMS: While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. METHODS: This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. RESULTS: We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. CONCLUSIONS: Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

Multicenter prospective registration study of efficacy and safety of capsule endoscopy in Crohn's disease in Japan (SPREAD-J study).

BACKGROUND: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn's disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. METHODS: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. RESULTS: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with 'confirmed CD'. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. CONCLUSION: SBCE is practical and safe in patients with CD.

Positioning and Usefulness of Biomarkers in Inflammatory Bowel Disease.

BACKGROUND: Mucosal healing (MH) was proposed to be an ideal treatment goal for patients with inflammatory bowel disease (IBD). Instead of endoscopy to confirm MH, biomarkers are frequently used and have become an indispensable modality for the clinical examination of patients with IBD. SUMMARY: Common biomarkers of IBD include C-reactive protein (CRP), erythrocyte sedimentation rate, antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, leucine-rich α2 glycoprotein, fecal calprotectin (FCP), and the fecal immunochemical test. Biomarkers play five major roles in the management of IBD: (1) diagnosing and distinguishing between IBD and non-IBD or ulcerative colitis and Crohn's disease; (2) predicting treatment response, especially before administrating biologics; (3) monitoring and grasping endoscopic or histological disease activity; (4) replacing endoscopy for diagnosing MH, including endoscopic and histological remission; and (5) predicting recurrence before disease activity appears through symptoms. Many reports have demonstrated the usefulness of CRP and FCP for those five roles; however, they have limitations for diagnosing MH or predicting treatment response. In general, FCP has better ability in those positions than CRP; additionally, leucine-rich α2 glycoprotein can diagnose endoscopic disease activity better than CRP. The novel biomarker, prostaglandin E-major urinary metabolite, and anti-αvß6 antibody are expected to be noninvasive and reliable biomarkers; however, more evidence is required for future studies. Oncostatin M and microRNA are also prospects, in addition to other familiar and novel biomarkers. KEY MESSAGES: Each biomarker has a useful feature; therefore, we should consider their features and use appropriate biomarkers for the five roles to enable noninvasive and smooth management of IBD.

Bowel frequency (night) and urgent defecation are improved by budesonide foam in patients with ulcerative colitis: a retrospective observational study.

INTRODUCTION: Patients with ulcerative colitis (UC) are known to have a significantly poor quality of life due to bowel frequency (night) and urgent defecation. Budesonide foam is a topical medication that was approved in Japan in 2017 for the treatment of UC. However, its efficacy in the treatment of bowel frequency (night) or urgent defecation is unknown. This study aimed to explore the efficacy of budesonide foam for the alleviation of these symptoms. METHODS: UC patients who received budesonide foam between December 2017 and January 2020 at the Jikei University School of Medicine in Tokyo were enrolled. The simple clinical colitis activity index (SCCAI) was evaluated at the start of budesonide foam treatment and 2 and 6 weeks later in patients who initially scored ≥ 1 for bowel frequency (night) and urgent defecation, respectively. We also studied the effect of budesonide foam on remaining symptoms in patients who had used 5-aminosalicylic acid (5-ASA) topical treatment, those with SCCAI ≥ 3, and those in remission with residual symptoms (SCCAI 1 or 2). RESULTS: Of the 233 enrolled patients, 102 were eligible for the study. In 36 patients with bowel frequency (night) treated with budesonide foam were significantly effective, score in SCCAI decreased from 1.17 ± 0.45 at baseline to 0.53 ± 0.61 at week 2 (p < 0.0001) and 0.17 ± 0.38 at week 6 (p < 0.0001). In 45 patients with urgent defecation score in SCCAI decreased significantly from 1.33 ± 0.52 at baseline to 0.44 ± 0.59 at week 2 (p < 0.0001) and 0.22 ± 0.40 at week 6 (p < 0.0001). Of 22 patients who switched from topical 5-ASA administration to budesonide foam, nine at week 2 (41%) and 11 (50%) at week 6 were improved with no symptoms, and there were no cases of worsened symptoms. No severe side effects associated with budesonide foam were observed. CONCLUSION: Budesonide foam administration significantly improves both bowel frequency (night) and urgent defecation-related UC activity and is also effective for the patients who were refractory to topical 5-ASA administration.

Prostaglandin E-major urinary metabolite diagnoses mucosal healing in patients with ulcerative colitis in remission phase.

BACKGROUND AND AIM: Ulcerative colitis (UC) is usually detected by clinical symptoms, such as bleeding and diarrhea; however, it is rather difficult to assess during asymptomatic clinical remission (CR). Hence, there is a need for a biomarker that can reliably detect UC during remission. We previously reported on the utility of the prostaglandin E-major urinary metabolite (PGE-MUM) as a biomarker reflecting UC activity. In this study, we evaluated the effectiveness of the PGE-MUM in the diagnosis of endoscopic, histological, and histo-endoscopic mucosal remission of UC, comparing with fecal tests. METHODS: This prospective study was conducted at the Jikei University Hospital between August 2017 and January 2021. Patients with UC in CR scheduled to undergo colonoscopy were included. The association between the PGE-MUM with endoscopic remission (ER), histological remission (HR), and complete mucosal healing (CMH, defined as histo-endoscopic remission) was analyzed. We also compared the area under the curve (AUC) for the receiver operating characteristic curves between PGE-MUM, fecal calprotectin (FC), and fecal immunochemical test (FIT). RESULTS: In total, 128 patients were analyzed. PGE-MUM differed significantly in ER versus non-ER (14.5 vs 16.7, P = 0.028), HR versus non-HR (14.2 vs 17.4, P = 0.004), and CMH versus non-CMH (14.3 vs 16.7, P = 0.021). There were no significant differences between the AUCs for PGE-MUM, FC, and FIT for ER, HR, or CMH. CONCLUSIONS: The PGE-MUM can determine CMH in UC even during CR, regardless of the disease phenotype, indicating its clinical benefit for non-invasive monitoring.

Characteristics and Endoscopic Classification of Ulcerative Lesions Affecting the Ileocecal Valve.

OBJECTIVES: The aim of this study was to propose an endoscopic classification system for ulcerative lesions on the ileocecal valve and investigate its relevance to the underlying etiology. METHODS: Among the 60,325 patients who underwent colonoscopy at our hospital from January 2006 to December 2018, patients with ulcerative lesions on the ileocecal valve were included. The following data were obtained using the hospital's medical records: sex, age, clinical diagnosis, laboratory data, and endoscopic and histological findings. Patients who have ulcerative colitis and who were not evaluated by histological examination were excluded. Ulcerative lesions on the ileocecal valve were classified into 3 groups according to their endoscopic appearance: small shallow ulcerative lesions without edematous change (group A), lateral spreading shallow ulcerative lesions with edematous change (group B), and deep deformed ulcerative lesions (group C). The association between this endoscopic classification and its clinical diagnosis, clinical course, and the interobserver reliability were evaluated. RESULTS: Of 72 patients who were eligible for analysis, 18 were assigned to group A, 9 to group B, and 45 to group C. Infectious enteritis was mainly assigned to group A (group A, 12; group B, none; and group C, 6; p < 0.0001), inflammatory bowel disease was mainly assigned to group C (group A, none; group B, 5; and group C, 35; p < 0.0001), and malignant tumor was assigned to group C only. Interobserver reliability was extremely high among the 3 examining doctors (kappa value 0.7-0.8). CONCLUSION: Endoscopic classification was divided into 3 groups for ulcerative lesions on the ileocecal valve, and this system could be beneficial for presuming their clinical diagnoses.

Need to Inspect the Total Gastrointestinal Tract of Patients With Malignant Lymphomas.

BACKGROUND/AIM: Malignant lymphoma (ML) cases with overlapping gastrointestinal (GI) lesions are often encountered. We aimed to elucidate the importance of examining the GI tract in patients with ML and assess the overlap rate. PATIENTS AND METHODS: We analysed 190 patients diagnosed with GI MLs. We compared the overlap rates among the different histopathological types. RESULTS: Twenty-five (13.2%) patients had overlapping GI lesions in more than two segments. The overlap rates were 100% in mantle cell lymphomas (MCL), 27.6% in follicular lymphomas (FL), and 16.3% in diffuse large B-cell lymphomas (DLBCL). MCL, FL, and DLBCL cases showed significantly higher overlap rates than mucosa-associated lymphoid tissue lymphoma cases (p<0.01). About 64.0% of cases of ML with overlapping lesions involved the small intestine. CONCLUSION: In GI ML cases, it is ideal to examine the entire GI tract by esophagogastroduodenoscopy, colonoscopy, and capsule endoscopy and/or balloon-assisted endoscopy, especially in MCL, FL, and DLBCL.

Small Neuroendocrine Tumors of the Whole Gastrointestinal Tract Performed Endoscopic or Surgical Resections Also Show Positive for Lymphovascular Invasion.

BACKGROUND AND AIMS: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. METHODS: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. RESULTS: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases <5 mm, with a lymphovascular invasion rate of 8.7% for those 5-10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. CONCLUSIONS: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

Correction to: Management of elderly ulcerative colitis in Japan.

Management of elderly ulcerative colitis in Japan.

Chronic intestinal pseudo-obstruction with pneumatosis cystoides intestinalis in a patient with systemic sclerosis: A case report.

RATIONALE: Chronic intestinal pseudo-obstruction (CIPO) and pneumatosis cystoides intestinalis (PCI) are rare abdominal diseases and the pathological mechanisms have not been fully elucidated. Systemic sclerosis (SSc), which is characterized by the progressive sclerotic changes of skin and internal organs, is a refractory collagen disease and is frequently associated with digestive disorders including CIPO. PATIENT CONCERNS: A 68-year-old woman who has been well managed for SSc over the long term, who presented with abdominal fullness for the first time. DIAGNOSES: Abdominal X-ray and computed tomography (CT) images showed PCI with pneumoperitoneum findings. Based on the diagnosis of CIPO, we evaluated the intestinal peristalsis of the patient by using cine magnetic resonance imaging (MRI). INTERVENTIONS: Oral medications of 15 g/d of Daikenchuto, 750 mg/d of Metronidazole and Sodium Picosulfate were started for improving the bowel peristaltic movement and decreasing intestinal gas production. OUTCOMES: A great improvement of CIPO and PCI by multidrug therapy without any surgical treatments for such an unusual case. LESSONS: This case indicates that SSc can be accompanied with not only CIPO but also PCI as digestive disorders and that cine MRI, which is a definitely beneficial imaging modality, can intelligibly visualize the peristalsis of the intestines and lead to successful medical control by noninvasive treatment.

Management of elderly ulcerative colitis in Japan.

Japan has the largest aging society, where many elderly people have intractable diseases including ulcerative colitis (UC). Along with the increasing total number of UC patients, the number of elderly UC patients has also been increasing and will continue to do so in the future. Although the clinical features and natural history of UC in the elderly have many similarities with UC in the non-elderly population, age-specific concerns including comorbidities, immunological dysfunction, and polypharmacy make the diagnosis and management of elderly UC challenging compared to UC in non-elderly patients. Based on increasing data related to elderly UC patients from Japan, as well as other countries, we reviewed the epidemiology, clinical course, differential diagnosis, management of comorbidities, surveillance, medical therapy, and surgery of UC in the elderly.

Next endoscopic approach for acute lower gastrointestinal bleeding without an identified source on colonoscopy: upper or capsule endoscopy?

Background and study aims We evaluated the utility of esophagogastroduodenoscopy (EGD) or capsule endoscopy (CE) as the next diagnostic approach after negative colonoscopy (CS) results in acute-onset hematochezia. Patients and methods We retrospectively analyzed 401 patients emergently hospitalized for acute hematochezia who underwent CS within 48 hours of arriving at two large emergency hospitals and in whom a definitive bleeding source was not identified. The positive endoscopic findings, requirement for additional therapeutic procedures, and 30-day rebleeding rates were compared among three strategies: EGD following CS (CS-EGD), CE following CS (CS-CE), and CS alone. Predictors of positive endoscopic findings in the CS-EGD strategy were determined. Results The rates of positive endoscopic findings and requirement for additional therapeutic procedures were 22 % and 16 %, respectively, in CS-EGD and 50 % and 28 % in CS-CE. The 30-day rebleeding rate did not significantly decrease in CS-EGD (8 %) or CS-CE (11 %) compared with CS alone (12 %). The rate of additional endoscopic therapies was lower in patients with a colonic diverticulum than in those without (CS-EGD: 3 % vs. 33 %, P  = 0.007; CS-CE: 11 % vs. 44 %, P  = 0.147). A history of syncope, low blood pressure, blood urea nitrogen/creatinine ratio of ≥ 30, and low albumin level significantly predicted EGD findings after negative CS results ( P  < 0.05). Conclusions When the definitive bleeding source is not identified by colonoscopy in patients with acute hematochezia, adjunctive endoscopy helps to identify the etiology and enables subsequent therapy, especially for patients without a colonic diverticulum. Upper gastrointestinal endoscopy is indicated for severe bleeding; other patients may be candidates for capsule endoscopy.

Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy.

BACKGROUND: There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. AIM: To identify the SNP that is most significantly involved with NSAID-induced enteropathy. METHODS: One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. RESULTS: After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10-7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p < 1 × 10-6). CONCLUSION: The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936).

Repeatability of small bowel transit time in capsule endoscopy in healthy subjects.

BACKGROUND: There are no reports to prove the repeatability of gastric transit time (GTT) and small bowel transit time (SBTT) in capsule endoscopy (CE). OBJECTIVE: To clarify the repeatability and factors that affect GTT/SBTT in CE. METHODS: We analyzed the data of 150 healthy subjects from our previous randomized controlled trial that compared small intestinal injuries between two 14-day treatment groups: 1) celecoxib and 2) loxoprofen + lansoprazole. Correlation of GTT/SBTT with pre- and post-treatment CE was analyzed. In addition, the associations of pre-treatment CE SBTT with physical factors, post-treatment CE SBTT and the presence of small intestinal mucosal injuries were analyzed. RESULTS: Analyses of 148 subjects pre-treatment CE and 146 subjects post-treatment CE were performed. There were no significant differences between mean GTT and SBTT before and after treatment. Both GTT (𝜌 = 0.22, p < 0.01) and SBTT (𝜌 = 0.47, p < 0.0001) showed positive correlations between pre- and post-treatment CE. In pre-treatment CE, physical factors and the presence of small intestinal mucosal injury had no associations with SBTT. CONCLUSIONS: Moderate correlation in SBTT and slight correlation in GTT were shown on repeated CE. The factors affecting SBTT were not clarified in this analysis.

Long-term recurrent bleeding risk after endoscopic therapy for definitive colonic diverticular bleeding: band ligation versus clipping.

BACKGROUND AND AIMS: Very few prospective studies with over 100 samples have evaluated the long-term outcomes of endoscopic therapy for colonic diverticular bleeding (CDB). This study sought to elucidate the recurrent bleeding risk of endoscopic band ligation versus clipping for definitive CDB based on stigmata of recent hemorrhage (SRH). METHODS: Patients emergently hospitalized for acute lower GI bleeding and examined by high-resolution colonoscopy were enrolled. Better visualization of SRH from a diverticulum was obtained using a water-jet device. Endoscopic band ligation or clipping was performed as first-line treatment, and patients were prospectively followed after discharge. RESULTS: No statistical difference was found between the ligation (n = 61) and clipping (n = 47) groups in baseline characteristics or follow-up period. The probability of 1-year recurrent bleeding was 11.5% in the ligation group versus 37.0% in the clipping group (P = .018). No patients required surgery or experienced perforation. One patient in the ligation group experienced diverticulitis the next day. In patients with recurrent bleeding within 7 days, the recurrent bleeding site was the same diverticulum, and ulceration was found in the ligation group on repeat colonoscopy. In patients with recurrent bleeding after 2 months, repeat colonoscopy identified that the recurrent bleeding site was different, and scar formation was seen in the ligation group. The left side of the colon was an independent predictor for recurrent bleeding in the ligation group but not in the clipping group. CONCLUSIONS: Band ligation for definitive CDB has better outcomes than clipping during long-term follow-up after endoscopic therapy, probably because of complete elimination of the diverticulum. CDB can recur at the same diverticulum in the short term but at a different diverticulum in the long term.

Contrast-enhanced CT for Colonic Diverticular Bleeding before Colonoscopy: A Prospective Multicenter Study.

Purpose To demonstrate the usefulness of precolonoscopy intravenous contrast material-enhanced CT for colonic diverticular bleeding (CDB). Materials and Methods A prospective, multicenter, observational study was performed. Patients with acute-onset hematochezia who were admitted to hospital were included, and those without CDB were excluded. CT was performed before colonoscopy. A Mann-Whitney U test, χ2 test, and multivariable logistic regression analysis were performed to determine the accuracy of CT before colonoscopy. Results A total of 442 patients (mean age, 71.2 years; 302 male patients; 68.3% men) were included between January 2014 and December 2015, and 202 patients were diagnosed as having CDB. The positive extravasation rate during CT was 50 of 202 (24.7%) among all patients and five of nine (55.6%) among patients who underwent CT within 1 hour of the last hematochezia. At multivariable analysis, the interval from the last hematochezia until CT was a predictor of extravasation (beta coefficient, -.0038 ± 0.0014 [standard deviation]). Extravasation at CT had a sensitivity of 38 of 66 (57.6%; 95% confidence interval: 44.8%, 69.7%) and a specificity of 124 of 136 (91.2%; 95% confidence interval: 85.1%, 95.4%) for the prediction of stigmata of recent hemorrhage of diverticula during colonoscopy. The sensitivity was higher in patients who underwent CT examination within 4 hours of hematochezia, compared with those examined after 4 hours (64.7% [33 of 51] vs 33.3% [five of 15]; P < .01). Conclusion Extravasation findings for CT with intravenous contrast material had high specificity for the prediction of stigmata of recent hemorrhage of diverticula during colonoscopy, regardless of the timing of the CT examination. Although the sensitivity was relatively low, it was higher when the CT examination was performed within 4 hours after the last hematochezia. Therefore, urgent precolonoscopy CT may contribute to decision making regarding whether an urgent colonoscopy should be performed.

New predictive model for acute gastrointestinal bleeding in patients taking oral anticoagulants: A cohort study.

BACKGROUND AND AIM: The study developed a predictive model of long-term gastrointestinal (GI) bleeding risk in patients receiving oral anticoagulants and compared it with the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, Drugs/alcohol concomitantly) score. METHODS: The study periodically followed a cohort of 508 patients taking oral anticoagulants (66 direct oral anticoagulants users and 442 warfarin users). Absence of GI bleeding at an initial examination and any subsequent GI bleeding were confirmed endoscopically. The bleeding model was developed by multivariate survival analysis and evaluated by Harrell's c-index. RESULTS: During a median follow-up of 31.4 months, 42 GI bleeds (8.3%) occurred: 42.8% in the upper GI tract, 50.0% in the lower GI tract, and 7.1% in the middle GI tract. The cumulative 5 and 10-year probability of GI bleeding was 12.6% and 18.5%, respectively. Patients who bled had a significantly higher cumulative incidence of all-cause mortality (hazard ratio 2.9, P < 0.001). Multivariate analysis revealed that absence of proton pump inhibitor therapy, chronic kidney disease, chronic obstructive pulmonary disease, history of peptic ulcer disease, and liver cirrhosis predicted GI bleeding. The c-statistic for the new predictive model using these five factors was 0.65 (P < 0.001), higher than the HAS-BLED score of 0.57 (P = 0.145). CONCLUSIONS: Gastrointestinal bleeding increased the risk of subsequent mortality during follow-up of anticoagulated patients, highlighting the importance of prevention. The study developed a new scoring model for acute GI bleeding risk based on five factors (no-proton pump inhibitor use, chronic kidney disease, chronic obstructive pulmonary disease, history of peptic ulcer disease, and liver cirrhosis), which was superior to the HAS-BLED score.

Colonic cytomegalovirus detection by mucosal PCR and antiviral therapy in ulcerative colitis.

BACKGROUND: We aimed to identify the risk factors associated with colonic cytomegalovirus (CMV) infection in ulcerative colitis (UC) and to compare the clinical course between antiviral therapy-treated and -untreated groups in mucosal CMV-polymerase chain reaction (PCR) -positive cases. METHODS: We retrospectively selected 46 UC patients (>15 years old) in active phase who underwent colonoscopy with biopsy and were analyzed for CMV infection by mucosal PCR between October 2011 and December 2015 at our institution. Colonic CMV in inflamed mucosa was detected using quantitative real-time PCR. The clinical course was evaluated, including need for drug therapy/surgery or drug therapy intensification. In addition, we evaluated the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral load. RESULTS: At baseline, CMV-DNA+ patients were significantly older, had higher endoscopic scores, and required higher corticosteroid doses during the past 4 weeks than CMV-DNA- patients (p< 0.05). No significant differences were observed in disease duration, disease distribution, laboratory data, or use of other medication between CMV-DNA+ and CMV-DNA- patients. In the anti-CMV-treated group with a median (range) DNA load of 16,000 (9,000-36,400), 3patients achieved remission without additional UC therapy, 2 required additional UC therapy, and 1 required colectomy despite azathioprine and infliximab therapy. In the CMV-untreated group with a median (range) DNA load of 919 (157-5,480), all patients achieved remission with UC therapy alone. No significant difference was observed in the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral loads. CONCLUSIONS: Aging, endoscopic UC activity, and corticosteroid dose predispose to colonic CMV infection, as determined by mucosal PCR, in UC. UC treatment without anti-CMV therapy may be warranted, particularly in patients with low-load CMV-DNA. Anti-CMV therapy alone does not always achieve clinical response in UC even in cases with high-load PCR.

PCR detection of human herpesviruses in colonic mucosa of individuals with inflammatory bowel disease: Comparison with individuals with immunocompetency and HIV infection.

BACKGROUND: Detection of human herpesviruses (HHVs) other than cytomegalovirus (CMV) in colonic mucosa of individuals with inflammatory bowel disease (IBD) remains unknown. This study identified eight HHVs in the colonic mucosa of individuals with IBD and compared the results with immunocompetent and human immunodeficiency virus (HIV)-infected individuals. METHODS: A total of 89 individuals who had colorectal ulcer on colonoscopy were enrolled: 26 with immunocompetency (n = 26), 41 with IBD, and 22 with HIV infection. We examined the colonic ulcers for the presence of eight HHVs-herpes simplex virus (HSV)-1/2, varicella zoster virus (VZV), CMV, Epstein-Barr virus (EBV), HHV-6, HHV-7, and HHV-8-using mucosal PCR. RESULTS: The IBD group had positivity rates of 0%, 0%, 0%, 53.7%, 24.4%, 39%, 39%, and 0% for HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8, respectively. The positivity rates of EBV and CMV in colonic mucosa increased significantly in the order of the immunocompetent, IBD, and HIV groups (EBV: 23.1%, 53.7%, 72.7%, P for trend = 0.0005; CMV, 7.7%, 24.4%, 54.5%, P for trend = 0.0003, respectively), but no increase was found in the other HHVs. Median mucosal EBV DNA values in the immunocompetent, IBD, and HIV groups were 0, 76, and 287 copies/µg DNA, respectively (P for trend = 0.002). Corresponding median mucosal CMV DNA values were 0, 0, and 17 copies/µg DNA (P for trend = 0.0001). There was no significant difference in the positivity rates of the eight HHVs between ulcerative colitis and Crohn's disease. CONCLUSION: The HHVs of EBV, CMV, HHV-6, and HHV-7, but not of HSV-1, HSV-2, VZV, or HHV-8, were identified in the colonic mucosa of IBD individuals. EBV and CMV in colonic mucosa was correlated with host immune status in increasing order of immunocompetent, IBD, and HIV-infected individuals.