Efficacy of Vonoprazan, a Novel Potassium-Competitive Acid Blocker, in Patients with Proton Pump Inhibitor-Refractory Acid Reflux.

BACKGROUND/AIM: We evaluated the efficacy of vonoprazan (VPZ), a novel potassium-competitive acid blocker, in patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD), exhibiting continued pathological esophageal acid exposure (EAE). METHODS: Despite ≥8 weeks of appropriate PPI therapy, patients with -persistent reflux symptoms and pathological EAE times (EAETs ≥4%) were invited to switch to VPZ treatment. After an 8-week-course of once-daily VPZ (20 mg), multichannel intraluminal impedance-pH (MII-pH) monitoring was repeated to compare gastric acid exposure times (GAETs), EAETs, and other reflux parameters relative to the baseline values. Before each MII-pH study, reflux symptom severities were scored using the Gastrointestinal Symptom Rating Scale; erosive esophagitis and fasting plasma gastrin levels were also assessed. RESULTS: From among the 124 patients undergoing MII-pH monitoring, 13 patients (median age, 69 years; females, 64%) were monitored at baseline (while on PPI therapy) and after VPZ therapy. The median GAET associated with VPZ treatment (23.8%) was less than that for PPI treatment (41.1%; p = 0.01), including both daytime and nighttime measurements. VPZ therapy resulted in better median EAET values (4.5%) than did PPI therapy (10.6%) during the 24-h monitoring period (p = 0.055). EAE normalization was achieved in 46% of VPZ-treated patients and was associated with complete gastric acid suppression (p = 0.005). After switching to VPZ, reflux symptoms (p < 0.01) and erosive esophagitis (p = 0.01) improved. CONCLUSION: In patients with PPI-refractory GERD, VPZ provides more potent gastric acid suppression, more effective EAE control, enhanced symptom improvement, and better esophagitis healing than PPIs.

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.

Acute Severe Gastrointestinal Tract Bleeding Is Associated With an Increased Risk of Thromboembolism and Death.

BACKGROUND & AIMS: We performed a retrospective cohort study of patients with and without gastrointestinal bleeding (GIB) to determine whether GIB increases the risks of thromboembolism and death. METHODS: We collected data from 522 patients with acute severe GIB and 1044 patients without GIB (control subjects, matched for age, sex, year of diagnosis, history of thromboembolism, and use of antithrombotic drugs) who underwent endoscopy at the National Center for Global Health and Medicine in Japan from January 2009 through December 2014. Hazard ratios of GIB for thromboembolism and mortality risk were estimated, adjusting for confounders. We also compared standardized mortality ratios between the GIB cohort and the age- and sex-matched general population in Japan. RESULTS: During a mean follow up of 23.7 months, thromboembolism was identified in 11.5% of patients with GIB and 2.4% of control subjects (hazard ratio, 5.3; 95% confidence interval, 3.3-8.5; P < .001). Multivariate analysis revealed GIB as a risk factor for all-thromboembolic events, cerebrovascular events, and cardiovascular events. During a mean follow-up of 24.6 months, 15.9% of patients with GIB and 8.6% of control subjects died (hazard ratio, 2.1; 95% confidence interval, 1.6-2.9; P < .001). Multivariate analysis revealed GIB as a risk factor for all-cause mortality. Compared with the general population, patients with GIB were at increased risk of death (standardized mortality ratio, 12.0). CONCLUSIONS: In a retrospective analysis of patients undergoing endoscopy in Japan, we identified acute GIB was a significant risk factor for late thromboembolism and death, compared with patients without GIB. GIB also increased risk of death compared with the general population.

Safety and Effectiveness of Early Colonoscopy in Management of Acute Lower Gastrointestinal Bleeding on the Basis of Propensity Score Matching Analysis.

BACKGROUND & AIMS: We investigated the safety and effectiveness of early colonoscopy (performed within 24 hours of hospital admission) for acute lower gastrointestinal bleeding (LGIB) vs elective colonoscopy (performed 24 hours after admission). METHODS: We conducted a retrospective study by using a database of endoscopies performed at the National Center for Global Health and Medicine in Tokyo, Japan from January 2009 through December 2014. We analyzed data from 538 patients emergently hospitalized for acute LGIB. We used propensity score matching to adjust for differences between patients who underwent early colonoscopy vs elective colonoscopy. Outcomes included rates of adverse events during bowel preparation and colonoscopy procedures, stigmata of recent hemorrhage, endoscopic therapy, blood transfusion requirement, 30-day rebleeding and mortality, and length of hospital stay. RESULTS: We selected 163 pairs of patients for analysis on the basis of propensity matching. We observed no significant differences between the early and elective colonoscopy groups in bowel preparation-related rates of adverse events (1.8% vs 1.2%, P = .652), colonoscopy-related rates of adverse events (none in either group), blood transfusion requirement (27.6% vs 27.6%, P = 1.000), or mortality (1.2% vs 0, P = .156). The early colonoscopy group had higher rates than the elective group for stigmata of recent hemorrhage (26.4% vs 9.2%, P < .001) and endoscopic therapy (25.8% vs 8.6%, P < .001), including clipping (17.8% vs 4.9%, P < .001), band ligation (6.1% vs 1.8%, P = .048), and rebleeding (13.5% vs 7.4%, P = .070). Patients in the early colonoscopy group stayed in the hospital for a shorter mean time (10 days) than patients in the elective colonoscopy group (13 days) (P < .001). CONCLUSIONS: Early colonoscopy for patients with acute LGIB is safe, allows for endoscopic therapy because it identifies the bleeding source, and reduces hospital stay. However, compared with elective colonoscopy, early colonoscopy does not reduce mortality and may increase the risk for rebleeding.

Development and Validation of a Risk Scoring System for Severe Acute Lower Gastrointestinal Bleeding.

BACKGROUND & AIMS: We aimed to develop and validate a risk scoring system to determine the risk of severe lower gastrointestinal bleeding (LGIB) and predict patient outcomes. METHODS: We first performed a retrospective analysis of data from 439 patients emergently hospitalized for acute LGIB at the National Center for Global Health and Medicine in Japan, from January 2009 through December 2013. We used data on comorbidities, medication, presenting symptoms, and vital signs, and laboratory test results to develop a scoring system for severe LGIB (defined as continuous and/or recurrent bleeding). We validated the risk score in a prospective study of 161 patients with acute LGIB admitted to the same center from April 2014 through April 2015. We assessed the system's accuracy in predicting patient outcome using area under the receiver operating characteristics curve (AUC) analysis. All patients underwent colonoscopy. RESULTS: In the first study, 29% of the patients developed severe LGIB. We devised a risk scoring system based on nonsteroidal anti-inflammatory drugs use, no diarrhea, no abdominal tenderness, blood pressure of 100 mm Hg or lower, antiplatelet drugs use, albumin level less than 3.0 g/dL, disease scores of 2 or higher, and syncope (NOBLADS), which all were independent correlates of severe LGIB. Severe LGIB developed in 75.7% of patients with scores of 5 or higher compared with 2% of patients without any of the factors correlated with severe LGIB (P < .001). The NOBLADS score determined the severity of LGIB with an AUC value of 0.77. In the validation (second) study, severe LGIB developed in 35% of patients; the NOBLADS score predicted the severity of LGIB with an AUC value of 0.76. Higher NOBLADS scores were associated with a requirement for blood transfusion, longer hospital stay, and intervention (P < .05 for trend). CONCLUSIONS: We developed and validated a scoring system for risk of severe LGIB based on 8 factors (NOBLADS score). The system also determined the risk for blood transfusion, longer hospital stay, and intervention. It might be used in decision making regarding intervention and management.

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.

Impact of INR monitoring, reversal agent use, heparin bridging, and anticoagulant interruption on rebleeding and thromboembolism in acute gastrointestinal bleeding.

BACKGROUND: Anticoagulant management of acute gastrointestinal bleeding (GIB) during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB. METHODS: Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users. Data were also compared between direct oral anticoagulants (DOACs) and warfarin users. RESULTS: Between anticoagulant users and non-users, of whom 70% underwent early endoscopy, no endoscopy-related adverse events or significant differences were found in the rate of endoscopic therapy need, transfusion need, rebleeding, or thromboembolism. Rebleeding was associated with shock, comorbidities, low platelet count and albumin level, and low-dose aspirin use but not HAS-BLED score, any endoscopic results, heparin bridge, or international normalized ratio (INR) ≥ 2.5. Risks for thromboembolism were INR ≥ 2.5, difference in onset and pre-endoscopic INR, reversal agent use, and anticoagulant interruption but not CHA2DS2-VASc score, any endoscopic results, or heparin bridge. In patients without reversal agent use, heparin bridge, or anticoagulant interruption, there was only one rebleeding event and no thromboembolic events. Warfarin users had a significantly higher transfusion need than DOACs users. CONCLUSION: Endoscopy appears to be safe for anticoagulant users with acute GIB compared with non-users. Patient background factors were associated with rebleeding, whereas anticoagulant management factors (e.g. INR correction, reversal agent use, and drug interruption) were associated with thromboembolism. Early intervention without reversal agent use, heparin bridge, or anticoagulant interruption may be warranted for acute GIB.

Effect of proton-pump inhibitors on the risk of lower gastrointestinal bleeding associated with NSAIDs, aspirin, clopidogrel, and warfarin.

BACKGROUND: We investigated the effects of proton-pump inhibitors (PPIs) on lower gastrointestinal bleeding (LGIB) and of their interactions with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, clopidogrel, and warfarin on LGIB risk. METHODS: We prospectively studied 355 patients emergently hospitalized for LGIB and 8,221 nonbleeding patients. All patients underwent colonoscopy. Smoking, alcohol drinking, drug exposure, and the Charlson comorbidity index score were assessed before colonoscopy. Adjusted odds ratios (AOR) of LGIB were estimated. RESULTS: LGIB was significantly associated with older age, higher comorbidity index, and NSAID, aspirin, clopidogrel, or warfarin use. PPI use was significantly associated with older age, male sex, being a current alcohol drinker, higher comorbidity index, and NSAID, aspirin, clopidogrel, warfarin, acetaminophen, or corticosteroid use. Multivariate analysis adjusted by the confounding factors revealed LGIB was not significantly associated with PPI use (AOR 0.87; 95 % confidence interval 0.68-1.13; p = 0.311), or specifically with omeprazole (AOR 1.18; p = 0.408), esomeprazole (AOR 0.76; p = 0.432), lansoprazole (AOR 0.93; p = 0.669), or rabeprazole (AOR 0.63; p = 0.140). In the interaction model, no significant interactions were observed between PPIs and NSAIDs (AOR 1.40; p = 0.293), aspirin (AOR 1.09; p = 0.767), clopidogrel (AOR 0.99, p = 0.985), or warfarin (AOR 1.52; p = 0.398). CONCLUSIONS: This large case-control study demonstrated that PPI use did not lead to an increased risk of LGIB, regardless of the type of PPI used. Further, LGIB risk was not affected by PPI use, irrespective of concomitant therapy with NSAIDs, low-dose aspirin, clopidogrel, or warfarin.

Risk factors for adverse in-hospital outcomes in acute colonic diverticular hemorrhage.

AIM: To investigate the factors associated with transfusion, further bleeding, and prolonged length of stay. METHODS: In total, 153 patients emergently hospitalized for diverticular bleeding who were examined by colonoscopy were prospectively enrolled. Patients in whom the bleeding source was identified received endoscopic treatment such as clipping or endoscopic ligation. After spontaneous cessation of bleeding with conservative treatment or hemostasis with endoscopic treatment, all patients were started on a liquid food diet and gradually progressed to a solid diet over 3 d, and were discharged. At enrollment, we assessed smoking, alcohol, medications [non-steroidal anti-inflammatory drugs (NSAIDs)], low-dose aspirin, and other antiplatelets, warfarin, acetaminophen, and oral corticosteroids), and co-morbidities [hypertension, diabetes mellitus, dyslipidemia, cerebro-cardiovascular disease, chronic liver disease, and chronic kidney disease (CKD)]. The in-hospital outcomes were need for transfusion, further bleeding after spontaneous cessation of hemorrhage, and length of hospital stay. The odds ratio (OR) for transfusion need, further bleeding, and prolonged length of stay were estimated by logistic regression analysis. RESULTS: No patients required angiographic embolization or surgery. Stigmata of bleeding occurred in 18% of patients (27/153) and was treated by endoscopic procedures. During hospitalization, 40 patients (26%) received a median of 6 units of packed red blood cells. Multivariate analysis revealed that female sex (OR = 2.5, P = 0.02), warfarin use (OR = 9.3, P < 0.01), and CKD (OR = 5.9, P < 0.01) were independent risk factors for transfusion need. During hospitalization, 6 patients (3.9%) experienced further bleeding, and NSAID use (OR = 5.9, P = 0.04) and stigmata of bleeding (OR = 11, P < 0.01) were significant risk factors. Median length of hospital stay was 8 d. Multivariate analysis revealed that age > 70 years (OR = 2.1, P = 0.04) and NSAID use (OR = 2.7, P = 0.03) were independent risk factors for prolonged hospitalization (≥ 8 d). CONCLUSION: In colonic diverticular bleeding, female sex, warfarin, and CKD increased the risk of transfusion requirement, while advanced age and NSAID increased the risk of prolonged hospitalization.

Role of urgent contrast-enhanced multidetector computed tomography for acute lower gastrointestinal bleeding in patients undergoing early colonoscopy.

BACKGROUND: The clinical significance of performing computed tomography (CT) for acute lower gastrointestinal bleeding (LGIB) remains unknown. This study aimed to evaluate the role of urgent CT in acute LGIB settings. METHODS: The cohort comprised 223 patients emergently hospitalized for LGIB who underwent early colonoscopy within 24 h of arriving at the hospital, including 126 who underwent CT within 3 h of arrival. We compared the bleeding source rate between two strategies: early colonoscopy following urgent CT or early colonoscopy alone. RESULTS: No significant differences in age, sex, comorbidities, vital signs, or laboratory data were observed between the strategies. The detection rate was higher with colonoscopy following CT for vascular lesions (35.7 vs. 20.6%, p = 0.01), leading to more endoscopic therapies (34.9 vs. 13.4%, p < 0.01). Of the 126 who underwent colonoscopy following CT, 26 (20.6%) had extravasation and 34 (27.0%) had nonvascular findings. The sensitivity and specificity of CT extravasation and nonvascular findings for predicting vascular lesions and inflammation or tumors were 37.8 and 88.9 and 81.3 and 80.9%, respectively. A high κ agreement (0.83, p < 0.01) for active bleeding locations was found between CT and subsequent colonoscopy. There were no cases of contrast-induced nephropathy after 1 week of CT. CONCLUSIONS: Urgent CT before colonoscopy had about 15% additional value for detecting vascular lesion compared to colonoscopy alone and thus enabled subsequent endoscopic therapies. Contrast-enhanced CT in acute LGIB settings was safe and correctly identified the presence and location of active bleeding, as well as severe inflammation or tumor stenosis, facilitating decision making.

Adverse Events during Bowel Preparation and Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding Compared with Elective Non-Gastrointestinal Bleeding.

BACKGROUND: There are limited data on the safety of colonoscopy in patients with lower gastrointestinal bleeding (LGIB). We examined the various adverse events associated with colonoscopy in acute LGIB compared with non-GIB patients. METHODS: Emergency hospitalized LGIB patients (n = 161) and age- and gender-matched non-GIB controls (n = 161) were selected. Primary outcomes were any adverse events during preparation and colonoscopy procedure. Secondary outcomes were five bowel preparation-related adverse events--hypotension, systolic blood pressure <100 mmHg, volume overload, vomiting, aspiration pneumonia and loss of consciousness--and four colonoscopy-related adverse events--including hypotension, perforation, cerebrocardiovascular events and sepsis. RESULTS: During bowel preparation, 16 (9%) LGIB patients experienced an adverse event. None of the LGIB patients experienced volume overload, aspiration pneumonia or loss of consciousness; however, 12 (7%) had hypotension and 4 (2%) vomited. There were no significant differences in the five bowel preparation-related adverse events between LGIB and non-GIB patients. During colonoscopy, 25 (15%) LGIB patients experienced an adverse event. None LGIB patient had perforation or sepsis; however, 23 (14%) had hypotension and 2 (1%) experienced a cerebrocardiovascular event. There was no significant difference in the four colonoscopy-related adverse events between LGIB and non-GIB patients. In addition, no significant difference in any of the nine adverse events was found among subgroups: patients aged ≥65 years, those with comorbidities, and those with antithrombotic drug use. CONCLUSIONS: Adverse events in bowel preparation and colonoscopy among acute LGIB patients were low. No significant difference was found in adverse events between LGIB and non-GIB patients. These adverse events were also low in elderly LGIB patients, as well as in those with co-morbidities and antithrombotic drug use, suggesting that colonoscopy performed during acute LGIB did not increase adverse events.