Risk Of Gastrointestinal Bleeding Research Articles

Safety Analysis of Spironolactone Use in Patients Undergoing Percutaneous Coronary Intervention with High Bleeding Risk: A Propensity Score-Matched Study.

Spironolactone has been reported to increase the risk of upper gastrointestinal bleeding in patients. We aimed to validate this perspective in a population of patients undergoing percutaneous coronary intervention with high bleeding risk (PCI-HBR). We prospectively included a total of 1616 PCI-HBR patients who were treated at West China Hospital of Sichuan University from May 2022 to July 2024. These patients were divided into a spironolactone treatment group (n = 301) and a non-spironolactone treatment group (n = 1315). A propensity score matching was performed at a 1:4 ratio, and Cox regression analysis was conducted on the matched data. Additionally, Kaplan-Meier curves were plotted to evaluate the direct correlation between spironolactone use and gastrointestinal bleeding. And the subgroup analysis is used to assess the robustness of the results. In this study, after propensity score matching, a total of 927 patients were included in the outcome analysis, with 259 in the spironolactone group and 668 in the non-spironolactone group. Throughout the follow-up period, 14 (5.4%) and 42 (6.3%) patients experienced BARC 2-5 gastrointestinal bleeding events in the spironolactone and non-spironolactone groups, respectively, while 6 (2.3%) and 24 (3.6%) patients experienced BARC 3-5 gastrointestinal bleeding. The incidence of BARC 2-5 gastrointestinal bleeding was comparable between the groups (14/259 [5.4%] vs. 42/668 [6.3%]; HR 0.88 [0.48-1.62], p = 0.689), as was the incidence of BARC 3-5 gastrointestinal bleeding (6/259 [2.3%] vs. 24/668 [3.6%]; HR 0.69 [0.28-1.68], p = 0.410). No statistically significant interactions were found between spironolactone use and clinical variables such as acute coronary syndrome, diabetes, and chronic kidney disease concerning the risk of gastrointestinal bleeding. In summary, our prospective cohort study, which used propensity score matching, represents the first comprehensive investigation of spironolactone usage in PCI-HBR patients. Our results underscore that cardiologists need not routinely consider the risk of spironolactone-induced bleeding when making decisions about its use in patients. Larger randomized trials or analyses from existing randomized trials on spironolactone are warranted to draw definitive conclusions about the potential association between spironolactone and bleeding.

Patient (pt) characteristics, treatment patterns, and outcomes in unresectable hepatocellular carcinoma (uHCC) treated with first-line (1L) systemic therapy in the United States (US).

572 Background: Guidelines recommend systemic therapy for uHCC ineligible for locoregional therapy. Until the approval of tremelimumab + durvalumab for uHCC, in Oct 2022, 1L systemic therapies in the US included multikinase inhibitors and atezolizumab (A) + bevacizumab (B). It is crucial to understand factors driving real-world treatment decisions and outcomes in uHCC. Characteristics, treatment patterns, and outcomes were assessed in US pts with uHCC treated with 1L systemic therapy. Methods: Data were collected from electronic medical records from US Mayo Clinic sites. Pts with uHCC who initiated an NCCN-recommended 1L systemic therapy between Jun 2020–Oct 2022 (A + B was the only approved 1L immunotherapy (IO)-based regimen) with ≥2 follow-up visits, were included. Index was the date of first 1L systemic therapy. Pts were assessed by risk of post-index gastrointestinal (GI) bleeding (pts with Child-Pugh class B or C, pre-index GI bleeding, uncontrolled hypertension [HTN] [≥2 anti-HTN drugs or ≥2 vital entries of SBP >140 mmHg or DBP >90 mmHg]), or significant varices and band ligation). Treatment patterns, overall survival (OS), and post-index GI bleeding were assessed. Results: A total of 186 pts met the inclusion criteria. Most common etiologies of liver disease were metabolic dysfunction-associated steatohepatitis (42.7%) and hepatitis C virus (40.2%). Pre-index GI bleeding was reported in 29.0% of pts, of which 46.3% occurred within 6 months (mo) pre-index; 62.4% of pts had EGD, of which 72.4% had varices. There were 128 (68.8%) pts with GI bleeding risk and 58 (31.2%) pts without GI bleeding risk. The most common 1L systemic therapies for pts with GI bleeding risk were A + B (72.7%) and A only (9.4%), while for pts without GI bleeding risk, A + B (29.3%), nivolumab + ipilimumab (13.8%), and B + chemotherapy (13.8%) were the most common. Median OS and OS rates at 12, 18, and 24 mo were lower, and post-index GI bleeding rate was higher in pts with vs without GI bleeding risk (Table). For pts treated with A + B, median OS and OS rates at 12, 18, and 24 mo were lower in pts with vs without GI bleeding risk (Table). Conclusions: In this network, prior to the approval of other 1L IO-based regimens for uHCC, many pts received A + B, despite risk of post-index GI bleeding. Median OS with A + B was shorter in pts with vs without GI bleeding risk. Data highlight the complexity of uHCC and the unmet need for guidance on characteristics-driven treatment decisions. Full cohort A + B cohort All ptsN=186 GI bleeding risk N=128 No GI bleeding risk N=58 All pts N=110 GI bleeding risk N=93 No GI bleeding risk N=17 Median follow-up, mo 20.6 20.9 20.4 21.3 21.6 20.3 Median OS, mo 14.4 11.4 40.3 13.9 12.8 Not reached OS rates, % 12 mo 55.2 48.9 68.9 55.2 52.3 70.6 18 mo 45.3 38.1 61.1 44.1 41.6 57.8 24 mo 39.4 31.8 56.8 37.1 34.6 51.3 Post-index GI bleed, % 17.2 23.4 3.4 17.3 19.4 5.9

Risk Factors for Gastrointestinal Bleeding in Patients With Acute Myocardial Infarction: Multicenter Retrospective Cohort Study.

Gastrointestinal bleeding (GIB) is a severe and potentially life-threatening complication in patients with acute myocardial infarction (AMI), significantly affecting prognosis during hospitalization. Early identification of high-risk patients is essential to reduce complications, improve outcomes, and guide clinical decision-making. This study aimed to develop and validate a machine learning (ML)-based model for predicting in-hospital GIB in patients with AMI, identify key risk factors, and evaluate the clinical applicability of the model for risk stratification and decision support. A multicenter retrospective cohort study was conducted, including 1910 patients with AMI from the Affiliated Hospital of Guangdong Medical University (2005-2024). Patients were divided into training (n=1575) and testing (n=335) cohorts based on admission dates. For external validation, 1746 patients with AMI were included in the publicly available MIMIC-IV (Medical Information Mart for Intensive Care IV) database. Propensity score matching was adjusted for demographics, and the Boruta algorithm identified key predictors. A total of 7 ML algorithms-logistic regression, k-nearest neighbors, support vector machine, decision tree, random forest (RF), extreme gradient boosting, and neural networks-were trained using 10-fold cross-validation. The models were evaluated for the area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, recall, F1-score, and decision curve analysis. Shapley additive explanations analysis ranked variable importance. Kaplan-Meier survival analysis evaluated the impact of GIB on short-term survival. Multivariate logistic regression assessed the relationship between coronary heart disease (CHD) and in-hospital GIB after adjusting for clinical variables. The RF model outperformed other ML models, achieving an area under the receiver operating characteristic curve of 0.77 in the training cohort, 0.77 in the testing cohort, and 0.75 in the validation cohort. Key predictors included red blood cell count, hemoglobin, maximal myoglobin, hematocrit, CHD, and other variables, all of which were strongly associated with GIB risk. Decision curve analysis demonstrated the clinical use of the RF model for early risk stratification. Kaplan-Meier survival analysis showed no significant differences in 7- and 15-day survival rates between patients with AMI with and without GIB (P=.83 for 7-day survival and P=.87 for 15-day survival). Multivariate logistic regression showed that CHD was an independent risk factor for in-hospital GIB (odds ratio 2.79, 95% CI 2.09-3.74). Stratified analyses by sex, age, occupation, marital status, and other subgroups consistently showed that the association between CHD and GIB remained robust across all subgroups. The ML-based RF model provides a robust and clinically applicable tool for predicting in-hospital GIB in patients with AMI. By leveraging routinely available clinical and laboratory data, the model supports early risk stratification and personalized preventive strategies.

Comparative Risk of Gastrointestinal Major Bleeding with Rivaroxaban and Warfarin

Comparative Risk of Gastrointestinal Major Bleeding with Rivaroxaban and Warfarin

Proton pump inhibitor use and all-cause mortality in stroke survivors on antiplatelet therapy: An NHANES analysis.

Stroke is a leading cause of death and disability worldwide. Antiplatelet therapy is essential for preventing ischemic stroke recurrence, but it carries a risk of gastrointestinal (GI) bleeding. Proton pump inhibitors (PPIs) are often prescribed to mitigate this risk, but their long-term use has been linked to increased all-cause mortality. Limited research exists on the impact of PPI use on mortality in stroke survivors receiving antiplatelet therapy. This study aims to evaluate the association between PPI use and all-cause mortality in this population. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 were used. A total of 335 stroke survivors on antiplatelet therapy were included and classified based on PPI use. All-cause mortality was determined by linkage to the National Death Index. Weighted Cox regression models were used to assess the association between PPI use and all-cause mortality, adjusting for key covariates such as age, sex, race, socioeconomic status, and comorbidities. Among 335 participants, 78 used PPIs. No significant association was found between PPI use and all-cause mortality across all models (HR 0.98, 95% CI 0.67-1.42, p=0.95). Subgroup analysis indicated that PPIs use was not associated with all-cause mortality risk in any of the subgroups. Kaplan-Meier curves showed no significant difference in survival between PPI and non-PPI groups (p=0.79). PPI use in stroke survivors on antiplatelet therapy was not associated with increased all-cause mortality. The decision to use PPIs should involve a careful evaluation of the potential benefits and risks.

P0764 Are anticoagulants safe in patients with Inflammatory Bowel Disease?

Abstract Background Inflammatory bowel disease (IBD) patients may have a higher risk of gastrointestinal bleeding during anticoagulant treatment due to mucosal erosions. Millions of patients worldwide receive classic oral anticoagulants or direct-acting anticoagulants (DOACs).The main indication is stroke prophylaxis in atrial fibrillation (AF), with an increasing prevalence in older age groups (8.5% of the Spanish population over 60 years old).Anticoagulants (especially DOACs) safety data are limited in IBD. Our objective was to evaluate the bleeding risk in IBD concerning these treatments. Methods A single-center retrospective study was conducted, collecting clinical characteristics, laboratory parameters and bleeding events. Bleeding risk was compared in two cohorts of IBD patients over 60 years old, treated with anticoagulants or not matched by age, sex, and type of IBD at a ratio of 2 controls for each anticoagulated case. We classified the severity of bleeding events as major or not according to the International Society on Thrombosis and Haemostasis criteria. Major bleeding is defined as fatal or symptomatic bleeding in a critical organ, with a decrease of 2 g/dL in hemoglobin or transfusion of 2 or more units. Chi-square test and Student's t-test were used to compare qualitative or quantitative variables respectively Results 186 subjects were analyzed (62 anticoagulated, 124 were not): 110 had ulcerative colitis (UC) and 76 Crohn's disease (CD). Baseline characteristics are described in Table 1. Of the 62 anticoagulated patients, 69% were on DOACs (26 apixaban,7 edoxaban,6 rivaroxaban,4 dabigatran)26% on classic oral anticoagulants and 5% on low molecular weight heparin. The main indication was AF (66%), followed by thrombosis (26%) and stroke (8%). No statistically significant differences were found in sex, age, location, behavior (CD), or extent of the disease, which was expected since controls were matched for these factors. There were 17 hemorrhagic events (9.1%) and 58,8% were major. The main bleeding cause was gastrointestinal (64.7%) followed by urinary (23.5%). Bleeding was significantly higher with anticoagulation (17.7 vs 4.8%, p=0.004) and specifically with NOACs (20.9 vs 4.8%; p=0.001). Analyzing only the bleeding cases, no statistically significant differences were found in the incidence of major bleeding, need for admission, iron therapy or transfusion with classic anticoagulants or NOACs, nor in hemoglobin or inflammatory parameters (Table 2). All cause mortality was higher in anticoagulated patients (19.4 vs 6.5%; p= 0.007); one case was 2º to digestive bleeding Conclusion IBD patients may have a higher risk of gastrointestinal bleeding during anticoagulant treatment (specifically DOACs), so they may require closer monitoring References -S. Schulman, C. Kearon. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost., 3 (2005), pp. 692-694 http://dx.doi.org/10.1111/j.1538-7836.2005.01204.x | Medline -Cea-Calvo L, Redón J, Lozano JV, et al. Prevalencia de fibrilación auricular en la población española de 60 o más años de edad. Estudio PREV-ICTUS. Rev Esp Cardiol. 2007; 60: 616-24 -Gu ZC, Wei AH, Zhang C, Wang XH, Zhang L, Shen L, Li Z, Pan MM, Liu XY, Pu J, Lin HW. Risk of Major Gastrointestinal Bleeding With New vs Conventional Oral Anticoagulants: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2020 Apr;18(4):792-799.e61. doi: 10.1016/j.cgh.2019.05.056. Epub 2019 Jun 11. PMID: 31195162. -Viola A, Chiappetta MF, Scolaro M, Bignoli F, Versace A, Fries W. Direct oral anticoagulants increase the risk of anaemia and hospitalization in IBD patients with active intestinal disease. Dig Liver Dis. 2020 Dec;52(12):1525-1526. doi: 10.1016/j.dld.2020.08.033. Epub 2020 Sep 6. PMID: 32900651.

P1155 Safety of Venous Thromboembolism Pharmacological Prophylaxis in Hospitalized Patients with Inflammatory Bowel Disease; A Single Center Retrospective Study (VISCOUS)

Abstract Background Hospitalization secondary to inflammatory bowel disease flare is a significant risk factor for venous thromboembolism (VTE). International guidelines recommend the use of pharmacological VTE prophylaxis; however, the risk of bleeding is unknown. We therefore aimed to evaluate the safety of pharmacological thromboprophylaxis in hospitalized patients with IBD. Methods This was a retrospective cohort study. A chart review of patients’ electronic health records with IBD hospitalized between August 2017 to December 2023 was reviewed. Our primary outcome is evaluating the safety of pharmacological VTE prophylaxis. This was investigated by examining increased bleeding risks during admission, which included worsening bloody stool frequency, drop in hemoglobin (>1g/dL from baseline) and development of hemorrhagic shock after starting VTE prophylaxis. Worsening bloody stool frequency was defined as increased bloody stool frequency >1 from baseline before starting VTE prophylaxis. Finally, any major bleeding was also considered. Results Between August 2017 and December 2023, 1045 patient encounters were reviewed. 524 patients met the study inclusion and exclusion criteria, of which 98 had missing information and 73 were duplicates and could not be included. Finally, 353 patients were included in our study. Mean age 34.7 years, 205 (58%) were female males and mean duration of hospitalization was 9 days. Majority of patients were hospitalized with acute severe ulcerative colitis (ASUC) 213 (60.3%), and 140 (39.7%) had Crohn’s disease (CD) flare. Of the total cohort, 264 (75%) patients received enoxaparin 40 mg for VTE prophylaxis, and the 89 (25%) patients received 5000 units of unfractionated heparin twice a day (figure 1). Eighteen (%5) patients had a history of VTE, and 4 female patients had VTE during admission. None of our cohort had any bleeding events including worsening bloody stool frequency, drop in hemoglobin, major bleeding and development of hemorrhagic shock after starting VTE prophylaxis up to the period patients were discharged. Conclusion we found no increased risk of gastrointestinal bleeding in patients admitted with IBD on pharmacological VTE prophylaxis. Therefore, it is important to reassure healthcare providers about the safety of pharmacological VTE prophylaxis in IBD and adopt strategies that guarantee prophylaxis is administered during hospitalization. Although that a balance should be established between the benefits and risks. References -Pleet JL, Vaughn BP, Morris JA, et al. The use of pharmacological prophylaxis against venous thromboembolism in hospitalised patients with severe active ulcerative colitis. Aliment Pharmacol Ther [Internet]. 2014;39(9):940–948. -Dawwas GK, Cuker A, Schaubel DE, et al. Effectiveness and safety of prophylactic anticoagulation among hospitalized patients with inflammatory bowel disease. Blood Adv [Internet]. 2024;8(5):1272–1280. -Kaddourah O, Numan L, Jeepalyam S, et al. Venous thromboembolism prophylaxis in inflammatory bowel disease flare-ups. Ann Gastroenterol. 2019;32(6):578–583.

Prevalence of medical conditions or comorbidities influencing first-line therapy in unresectable hepatocellular carcinoma in the United States.

Given treatment landscape changes, understanding the prevalence of medical conditions/comorbidities influencing real-world unresectable hepatocellular carcinoma (uHCC) treatment decisions is key for improving outcomes. In a retrospective chart review, physicians abstracted data from uHCC patients initiating first-line treatment (1L) between June 2020 and April 2022. Frequencies of medical conditions/comorbidities at 1L initiation were reported. Among 433 patients, 77% had Barcelona Cancer Liver Clinic (BCLC)-C and 37% had Child-Pugh B status. Overall, 51% had ≥ 1 condition/comorbidity making them potentially less suitable for a 1L immunotherapy combination regimen (e.g. atezolizumab plus bevacizumab), including upper/lower gastrointestinal bleeding risk (38%), chronic kidney disease (15%), history of thromboembolic events (12%), and autoimmune disorders (5%). More than half of the patients had ≥ 1 medical condition/comorbidity making them potentially less suitable for a 1L immunotherapy combination. This study provides timely insight into how immunotherapy combinations are being used in the real-world setting among a large number of patients.

Gastrointestinal bleed mortality disparities in patients with atrial fibrillation: A cross-sectional analysis 1999-2020.

Gastrointestinal bleeding (GIB) is often encountered among patients with atrial fibrillation (AF) due to the use of anticoagulation. This study assesses disparities in GIB-related mortality among decedents with AF in the United States. GIB mortality data in patients with AF from 1999 to 2020 was queried from the CDC database. Decedent demographic information (age, sex, race and ethnicity, and geographic residence) was obtained from death certificates. We calculated age-adjusted mortality rates (AAMRs) through the direct method and estimated the annual percentage change (APC) in mortality using log-linear regression models. From 11,209 GIB-related deaths among AF decedents, we observed an increase in AAMR from 0.12 in 1999 to 0.21 in 2020, particularly during the 2009 to 2020 period (APC +4.8, p < .001). Disproportionate mortality rates were noted in males (AAMR 0.18) and White populations (AAMR 0.15) as compared to females (AAMR 0.13) and Black populations (AAMR 0.10), respectively. Rural regions also reported higher mortality (AAMR 0.18) than urban areas (AAMR 0.14). Mortality shifts in urban regions remained stagnant from 1999 to 2009 (APC -0.15, p = .806) followed by an increase from 2009 to 2020 (APC +4.83, p < .001). However, mortality increased consistently from 1999 to 2020 in rural regions (APC +4.08, p < .001). The Northeast US exhibited the highest mortality rate (AAMR 0.18), followed by the Midwest (AAMR 0.16), West (AAMR 0.14), and South (AAMR 0.13). Disparities in GIB mortality among AF decedents were identified. These findings accentuate the need for targeted interventions to mitigate GIB risks in vulnerable subgroups.

Time-varying analyses of survival and outcomes in patients with HeartMate 3 left ventricular assist devices.

As patients experience longer survival on HeartMate 3 left ventricular assist devices, there is a need to characterize long-term risks of adverse outcomes more precisely. This study characterized temporal variations in risks of mortality and adverse outcomes in patients with a HeartMate 3. From October 2015 to January 2023, 431 HeartMate 3 devices were implanted at Cleveland Clinic. Survival was estimated to 5 years post-implant. Time-varying risks of death, neurological events, gastrointestinal bleeding, device-related infections, and other adverse events were characterized using multiphase hazard modelling. Survival on HeartMate 3 at 1 and 5 years was 88% and 58%, respectively. Risk of death peaked in the first postoperative month before declining rapidly to a constant, lower hazard. Cumulative number of neurological events/patient at 1 year and 5 years was 0.13 and 0.29, respectively; risk was highest within the first postoperative week, then rapidly declined by 1 month. Cumulative number of gastrointestinal bleeding events/patient at 1 year and 5 years was 0.32 and 0.78, respectively; risk was highest within 1 week postoperatively and gradually declined to a constant risk over the first year. Device-related infections developed in 136 patients. One- and 5-year freedom from device-related infection was 77% and 45%, respectively; risk was initially low before peaking at 6 months postoperatively and then gradually declining to a steady hazard. Long-term survival on HeartMate 3 support was favourable in a large single-centre cohort. Strategies to reduce early postoperative risk of neurological events and late risks of gastrointestinal bleeding, infections and other adverse events are needed.

Comparative safety and effectiveness of oral anticoagulants in key subgroups of patients with non-valvular atrial fibrillation and at high risk of gastrointestinal bleeding: A cohort study based on the French National Health Data System (SNDS).

Risk factors and comorbidities can complicate management of non-valvular atrial fibrillation. We describe and compare real-world safety and effectiveness of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) and vitamin K antagonists (VKAs) in subgroups of patients with non-valvular atrial fibrillation at high risk for gastrointestinal (GI) bleeding, utilizing data from a national quasi-exhaustive French database. Anticoagulant-naïve adults with non-valvular atrial fibrillation with ≥1 gastrointestinal bleeding risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. The following subgroups were evaluated: patients age ≥75 years, receiving concomitant medications, HAS-BLED score ≥3, and chronic kidney disease stage 3-4. Outcomes included major bleeding and stroke/systemic embolism. Patient characteristics were balanced using propensity score matching. A total of 314,184 patients were identified; characteristics were similar for propensity score-matched subgroups in VKA/DOAC and DOAC/DOAC comparisons. DOACs showed lower risk of major bleeding versus VKAs in all subgroups evaluated (p<0.0001 for all). Apixaban showed lower risk of major bleeding and gastrointestinal bleeding versus rivaroxaban in all subgroups (p≤0.05 for all) and versus dabigatran in elderly patients, patients with HAS-BLED score ≥3, and those receiving concomitant medications (p<0.05 for all). Stroke/systemic embolism risk was lower with apixaban versus rivaroxaban in elderly patients, those with HAS-BLED ≥3, and those receiving concomitant medications; risks were similar for other comparisons. DOACs were associated with improved safety and effectiveness when compared to VKAs among subgroups of non-valvular atrial fibrillation patients at high risk of gastrointestinal bleeding. Apixaban was associated with lower risks of major bleeding, gastrointestinal bleeding, and stroke/systemic embolism versus rivaroxaban as well as lower risk of major bleeding, gastrointestinal bleeding bleed and similar risk of stroke/systemic embolism versus dabigatran among several of these patient subgroups.

Early Enteral Nutrition May Improve Survival in Patients With Cardiogenic Shock.

Background and Aim: International guidelines recommend early enteral nutrition (EEN) for critically ill patients. However, evidence supporting the optimal timing of EN in patients diagnosed with cardiogenic shock (CS) is lacking. As such, this study aimed to compare the clinical outcomes and safety of EEN versus delayed EN in patients diagnosed with CS. Methods: This retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care IV version 2.2 database. Patients who received EN within 2 days of admission were assigned to the EEN group. A 1:1 propensity score-matched (PSM) analysis was performed to control for bias in baseline characteristics and ensure the reliability of the results. To exclude the impact of confounders, an adjusted proportional hazards regression model was used to verify the independence between EEN and survival outcomes. Results: Of 1846 potentially eligible patients, 1398 received EEN and 448 received delayed EN. After 1:1 PSM, 818 patients were assigned to the EEN (n = 409) and delayed EN (n = 409) groups. Regarding cumulative survival, patients with CS receiving EEN experienced better 30-, 90-, and 180-day survival outcomes than the delayed EN group (hazard ratio [HR] 0.803 [95% confidence interval [CI] 0.647-0.998], p=0.045; HR 0.729 [95% CI 0.599-0.889], p=0.001; and HR 0.778 [95% CI 0.644-0.938], p=0.008, respectively). After adjusting for confounders, EEN was found to be independently associated with survival outcomes. Moreover, EEN did not increase the risk(s) for ileus, aspiration pneumonia, or gastrointestinal bleeding. Patients who received delayed EN experienced longer hospital stays than those receiving EEN (17 days [interquartile range [IQR] 10-25] versus 12 days [IQR 7-19 days], respectively; p < 0.001). Conclusion: EEN was not associated with harm, but rather with improved survival outcomes in patients diagnosed with CS. Further studies are required to verify these findings.

Safety of steroids in severe community-acquired pneumonia.

The systemic use of corticosteroids for patients with severe community-acquired pneumonia (sCAP) remains controversial in clinical practice, particularly in terms of the safety profile of these drugs. This narrative review aims to analyse the available literature data concerning the safety of short-term steroid use in the treatment of sCAP, while also highlighting potential future research directions. Several trials and meta-analyses have evaluated corticosteroid therapy as an adjuvant treatment for sCAP, yielding heterogeneous results regarding its efficacy and safety. Despite the wide variability in results, it is generally accepted that steroids are not associated with a significant risk of healthcare-associated infections, gastrointestinal bleeding or acute kidney injury in patients with sCAP in the short term. Nevertheless, such drugs are linked to hyperglycaemia, necessitating regular monitoring and appropriate management. The influence of steroids on long-term outcomes and their potential risks in viral sCAP still needs to be investigated.

Potential interactions between antimicrobials and direct oral anticoagulants: Population-based cohort and case-crossover study.

Although drug interactions between clarithromycin/erythromycin/fluconazole and direct oral anticoagulants (DOACs) are mechanistically plausible, it is uncertain whether they are clinically relevant. This study aims to investigate the association among coprescribed DOACs and antimicrobials and bleeding, cardiovascular disease and mortality. We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011 to March 29, 2021. We used a cohort design to estimate hazard ratios (HRs) for bleeding outcomes (intracranial bleeding, gastrointestinal bleeding, other bleeding), comparing DOACs + clarithromycin/erythromycin/fluconazole users with DOACs users not receiving these antimicrobials. Cardiovascular outcomes were ischaemic stroke, myocardial infarction, venous thromboembolism, cardiovascular mortality, and all-cause mortality. A 6-parameter case-crossover design comparing odds of exposure with different drug initiation patterns for all outcomes in hazard window vs referent window within an individual was also conducted. Of 483,815 DOAC users, we identified 21,701 coprescribed clarithromycin, 4532 coprescribed erythromycin, and 4840 coprescribed fluconazole. We observed an increased risk of gastrointestinal bleeding over 7 days following coprescription of DOAC + erythromycin vs DOAC alone (HR 3.66; 99% confidence interval [CI] 1.27-10.51), with wide CIs in case-crossover analysis. No evidence of increased risk of bleeding outcomes was seen for DOAC + clarithromycin/fluconazole in cohort and case-crossover analyses. For cardiovascular outcomes, compared with DOAC alone, an increased risk of cardiovascular mortality with DOAC + clarithromycin (HR 3.36; 99% CI 1.73-6.52) and increased risk of all-cause mortality with DOAC + clarithromycin/erythromycin/fluconazole were observed in cohort analysis. However, similar risks were found when initiating erythromycin/fluconazole with and without DOACs. We found no strong evidence of increased risks of bleeding and cardiovascular outcomes in DOACs + clarithromycin/fluconazole/erythromycin users except a possible short-term increased risk of gastrointestinal bleeding in DOACs + erythromycin users.

Machine Learning in Gastrointestinal Bleeding Risk Stratification: Promising Advances and Remaining Challenges

Machine Learning in Gastrointestinal Bleeding Risk Stratification: Promising Advances and Remaining Challenges

Proton Pump Inhibitors Use in Patients With Ischemic Stroke on Dual Antiplatelet Therapy at Low Risk of Upper Gastrointestinal Bleeding.

Current guidelines lack recommendations regarding the use of proton pump inhibitors (PPIs) for preventing upper gastrointestinal bleeding (UGIB) among patients at low risk for UGIB treated with dual antiplatelet therapy for ischemic stroke (IS). Our objective was to assess the effectiveness of PPIs in lowering the risk of significant UGIB in this patient group. A retrospective cohort study was conducted involving patients at low risk for UGIB admitted for IS between 2014 and 2018 and treated with dual antiplatelet therapy. The study used a nationwide claims database in Korea. The primary end point was significant UGIB during 12 months after IS. To evaluate the risk of significant UGIB based on PPI use, we performed a multivariable Cox regression analysis. Subgroup analyses and propensity score matching analysis were conducted for validation. Among 96 722 patients with IS at low risk for UGIB who were on dual antiplatelet therapy (mean age, 67.0 years; men: 63.0%), 16 084 (16.6%) were treated with PPIs. During 12 months of follow-up, 325 patients experienced significant UGIB, and 479 experienced any UGIB. PPI use was associated with a reduced risk of significant UGIB (hazard ratio, 0.63 [95% CI, 0.45-0.89]; P=0.009). This association was consistent in the subgroup and propensity score matching analyses. In patients with IS receiving dual antiplatelet therapy, PPI use reduced the risk of significant UGIB by 37% on average, even among low-risk patients. However, the use of PPIs in this patient group was limited, highlighting the need for additional prospective studies.

Comparison of Risk-Scoring Models to Predict Gastrointestinal Bleeding in Patients With Direct Oral Anticoagulants.

The risk of gastrointestinal bleeding (GIB) remains a concern with the use of direct oral anticoagulants (DOAC). We evaluated the efficacy of four risk-scoring models (HAS-BLED, ATRIA, VTE-BLEED, and ORBIT) in predicting GIB according to the concomitant use of antiplatelet therapy in DOAC users. Patients prescribed DOAC between December 2014 and October 2020 were enrolled in two university-affiliated hospitals. The performance of the four models was compared based on the concomitant use of antiplatelet therapy. The primary outcomes were likelihood ratios and the area under the receiver operating characteristic (AUROC) curve to predict GIB. A total of 4494 patients were included in the study. The AUROC values for the entire cohort were 0.643 (95% CI: 0.601-0.686) for HAS-BLED, 0.693 (95% CI: 0.649-0.737) for ATRIA, 0.708 (95% CI: 0.665-0.750) for VTE-BLEED, and 0.709 (95% CI: 0.667-0.751) for ORBIT. The AUROC for all scoring models increased in patients without antiplatelet therapy compared to the entire cohort and patients with antiplatelet therapy. The specificity and diagnostic accuracy for all scoring models increased in patients without antiplatelet therapy compared to patients with antiplatelet. Our results confirmed that current risk-scoring models for predicting GIB perform better in patients without antiplatelet therapy than in those on concomitant antiplatelet therapy. This suggests that future risk prediction models should consider the concomitant use of antiplatelet therapy for diagnostic accuracy.

Evaluation of gastric tolerability for long-term use of diclofenac and celecoxib in male albino rats and potential gastroprotective benefits of royal jelly: a randomized controlled trial.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain and inflammation relief. Our study aimed to explore the ulcerogenic effect of long-term diclofenac and celecoxib administration on male albino stomachs, focusing on the possible gastroprotective effect of royal jelly administration. Five equal groups of 50 male albino rats. The drug dosages were: diclofenac potassium (10 mg/kg/day), celecoxib (50 mg/kg/day), and RJ (300 mg/kg/day), for 4weeks. Group 1 received no medication. Group 2 received oral diclofenac potassium. Group 3 received oral RJ plus diclofenac potassium. Group 4 received celecoxib orally. Group 4 received oral RJ plus celecoxib. When the experiment was over, rats were euthanized, blood samples were gathered, and stomachs were dissected out. Stomachs were examined for ulcer counts. Serum levels of MDA and SOD were determined. Gastric mucosa contents of MDA, SOD, PGE2, MPO, apoptotic (Bax), and anti-apoptotic (Bcl-2) genes were measured. Gastric tissue was also analyzed histopathologically. Long-term administration of diclofenac and celecoxib, in such dose and duration, caused each of the aforementioned parameters to significantly deteriorate, with significant improvement with RJ co-administration. Diclofenac developed severe gastric ulcers in group 2, and RJ co-administration significantly reduced the gastric mucosa damage in group 3. Celecoxib developed no gastric ulcer in both groups 4 and 5. Long-term use of diclofenac in male albino rats caused severe gastric ulcers with significant gastroprotective effects of RJ.Celecoxib provides preferable GI tolerability; thus, it should be prescribed for patients at increased risk of gastrointestinal bleeding requiring NSAIDs.

Does enteral nutrition protect against stress ulceration in the critically ill?

Critically ill patients are at risk of gastrointestinal bleeding (GIB) due to stress ulceration. Strategies to reduce the risk include administration of prophylactic ulcer healing medications. Enteral nutrition (EN) may be favourably associated with GIB risks. This manuscript summarizes available evidence regarding EN effects on GIB. There are few data available to directly compare the effect of EN on GIB. Direct comparison in animal models generally indicate a beneficial effect. Human data provide indirect evidence from pharmacological stress ulcer prophylaxis studies. EN exposure has been randomized in nutrition trials of critically ill patients, but GIB outcomes were not recorded. Detailed EN exposure data were recorded in two large pharmacological stress ulcer trials. One finds EN is associated with lower GIB, lower mortality, and increased pneumonia, and notes a possible interaction between EN and pharmacological stress ulcer prophylaxis. The second has yet to report associations with EN. EN may reduce the risk of GIB, although robust direct evidence is absent. Potential interactions between EN and pharmacological stress ulcer prophylaxis require further study.

Systematic Review and Meta-Analysis: Role of Proton Pump Inhibitors in Prevention of Upper Gastrointestinal Bleeding in Patients on Dual Antiplatelet Therapy.

Dual antiplatelet therapy (DAPT) with oral P2Y12 inhibitors and aspirin is crucial for patients with acute coronary syndrome (ACS) and postpercutaneous coronary interventions (PCI). Concomitant proton pump inhibitor (PPI) therapy with DAPT can potentially reduce the risk of upper gastrointestinal bleeding (UGIB). We conducted a meta-analysis of randomized controlled trials to evaluate the prevention of UGIB with concomitant use of PPI with DAPT. We reviewed several databases to identify randomized controlled trials comparing the risk of UGIB in patients using DAPT + PPI vs. DAPT with no PPI or DAPT + Histamine 2 receptor antagonists. Our outcomes of interest were UGIB, major cardiovascular adverse events (MACE), myocardial infarction, and all-cause mortality. We calculated pooled risk ratio (RR) with 95% confidence intervals (CI) for all of the outcomes and analyzed data using random effect model. Heterogeneity was assessed using I2 statistic. Seven randomized controlled trials comprising 6708 patients were included. Rate of UGIB was significantly lower in the PPI + DAPT group, RR (95% CI): 0.39 (0.25-0.60). There was no significant difference in the rate of MACE between groups, RR (95% CI): 0.87 (0.69-1.10). Rate of MI was also not significantly different between groups, RR (95% CI): 0.93 (0.75-1.14). Rate of mortality was significantly lower in the PPI + DAPT group, RR (95% CI) 0.46 (0.27-0.80). Our meta-analysis demonstrates that adding PPI therapy to DAPT significantly lowers the risk of UGIB and all-cause mortality, without adversely affecting major cardiovascular outcomes.