Dual-Energy CT Evaluation of Gastrointestinal Bleeding.

Gastrointestinal (GI) bleeding is a potentially life-threatening condition accounting for more than 300 000 annual hospitalizations. Multidetector abdominopelvic CT angiography is commonly used in the evaluation of patients with GI bleeding. Given that many patients with severe overt GI bleeding are unlikely to tolerate bowel preparation, and inpatient colonoscopy is frequently limited by suboptimal preparation obscuring mucosal visibility, CT angiography is recommended as a first-line diagnostic test in patients with severe hematochezia to localize a source of bleeding. Assessment of these patients with conventional single-energy CT systems typically requires the performance of a noncontrast series followed by imaging during multiple postcontrast phases. Dual-energy CT (DECT) offers several potential advantages for performing these examinations. DECT may eliminate the need for a noncontrast acquisition by allowing the creation of virtual noncontrast (VNC) images from contrast-enhanced data, affording significant radiation dose reduction while maintaining diagnostic accuracy. VNC images can help radiologists to differentiate active bleeding, hyperattenuating enteric contents, hematomas, and enhancing masses. Additional postprocessing techniques such as low-kiloelectron voltage virtual monoenergetic images, iodine maps, and iodine overlay images can increase the conspicuity of contrast material extravasation and improve the visibility of subtle causes of GI bleeding, thereby increasing diagnostic confidence and assisting with problem solving. GI bleeding can also be diagnosed with routine single-phase DECT scans by constructing VNC images and iodine maps. Radiologists should also be aware of the potential pitfalls and limitations of DECT. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Management of Patients With Acute Lower Gastrointestinal Bleeding: An Updated ACG Guideline.

Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization in the United States and is associated with significant utilization of hospital resources, as well as considerable morbidity and mortality. These revised guidelines implement the Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the use of risk stratification tools, thresholds for red blood cell transfusion, reversal agents for patients on anticoagulants, diagnostic testing including colonoscopy and computed tomography angiography (CTA), endoscopic therapeutic options, and management of antithrombotic medications after hospital discharge. Important changes since the previous iteration of this guideline include recommendations for the use of risk stratification tools to identify patients with LGIB at low risk of a hospital-based intervention, the role for reversal agents in patients with life-threatening LGIB on vitamin K antagonists and direct oral anticoagulants, the increasing role for CTA in patients with severe LGIB, and the management of patients who have a positive CTA. We recommend that most patients requiring inpatient colonoscopy undergo a nonurgent colonoscopy because performing an urgent colonoscopy within 24 hours of presentation has not been shown to improve important clinical outcomes such as rebleeding. Finally, we provide updated recommendations regarding resumption of antiplatelet and anticoagulant medications after cessation of LGIB.

Deep Learning Computer-aided Polyp Detection Reduces Adenoma Miss Rate: A United States Multi-center Randomized Tandem Colonoscopy Study (CADeT-CS Trial).

BACKGROUND & AIMS: Artificial intelligence-based computer-aided polyp detection (CADe) systems are intended to address the issue of missed polyps during colonoscopy. The effect of CADe during screening and surveillance colonoscopy has not previously been studied in a United States (U.S.) population. METHODS: We conducted a prospective, multi-center, single-blind randomized tandem colonoscopy study to evaluate a deep-learning based CADe system (EndoScreener, Shanghai Wision AI, China). Patients were enrolled across 4 U.S. academic medical centers from 2019 through 2020. Patients presenting for colorectal cancer screening or surveillance were randomized to CADe colonoscopy first or high-definition white light (HDWL) colonoscopy first, followed immediately by the other procedure in tandem fashion by the same endoscopist. The primary outcome was adenoma miss rate (AMR), and secondary outcomes included sessile serrated lesion (SSL) miss rate and adenomas per colonoscopy (APC). RESULTS: A total of 232 patients entered the study, with 116 patients randomized to undergo CADe colonoscopy first and 116 patients randomized to undergo HDWL colonoscopy first. After the exclusion of 9 patients, the study cohort included 223 patients. AMR was lower in the CADe-first group compared with the HDWL-first group (20.12% [34/169] vs 31.25% [45/144]; odds ratio [OR], 1.8048; 95% confidence interval [CI], 1.0780-3.0217; P = .0247). SSL miss rate was lower in the CADe-first group (7.14% [1/14]) vs the HDWL-first group (42.11% [8/19]; P = .0482). First-pass APC was higher in the CADe-first group (1.19 [standard deviation (SD), 2.03] vs 0.90 [SD, 1.55]; P = .0323). First-pass ADR was 50.44% in the CADe-first group and 43.64 % in the HDWL-first group (P = .3091). CONCLUSION: In this U.S. multicenter tandem colonoscopy randomized controlled trial, we demonstrate a decrease in AMR and SSL miss rate and an increase in first-pass APC with the use of a CADe-system when compared with HDWL colonoscopy alone.

Comparative Efficacy and Rapidity of Action for Infliximab vs Ustekinumab in Biologic Naïve Crohn's Disease.

BACKGROUND & AIMS: Comparative effectiveness has become increasingly important to help position therapies for inflammatory bowel disease. We compared the efficacy and rapidity of onset of action of infliximab vs ustekinumab induction therapy for moderate to severe biologic-naïve Crohn's disease (CD) using patient-level data from randomized controlled trials. METHODS: This was a post hoc analysis of 2 large CD clinical trial programs that included data on 420 biologic-naïve CD patients. Differences in proportions of patients achieving week 6 clinical remission, clinical response, and normalization of calprotectin were compared. Multivariate logistic regression was used to adjust for confounders. Sensitivity analysis was conducted using propensity scores to create a cohort of matched participants with similar distribution of baseline covariates. RESULTS: At week 6, a comparable number of patients achieved clinical remission with infliximab compared with patients treated with ustekinumab (44.9% vs 37.9%; adjusted odds ratio [aOR], 1.22; 95% CI, 0.79-1.89). Similarly, at week 6 the clinical response rates were not significantly different (58.4% infliximab vs 54.9% ustekinumab; aOR, 1.25; 95% CI, 0.82-1.90). No significant difference was observed between treatment groups for achieving a week 6 fecal calprotectin level less than 250 mcg/L in those with increased values at baseline (42.3% infliximab vs 34.7% ustekinumab; aOR, 1.34; 95% CI, 0.79-2.28). Similar results were seen for all analyses performed within the propensity matched cohort. CONCLUSIONS: Based on this post hoc analysis, infliximab and ustekinumab appear to have similar efficacy and speed of onset in patients with CD who are biologic-naïve.

Digital Navigation Improves No-Show Rates and Bowel Preparation Quality for Patients Undergoing Colonoscopy: A Randomized Controlled Quality Improvement Study.

OBJECTIVES: Because of high historical no-show rates and poor bowel preparation quality in our unit, we sought to evaluate whether text message navigation for patients scheduled for colonoscopy would reduce no-show rates and improve bowel preparation quality compared with usual care. METHODS: We performed a randomized controlled quality improvement study from April to August 2019 in an urban academic endoscopy unit. All patients scheduled for colonoscopy were randomly assigned to a control group that received usual care (paper instructions/nursing precalls) or to the intervention group that received usual care plus the text message program [short message service (SMS)]. The program provided timed-release instructions on dietary modifications and bowel preparation before colonoscopy. The primary outcome was no-shows. Secondary outcomes were no-show/same-day cancellations, no-show/cancellations within 7 days of the procedure, and bowel preparation quality. RESULTS: A total of 1625 patients were randomized (SMS=833, control=792). No-show rates were significantly lower in the SMS group compared with the control group (8% vs. 14%; P<0.0001). Similar results were found for no-show/same-day cancellations (10% vs. 16%; P=0.0003), and no-show/cancellations within 7 days (18% vs. 26%; P=0.0008). There was no difference in adequate bowel preparation for all colonoscopies between the groups (89% vs. 87%; P=0.47). However, rates of adequate bowel preparation for screening/surveillance colonoscopies were significantly higher in SMS versus control groups (93% vs. 88%; P=0.04). CONCLUSIONS: Text message navigation for patients scheduled for colonoscopy improved the quality of colorectal cancer screening by decreasing no-show rates and increasing adequate bowel preparation rates in patients undergoing screening colonoscopy compared with usual care.

Interventional treatments for chronic, axial or radicular, non-cancer, spinal pain: a protocol for a systematic review and network meta-analysis of randomised trials.

INTRODUCTION: Chronic, non-cancer, axial or radicular spinal pain is a common condition associated with considerable socioeconomic burden. Clinicians frequently offer patients various interventional procedures for the treatment of chronic spine pain; however, the comparative effectiveness and safety of available procedures remains uncertain. METHODS: We will conduct a systematic review of randomised controlled trials that explores the effectiveness and harms of interventional procedures for the management of axial or radicular, chronic, non-cancer, spine pain. We will identify eligible studies through a systematic search of Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and Web of Science from inception without language restrictions. Eligible trials will: (1) enrol primarily adult patients (≥18 years old) with axial or radicular, chronic, non-cancer, spine pain, (2) randomise patients to different, currently available, interventional procedures or to an interventional procedure and a placebo/sham procedure or usual care, and (3) measure outcomes at least 1 month after randomisation.Pairs of reviewers will independently screen articles identified through searches and extract information and assess risk of bias of eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. We will use frequentist random-effects network meta-analyses to assess the relative effects of interventional procedures, and five a priori hypotheses to explore between studies subgroup effects. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome, including direct, indirect and network estimates. ETHICS AND DISSEMINATION: No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence. PROSPERO REGISTRATION NUMBER: CRD42020170667.

Triage of General Gastrointestinal Endoscopic Procedures During the COVID-19 Pandemic: Results From a National Delphi Consensus Panel.

BACKGROUND AND AIMS: As the COVID-19 pandemic moves into the postpeak period, the focus has now shifted to resuming endoscopy services to meet the needs of patients who were deferred. By using a modified Delphi process, we sought to develop a structured framework to provide guidance regarding procedure indications and procedure time intervals. METHODS: A national panel of 14 expert gastroenterologists from throughout the US used a modified Delphi process, to achieve consensus regarding: (1) common indications for general endoscopy, (2) critical patient-important outcomes for endoscopy, (3) defining time-sensitive intervals, (4) assigning time-sensitive intervals to procedure indications. Two anonymous rounds of voting were allowed before attempts at consensus were abandoned. RESULTS: Expert panel reached consensus that procedures should be allocated to one of three timing categories: (1) time-sensitive emergent = scheduled within 1 week, (2) time-sensitive urgent = scheduled within 1-8 weeks, (3) nontime sensitive = defer to > 8 weeks and reassess timing then. The panel identified 62 common general endoscopy indications (33 for EGD, 21 for colonoscopy, 5 for sigmoidoscopy). Consensus was reached on patient-important outcomes for each procedure indication, and consensus regarding timing of the procedure indication was achieved for 74% of indications. Panelists also identified adequate personal-protective-equipment, rapid point-of-care testing, and staff training as critical preconditions before endoscopy services could be resumed. CONCLUSION: We used the validated Delphi methodology, while prioritized patient-important outcomes, to provide consensus recommendations regarding triaging a comprehensive list of general endoscopic procedures.

PPIs and Beyond: A Framework for Managing Anticoagulation-Related Gastrointestinal Bleeding in the Era of COVID-19.

Coronavirus disease of 2019 (COVID-19) can be associated with high morbidity and mortality; patients with severe clinical manifestations may develop significant coagulopathy as well as unexpected thromboembolic complications. In response, centers are increasingly treating selected patients with intermediate-dose prophylactic or even therapeutic dose anticoagulation in order to prevent potentially catastrophic thrombotic complications. With this changing practice, the authors suspect that inpatient gastrointestinal consult teams across the country will be frequently managing COVID-19 patients with gastrointestinal bleeding (GIB). In order to reduce potentially avoidable hospital readmissions for GIB while improving patient outcomes, it is imperative to appropriately risk-stratify patients prior to initiation of anticoagulation. In this review, we discuss how to appropriately identify high-risk patients for GIB and how to mitigate GIB risk with proton-pump inhibitor co-therapy, medication reconciliation, and Helicobacter pylori testing and treating in this complex and morbid population.

The role of colonoscopy and endotherapy in the management of lower gastrointestinal bleeding.

Colonoscopy is an integral diagnostic and therapeutic tool in the management of patients with lower gastrointestinal bleeding (LGIB). After resuscitation, reversal of coagulopathy, and exclusion of a proximal source of bleeding, colonoscopy should be performed in most patients with LGIB. Bowel preparation, typically with polyethylene glycol based solutions, is needed to closely inspect the colonic mucosa for bleeding sources. Colonoscopy within 24 h is recommended for high-risk patients with ongoing bleeding, although there is limited evidence that this strategy improves clinical outcomes. When active or stigmata of bleeding is detected, endoscopic intervention is indicated and can reduce future rebleeding. The most common options for endoscopic intervention include clipping, endoscopic band ligation, and coagulation, however rigorous head-to-head comparisons of different endoscopic tools are unavailable. Future research is needed to determine the optimal timing of colonoscopy, appropriate reversal strategies for patients on antithrombotics, and the most effective endoscopic hemostatic therapy.

Early Colonoscopy for Diverticular Bleeding Does Not Reduce Risk of Postdischarge Recurrent Bleeding: A Propensity Score Matching Analysis.

BACKGROUND & AIMS: Colonoscopy within 24 hours (early colonoscopy) is recommended for patients with colonic diverticular bleeding, but it is unclear if this strategy improves postdischarge outcomes. We aimed to determine whether early colonoscopy is associated with decreased risk of rebleeding and hospital re-admission within 30 days. METHODS: We performed a retrospective cohort study using Marketscan (Truven Health Analytics, Inc, Ann Arbor, MI), a nationwide insurance claims database. From January 2004 through September 2015, patients with a primary diagnosis of diverticular bleeding who underwent inpatient colonoscopy were included. We used propensity score matching to account for differences between recipients of early vs delayed colonoscopy. Multivariable logistic regression was performed to determine the association between early colonoscopy and rebleeding or hospital re-admission within 30 days of discharge. RESULTS: In total, 20,010 patients underwent colonoscopy for diverticular bleeding; 11,690 underwent early colonoscopy. After propensity matching, 8320 pairs of patients were analyzed. In the matched analysis, higher proportions of patients who received early colonoscopy underwent additional colonoscopies (73%), compared with patients who did not receive early colonoscopy (4%) (P < .0001), but lower proportions received endoscopic interventions (3% vs 8%; P < .0001). On multivariable analysis, early colonoscopy (odds ratio [OR], 1.34; 95% CI, 1.08-1.66; P = .007), transfusion requirement (OR, 2.31; 95% CI, 1.88-2.83; P < .0001), and baseline chronic kidney disease (OR, 2.13; 95% CI, 1.49-3.04; P < .0001) were associated with increased risk of rebleeding within 30 days. Early colonoscopy (OR, 1.18; 95% CI, 1.02-1.36; P = .03), endoscopic intervention (OR, 1.37; 95% CI, 1.03-1.81; P = .03), transfusion requirement (OR, 2.17; 95% CI, 1.88-2.51; P < .0001), coronary artery disease (OR, 1.27; 95% CI, 1.06-1.51; P = .009), and chronic kidney disease (OR, 1.98; 95% CI, 1.54-2.54; P < .0001) were associated with increased re-admission to the hospital within 30 days. CONCLUSIONS: In a propensity-matched analysis, we associated early colonoscopy with increased risk of rebleeding events and hospital re-admissions. However, these observations might be due to confounding factors.

Risk Factors for 30-day Hospital Readmission for Diverticular Hemorrhage.

INTRODUCTION: The 2010 Affordable Care Act introduced the Hospital Readmissions Reduction Program to reduce health care utilization. Diverticular disease and its complications remain a leading cause of hospitalization among gastrointestinal disease. We sought to determine risk factors for 30-day hospital readmissions after hospitalization for diverticular bleeding. MATERIALS AND METHODS: We utilized the 2013 National Readmission Database sponsored by the Agency for Healthcare Research and Quality focusing on hospitalizations with the primary or secondary discharge diagnosis of diverticular hemorrhage or diverticulitis with hemorrhage. We excluded repeat readmissions, index hospitalizations during December and those resulting in death. Our primary outcome was readmission within 30 days of index hospital discharge. Secondary outcomes of interest included medical and procedural comorbid risk factors. The data were analyzed using logistic regression analysis. RESULTS: In total, 29,090 index hospitalizations for diverticular hemorrhage were included. There were 3484 (12%) 30-day readmissions with recurrent diverticular hemorrhage diagnosed in 896 (3%).Index admissions with renal failure [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.19-1.43], congestive heart failure (OR, 1.30; 95% CI, 1.17-1.43), chronic pulmonary disease (OR, 1.19; 95% CI, 1.09-1.29), coronary artery disease (OR, 1.12; 95% CI, 1.03-1.21), atrial fibrillation (OR, 1.12; 95% CI, 1.02-1.22) cirrhosis (OR, 1.95; 95% CI, 1.29-2.93, performance of blood transfusion (OR, 1.23; 95% CI, 1.15-1.33), and abdominal surgery (OR, 1.24; 95% CI, 1.03-1.49) had increased risk of 30-day readmission. CONCLUSIONS: The 30-day readmission rate for diverticular hemorrhage was 12% with multiple identified comorbidities increasing readmission risk.

Comparison of clinical prediction tools and identification of risk factors for adverse outcomes in acute lower GI bleeding.

BACKGROUND AND AIMS: Limited data exist on prediction of adverse outcomes in patients with acute lower GI bleeding (LGIB). The purpose of our study was to compare the ability of existing validated clinical risk scores to predict relevant outcomes in LGIB. METHODS: We performed a prospective observational study of patients admitted with LGIB who underwent colonoscopy at a single center between April 2016 and September 2017. Seven risk scores were calculated at admission (Strate, NOBLADS, Sengupta, Oakland, Blatchford, AIMS65, and Charlson Comorbidity Index). The risk of severe LGIB was determined via univariable and multivariable logistic regression. Area under the receiver operating characteristic curve (AUC) analysis was used to compare the scores. RESULTS: We included 170 patients admitted with LGIB requiring colonoscopy. Fifty-two percent (n = 89) fit criteria for severe bleeding. Patients with severe bleeding had lower admission hemoglobin levels (8.6 g/dL vs 11.1 g/dL; P = .0001), were more likely to have blood transfusions (85% vs 36%; P < .0001), intensive care unit stays (49% vs 19%; P < .0001), and had a longer length of stay (6 days vs 4 days; P = .0009). The Oakland score was best for prediction of severe bleeding (AUC, .74), Blatchford score for blood transfusion (AUC, .87), and Strate score for in-hospital recurrent bleeding (AUC, .66) and endoscopic intervention (AUC, .62). The strongest individual predictors of severe bleeding were low admission hemoglobin (odds ratio, 1.28 per 1-g/dL decrease; P = .0015; 95% confidence interval, 1.10-1.49) and low albumin (odds ratio, 2.56 per 1-g/dL decrease; P = .02; 95% confidence interval, 1.16-5.56). CONCLUSION: Admission albumin and hemoglobin levels were the strongest predictors of severe bleeding. No singular clinical risk tool had the best predictive ability across all outcomes.

Efficacy of liquid nitrogen cryotherapy for Barrett's esophagus after endoscopic resection of intramucosal cancer: A multicenter study.

BACKGROUND AND AIM: Liquid nitrogen cryotherapy (LNC) allows increased depth of ablation compared with radiofrequency ablation in Barrett's esophagus (BE). Expert centers may use LNC over radiofrequency ablation to ablate Barrett's esophagus after endoscopic resection of intramucosal cancer (IMCA). The aim of our study was to (1) evaluate the safety and efficacy of LNC ablation in patients with BE and IMCA and (2) to evaluate the progression to invasive disease despite therapy. METHODS: This was a multicenter, retrospective study of consecutive patients with BE who received LNC following endoscopic mucosal resection (EMR) of IMCA. The outcomes evaluated were complete eradication of dysplasia and intestinal metaplasia and development of invasive cancer during follow up. The follow-up period was at least 1 year from initial LNC. RESULTS: Twenty-seven patients were identified. The median Prague score was C3M5 (range C0M1-C14M14). After EMR+LNC, the median Prague score was C0M1 (range C0M0-C9M10); 22/27 patients (82%) achieved complete eradication of dysplasia after cryotherapy, and 19/27 patients (70%) achieved complete eradication of intestinal metaplasia. One out of 27 patients (4%) developed invasive cancer (disease beyond IMCA) over the study period. CONCLUSION: Cryotherapy is an effective endoscopic tool for eradication of BE dysplasia after EMR for IMCA. Development of invasive cancer is low for this high-risk group.

Outcomes of Early Versus Delayed Colonoscopy in Lower Gastrointestinal Bleeding Using a Hospital Administrative Database.

BACKGROUND: Limited data exist on whether early colonoscopy for lower gastrointestinal bleeding (LGIB) alters 30-day mortality, performance of endoscopic intervention, or need for blood transfusion. Our primary objective was to determine whether early colonoscopy in LGIB is associated with decreased 30-day mortality using a large hospital administrative database. METHODS: Patients hospitalized between January 2008 and September 2015 were identified using a validated, machine learning algorithm for identifying patients with LGIB. "Early" colonoscopy occurred by day 2 of admission and "late" colonoscopy between days 3 and 5. A propensity score for early colonoscopy was constructed using plausible confounders. Univariable and multivariable logistic regression were used to determine factors associated with 30-day mortality, endoscopic intervention, and transfusion need. The propensity score was included as a confounding factor for mortality analysis in the multivariable model. RESULTS: In total, 1204 patients underwent colonoscopy for LGIB. Of these, 295 patients (25%) underwent early colonoscopy, and these patients had a lower Charlson Comorbidity Index (P=0.001) and shorter length of stay (3 vs. 5 d, P=0.0001). Early colonoscopy was not associated with decreased 30-day mortality [odds ratio (OR), 0.73; confidence interval (CI), 0.27-1.69], but was associated with increased endoscopic intervention (OR, 2.62; CI, 1.37-4.95) and decreased need for transfusion (OR, 0.65; CI, 0.49-0.87). On multivariable analysis adjusting for timing of colonoscopy, age, and propensity score for early colonoscopy, early colonoscopy was not associated with a decrease in 30-day mortality (OR, 1.37; CI, 0.50-3.79). CONCLUSIONS: Early colonoscopy does not affect 30-day mortality but may allow for earlier endoscopic intervention and decreased transfusion need.

Derivation and Internal Validation of a Clinical Prediction Tool for 30-Day Mortality in Lower Gastrointestinal Bleeding.

BACKGROUND: There are limited data to predict which patients with lower gastrointestinal bleeding are at risk for adverse outcomes. We aimed to develop a clinical tool based on admission variables to predict 30-day mortality in lower gastrointestinal bleeding. METHODS: We used a validated machine learning algorithm to identify adult patients hospitalized with lower gastrointestinal bleeding at an academic medical center between 2008 and 2015. The cohort was split randomly into derivation and validation cohorts. In the derivation cohort, we used multiple logistic regression on all candidate admission variables to create a prediction model for 30-day mortality, using area under the receiving operator characteristic curve and misclassification rate to estimate prediction accuracy. Regression coefficients were used to derive an integer score, and mortality risk associated with point totals was assessed. RESULTS: In the derivation cohort (n = 4044), 8 variables were most associated with 30-day mortality: age, dementia, metastatic cancer, chronic kidney disease, chronic pulmonary disease, anticoagulant use, admission hematocrit, and albumin. The model yielded a misclassification rate of 0.06 and area under the curve of 0.81. The integer score ranged from -10 to 26 in the derivation cohort, with a misclassification rate of 0.11 and area under the curve of 0.74. In the validation cohort (n = 2060), the score had an area under the curve of 0.72 with a misclassification rate of 0.12. After dividing the score into 4 quartiles of risk, 30-day mortality in the derivation and validation sets was 3.6% and 4.4% in quartile 1, 4.9% and 7.3% in quartile 2, 9.9% and 9.1% in quartile 3, and 24% and 26% in quartile 4, respectively. CONCLUSIONS: A clinical tool can be used to predict 30-day mortality in patients hospitalized with lower gastrointestinal bleeding.