Risk of Colorectal Cancer in Serrated Polyposis Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Serrated polyposis syndrome (SPS) is characterized by development of numerous serrated lesions throughout the colorectum and increased risk of colorectal cancer (CRC). However, SPS has been an underrecognized CRC predisposition syndrome, and the true risk of CRC in SPS, both overall and in surveillance, is not known. The aim of this systematic review and meta-analysis is to describe the risk of CRC in patients with SPS. METHODS: Electronic databases were searched on March 25, 2021, for studies describing CRC risk in SPS. Random-effects meta-analysis was performed to assess pooled risk of CRC among SPS patients. Primary outcomes were risk of CRC at time of SPS diagnosis and during surveillance following diagnosis of SPS. Secondary outcomes included risk of CRC prior to diagnosis of SPS and effect of World Health Organization subtype on CRC risk. RESULTS: Thirty-six studies including 2788 patients with SPS were included in the analysis. Overall risk of CRC in SPS was 19.9% (95% confidence interval [CI], 15.3%-24.5%). CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%-18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%-4.4%), or 7 cases per 1000 person-years. SPS patients also had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%-11.7). Subgroup analysis did not reveal any significant differences based on World Health Organization subtype. CONCLUSIONS: Our meta-analysis demonstrated that patients with SPS have an elevated risk of CRC, which is highest at the time of diagnosis and suggests the importance of early SPS recognition and screening to modify CRC risk. The persistently elevated CRC risk during surveillance supports current guidelines recommending heightened surveillance protocols.

Risk of Cancers in Patients with Pediatric Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVES: We performed a systematic review and meta-analysis to evaluate the risk of the development of cancers in patients with pediatric-onset inflammatory bowel disease (IBD). STUDY DESIGN: A computerized literature search was performed. The primary outcome was the pooled incidence of cancer in studies reporting the risk as a standardized incidence ratio. The secondary outcomes were the pooled incidence rates of all cancers and site-specific cancers including colorectal cancer and hematologic cancers. RESULTS: Sixty-six studies reporting outcomes in 38 092 patients were included. The pooled standardized incidence ratio for cancer was 2.39 (P < .0001, 95% CI 2.00-2.86) in IBD. The pooled incidence rates for cancer in patients with Crohn's disease (CD) and ulcerative colitis (UC) were 0.014 (95% CI 0.0087-0.021) and 0.031 (95% CI 0.018-0.052), respectively. The pooled incidence rate of colorectal cancer in CD and UC were 0.0075 (95% CI 0.0049-0.011) and 0.020 (95% CI 0.012-0.034), respectively. The pooled rates of hematologic cancers in CD and UC were 0.0061 (95% CI 0.0040-0.0090) and 0.0045 (95% CI 0.0026-0.0079), respectively. Cumulative meta-analyses showed a decreasing trend in the incidence of these cancers in both CD and UC. CONCLUSIONS: Patients with pediatric-onset IBD had an increased risk of cancer development compared with the general population, however, incidence appeared to be decreasing in recent years.

Efficacy and Safety of Monoclonal Antibodies Against Clostridioides difficile Toxins for Prevention of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Clostridioides difficile infection is one of the most common health care-associated infections. To reduce the recurrent Clostridioides difficile infection (rCDI), monoclonal antibodies against Clostridioides difficile toxin A (actoxumab) and toxin B (bezlotoxumab) were developed. In the present study, we performed a systematic review and meta-analysis to assess their efficacy and safety. MATERIALS AND METHODS: An electronic database was searched for relevant randomized controlled trials assessing bezlotoxumab and/or actoxumab. Outcomes included rate of rCDI and adverse events including cardiovascular and gastrointestinal events. RESULTS: Four randomized controlled trials comparing antitoxin antibodies (n=1916) versus placebo (n=889) were identified. rCDI was significantly reduced by bezlotoxumab plus actoxumab (risk ratio=0.54, 95% confidence interval=0.41-0.70, P<0.001) and bezlotoxumab monotherapy (risk ratio=0.62, 95% confidence interval=0.51-0.76, P<0.001) compared with placebo. Subgroup analysis showed that bezlotoxumab plus actoxumab was remarkably preventive for patients with the following high-risk features: inpatients, vancomycin treatment, and BI/NAP/027 strain. Regarding safety, there was no difference in cardiovascular and gastrointestinal events as well as all-cause mortality between bezlotoxumab-treated patients and placebo. CONCLUSIONS: The results of our meta-analysis demonstrated the effectiveness and safety of bezlotoxumab for the prevention of rCDI. Bezlotoxumab may be a good therapeutic option for severe C. difficile infection rather than mild cases.

Predictability of simple endoscopic score for Crohn's disease for postoperative outcomes in Crohn's disease.

BACKGROUND AND AIM: Approximately half of patients with Crohn's disease (CD) who have surgery will experience clinical recurrence within 10 years of their surgery. This study aimed to assess the postoperative outcomes according to disease location and validated the simple endoscopic score for CD (SES-CD) to predict disease-related outcomes. METHODS: We retrospectively assessed medical records of CD patients who underwent ileocolonoscopy within 12 months after surgery at the University of Chicago between 2005 and 2016. We defined patients with postoperative colonic inflammation at the first postoperative ileocolonoscopy or had Montreal classification L2 as colon-dominant disease and patients without colonic involvement or who had L1 as small intestine (SI)-dominant disease. The outcomes included clinical and surgical recurrence. RESULTS: Among 207 CD patients, 51 (24.6%) and 156 (75.4%) patients had colon-dominant and SI-dominant disease, respectively. Patients with colon-dominant disease had a greater risk of postoperative clinical recurrence compared with those with SI-dominant disease (P = 0.018). Colon-dominant disease was a risk of earlier surgical recurrence compared with SI-dominant disease, although there were no significant differences in the recurrence-free survivals. SES-CD > 2 at the first postoperative ileocolonoscopy was a significant risk of clinical recurrence on log-rank test (P < 0.001) and Cox proportional hazards model (hazard ratio = 2.25; 95% confidence interval = 1.14-4.47; P = 0.020). An SES-CD of 1 was an appropriate cut-off to predict the clinical recurrence of SI-dominant disease, but a higher SES-CD cut-off value of 5 was required for colon-dominant disease. CONCLUSIONS: We demonstrated that SES-CD predicts postoperative clinical recurrence of CD, regardless of disease location.

The Correlation between Vitamin D Levels and the Risk of Postoperative Recurrence in Crohn's Disease.

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with disease activity in Crohn's disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. METHODS: CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6-12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. RESULTS: Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of <15, 15-30, and >30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; p = 0.028). On multivariate analysis, vitamin D >30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.66, p = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08-0.83, p = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (p = 0.17, 0.55, 0.062, respectively). CONCLUSION: In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.

Risk of Fractures in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Studies assessing the risk of fractures in inflammatory bowel diseases (IBD) have shown controversial results. GOALS: We performed a systematic review and meta-analysis to assess the risk of fractures in IBD. STUDY: Electronic databases were searched for cohort studies assessing the risk of fractures in IBD. The outcomes were the risk of overall fractures and at specific sites, and the association between the risk of fractures and the proportion of patients with corticosteroid use or osteoporosis. RESULTS: Ten studies including 470,541 patients were identified. The risk of overall fractures in IBD patients was similar to controls [odds ratio (OR), 1.08; P=0.70; 95% confidence interval (CI), 0.72-1.62) with moderate heterogeneity (I=74.4%) which appeared to be due to the variable power and outcomes among the studies. The OR of fractures at the spine was significantly elevated at 2.21 (P<0.0001; 95% CI, 1.39-3.50) with low heterogeneity (I=26.1%). Meta-regression showed a correlation with the proportion of patients with steroid use. Risks of fractures at other sites (hip, rib, and wrist) were not elevated. Patients with fractures were more commonly on steroids compared with those without fractures (OR, 1.47; P=0.057; 95% CI, 0.99-2.20; I<0.0001%), but there was no correlation with osteoporosis. CONCLUSIONS: IBD patients had no increased risk of overall fractures, but were at significantly increased risk of fractures at the spine, which was associated with steroid use. Strict surveillance and prevention of spine fractures are indicated in patients with IBD.

Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis.

BACKGROUND: The management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. Our aim was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis. METHODS: In this systematic review and meta-analysis, we searched PubMed, MEDLINE, Google Scholar, Scopus, Embase, and Cochrane databases with no language restrictions for studies published from inception of the databases to Aug 1, 2017, assessing the risk of gastrointestinal cancers in patients with cystic fibrosis. We also searched abstracts from scientific meetings and the bibliographies of identified articles for additional references. Studies were included if they reported the standardised incidence ratio (SIR) or incidence ratio per person-years. No exclusion criteria with regard to patient characteristics (age, sex, comorbidities, cystic fibrosis mutation type), study setting (location and time period), or method of reporting cancer diagnoses were applied. The primary outcome was risk of gastrointestinal cancer and site-specific gastrointestinal cancers in patients with cystic fibrosis compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of gastrointestinal cancer varied according to patient lung transplant status. The study is registered with PROSPERO, number CRD42017075396. FINDINGS: Our search identified 95 681 records, of which six cohort studies including 99 925 patients (544 695 person-years) were eligible for the meta-analysis. The overall risk of gastrointestinal cancer was significantly higher in patients with cystic fibrosis than in the general population (pooled SIR 8·13, 95% CI 6·48-10·21; p<0·0001; log SIR 2·10, 95% CI 1·87-2·32; p<0·0001, I2=93·93%). Subgroup analyses showed that the risk of gastrointestinal cancer among patients with cystic fibrosis who had a lung transplant was increased compared with that of patients who did not receive a transplant (pooled SIR 21·13, 95% CI 14·82-30·14; p<0·0001; log SIR 3·05, 95% CI 2·70-3·41; p<0·0001, I2=28·52% vs pooled SIR 4·18, 3·10-5·62; p<0·0001; log SIR 1·43, 1·13-1·73; p<0·0001, I2=22·66%). The risk for the following site-specific cancers was also significantly increased in patients with cystic fibrosis compared with the general population: small bowel cancer (pooled SIR 18·94, 95% CI 9·37-38·27; p<0·0001; log SIR 2·94, 95% CI 2·24-3·64; p<0·0001, I2=38·61%), colon cancer (10·91, 8·42-14·11; p<0·0001; log SIR 2·39, 2·13-2·65; p<0·0001, I2=88·09%), biliary tract cancer (17·87, 8·55-37·36; p<0·0001; log SIR 2·88, 2·15-3·62; p<0·0001, I2=10·16%), and pancreatic cancer (6·18, 1·31-29·27; p=0·022; log SIR 1·82, 0·27-3·38; p<0·0001, I2=62·57%). INTERPRETATION: Our study suggests that patients with cystic fibrosis had a significantly increased risk of gastrointestinal cancer compared with the general population, including small bowel, colon, biliary tract, and pancreatic cancers. These findings highlight the need to develop individualised screening strategies for site-specific gastrointestinal cancers in patients with cystic fibrosis. FUNDING: None.

Risk of Colorectal Cancer in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Association between chronic kidney disease and colorectal cancer (CRC) remains unclear. GOALS: To assess the risk of CRC in patients with various chronic kidney diseases before and after kidney transplantation. STUDY: Electronic databases were searched for cohort studies assessing the risk of CRC in patients with chronic kidney diseases. The primary outcome was the risk of CRC among studies that reported the risk as standardized incidence rate (SIR). RESULTS: Fifty-four studies, including 1,208,767 patients that reported the incidence of CRC in chronic kidney diseases were identified. SIR of CRC were obtained from 17 retrospective cohort studies. Among the 3 studies (4 reports) that included chronic kidney disease patients without kidney transplantation, there was a significant increased risk of CRC (pooled SIR 1.18) (95% confidence interval, 1.01-1.37; P=0.033). High heterogeneity was seen (I=85.6%), and metaregression showed that there were positive correlations between the risk of CRC and the proportions of males, age and follow-up period. Among the 15 studies (17 reports) that included postkidney transplant patients, the pooled SIR was significantly increased at 1.40 (95% confidence interval, 1.15-1.71; P=0.00080). High heterogeneity was seen (I=88.9%), and metaregression showed that the follow-up period correlated with the risk of CRC. CONCLUSIONS: In the present systematic review and meta-analysis, we demonstrated that patients with chronic kidney disease, regardless of a history of transplant, have a significant increased risk of CRC. A more intensive surveillance for CRC is required in this population.

Risk of Postoperative Complications Among Inflammatory Bowel Disease Patients Treated Preoperatively With Vedolizumab.

OBJECTIVES: Vedolizumab is increasingly used to treat patients with ulcerative colitis (UC) and Crohn's disease (CD), however, its safety during the perioperative period remains unclear. We compared the 30-day postoperative complications among patients treated preoperatively with vedolizumab, anti-tumor necrosis factor (TNF)-α agents or non-biological therapy. METHODS: The retrospective study cohort was comprised of patients receiving vedolizumab, anti-TNF-α agents or non-biological therapy within 4 weeks of surgery. The rates of 30-day postoperative complications were compared between groups using univariate and multivariate analysis. Propensity score-matched analysis was performed to compare the outcome between groups. RESULTS: Among 443 patients (64 vedolizumab, 129 anti-TNF-α agents, and 250 non-biological therapy), a total of 144 patients experienced postoperative complications (32%). In multivariate analysis, age >65 (odds ratio (OR) 3.56, 95% confidence interval (CI) 1.30-9.76) and low-albumin (OR 2.26, 95% CI 1.28-4.00) were associated with increased risk of 30-day postoperative complications. For infectious complications, steroid use (OR 3.67, 95% CI 1.57-8.57, P=0.003) and low hemoglobin (OR 3.03, 95% CI 1.32-6.96, P=0.009) were associated with increased risk in multivariate analysis. Propensity score matched analysis demonstrated that the risks of postoperative complications were not different among patients preoperatively receiving vedolizumab, anti-TNF-α agents or non-biological therapy (UC, P=0.40; CD, P=0.35). CONCLUSIONS: In the present study, preoperative vedolizumab exposure did not affect the risk of 30-day postoperative complications in UC and CD. Further, larger studies are required to confirm our findings.

Outcome of pregnancy and neonatal complications with anti-tumor necrosis factor-α use in females with immune mediated diseases; a systematic review and meta-analysis.

BACKGROUND: Immune mediated diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) commonly affect young and adolescent females. Anti-tumor necrosis factor (TNF)-α agents are increasingly used to treat these conditions, but their safety during pregnancy remains unclear. OBJECTIVES: To evaluate the risk of pregnancy related outcomes in patients with various immune mediated diseases treated with anti-TNF-α agents. METHODS: Electronic databases were searched for studies assessing the outcome of pregnancy in female patients with various immune mediated diseases who were treated with anti-TNF-α agents. Direct and network meta-analyses were performed between anti-TNF-α users, non-users, and the general population. RESULTS: Thirteen studies (including RA, IBD and various immune mediated diseases) were identified. Among the studies that compared the outcome between anti-TNF-α users and the general population, anti-TNF-α users had a non-significant trend towards reduced rate of live birth (odds ratio (OR) = 0.38 (P = 0.081), 95% confidence interval (CI) = 0.13-1.13) and were at significantly increased risk of preterm birth (OR = 2.62 (P < 0.0001), 95% CI = 2.12-3.23), spontaneous abortion (OR = 4.08 (P = 0.033), 95% CI = 1.12-14.89) and low birth weight (OR = 5.95 (P = 0.032), 95% CI = 1.17-30.38) compared to the general population. Risk of anomalies was not elevated (OR = 1.46 (P = 0.18), 95% CI = 0.84-2.56). Among the studies that compared the outcome between anti-TNF-α users and non-users, there were no significant differences in the rates of live birth and pregnancy related complications. Among the studies that compared the outcome between non-anti-TNF-α users and the general population, risk of spontaneous abortion was elevated (OR = 2.60 (P = 0.033), 95% CI = 1.08-6.27), but there were no significant differences in the rates of live birth and other pregnancy related complications. Network meta-analysis confirmed the rank order of all outcomes as general population, non-users and users of anti-TNF-α agents (ascending order based on safety). CONCLUSIONS: Female patients with immune mediated diseases treated with anti-TNF-α agents were at significantly increased risks of preterm birth, spontaneous abortion and low birth weight compared to the general population, but had comparable outcomes with non-users. These results provide useful information for female patients in their reproductive age and raise awareness of the conditions that they are facing among clinicians managing their care.

Efficacy, safety and pharmacokinetics of biosimilars of anti-tumor necrosis factor-α agents in rheumatic diseases; A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of biosimilars of anti-tumor necrosis factor (TNF)-α agents compared to their reference agents in immune mediated diseases. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the efficacy and safety of biosimilars of anti-TNF-α agents compared to their reference agents in patients with various immune mediated diseases. The outcomes were the rates of clinical response and adverse events among patients treated with biosimilars compared to their reference agents. Additionally, occurrence of anti-drug antibodies with the use of biosimilars was compared to the reference agents. RESULTS: Nine studies reporting outcomes in 3291 patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were identified (5 infliximab, 2 adalimumab, and 2 etanercept). No RCTs in other diseases were found. Biosimilars of infliximab showed similar rates of clinical response compared to the reference agent in RA and AS. Frequency of anti-drug antibody and adverse events were similar except for a slightly, but significantly, higher risk of upper respiratory tract infections with biosimilar (RR 1.54, P = 0.047, 95% confidence interval (CI) = 1.01-2.37). Biosimilar of adalimumab showed no differences among any outcomes compared to the reference agent. Biosimilars of etanercept showed no differences for clinical response and frequency of adverse events, but showed a significantly lower rate of anti-drug antibodies at 24-30 weeks (RR 0.05, P <0.0001%, 95% CI = 0.01-0.21). CONCLUSION: In the present study, biosimilars of anti-TNF-α agents had an overall comparable efficacy and safety profile compared to their reference agents in RA and AS supporting their use for these conditions.

Risk of colorectal cancer in chronic liver diseases: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of colorectal cancer (CRC) in various chronic liver diseases compared with the general population remains unclear. We performed a systematic review and meta-analysis to assess the risk of CRC in patients with chronic liver diseases before and after liver transplantation. METHODS: Electronic databases were searched for studies assessing the risk of CRC in patients with chronic liver diseases. The primary outcome was the pooled risk of CRC among studies that reported the risk as standardized incidence rate (SIR). RESULTS: Fifty studies that included 55,991 patients were identified. Among studies that included hepatitis and cirrhotic patients, the pooled SIR was 2.06 (P < .0001; 95% confidence interval (CI), 1.46-2.90) with moderate heterogeneity (I2 = 49.2%), which appeared to be because of the difference between subgroup of diseases and the power of studies. Three studies reported an increased risk of CRC in primary sclerosing cholangitis patients (pooled SIR 6.70; P < .0001; 95% CI, 3.48-12.91) with moderate heterogeneity (I2 = 36.3%), which appeared to be because of the difference between the power of studies. Among studies that included post-transplant patients, the pooled SIR was 2.16 (P < .0001; 95% CI, 1.59-2.94) with moderate heterogeneity (I2 = 56.4%). Meta-regression showed a correlation between the proportion of autoimmune-related liver diseases and the risk of CRC. CONCLUSIONS: Patients with chronic liver diseases had an increased risk of CRC compared with the general population, which persisted after liver transplantation. A more intensive surveillance for CRC is warranted in this population.

Pharmacologic therapies for severe steroid refractory hospitalized ulcerative colitis: A network meta-analysis.

BACKGROUND AND AIM: A limited option of therapies is available for hospitalized patients with severe steroid refractory ulcerative colitis (UC). Furthermore, there exists a paucity of direct comparisons between them. To provide a comparative evaluation of the efficacy and safety of pharmacologic therapies, we conducted a network meta-analysis combined with a benefit-risk analysis of randomized controlled trials (RCTs) performed in hospitalized patients with severe steroid refractory UC. METHODS: Electronic databases were searched through November 2015 for RCTs evaluating the efficacy of therapies for severe steroid refractory hospitalized UC. The outcomes were clinical response, colectomy free rate, and severe adverse events leading to discontinuation of therapy. The primary endpoints were the rank of therapies based on network meta-analysis combined with benefit-risk analysis between clinical response and severe adverse events as well as colectomy free rate and severe adverse events. RESULTS: Eight RCTs of 421 patients were identified. Cyclosporine, infliximab, and tacrolimus as well as placebo were included in our analysis. Network meta-analysis with benefit-risk analysis simultaneously assessing clinical response and severe adverse events demonstrated the rank order of efficacy as infliximab, cyclosporine, tacrolimus, and placebo. Similar analysis for colectomy-free rate and severe adverse events demonstrated the same rank order of efficacy. The differences among infliximab, cyclosporine, and tacrolimus were small in all analyses. CONCLUSION: The results of the present comprehensive benefit-risk assessment using network meta-analysis provide RCT-based evidence on efficacy and safety of infliximab, cyclosporine, and tacrolimus for hospitalized patients with severe steroid refractory UC.

Factors associated with long-term clinical outcome in microscopic colitis.

BACKGROUND AND AIMS: Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the clinical outcomes of microscopic colitis. METHODS: We retrospectively reviewed the medical records of patients with microscopic colitis who were treated at the University of Chicago and Oregon Health & Science University between August 2010 and May 2016. Patient characteristics and treatments were evaluated as predictors of clinical outcomes using univariate and multivariate analyses. Clinical remission was defined as no symptoms associated with microscopic colitis based on physician assessment and histologic remission was defined as no evidence of histological inflammation of microscopic colitis. RESULTS: Seventy-two patients with microscopic colitis were included in the study (28 with lymphocytic colitis and 44 with collagenous colitis). Non-steroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors were used in 23 (31.9%), 14 (19.4%) and 15 (20.8%), respectively, at the time of diagnosis. Among 46 patients with adequate follow-up data, 25 (54.3%) patients achieved clinical remission. Response to budesonide (p = .0002) and achieving histologic remission (p = .0008) were associated with clinical remission on univariate analysis. On multivariate analysis, budesonide response (p = .0052) was associated with clinical remission (odds ratio 25.00, 95% confidence interval 2.63-238.10). Among 22 patients who underwent a follow-up colonoscopy, five patients (22.7%) achieved histologic remission. All patients with histologic remission maintained clinical remission without medication, whereas only two patients (11.8%) were able to discontinue medical therapy when histologic inflammation was present (p = .0002). CONCLUSIONS: In the present cohort of patients with microscopic colitis, a favourable response to budesonide was significantly associated with long-term clinical remission, and all patients achieving histological remission were able to maintain clinical remission without further medical therapy. Larger studies are required to confirm these findings.

Clinical features of obscure gastrointestinal bleeding undergoing capsule endoscopy: A retrospective cohort study.

BACKGROUND: Capsule endoscopy has been widely used to investigate obscure gastrointestinal bleeding (OGIB) in the small intestine since its approval in 2001. However, the clinical features of OGIB remain unclear. AIM: We retrospectively examined the clinical features and risk factors of OGIB in patients who underwent capsule endoscopy in our hospital. METHODS: We included 420 of the 431 patients who underwent capsule endoscopy from June 2014 to May 2021, in whom the small intestine could be observed. We retrospectively compared the clinical features and treatment of OGIB cases, with or without active small bowel bleeding (n = 173), with other cases (n = 247). Patient sex, age, diabetes mellitus, and heart failure histories were matched for the analysis. RESULTS: The male/female ratio was 247/173 and the average age was 51.54 years. In multivariate analysis, the use of direct oral anticoagulants was significant (P = 0.016), and vascular lesions (P = 0.018) were observed in OGIB cases. When OGIB cases with and without active small bowel bleeding were compared, serum albumin level was lower in cases with active bleeding (P = 0.031). When treatment of OGIB cases were compared, those without vascular lesions could be treated conservatively (P = 0.0047). In the 1:1 propensity score matching analysis, serum creatinine level was elevated in cases of active bleeding (P = 0.029), and cases without vascular lesions were treated conservatively (P = 0.010). CONCLUSIONS: Use of direct oral anticoagulants is frequently associated with OGIB. OGIB patients without vascular lesions may be treated conservatively.

Infliximab therapy intensification based on endoscopic activity is related to suppress treatment discontinuation in patients with Crohn disease: A retrospective cohort study.

ABSTRACT: Administering double doses of infliximab or shortening its dosing interval for patients with Crohn disease who experience a loss of response to treatment is an accepted treatment method; however, the effectiveness and appropriate timing of treatment intensification remain unclear. We examined the treatment outcomes of patients with Crohn disease receiving infliximab therapy intensification.Among 430 patients with Crohn disease who were seen at our related facilities from July 2002 to July 2018, 46 patients (30 men and 16 women) who were followed up for diminished infliximab effects for >1 year after therapy intensification were included in this study. The relationship between patient background and continuation of therapy intensification was retrospectively examined through a logistic regression analysis.Among the 46 patients, 67.4% (31 cases) continued therapy intensification for 12 months. The treatment discontinuation rate after 12 months (7.1% vs 43.8%, P = .015) and the C-reactive protein levels at the start of therapy intensification (P = .0050) were significantly lower in the group in which treatment was strengthened due to remaining endoscopic findings (n = 14) than that due to clinical symptoms (n = 32). There was no significant difference in the rates of treatment discontinuation after 12 months of treatment strengthening between patients receiving double doses (n = 34) and those with shortened dosing intervals (n = 12).Infliximab treatment discontinuation seems to be less likely to occur in patients with Crohn disease who are receiving infliximab treatment intensification based on endoscopic findings of exacerbations than in patients whose treatment is based on clinical symptoms.

Systemic review and network meta-analysis: Prophylactic antibiotic therapy for spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is an important prognostic factor for outcomes in patients with cirrhosis. Antibiotic prophylaxis is recommended in patients at high risk for developing SBP, but the choice of antibiotics remains unclear. AIM: To evaluate the efficacy of various antibiotics for prophylaxis of SBP based on randomized control trials (RCTs). METHODS: Electronic databases were searched through November 2018 for RCTs evaluating the efficacy of therapies for primary or secondary prophylaxis of SBP. The primary outcome was the development of SBP. Sensitivity analyses limited to studies of primary or secondary prophylaxis and studies reported after 2010 were performed. The secondary outcome was the risk of all-cause mortality or transplant. The outcomes were assessed by rank of therapies based on network meta-analyses. Individual meta-analyses were also performed. RESULTS: Thirteen RCTs (1742 patients) including norfloxacin, ciprofloxacin, rifaximin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo/no comparator were identified. Individual meta-analyses showed superiority of rifaximin over norfloxacin as well as norfloxacin and TMP-SMX over placebo. Network meta-analysis demonstrated the rank of efficacy in reducing the risk of SBP as: Rifaximin, ciprofloxacin, TMP-SMX, norfloxacin, and placebo/no comparator. Rifaximin ranked highest in sensitivity analyses limited to studies of primary or secondary prophylaxis and studies reported after 2010. Similarly, rifaximin ranked highest in reducing the risk of death/transplant. CONCLUSION: The present comprehensive network meta-analysis provides RCT based evidence for superior efficacy of rifaximin compared to other antibiotics for the prophylaxis of SBP and reducing risk of death/transplant. Further RCTs are warranted to confirm our findings.

Efficacy of various endoscopic modalities in detecting dysplasia in ulcerative colitis: A systematic review and network meta-analysis.

BACKGROUND: Longstanding ulcerative colitis (UC) is associated with an increased risk of colonic neoplasia. Various endoscopic modalities, such as chromoendoscopy (CE), narrow band imaging (NBI) and random biopsy have been introduced for surveillance, however, there exists a paucity of direct comparisons between them. We aimed to conduct a network meta-analysis of randomized controlled trials (RCTs) performed for surveillance of neoplasia in UC. AIM: To provide a comparative evaluation of the efficacy of the above-mentioned various modalities. METHODS: We searched MEDLINE/PubMed, Web of Science, Embase, Google Scholar and Cochrane Central Registry through May 2016 for RCTs evaluating the efficacy of endoscopic modalities for surveillance of neoplasia in UC. The primary outcomes of interest were dysplasia (low- or high-grade) detection rates per biopsy and per patient, and dysplasia numbers per patient. Studies were simultaneously analyzed using a random-effects network meta-analysis under the Bayesian framework to identify the modality with the highest dysplasia detection rate. The best ranking probability for the dysplasia detection rate was analyzed by surface under the cumulative ranking (SUCRA) technique. RESULTS: Six prospective RCTs of a total 1038 patients were identified. We identified 4 different modalities; white light (WL) high definition (HD) or standard definition (SD), CE HD, and NBI HD. For dysplasia per biopsy, direct meta-analysis showed superiority of NBI HD over WL HD and CE HD over WL SD. Network meta-analysis demonstrated the rank order of best modality as NBI HD, CE HD, WL HD and WL SD with close SUCRA scores of the first two. For dysplasia per patient, direct meta-analyses showed equivocal results between each modality. Network meta-analysis demonstrated the rank order of best modality as WL HD, NBI HD, CE HD and WL SD with small differences of the SUCRA score among the first two. For dysplasia numbers per patient, direct meta-analysis showed superiority of CE HD over WL SD. Network meta-analysis demonstrated the rank order of best modality as WL HD, NBI HD, CE HD, and WL SD with small differences of the SUCRA score among the first three. CONCLUSION: We demonstrated that there were small differences among WL HD, NBI HD, and CE HD, while WL SD was inferior, in detecting dysplasia in UC.