Gastrointestinal Bleeding Events Research Articles

Comparative incidence and risk factors for gastrointestinal bleeding following percutaneous coronary intervention for coronary artery disease: Insights from the Keio Cardiovascular Registry in Japan

BackgroundIn patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet medication usage is crucial for preventing thrombotic events. However, it requires careful monitoring, especially because of the risk of life-threatening bleeding complications. In hemorrhagic complications, assessment of patient background and risk of gastrointestinal bleeding (GIB) remain limited for GIB that develops during long-term observation after hospital discharge. This study aimed to examine the incidence of GIB and patient characteristics in CAD post-PCI. MethodsAll CAD patients undergoing PCI for urgent, emergent, or elective indications were enrolled in the Keio Interhospital Cardiovascular Studies (JCD-KiCS)-PCI registry (January 2009 and December 2017) and followed up to 2 years after PCI discharge. From the JCD-KiCS PCI registry, 8864 patients (median [interquartile range [IQR]] age: non-GIB: 69.0 y [16 y], upper GIB (UGI): 72.0 y [15.5 y], lower GIB (LGI): 73.0 y [IQR: 13 y]) were categorized based on the occurrence of hospitalization-requiring GIB. Patient characteristics and detailed information regarding these GIB events, including the location (upper vs lower GI) and bleeding severity, were analyzed. ResultsOverall, 36 patients experienced UGI, while 85 patients experienced LGI. The rates of dual antiplatelet therapy (DAPT) and triple therapy were significantly different among the non-GIB (n = 8734), UGI (n = 36) and LGI (n = 85) groups (DAPT [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)]: 64 [76.2 %] in the LGI group vs 24 [68.6 %] in the UGI group vs 7330 [84.6 %] in the non-GIB group; triple therapy [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)] + oral anticoagulant (OAC) (warfarin/direct oral anticoagulant [DOAC]): 17 [20.2 %] in the LGI group vs 8 [22.9 %] in the UGI group vs 836 [9.6 %] in the non-GIB group; p < 0.001). In the LGI and UGI groups, aspirin and warfarin were used in 2 (2.4 %) and 2 (5.7 %) patients, respectively, but not in combination with DOAC. The 2-year post-PCI hospitalization incidence for GIB was 1.4 % (LGI, 1.0 %; UGI, 0.4 %). The most common causes were colonic diverticular hemorrhage (43.5 %) for LGI and duodenal ulcer (21.9 %) for UGI. No significant differences were found in the cumulative 2-year post-PCI risks between the LGI and UGI groups (log-rank p = 0.97). Most GIB events were Bleeding Academic Research Consortium 2-equivalent (hemoglobin decrease <3 g/dL). Notably, the use of OACs at PCI discharge, bleeding complications within 72 h, and preprocedural anemia were significantly correlated with an increased GIB risk. ConclusionsThe real-world incidence of LGI is two times higher than that of UGI in CAD patients undergoing PCI, and most events are mild. OAC use at PCI discharge is the strongest potential risk factor for GIB development.

Analysis of thromboembolism and prognosis in metastatic pancreatic cancer from the Tokushukai REAl‑world data project.

Cancer-associated thromboembolism (CAT), including venous thromboembolism (VTE) and arterial thromboembolism (ATE), is a frequent complication of advanced pancreatic cancer. However, reports on its incidence and clinical outcomes, especially on ATE, are limited. The present study aimed to investigate the incidence of CAT and its effects on overall survival in patients with metastatic pancreatic cancer. As part of the Tokushukai REAl-world data project in Japan, 846 eligible patients with metastatic pancreatic cancer treated with first-line chemotherapy were identified between April 2010 and March 2020. Using diagnosis procedure combination data from these patients, the present study investigated the incidence of VTE, ATE and cerebral and gastrointestinal bleeding requiring hospitalization. Blood laboratory data were collected within 14 days of the start of first-line treatment, and Khorana scores were calculated. The associations between CAT complications and comorbidities, concomitant medications and prognosis were examined. Among the 846 patients, 21 (2.5) and 70 (8.3%) had VTE and ATE, respectively (including five with overlapping VTE and ATE). CAT-positive patients had a significantly higher rate of gastrointestinal bleeding events compared with CAT-negative patients [13 of 86 (15.2%) vs. 46 of 760 (6.1%); P=0.01]. CAT-positive patients had a poorer prognosis [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.01-1.62] compared with CAT-negative patients, even after adjusting for background factors (HR, 1.20; 95% CI, 0.95-1.52). Cox regression analyses showed that higher Khorana scores were associated with significantly worse prognosis. This real-world data demonstrated that the incidence rate of CAT in patients with metastatic pancreatic cancer was 10.2%, and no statistically significant differences were observed, although there was a trend toward an adverse prognosis. The Khorana score may also be useful for predicting prognosis, even in the absence of CAT. This study was registered in the UMIN Clinical Trial Registry (http://www.umin.ac.jp/ctr/index.htm; clinical trial no. UMIN000050590).

Early and late hospital readmissions after percutaneous left atrial appendage closure

Introduction and objectivesPercutaneous left atrial appendage closure (LAAC) has emerged as a nonpharmacological alternative for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation. However, there are few data on readmissions after LACC. The aim of this study was to determine the rate of early (≤ 30 days) and late (31-365 days) readmission after LAAC, and to assess the predictors and clinical impact of rehospitalization. MethodsThis multicenter study included 1419 consecutive patients who underwent LAAC. The median follow-up was 33 [17-55] months, and follow-up was complete in all but 54 (3.8%) patients. The primary endpoint was readmissions for any cause. Logistic regression and Cox regression analysis were performed to determine the predictors of readmission and its clinical impact. ResultsA total of 257 (18.1%) patients were readmitted within the first year after LAAC (3.2% early, 14.9% late). The most common causes of readmission were bleeding (24.5%) and heart failure (20.6%). A previous gastrointestinal bleeding event was associated with a higher risk of early readmission (OR, 2.65; 95%CI, 1.23-5.71). The factors associated with a higher risk of late readmission were a lower body mass index (HR, 0.96-95%CI, 0.93-0.99), diabetes (HR, 1.38-95%CI, 1.02-1.86), chronic kidney disease (HR, 1.60; 95%CI, 1.21-2.13), and previous heart failure (HR, 1.69; 95%CI, 1.26-2.27). Both early (HR, 2.12-95%CI, 1.22-3.70) and late (HR, 1.75; 95%CI, 1.41-2.17) readmissions were associated with a higher risk of 2-year mortality. ConclusionsReadmissions within the first year after LAAC were common, mainly related to bleeding and heart failure events, and associated with patients’ comorbidity burden. Readmission after LAAC confered a higher risk of mortality during the first 2 years after the procedure.

A network meta-analysis: evaluating the efficacy and safety of concurrent proton pump inhibitors and clopidogrel therapy in post-PCI patients.

The objective of this research was to evaluate the risk of major adverse cardiovascular events (MACEs) associated with the use of various proton pump inhibitors (PPIs) in combination with clopidogrel in patients who underwent percutaneous coronary intervention (PCI). To accomplish this, we analyzed data from randomized controlled trials and retrospective cohort studies sourced from key electronic databases. These studies specifically examined the effects of different PPIs, such as lansoprazole, esomeprazole, omeprazole, rabeprazole, and pantoprazole, when used in conjunction with clopidogrel on MACEs. The primary focus was on the differential impact of these PPIs, while the secondary focus was on the comparison of gastrointestinal (GI) bleeding events in groups receiving different PPIs with clopidogrel vs. a placebo group. This study's protocol was officially registered with INPLASY (INPLASY2024-2-0009). We conducted a network meta-analysis involving 16 studies with a total of 145,999 patients. Our findings indicated that rabeprazole when combined with clopidogrel, had the lowest increase in MACE risk (effect size, 1.05, 95% CI: 0.66-1.66), while lansoprazole was associated with the highest risk increase (effect size, 1.48, 95% CI: 1.22-1.80). Esomeprazole (effect size, 1.28, 95% CI: 1.09-1.51), omeprazole (effect size, 1.23, 95% CI: 1.07-1.43), and pantoprazole (effect size, 1.38, 95% CI: 1.18-1.60) also significantly increased MACE risk. For the secondary outcome, esomeprazole (effect size, 0.30, 95% CI: 0.09-0.94), omeprazole (effect size, 0.34, 95% CI: 0.14-0.81), and pantoprazole (effect size, 0.33, 95% CI: 0.13-0.84) demonstrated an increased potential for GI bleeding prevention. In conclusion, the combination of lansoprazole and clopidogrel was found to significantly elevate the risk of MACEs without offering GI protection in post-PCI patients. This study is the first network meta-analysis to identify the most effective regimen for the concurrent use of clopidogrel with individual PPIs. https://inplasy.com/inplasy-2024-2-0009/, identifier (INPLASY2024-2-0009).

Early Postoperative Changes in Von Willebrand Factor Activity Are Associated With Future Bleeding and Stroke in HeartMate 3 Patients.

Hemocompatibility-related adverse events (HRAEs), particularly gastrointestinal bleeding, remain a frequent complication after left ventricular assist device (LVAD) implantation. The current study sought to describe and analyze whether early (<60 days) postoperative von Willebrand factor (VWF) activity assays predict the risk of gastrointestinal bleeding and stroke. A prospective single-center study including 74 HeartMate 3 device recipients between 2016 and 2023 was undertaken. The postoperative trajectory of the VWF profile was analyzed using linear mixed-effect models and Cox models were used to quantify associations between an early postoperative dip (≤0.7) in VWF activity assay measurements and late outcomes. Preoperatively, the mean VWF:Activity (Act)/Antigen (Ag) and VWF:Collagen Binding (CB)/Ag ratios were 0.94 (95% confidence interval [CI] = 0.81-1.02) and 0.95 (95% CI = 0.80-1.03), respectively, decreasing to 0.66 (95% CI = 0.57-0.73) and 0.67 (95% CI = 0.58-0.74) within 40 days (p < 0.05). In patients with VWF:CB/Ag and VWF:Act/Ag ratios ≤0.7 significantly more gastrointestinal bleeding (hazard ratio [HR]: 2.53; 95% CI = 1.1-5.8, and HR: 3.7; 95% CI = 1.5-9.2, respectively) and hemorrhagic stroke events (HR: 3.5; 95% CI = 1.6-7.6 and HR: 4.9; 95% CI = 2.1-11.7, respectively) were observed throughout the entire late (>60 days) postoperative period. In patients with VWF:Act/Ag ratio ≤0.7 less ischemic stroke events were observed (HR: 0.11; 95% CI = 0.01-0.85). In conclusion, VWF:Act/Ag and VWF:CB/Ag ratios ≤0.7 in the early postoperative phase can be used as biomarkers to predict HRAEs during long-term LVAD support.

One-year effectiveness and safety outcomes of edoxaban treatment in Chinese patients with atrial fibrillation: First snapshot of more than 4,800 patients from the ETNA-AF-China study

Abstract Background Direct oral anticoagulants (DOACs) have become the first-line therapy for ischaemic stroke prevention in atrial fibrillation (AF) patients. Data on the effectiveness and safety of single DOAC in large Chinese populations are scarce. Purpose We firstly present the one-year outcome data of edoxaban treatment in 5001 Chinese AF patients. Methods This is a multi-centre, prospective, observational study, ETNA-AF-China, conducted in 89 centres from four economic regions in Mainland of China with a follow-up of two years. Primary endpoint of safety [bleeding events including intracranial hemorrhage (ICH), all-cause and cardiovascular (CV) mortality] and efficacy endpoints [stroke, systemic embolic events (SEE), transient ischemic attack (TIA)] were adjudicated. Annualised event rates and Kaplan­Meier (KM) survival curves are given. Results A total of 4822 patients (57.1% male) using edoxaban (60 mg OD: n=2614, 30 mg OD: n=2208) who completed one-year follow-up were included in the full analysis set. The mean (SD) age of the overall patient population was 70.3 (9.5) years, CHA2DS2-VASc and HAS-BLED scores were 2.9 (1.4), 1.7 (1.0), with creatinine clearance (CrCl) of 71.2 (27.7) mL/min. Patients receiving 30 mg OD edoxaban at baseline were older (73.4 vs 67.7 years), with higher CHA2DS2-VASc score (3.3 vs 2.6), larger percentage of frail (9.9% vs 3.4%), and higher renal impairment (defined as CrCl ≤80 mL/min, 70.3% vs 42.9%). Annualised rates for all-cause and cardiovascular death in the overall population were very low with 2.22%/year and 0.41%/year, respectively. (Figure 1) The death rates were nearly three times lower in those receiving standard dose (60 mg) than reduction dose (30 mg) of edoxaban. Annualised event rates for all stroke/SEE (1.03%/year) and ischemic stroke (0.60%/year) were similar between two dose groups. Overall, annualised rates for major bleeding (1.03%/year), ICH (0.18%/year), major gastrointestinal (GI) bleeding (0.48%/year) events were relatively low, and those on 60 mg dose experienced less above bleeding events. Cumulative survival analysis demonstrated a slow increase in time-to-first event curve of all-cause death; and from baseline to 1-year follow-up, significant lower events of all-cause death (log-rank p&amp;lt;0.001), major bleeding (p=0.002) in 60 mg vs 30 mg edoxaban groups. (Figure 2). Conclusion Low incidences of major bleeding, notably ICH, major GI bleeding, and CV death were observed in unselected 4822 patients with AF during 1-year of edoxaban treatment. These findings confirm the effectiveness and safety of routine edoxaban use in China, consistent with other countries, and reinforce the results of the ENGAGE AF-TIMI 48 trial.Figure 1Figure 2

#688 Major gastrointestinal bleeding in dialysis: influence of age, sex, race &amp; comorbidities

Abstract Background and Aims Gastrointestinal bleeding (GIB) is considered the most common type of bleeding event in the dialysis population [1]. However, studies to date are small and not representative of the dialysis population, and the influence of patient characteristics has not been considered. We used a nationally representative sample of dialysis patients treated in the United States (US) to characterize the rates of major GIB episodes requiring hospitalization overall and by age, sex, race, and history of GIB comorbidity. Method We used data from a kidney care network from Jan 2018 through Mar 2021. We included data from adult dialysis patients (age ≥18 years) who were treated with dialysis for at least 30 days. We excluded patients who started dialysis on or after Jan 2021 to provide a three-month minimum follow up time for outcomes to occur. GIB hospitalizations were identified from international classification of diseases (ICD) diagnosis codes recorded as the primary, secondary, or tertiary discharge reason for hospitalization. ICD clusters defining GIB hospitalizations and lesion location were based on the US Healthcare Cost and Utilization Project [2]. We calculated proportion of patients with one or more GIB hospitalization, and the proportion of GIB observations per patient during the 3.25-year period by patient characteristics (GIB comorbidity, sex, age, race). Results Among 366,839 adult dialysis patients, 6.8% (n = 25,057) experienced one or more GIB hospitalization during the 3.25-year period. In total, there were 36,791 GIB hospitalization observations with 73.5% (n = 18,422) of patients with one GIB hospitalization, 16.8% (n = 4208) with two GIB hospitalizations, and 9.7% (n = 2,427) with three or more GIB hospitalizations. The lesion location was unspecified in diagnosis codes for 64.7% (n = 23,576) of GIB hospitalization observations. Among GIB hospitalization observations with a recorded lesion location, 60.3% (n = 7,968) were an upper GIB and 39.7% (n = 5,247) were a lower GIB. A baseline history of a GIB comorbidity was associated with a 2.9-fold higher rate for the occurrence of one or more GIB hospitalization in a unique patient, and a 3.5-fold higher rate of a GIB hospitalization event considering all observations (Fig. 1A). GIB hospitalization rates were relatively consistent between females and males on both a patient- and observation-level (Fig. 1B). There were positive increases in GIB hospitalization rates with older age categories, with about a 2-fold higher rate among those with an age ≥75 years compared to an age 18-44 years on both a patient- and observation-level (Fig. 2A). GIB hospitalization rates were relatively consistent for race groups, albeit there may be a trend for slightly higher rates among those with a black race, in particular on an observation level that accounts for multiple events per patient (Fig. 2B). Conclusion Major GIB events requiring hospitalization affect about 7% of dialysis patients. It appears about 60% of GIB hospitalizations were for an upper GIB, and about 40% were for a lower GIB. Patients who experienced one GIB hospitalization commonly had multiple GIB events, with more than 25% having two or more GIB hospitalizations during the observation period. Older age and a history of a baseline GIB comorbidity were associated with higher GIB hospitalization rates. Biological sex and race did not appear to be associated to GIB hospitalization rates. Ongoing analysis of GIB incidence accounting for person-years at risk is needed to confirm these observations.

Retrospective chart review of GI bleeding in people with von Willebrand disease.

Gastrointestinal (GI) bleeding events (BEs) in von Willebrand disease (VWD) are difficult to diagnose and often recurrent. Limited data from clinical trials has led to lack of consensus on treatment options. Describe current treatments and outcomes for GI BEs in people with VWD. This retrospective, observational, multicentre chart review study was conducted from January 2018 through December 2019 and included patients with inherited VWD with ≥1 GI BE in the preceding 5years. Baseline characteristics, number and aetiology of BEs, associated GI-specific morbidities/lesions, treatment and outcomes were analysed descriptively. Sixty bleeds were reported in 20 patients with type 1 (20%), type 2 (50%) and type 3 (30%) VWD. During the 5-year study period, 31 (52%) BEs had one identified or suspected cause; multiple causes were reported in 11 (18%). Most GI BEs (72%) were treated with a combination of von Willebrand factor (VWF), antifibrinolytics and/or other haemostatic or non-haemostatic treatments. Time to resolution did not differ by VWF treatment use; however, BEs treated with non-VWF treatments tended to resolve later. In patients with GI-specific morbidities/lesions, 84% resolved with first-line treatment; time to resolution tended to be longer than in patients without such morbidities/lesions. Thirteen BEs occurred in patients receiving prophylaxis and 47 in patients receiving on-demand treatment; 18 BEs resulted in a switch to prophylaxis after bleed resolution. This study confirms the unmet need for the management of recurrent GI BEs in people with VWD and the need for prospective data, especially on prophylaxis.

Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis

Gastrointestinal (GI) bleeding control is critical in elderly patients with atrial fibrillation (AF) receiving oral anticoagulants (OAC). This subgroup analysis aimed to clarify the actual state and significance of GI bleeding in elderly non-valvular AF (NVAF) patients. We evaluated the incidence and risk factors of GI bleeding during the 2-year follow-up and examined the GI bleeding impact on mortality. Of the 32,275 patients in the ANAFIE Registry, 1139 patients (3.5%) experienced GI bleeding (incidence rate, 1.92 events per 100 person-years; mean follow-up, 1.88 years); 339 upper and 760 lower GI bleeding events occurred. GI bleeding risk factors included age ≥ 85 years, body mass index ≥ 25.0 kg/m2, prior major bleeding, hyperuricaemia, heart failure, P-glycoprotein inhibitor use, GI disease, and polypharmacy (≥ 5 drugs). No significant differences in GI bleeding risk were found between direct OAC (DOAC) vs warfarin users (adjusted hazard ratios [95% confidence interval], 1.01 [0.88–1.15]). The 1-year post-GI bleeding mortality rate was numerically higher in patients with upper (19.6%) than lower GI bleeding (8.9%). In elderly Japanese NVAF patients, this large-scale study found no significant difference in GI bleeding risk between DOAC vs. warfarin users or 1-year mortality after upper or lower GI bleeding.

Temporal Analysis in Outcomes of Long-Term Mechanical Circulatory Support: Retrospective Study.

Mechanical assist device indications have changed in recent years. Reduced incidence of complications, better survival, and the third generation of mechanical support devices contributed to this change. In this single-center study, we focused on two time periods that are characterized by the use of different types of mechanical support devices, different patient characteristics, and change in the indications. The data were processed from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). We retrospectively defined two time intervals to reflect changes in ventricular assist device technology (period 1: 2007-2015; period 2: 2016-20222). A total of 181 patients underwent left ventricular assist device implantation. Device utilization was the following: HeartMate II = 52 (76.4%) and HeartWare = 16 (23.6%) in period 1 and HeartMate II = 2 (1.8%), HeartMate 3 = 70 (61:9%), HeartWare = 29 (25.7%), SynCardia TAH = 10 (8.8%), and BerlinHeart EXCOR = 2 (1.8%) in period 2. The outcomes of the time intervals were analyzed and evaluated. Survival was significantly higher during the second time period. Multivariate analysis revealed that age and bypass pump time are independent predictors of mortality. Idiopathic cardiomyopathy, bypass time, and the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score are independent predictors of adverse events. Furthermore, the first period was noted to be at an increased risk of the following adverse events: pump thrombosis, gastrointestinal bleeding, and bleeding events. Despite the higher risk profile of the patients and persistent challenges, during the second period, there was a significant decrease in mortality and morbidity. The use of the HeartMate 3 device may have contributed to this result.

114 Burn Specific VTE Prophylaxis: Higher Enoxaparin Dose and Anti-Xa Adjustments Is Safe and Potentially Beneficial

Abstract Introduction Burn and trauma patients are at high risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolus (PE). VTE prophylaxis guidelines for trauma patients recommends a higher standard dose of enoxaparin and anti-Xa level adjustments in select patients; however, no guidelines specific to burn patients exist. We hypothesize that higher standard doses of enoxaparin and anti-Xa level adjustments will be safe and effective at reducing VTE complications in burn patients. Methods This retrospective review included patients admitted to a regional burn center six months prior to and after the initiation of a VTE prophylaxis quality improvement protocol. The protocol doubled the standard dose of enoxaparin, 40 mg daily to 40 mg twice a day, for all burn patients who were &amp;gt; 50 kg and had creatinine clearance &amp;gt; 60mg/dl. Peak anti-Xa level monitoring was indicated if a high-risk factor (TBSA ≥20%, inhalation injury, burn shock, BMI ≥40) was present. Patients on therapeutic anticoagulation or anti-platelet therapy, had a history of chronic kidney disease, decompensated cirrhosis, coagulation disorder, heparin induced thrombocytopenia (HIT), or were admitted for polytrauma were excluded. Efficacy was evaluated by rates of VTE within 31 days of discharge. Safety was evaluated by bleeding complications, including estimated blood loss (EBL), number of transfusions and gastrointestinal (GI) bleeding events. Differences between groups were compared using a two-sample t-test or Wilcoxon rank-sum test. A p-value of &amp;lt; 0.05 signified statistical significance. Results The pre-protocol group included 217 patients and the post-protocol group included 207 patients. There were no significant differences in age (45 vs 44 years), BMI (27 vs 26.4 kg/m2), TBSA (5.9 vs 5.3%), IHI (4.6 vs 7%), number of procedures (3 vs 3), mortality (4.1 vs 3%), or ICU length of stay (1.9 vs 1.6 days) between groups. No significant difference in EBL (50 vs 25 cc), number of transfusions (3.3 vs 2.4 units), or GI bleeding events (1 vs 1) was noted between groups, and no patient developed thrombocytopenia or HIT. There were 5 patients (2.3%) with a VTE within 31 days of discharge in the pre-protocol group compared to 1 patient (0.4%) in the post-protocol group (p=0.19). There was not enough power to determine statistically significant VTE prevention. Conclusions A lack of VTE prophylaxis recommendations for burn patients leads to variability in protocols among burn centers. These protocols are infrequently studied. This protocol, which doubled the standard dose of enoxaparin and adjusted based on anti-Xa levels for high-risk patients, was safe. Efficacy and applicability to other centers needs further elucidation. Applicability of Research to Practice Enoxaparin 40mg twice a day with anti-Xa level adjustments is safe and a promising strategy to reduce the rates of VTE in the burn population without increasing bleeding complications.

Adjudication of a primary trial outcome: Results of a calibration exercise and protocol for a large international trial

BackgroundAscertainment of the severity of the primary outcome of upper gastrointestinal (GI) bleeding is integral to stress ulcer prophylaxis trials. This protocol outlines the adjudication process for GI bleeding events in an international trial comparing pantoprazole to placebo in critically ill patients (REVISE: Re-Evaluating the Inhibition of Stress Erosions). The primary objective of the adjudication process is to assess episodes submitted by participating sites to determine which fulfil the definition of the primary efficacy outcome of clinically important upper GI bleeding. Secondary objectives are to categorize the bleeding severity if deemed not clinically important, and adjudicate the bleeding site, timing, investigations, and treatments. MethodsResearch coordinators follow patients daily for any suspected clinically important upper GI bleeding, and submit case report forms, doctors' and nurses’ notes, laboratory, imaging, and procedural reports to the methods center. An international central adjudication committee reflecting diverse specialty backgrounds conducted an initial calibration exercise to delineate the scope of the adjudication process, review components of the definition, and agree on how each criterion will be considered fulfilled. Henceforth, bleeding events will be stratified by study drug, and randomly assigned to adjudicator pairs (blinded to treatment allocation, and study center). ResultsCrude agreement, chance-corrected agreement, or chance-independent agreement if data have a skewed distribution will be calculated. ConclusionsFocusing on consistency and accuracy, central independent blinded duplicate adjudication of suspected clinically important upper GI bleeding events will determine which events fulfil the definition of the primary efficacy outcome for this stress ulcer prophylaxis trial. RegistrationNCT03374800 (REVISE: Re-Evaluating the Inhibition of Stress Erosions)

Permissibility of an Intermittent Fasting in Patients with Chronic Lymphocytic Leukemia in the Era of Novel Therapies :a Pharmacology Based Review

Introduction Chronic Lymphocytic Leukemia (CLL) is a mature neoplasm characterized by the proliferation of immunologically dysfunctional B cells. Inhibitors of BCL2 (venetoclax) and Bruton Tyrosine Kinase (BTK) (ibrutinib, acalabrutinib and zanubrutinib) are novel agents that have revolutionized outcomes in CLL patients in the newly diagnosed and relapsed/refractory settings. Nevertheless, tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) remains concerning adverse events. In clinical trials, fasting has demonstrated reductions in chemotherapy-related side effects and improved treatment tolerability . However, with novel agents in CLL this can be challenging with the need for aggressive hydration in fluid-restricting fasting practices and the higher risk for GI bleeding and peptic ulcer disease complications with fasting. This review aims to explore the literature available to answer the permissibility of intermittent fasting (IF) in CLL patients who are being treated with first line novel agents (FLNAs). Methods Literature exploration was performed to identify IF practices and the effects of fasting conditions and fluid-restriction on the pharmacokinetics (PK) of FLNAs. Literature was also scoped for data on TLS and GIB risk associated with FLNAs in CLL patients as well as the effects of fasting and or fluid-restricted states on GIB and TLS risks. Lastly, the identified risks were accumulated to build a pathway for permissibility of IF in this patient population. Results Venetoclax has amplified the historical low risk of TLS in patients with CLL to a significant degree. Approaches to prevent TLS such as aggressive hydration and use of uric acid reducing drugs hinder patients wishing to practice fluid restricting IF ( See Table 1 and Figure 1), especially during ramp-up phase. Moreover, venetoclax should be administered with food and on daily basis. Hence, only fluid liberal IF practices with daily food intake and medication administration may be possible in venetoclax CLL patients. Furthermore, studies have indicated a possible increased baseline risk of GIB in patients who practice IF. Also, FDA reporting system for adverse events (AE) had higher GIB events among ibrutinib patients compared to other FLNAs. Overall, there was scarcity in the clinical data available on the effects of IF on treatment outcomes with FLNA in CLL patients. There was also evident variability in the number of reported AE between the relatively older (ibrutinib and venetoclax) and newer medications (acalabrutinib and zanubrutinib), which may be causing an underestimation of treatment risks. Conclusion Until further data is available, patients on BTK inhibitors should refrain from practicing IF for GI bleeding risk. However, it may be possible for patients on venetoclax to practice fluid liberal IF conditionally and conservatively for TLS risk. This is on the conditions that adequate hydration and daily administration with food are achieved. Fasting's risks and benefits must be discussed with patients . Further prospective clinical trials, including exploration of different forms of IF, are needed to better elucidate the effect of IF on FLNAs treatment -related outcomes in CLL patients .

Predicting functional outcome in acute ischemic stroke patients after endovascular treatment by machine learning.

Endovascular therapy (EVT) was the standard treatment for acute ischemic stroke with large vessel occlusion. Prognosis after EVT is always a major concern. Here, we aimed to explore a predictive model for patients after EVT. A total of 156 patients were retrospectively enrolled. The primary outcome was functional dependence (defined as a 90-day modified Rankin Scale score ≤ 2). Least absolute shrinkage and selection operator and univariate logistic regression were used to select predictive factors. Various machine learning algorithms, including multivariate logistic regression, linear discriminant analysis, support vector machine, k-nearest neighbors, and decision tree algorithms, were applied to construct prognostic models. Six predictive factors were selected, namely, age, baseline National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT (ASPECT) score, modified thrombolysis in cerebral infarction score, symptomatic intracerebral hemorrhage (sICH), and complications (pulmonary infection, gastrointestinal bleeding, and cardiovascular events). Based on these variables, various models were constructed and showed good discrimination. Finally, a nomogram was constructed by multivariate logistic regression and showed a good performance. Our nomogram, which was composed of age, baseline NIHSS score, ASPECT score, recanalization status, sICH, and complications, showed a very good performance in predicting outcome after EVT.

Gastrointestinal bleeding and cardiovascular events in patients with atrial fibrillation: results from the SAKURA AF registry and RAFFINE registry

Abstract Background Anticoagulants for patients with atrial fibrillation (AF) reduce cardiovascular events but increase gastrointestinal bleeding. However, the association between gastrointestinal bleeding and cardiovascular events is unclear. The present study aimed to evaluate the association between bleeding and major adverse cardiac and cerebrovascular events (MACCE) among patients with AF. Methods We analyzed the data of 2 Japanese multicenter registries (the SAKURA AF registry and RAFFINE registry). Primary endpoint was MACCE, which was defined as a composite of death, myocardial infarction and stroke. The association of gastrointestinal bleeding with subsequent MACCE risk was investigated using time-adjusted Cox multivariate analysis after adjusting for baseline characteristics and time from bleeding. Results Among 7,133 AF patients, 192 (2.7%) had gastrointestinal bleeding events during follow-up. Multivariate logistic regression analysis showed that age (Odds ratio (OR) 1.02, 95% CI 1.00-1.05, p=0.046), hypertension (OR 1.52, 95% CI 1.04-2.21, p=0.03), diabetes mellitus (OR 1.38, 95% CI 1.02-1.88, p=0.04) and lower hemoglobin level (OR 0.84, 95% CI 0.76-0.92, p=0.0002) were independent predictors of gastrointestinal bleeding. Incidence of MACCE was significantly higher in patients with gastrointestinal bleeding than those without (13.93% versus 3.54% per patient-year; p&amp;lt;0.0001, Figure). Even after adjusted for other risk factors, patients who experienced gastrointestinal bleeding had significantly higher risk of MACCE (hazard ratio, 3.09; 95% CI, 2.20-4.33; p&amp;lt;0.0001). Conclusions In patients with AF, gastrointestinal bleeding was strongly associated with incidence of MACCE. Thus, it is important to prevent gastrointestinal bleeding to avoid adverse cardiovascular events.Figure

Changing Strategy Between Bridge to Transplant and Destination LVAD Therapy After the First 3 Months: Analysis of the STS-INTERMACS Database

Background: Left ventricular assist devices (LVADs) have been implanted as bridge to transplantation (BTT), bridge to candidacy (BTC) or destination therapy (DT) based on relative and absolute contraindications to transplantation. Multiple factors may lead to change in the strategy of support after LVAD implantation. Methods: From INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) 2012-2020, 11,262 patients survived to 3 months on continuous flow LVADs with intent of BTT or DT. Pre-implant characteristics and early events post-LVAD were analyzed in relation to changes in BTT or DT strategy during the next 12 months. Results: Among 3216 BTT patients at 3 months, later transplant de-listing or death without transplant occurred in 536 (16.7%) and, was more common with age, Profiles 1-2, renal dysfunction, and independently for prior cardiac surgery (HR 1.25, 95% CI 1.04-1.51, p = 0.02). Post-LVAD events of infections, gastrointestinal bleeding, stroke, and right heart failure defined by inotropic therapy predicted de-listing and death, as did in-hospital location at 3 months (HR 1.67, 95% CI 1.20-2.33, p =0.0024). Of 8046 patients surviving to 3 months with intent as destination therapy, 750 (9.3%) subsequently underwent listing or transplant, often with initial history of acute HF (HR 1.70, 95% CI 1.27-2.27, p = 0.0012) or malnutrition-cachexia (1.73, 95% CI 1.14-2.63, p = 0.0099). Multiple gastrointestinal bleeding events (≥4) with LVAD increased transition from BTT to DT (HR 4.22, 95% CI 1.46-12.275, p = 0.0078) but also from DT to BTT (HR 5.17, 95% CI 1.92-13.9, p = 0.0011). Conclusions: Implant strategies change over time in relation to pre-implant characteristics and adverse events post implant. Pre-implant recognition of factors predicting later change in implant strategy will refine initial triage, while further reduction of post-LVAD complications will expand options including eventual consideration of heart transplant.

The Prevalence of Gastrointestinal Bleeding in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Introduction: Severe acute respiratory syndrome coronavirus 2 caused the coronavirus disease of 2019 (COVID-19), which rapidly became a pandemic, claiming millions of lives. Apart from the main manifestations of this infection concerning the respiratory tract, such as pneumonia, there are also many manifestations from the gastrointestinal tract. Of these, bleeding from the gastrointestinal tract is a significant complication quite dangerous for life. This bleeding is divided into upper and lower, and the primary pathophysiological mechanism is the entering of the virus into the host cells through the Angiotensin-converting enzyme 2 receptors. Also, other comorbidities and the medication of corticosteroids and anticoagulants are considered to favor the occurrence of gastrointestinal bleeding (GIB). Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the studies were searched in two different databases (Scopus and PubMed) from November 2019 until February 2023. All studies that reported GIB events among COVID-19 patients were included. Results: 33 studies were selected and reviewed to estimate the prevalence of GIB. A total of 134,905 patients with COVID-19 were included in these studies, and there were 1458 episodes of GIB. The prevalence of GIB, in these 33 studies, ranges from 0.47% to 19%. This range of prevalence is justified by the characteristics of the COVID-19 patients. These characteristics are the severity of COVID-19, anticoagulant and other drug treatments, the selection of only patients with gastrointestinal manifestations, etc. The pooled prevalence of gastrointestinal bleeding was estimated to be 3.05%, rising to 6.2% when only anticoagulant patients were included. Conclusions: GIB in COVID-19 patients is not a rare finding, and its appropriate and immediate treatment is necessary as it can be life-threatening. The most common clinical findings are melena and hematemesis, which characterize upper GIB. Treatment can be conservative; however, endoscopic management of bleeding with embolization is deemed necessary in some cases.

Gastrointestinal bleeding on continuous-flow left ventricular assist device therapy.

While technological advances in the field of continuous-flow left ventricular assist device (CF-LVAD) are constantly being made, CF-LVAD recipients are still subjected to a relatively high rate of LVAD-related adverse events, with post-LVAD gastrointestinal bleeding (GIB) being the most common one. GIB is associated with a significant impairment in quality of life, multiple hospital admissions, blood transfusion requirements and possibly death. Furthermore, of those patients who bled once, many will experience recurrent GIB events, which further aggravates their discomfort. While some medical and endoscopic treatment options are available, evidence regarding their benefit remains largely equivocal, with all related studies based on data from registries rather than clinical trials. Although having a major impact on LVAD recipients, an effective and validated pre-implant screening options to predict GIB events post-implant are scarce. This review focuses on the aetiology, incidence, risk factors, treatment options and the effect of new generation devices on post-LVAD GIB.

#2868 PREDICTION OF MAJOR GASTROINTESTINAL BLEEDING EVENTS IN HEMODIALYSIS

Abstract Background and Aims INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. At the inaugural INSPIRE meeting, the group came to a consensus that major bleeding events represent potentially preventable complications that occur more frequently in people with kidney disease versus the general population [1]. Given the most common class of bleeding event is gastrointestinal bleeding (GIB) [2], the INSPIRE group assessed if a machine learning model could be developed to assist with determining a hemodialysis (HD) patient's 180-day GIB hospitalization risk. Method Model was developed using adult HD patient data from United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤180 days before GIB hospitalization were classified as positive observations, and others were negative observations. Datasets were randomly sampled to build an XGBoost model that considered 386 exposures initially and was refined to the top 50 exposures. Unseen testing dataset was used to determine final model performance. Results The incidence of 180-day GIB hospitalization was 1.18% in the HD population (n = 451,579), and 1.16% among patients in the testing dataset (n = 27,991). The model showed an area under the curve = 0.69, sensitivity = 57.9%, specificity = 68.9%, accuracy = 68.8% and balanced accuracy = 63.4%. Exposures with largest effect size observed via Shapley values were older age (group mean GIB event = 68.2 years vs no GIB event = 63.4 years), shorter days since last all-cause hospital admission (group mean GIB event = 203.2 days vs no GIB event = 253.2 days), and higher serum 25-hydroxy (OH) vitamin D levels from most recent lab (group mean GIB event = 33.4 ng/mL vs no GIB event = 30.5 ng/mL). Other important predictors included lower hemoglobin and iron indices, longer dialysis vintage, and proton pump inhibitor use (Fig. 1). Conclusion The machine learning model appears suitable for early detection of GIB event risk in HD, yet prospective testing is needed. The association between higher 25OH vitamin D and GIB events was unexpected and warrants investigation. A consistent signal has been observed in warfarin users without kidney disease among which 25OH vitamin D levels of 30–100 ng/mL were shown to associate with the highest GIB risk [3].

Nationwide phase II randomized controlled trial of low-dose ibuprofen vs placebo for cancer-related cognitive impairment (CRCI).

12116 Background: CRCI is an important clinical problem encompassing difficulties in attention, memory, and executive function. Interventions for CRCI during chemotherapy have not been established. Inflammation is associated with CRCI and thus targeting inflammation may alleviate CRCI. In a nationwide study, we investigated a low-dose of ibuprofen for alleviating CRCI in patients self-reporting cognitive problems during chemotherapy or after recent completion of chemotherapy. Methods: Participants with cancer currently on or recently completed chemotherapy and who self-reported cognitive problems were recruited via the NCI Community Oncology Research Program (URCC NCORP) and 11 affiliates. Participants completed pre-intervention assessments and were stratified by disease type (breast cancer; gastrointestinal cancer; other) and randomized to one of 2 groups for 6 weeks: ibuprofen (200 mg BID) or blinded placebo equivalent. At pre-intervention and post-intervention, participants completed a perceived cognitive function measure (FACT-Cog Perceived Cognitive Impairment (PCI)) and cognitive assessments including Rapid Visual Processing (RVP) latency, Delayed Match to Sample (DMS) visual memory, and Verbal Recognition Memory (VRM) word recall. ANCOVA was used to assess between group differences pre- to post-intervention adjusting for baseline cognitive test score. Results: In total, 87 participants were randomized; 45 were randomized to ibuprofen and 42 randomized to placebo (mean age = 55; 85% female; 47% breast cancer, 29% colon/colorectal cancer; 24% other diagnoses). Most participants were fully compliant and completed post-intervention assessments (86% in Ibuprofen arm, 87% in placebo arm). There were no gastrointestinal bleeding events of any grade in the ibuprofen arm and serious adverse events were rare in both arms occurring in only 4% and 7% of patients in the ibuprofen and placebo arms, respectively. For PCI, both groups significantly reported less impairment from pre- to post-intervention; there were no difference between groups. Patients randomized to ibuprofen had a significant improvement on RVP latency time compared to placebo (110.63 milliseconds; p &lt; 0.005). On the DMS, patients receiving ibuprofen had a trend toward improved function compared to placebo (7.39%; p = 0.08). However, patients in placebo performed better in word recall compared to ibuprofen from pre- to post-intervention (1.64 words; p &lt; 0.05). Conclusions: Low-dose, short duration ibuprofen was safe with minimal adverse events in patients with cancer receiving chemotherapy or recently completed chemotherapy. Ibuprofen showed improvements in processing speed time and visual memory in patients with cancer as hypothesized, but not verbal memory. These novel Phase II findings need to be replicated in a Phase III RCT. Funding: R21CA187500, UG1CA189961. Clinical trial information: NCT03186638 .