Glucagon-like peptide-1 receptor agonists and risk of gastrointestinal cancers: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used for glucose lowering and weight-loss. However, their association with gastrointestinal cancer remains uncertain. This meta-analysis assesses the risk of gastrointestinal cancer in patients treated with GLP-1 RAs. METHODS: We searched Medline/PubMed, Embase, and Scopus databases from inception to November 15, 2023, for randomized controlled trials (RCTs) with at least 24 weeks of safety follow-up. Pooled risk ratios (RRs) were calculated using fixed- and random-effect models. Risk of bias was assessed using the revised Cochrane risk-of-bias tool, and certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: We included 90 RCTs with 124,791 participants, with an average follow-up of 3.1 years per participant. No significant association was found between GLP-1 RAs and the risk of any gastrointestinal cancer (RRrandom=0.99, 95 % CI: 0.86-1.13), or site-specific gastrointestinal cancers including biliary tract (RR=0.98, 0.54-1.78), colorectal (RR=1.13, 0.92-1.39), gallbladder (RR=1.32, 0.43-4.00), gastric (RR=0.88, 0.58-1.33), hepatic (RR=0.79, 0.51-1.21), oesophageal (RR=0.70, 0.38-1.28), pancreatic (RR=1.05, 0.77-1.43), and small intestine cancer (RR=0.78, 0.20-3.04). The corresponding absolute risk differences excluded important impacts on risk. Additional analyses, limited to placebo-controlled trials, high-dose studies, or those with a follow-up duration of ≥5 years, confirmed these findings. Risk of bias was generally low and the certainty of evidence was high for all outcomes. CONCLUSIONS: This meta-analysis found no significant impact of GLP-1 RAs on gastrointestinal cancer risk. Long-term safety monitoring of these agents remains important. SYSTEMATIC REVIEW REGISTRATION: CRD42023476762.

Safety of Direct Oral Anticoagulants for Gastrointestinal Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Studies.

GOALS AND BACKGROUND: Since the introduction of Direct Oral Anticoagulants (DOACs), "real-world" studies have investigated their safety profile on gastrointestinal hemorrhage (GIH) when used by patients with Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis to compile and summarize this data after Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. STUDY: Medline and Embase were systematically searched until April 2021. Observational studies that met predefined inclusion criteria were included and hazard ratios (HRs) with 95% CI were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, prior exposure to VKA (vitamin K antagonist), age, gender, geographic location of population samples, as well as Leave-One-Out and Low/Moderate Risk of Bias sensitivity analyses were performed. A random effects model was used. RESULTS: A total of 46 studies were included. Apixaban was associated with a reduced risk of GIH compared with Dabigatran (HR: 0.67, 95% CI, 0.56 to 0.81, I2 : 53.28%), Rivaroxaban (HR: 0.56, 95% CI, 0.44 to 0.70, I2 : 79.17%), and VKA (HR: 0.68, 95% CI, 0.60 to 0.78, I2 : 71.93%). Rivaroxaban was associated with increased GIH risk compared with Dabigatran (HR: 1.19, 95% CI, 1.02 to 1.40, I2 : 72.96%) and VKA (HR: 1.16, 95% CI, 1.05 to 1.27, I2 : 81.95%). Dabigatran was associated with similar GIH risk compared with VKA (HR: 1.11, 95% CI, 0.98 to 1.26, I2 : 87.28%). CONCLUSIONS: Our study shows that Apixaban was associated with a reduction in GIH risk compared with Dabigatran, Rivaroxaban and VKA, whereas Rivaroxaban was associated with an increase in GIH risk compared with both Dabigatran and VKA.

Efficacy and safety of gastric per-oral endoscopic myotomy (GPOEM) in lung transplant patients with refractory gastroparesis: a systematic review and meta-analysis.

BACKGROUND: Post-lung transplant gastroparesis is a frequent debilitating complication of lung transplant recipients, as it can increase the risk for gastro-esophageal reflux disease and subsequent graft dysfunction. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of GPOEM in lung transplant patients with refractory gastroparesis. METHODS: The present systematic review and meta-analysis wer performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We selected studies that analyzed the gastroparesis cardinal symptom index (GCSI) before and after the procedure to verify the efficacy of GPOEM. Random-effects model was used and the analysis was performed with STATA 17. RESULTS: Four observational studies (one conference abstract) with 104 patients were included in the meta-analysis. Prior treatments for gastroparesis included prokinetic agents and botulinum toxin in 78% (78/104) and 66.7% (66/99), respectively. Pooled estimate for clinical efficacy of GPOEM was 83% (95% CI 76%-90%). The pooled mean reduction in GCSI following the procedure was - 2.01 (- 2.35, - 1.65, p = 0.014). Three studies reported statistically significant improvement of gastro-esophageal retention or emptying in the post-GPOEM period. 30-day post-operative complications included minor or major bleeding (11.6%), severe reflux (1.2%), and pyloric stenosis (1.2%) requiring re-intervention. 90-day all-cause mortality was 2.6% with one patient dying from severe allograft rejection. CONCLUSION: Our study showed that GPOEM is an effective and safe strategy for lung transplant patients with refractory gastroparesis and should be considered as a therapeutic strategy in this population. Larger multicenter trials are needed in the future to further evaluate the effect of GPOEM on allograft function and rates of rejection.

A Systematic Review and Meta-Analysis on the Efficacy and Safety of Direct Oral Anticoagulants in Patients with Peripheral Artery Disease.

BACKGROUND: PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide. Current guidelines recommend at least a single antiplatelet or anticoagulant agent in symptomatic PAD and lifelong antithrombotic treatment after a revascularization procedure. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with peripheral artery disease (PAD). PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide. METHODS: The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Risk ratios (RR) were calculated using the random effects model. RESULTS: Overall, 10 studies were included in this systematic review and meta-analysis. In 4 studies, 14,257 patients with PAD were enrolled and they were assigned to receive either aspirin (ASA)+/- clopidogrel (N = 5,894) or DOAC+/- anti-platelet (e.g., ASA, clopidogrel) (n = 8,363). Non DOAC users were found to have higher reintervention rates (RR 1.12; 95% CI 1.01-1.24; P = 0.025) compared to DOAC users. No statistically significant difference was observed between the 2 groups, in terms of major bleeding (RR 0.78; 95% CI 0.50-1.23; P = 0.285), all-cause mortality (RR 0.98; 95% CI: 0.83-1.16; P = 0.818) and cardiovascular mortality (RR: 0.99; 95% CI: 0.73-1.333; P = 0.946) mortality. In addition, two real-world studies comparing DOAC with warfarin showed decreased rates of major cardiovascular events in the DOAC group. CONCLUSION: DOAC use alone or combined with an anti-platelet agent could be associated with lower re-intervention rates, without increasing the risk for adverse bleeding events. However, this study failed to detect any difference in terms of all-cause mortality, MACEs and MALEs between DOAC users and DOAC naïve patients. Future studies are needed to better determine the efficacy and safety of DOACs in patients with PAD.

Portopulmonary Hypertension: A Review of the Current Literature.

Portopulmonary hypertension is defined as the development of pulmonary arterial hypertension in the setting of portal hypertension with or without liver cirrhosis. Portal hypertension-associated haemodynamic changes, including hyperdynamic state, portosystemic shunts and splanchnic vasodilation, induce significant alterations in pulmonary vascular bed and play a pivotal role in the pathogenesis of the disease. If left untreated, portopulmonary hypertension results in progressive right heart failure, with a poor prognosis. Although Doppler echocardiography is the best initial screening tool for symptomatic patients and liver transplantation candidates, right heart catheterisation remains the gold standard for the diagnosis of the disease. Severe portopulmonary hypertension exerts a prohibitive risk to liver transplantation by conferring an elevated perioperative mortality risk. It is important for haemodynamic parameters to correspond with non-severe portopulmonary hypertension before patients can proceed with the liver transplantation. Small uncontrolled studies and a recent randomised controlled trial have reported promising results with vasodilatory therapies in clinical and haemodynamic improvement of patients, allowing a proportion of patients to undergo liver transplantation. In this review, the epidemiology, pathogenesis, diagnostic approach and management of portopulmonary hypertension are discussed. We also highlight fields of ongoing investigation pertinent to risk stratification and optimal patient selection to maximise long-term benefit from currently available treatments.

Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn's Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Vedolizumab is effective and safe for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug. METHODS: We searched PubMed, Scopus and conference abstracts (Digestive Disease Week, European Crohn's and Colitis Organization, and United European Gastroenterology Week), through December 2017, for experimental or observational cohort studies of vedolizumab use in adult patients with CD or UC; we identified studies that provided sufficient data to determine the incidence rate of loss of response among initial responders and the ability of dose intensification to restore response. Two reviewers independently abstracted study data and outcomes and rated each study's risk of bias. The studies were evaluated for heterogeneity and publication bias. Summary estimates were calculated using random effects models. RESULTS: We analyzed data from 10 eligible cohorts; most patients had received prior treatment with a tumor necrosis factor antagonist. The pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up (95% CI, 26.3‒87.0; I2 = 74%) among patients with CD and 39.8 per 100 person-years of follow up (95% CI, 35.0‒45.3; I2 = 0%) among patients with UC. Dose intensification restored response to the drug in 53.8% of secondary non-responders (95% CI, 21.8%‒82.9%; I2 = 77%). CONCLUSIONS: In a systematic review and meta-analysis, we found high proportions of patients with CD or UC to lose responsiveness to vedolizumab maintenance therapy. Dose intensification restores responsiveness to more than half of these patients. Additional studies are warranted to inform clinical decision making.

Clinical outcomes with metformin use in diabetic patients with compensated cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Previous studies have demonstrated a beneficial effect of metformin in patients with cirrhosis, but no improvement in liver histology. AIM: To investigate the impact of metformin on mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. METHODS: Medline, Embase and Cochrane databases were searched from inception to February 2023 for studies reporting results regarding the impact of metformin on all-cause mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. The risk of bias was assessed by ROBINS-I Cochrane tool. R software 4.3.1 was used for all analyses. RESULTS: Six observational studies were included in the final analysis. Metformin use was associated with reduced all-cause mortality or liver transplantation [hazard ratio (HR): 0.55; 95% confidence interval (CI) 0.37-0.82], while no benefit was shown in the prevention of hepatic decompensation (HR: 0.97; 95% CI: 0.77-1.22). In the subgroup analysis, metformin use was associated with reduced all-cause mortality or liver transplantation (HR: 0.50; 95% CI 0.38-0.65) in patients with metabolic-associated steatohepatitis cirrhosis, while two studies reported no survival benefit in patients with cirrhosis due to hepatitis C (HR: 0.39; 95% CI 0.12-1.20). CONCLUSION: Metformin use is associated with reduced all-cause mortality, but not with the prevention of hepatic decompensation in people with diabetes with compensated cirrhosis. The mortality benefit is most likely driven by better diabetes and cardiovascular health control.

Esophageal squamous papilloma: Literature review and case-control retrospective study with histopathological exam of human papillomavirus.

Background and Aim: Esophageal squamous papilloma (ESP) is a benign growth in the esophagus with unknown malignant potential. The mechanism underlying ESP formation is unknown, but human papillomavirus (HPV) infection has been proposed as a potential etiology. We sought to investigate the clinical characteristic of ESP in our population, review the current literature, and highlight the role of HPV. Methods: This is a retrospective case-control study conducted at two referral centers. We selected the ESP population by free-text search in the pathology department database and selected controls randomly from the general endoscopy population. Immunostains were used to evaluate ESP tissue for HPV. Results: Between January 2016 and December 2021, we identified 66 patients with ESP, with a prevalence of 0.72%. ESP patients were younger, with a median age of 52 years (P = 0.021), and more likely African American (34.4 vs 7.5%, P < 0.001) compared to controls. On endoscopy images, the growth was predominantly solitary (92.5%) in the middle of the esophagus (39.4%), with sizes ranging from 0.2 to 2.3 cm. A total of 62 patients had available tissue for HPV immune staining, and none tested positive for HPV. Eighteen patients had a follow-up endoscopy with an average of 504.5 days follow-up period. One patient developed esophageal squamous cell carcinoma during follow-up. Conclusions: We observed a higher prevalence of ESP compared to previous studies. The formation of ESP is multifactorial and partially explained by HPV infection in selected populations. The malignant potential of ESP is low but not negligible.

Ethnic and sex-based differences in outcomes after out-of-hospital cardiac arrest: a glimpse of the largest municipal healthcare system in the United States.

Background: Ethnic and sex-based disparity in outcomes after out-of-hospital cardiac arrest (OHCA) may exist and could be due to social factors and inequality in care. We aimed to study whether ethnic and sex-based differences in out-of-hospital cardiac arrest outcomes occurred in a safety net hospital within the largest municipal healthcare system in the United States. Methods: We conducted a retrospective cohort study of patients successfully resuscitated from an OHCA and brought to New York City Health + Hospitals/Jacobi, from January 2019 to September 2021. Out-of-hospital cardiac arrest characteristics, do not resuscitate and withdrawal of life-sustaining therapy orders, and disposition data were collected and analyzed using regression models. Results: Out of 648 patients screened, 154 were included (48.1% women). On multivariable analysis, sex [odds ratio (OR): 0.84; 95% CI: 0.30-2.4; P=0.74] and ethnic background (OR: 0.80; 95% CI: 0.58-1.12; P=0.196) did not predict discharge survival. No significant sex difference in do not resuscitate (P=0.76) or withdrawal of life-sustaining therapy (P=0.39) orders was found. Younger age (OR: 0.96; P=0.04) and initial shockable rhythm (OR: 7.26; P=0.01) independently predicted survival, both at discharge and at one year. Conclusions: Among patients resuscitated after an out-of-hospital cardiac arrest, neither sex nor ethnic background predicted discharge survival and no sex differences in end-of-life preferences were found. These findings are distinct from those of previously published reports. Given the unique population studied, distinct from those of registry-based studies, socioeconomic factors likely served as bigger drivers of out-of-hospital cardiac arrest outcomes rather than ethnic background or sex.

Right-to-Left Shunt in Divers with Neurological Decompression Sickness: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to assess the association between the presence of a right-to-left shunt (RLS) and neurological decompression sickness (NDCS) and asymptomatic brain lesions among otherwise healthy divers. BACKGROUND: Next to drowning, NDCS is the most severe phenotype of diving-related disease and may cause permanent damage to the brain and spinal cord. Several observational reports have described the presence of an RLS as a significant risk factor for neurological complications in divers, ranging from asymptomatic brain lesions to NDCS. METHODS: We systematically reviewed the MEDLINE, Embase, and CENTRAL databases from inception until November 2021. A random-effects model was used to compute odds ratios. RESULTS: Nine observational studies consisting of 1830 divers (neurological DCS: 954; healthy divers: 876) were included. RLS was significantly more prevalent in divers with NDCS compared to those without (62.6% vs. 27.3%; odds ratio (OR): 3.83; 95% CI: 2.79-5.27). Regarding RLS size, high-grade RLS was more prevalent in the NDCS group than the no NDCS group (57.8% versus 18.4%; OR: 4.98; 95% CI: 2.86-8.67). Further subgroup analysis revealed a stronger association with the inner ear (OR: 12.13; 95% CI: 8.10-18.17) compared to cerebral (OR: 4.96; 95% CI: 2.43-10.12) and spinal cord (OR: 2.47; 95% CI: 2.74-7.42) DCS. RLS was more prevalent in divers with asymptomatic ischemic brain lesions than those without any lesions (46.0% vs. 38.0%); however, this was not statistically significant (OR: 1.53; 95% CI: 0.80-2.91). CONCLUSIONS: RLS, particularly high-grade RLS, is associated with greater risk of NDCS. No statistically significant association between RLS and asymptomatic brain lesions was found.

Cardiac risk stratification of the liver transplant candidate: A comprehensive review.

Cardiovascular diseases (CVD) form a principal consideration in patients with end-stage liver disease (ESLD) undergoing evaluation for liver transplant (LT) with prognostic implications in the peri- and post-transplant periods. As the predominant etiology of ESLD continues to evolve, addressing CVD in these patients has become increasingly relevant. Likewise, as the number of LTs increase by the year, the proportion of older adults on the waiting list with competing comorbidities increase, and the demographics of LT candidates evolve with parallel increases in their CVD risk profiles. The primary goal of cardiac risk assessment is to preemptively reduce the risk of cardiovascular morbidity and mortality that may arise from hemodynamic stress in the peri- and post-transplant periods. The complex hemodynamics shared by ESLD patients in the pre-transplant period with adverse cardiovascular events occurring in only some of these recipients continue to challenge currently available guidelines and their uniform applicability. This review focusses on cardiac assessment of LT candidates in a stepwise manner with special emphasis on preoperative patient optimization. We hope that this will reinforce the importance of cardiovascular optimization prior to LT, prevent futile LT in those with advanced CVD beyond the stage of optimization, and thereby use the finite resources prudently.

The Brain-Gut Axis: Psychological Functioning and Inflammatory Bowel Diseases.

The brain-gut axis represents a complex bi-directional system comprising multiple interconnections between the neuroendocrine pathways, the autonomous nervous system and the gastrointestinal tract. Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract with a multifactorial etiology. Depression and anxiety are prevalent among patients with chronic disorders characterized by a strong immune component, such as diabetes mellitus, cancer, multiple sclerosis, rheumatoid arthritis and IBD. Although psychological problems are an important aspect of morbidity and of impaired quality of life in patients with IBD, depression and anxiety continue to be under-diagnosed. There is lack of evidence regarding the exact mechanisms by which depression, anxiety and cognitive dysfunction may occur in these patients, and whether psychological disorders are the result of disease activity or determinants of the IBD occurrence. In this comprehensive review, we summarize the role of the brain-gut axis in the psychological functioning of patients with IBD, and discuss current preclinical and clinical data on the topic and therapeutic strategies potentially useful for the clinical management of these patients. Personalized pathways of psychological supports are needed to improve the quality of life in patients with IBD.

Statins and inflammatory bowel disease: Where do we stand?

Inflammatory bowel disease is a chronic autoimmune disorder of the western world that is rapidly expanding in newly industrialized countries. Novel strategies are urgently needed to prevent and improve the treatment of this costly and disabling disease. Statins are the most commonly prescribed drugs worldwide. Besides their lipid-lowering effects, statins may exert complex immunomodulatory properties and multiple pleiotropic effects including the inhibition of T-cell activation, antigen-presenting function and leukocyte infiltration of target organs which might render statins as beneficial agents for inflammatory and autoimmune conditions. In this review, we summarize the experimental findings on the topic, and critically appraise the epidemiological evidence regarding the value of statins as a potential strategy for preventing and treating inflammatory bowel disease. Several experimental studies have shown that statins reduce inflammation in animal models of colitis; however, clinical studies investigating their disease-modifying and preventive potential in IBD have demonstrated some limitations and conflicting results. The available epidemiological evidence is not yet sufficient to support the use of statin for preventing or treating inflammatory bowel disease. Additional high-quality research is warranted.