Low molecular weight heparin decreases mortality and major complication rates in moderately severe and severe acute pancreatitis-a systematic review and meta-analysis.

Background: Routine anticoagulation therapy in acute pancreatitis (AP) is not recommended by the guidelines in the field, although it is frequently used in clinical practice. Objectives: We aimed to analyze the efficacy and safety of adding anticoagulants therapy to AP management. Methods: The systematic search was performed in three databases on the 14th of October 2022 without restrictions. Randomized controlled trials (RCTs) and observational studies that reported the differences in the outcomes of AP for patients receiving anticoagulants (intervention group) in addition to the standard of care (SOC), compared to patients managed by SOC alone (control group), were eligible. A random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding 95%-confidence intervals (CI). We performed subgroup analysis for study design and disease severity, among other criteria. Results: Of the 8,223 screened records, we included eight in the meta-analysis. Except one, all studies reported on low-molecular-weight heparin (LMWH). Both RCTs and observational studies reported results in favor of the LMWH group. Subgroup RCTs' analysis revealed significantly decreased odds of mortality [OR 0.24; 95%CI 0.17-0.34] and multiple organ failure [OR 0.32; 95%CI 0.17-0.62] in the intervention group. Moreover, the need for endoscopic or surgical interventions [OR 0.41; 95%CI 0.28-0.61] were significantly reduced by LMWH. The subgroup analyzes for moderate and severe cases, respectively, yielded similar results. Due to limited data, we could no perform subgroup analysis for mild cases. Conclusion: LMWH therapy reduces major complication rates in moderate and severe AP. Across all identified RCTs, LMWH were initiated early after AP diagnosis and improved its prognosis.

At admission hemodynamic instability is associated with increased mortality and rebleeding rate in acute gastrointestinal bleeding: a systematic review and meta-analysis.

Background: Acute gastrointestinal bleeding (GIB) is a life-threatening event. Around 20-30% of patients with GIB will develop hemodynamic instability (HI). Objectives: We aimed to quantify HI as a risk factor for the development of relevant end points in acute GIB. Design: A systematic search was conducted in three medical databases in October 2021. Data sources and methods: Studies of GIB patients detailing HI as a risk factor for the investigated outcomes were selected. For the overall results, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated based on a random-effects model. Subgroups were formed based on the source of bleeding. The Quality of Prognostic Studies tool was used to assess the risk of bias. Results: A total of 62 studies were eligible, and 39 were included in the quantitative synthesis. HI was found to be a risk factor for both in-hospital (OR: 5.48; CI: 3.99-7.52) and 30-day mortality (OR: 3.99; CI: 3.08-5.17) in upper GIB (UGIB). HI was also associated with higher in-hospital (OR: 3.68; CI: 2.24-6.05) and 30-day rebleeding rates (OR: 4.12; 1.83-9.31) among patients with UGIB. The need for surgery was also more frequent in hemodynamically compromised UGIB patients (OR: 3.65; CI: 2.84-4.68). In the case of in-hospital mortality, the risk of bias was high for 1 (4%), medium for 13 (48%), and low for 13 (48%) of the 27 included studies. Conclusion: Hemodynamically compromised patients have increased odds of all relevant untoward end points in GIB. Therefore, to improve the outcomes, adequate emergency care is crucial in HI. Registration: PROSPERO registration number: CRD42021285727.

Dyspepsia-Like Symptoms in Helicobacter pylori-Negative Chronic Gastritis are Associated with ASCA-, ANCA-, and Celiac Seropositivity but Not with Other Autoimmune Parameters: A Single-Centre, Retrospective Cross-Sectional Study.

Introduction: Dyspeptic symptoms are frequent in the general population, with a high socioeconomic burden. Helicobacter pylori (H. pylori) might be a possible etiological factor; however, it is also common in H. pylori negative gastritis. Clarification of the underlying aetiology might be beneficial to set up the optimal treatment strategy for dyspepsia and chronic gastritis (CG) itself. We aimed to assess the prevalence of dyspeptic symptoms in patients with H. pylori negative CG and explore autoimmunity's possible role. Methods: This retrospective study included data from patients with H. pylori negative CG. Exclusion criteria were (1) acute gastritis; (2) reactive gastropathy; (3) subjects without any serology testing results; (4) H. pylori positivity; (5) presence of atrophy, intestinal metaplasia (IM), gastroesophageal reflux disease (GERD), ulcer, or cancer. The following endpoints were assessed (1) the rate of dyspepsia-like symptoms; (2) association between dyspepsia and autoimmune disease-related seromarker positivity (AISP); (3) frequency of other symptoms in CG and its association with AISP; (4) location of the inflammation and its association with AISP. Results: From a total of 285 patients, 175 were included in this study. Among these patients, 95 experienced dyspeptic symptoms (54.29%) and were associated more with AISP (p = 0.012), especially with celiac seropositivity (p = 0.045), anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) positivity (p = 0.043). A significant association was not found with other tested autoimmune (AI)-related antibody positivity. Conclusion: Positivity of seromarkers of autoimmune diseases in chronic gastritis may predispose to have dyspeptic symptoms and may be the causative factor behind some cases of uninvestigated dyspepsia. These data suggest that further prospective studies are needed to clarify whether screening for autoantibodies in patients with dyspepsia is cost-effective and helps the earlier diagnosis of autoimmune diseases.

Prevalence of Autoimmune-phenomena behind Chronic Gastritis of Unknown Origin, and their Role in the Poor Histological Outcome of the Stomach: A Single-centre, Retrospective Cross-sectional Study.

BACKGROUND AND AIMS: The underlying aetiology of chronic gastritis (CG) often remains unknown due to its underrated significance in clinical practice. However, the role of chronic inflammation of the stomach in the development of atrophy, intestinal metaplasia (IM) and eventually of gastric cancer is well documented. We aimed to explore the possible aetiological factors of CG, determine the prevalence of systemic autoimmune disorders in patients with CG of unknown aetiology, and clarify the role of autoantibodies in the development of precancerous lesions in the stomach. METHODS: This is a retrospective, cross-sectional study, conducted from January 2016 to January 2020, including data from 175 patients with CG. Exclusion criteria were: (1) acute gastritis; (2) reactive gastropathy; (3) gastric cancer; (4) subjects without any serology testing results; and (5) Helicobacter pylori positivity. The primary endpoint was a composite endpoint involving gastric atrophy and IM. RESULTS: Fifty-five per cent of patients with CG had autoantibodies. Systemic lupus erythematosus (SLE)-related antibodies were positive in most of the cases, including antinuclear antibody (ANA) positivity, which was found in 19.13% of the patients. Autoimmune positivity was shown to be associated with precancerous lesions in the stomach (p<0.001): IM, atrophy and IM with atrophy. Anti-parietal cell antibody positivity seems to be a significant risk factor for IM and IM with atrophy. Autoimmune thyroiditis-related antibodies and ANA positivity by itself were only associated with atrophy; SLE-related antibodies and inflammatory bowel diseases related antibodies (ASCA and ANCA) correlated either with IM or with atrophy. No significant relation was found between any other investigated autoimmune disease-related antibodies and precancerous lesions. CONCLUSIONS: Autoimmune positivity often underlies gastritis of unknown aetiology and predisposes to precancerous lesions in the stomach. These antibodies can serve as non-invasive markers for the of optimal timing of an endoscopic follow-up strategy. Furthermore, CG can be an early symptom of a systemic autoimmune disorder.

Six Autoimmune Disorders Are Associated With Increased Incidence of Gastric Cancer: A Systematic Review and Meta-Analysis of Half a Million Patients.

Background: Gastric cancer is one of the most common cancers worldwide, with a high mortality rate. The potential etiological role of autoimmune (AI) disorders has been described in gastric cancer; however, the literature is controversial. This study aims to provide a comprehensive summary of the association between autoimmune disorders and the incidence of gastric cancer. Methods: This study was registered on PROSPERO under registration number CRD42021262875. The systematic literature search was conducted in four scientific databases up to May 17, 2021. Studies that reported standardized incidence rate (SIR) of gastric cancer in autoimmune disorders were eligible. We calculated pooled SIRs with 95% confidence intervals (CIs) in this meta-analysis. Results: We included 43 articles describing 36 AI disorders with data of 499,427 patients from four continents in our systematic review and meta-analysis. Significantly increased incidence of gastric cancer was observed in dermatomyositis (SIR = 3.71; CI: 2.04, 6.75), pernicious anemia (SIR = 3.28; CI: 2.71, 3.96), inflammatory myopathies (SIR = 2.68; CI:1.40; 5.12), systemic lupus erythematosus (SIR = 1.48; CI: 1.09, 2.01), diabetes mellitus type I (SIR = 1.29; CI:1.14, 1,47), and Graves' disease (SIR = 1.28; CI: 1.16, 1.41). No significant associations could be found regarding other AI disorders. Conclusions: Pernicious anemia, Graves' disease, dermatomyositis, diabetes mellitus type I, inflammatory myopathies, and systemic lupus erythematosus are associated with higher incidence rates of gastric cancer. Therefore, close gastroenterological follow-up or routinely performed gastroscopy and application of other diagnostic measures may be cost-effective and clinically helpful for patients diagnosed with these autoimmune diseases.

Prophylactic transcatheter arterial embolization reduces rebleeding in non-variceal upper gastrointestinal bleeding: A meta-analysis.

BACKGROUND: Despite the improvement in the endoscopic hemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB), rebleeding remains a major concern. AIM: To assess the role of prophylactic transcatheter arterial embolization (PTAE) added to successful hemostatic treatment among NVUGIB patients. METHODS: We searched three databases from inception through October 19th, 2020. Randomized controlled trials (RCTs) and observational cohort studies were eligible. Studies compared patients with NVUGIB receiving PTAE to those who did not get PTAE. Investigated outcomes were rebleeding, mortality, reintervention, need for surgery and transfusion, length of hospital (LOH), and intensive care unit (ICU) stay. In the quantitative synthesis, odds ratios (ORs) and weighted mean differences (WMDs) were calculated with the random-effects model and interpreted with 95% confidence intervals (CIs). RESULTS: We included a total of 3 RCTs and 9 observational studies with a total of 1329 patients, with 486 in the intervention group. PTAE was associated with lower odds of rebleeding (OR = 0.48, 95%CI: 0.29-0.78). There was no difference in the 30-d mortality rates (OR = 0.82, 95%CI: 0.39-1.72) between the PTAE and control groups. Patients who underwent PTAE treatment had a lower chance for reintervention (OR = 0.48, 95%CI: 0.31-0.76) or rescue surgery (OR = 0.35, 95%CI: 0.14-0.92). The LOH and ICU stay was shorter in the PTAE group, but the difference was non-significant [WMD = -3.77, 95%CI: (-8.00)-0.45; WMD = -1.33, 95%CI: (-2.84)-0.18, respectively]. CONCLUSION: PTAE is associated with lower odds of rebleeding and any reintervention in NVUGIB. However, further RCTs are needed to have a higher level of evidence.

Endoscopic ultrasound-guided ethanol and radiofrequency ablation of pancreatic insulinomas: a systematic literature review.

BACKGROUND: Insulinoma is the most common neuroendocrine neoplasm of the pancreas, characterised by hypoglycaemic symptoms. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and ethanol ablation (EUS-EA) are novel methods for treating insulinoma.We aimed to perform a systematic review to assess the efficacy and safety of EUS-guided ablation techniques for pancreatic insulinomas. METHODS: We systematically searched for articles detailing EUS-guided ablations of insulinomas. We performed a qualitative analysis and summarised data on the efficacy and safety of EUS-RFA and EUS-EA techniques. RESULTS: In total, we identified 35 case reports and case series describing 75 patients with insulinomas treatment with EUS-guided ablation. Twenty-seven patients were treated with EUS-RFA, 47 patients with EUS-EA, and 1 patient received EUS-EA and EUS-RFA in the same session. In total, 84 insulinomas were ablated (EUS-RFA: 31, EUS-EA: 53). Most insulinomas were in the head of the pancreas (40%). The clinical success rate for EUS-guided ablation techniques was 98.5%. The median glucose level was 1.95 (Q1-Q3: 1.69-2.13) mmol/L before ablation compared to 6.20 (Q1-Q3: 5.30-7.05) mmol/L after treatment. The median insulin and C-peptide levels before and after RFA/EA were 230 (Q1-Q2: 120-257) pmol/L and 41 (Q1-Q2 35-42) pmol/L; 2077 (Q1-Q2 1644-2459) pmol/L and 819 (Q1-Q2 696-1072) pmol/L, respectively. There were eleven adverse events: seven abdominal pain, two mild acute pancreatitis, one necrotising acute pancreatitis and one local hematoma. All patients recovered, and there were no periprocedural deaths. CONCLUSIONS: EUS-guided ablation of insulinoma seems to be a safe and effective treatment and is an alternative to surgical resection in selected cases.

Mucoprotective drugs can prevent and treat nonsteroidal anti-inflammatory drug-induced small bowel enteropathy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Small bowel enteropathy (SBE) is a complication of nonsteroidal anti-inflammatory drug (NSAID) therapy occurring in 71% of NSAID users. We aimed to analyse the efficacy and safety of medications to prevent and treat NSAID-induced SBE in randomized controlled trials (RCTs). METHODS: This review was registered on PROSPERO (CRD42021223371). We systematically searched four databases until 20 October for comparing mucoprotective (MP), antibiotic and probiotic treatments to placebo, proton-pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists in NSAID-associated small intestinal injuries. The main outcomes were mucosal integrity, mucosal breaks after treatment, mucosal injury improvement and complete healing of mucosal breaks. Meta-analytical calculations for weighted mean differences (WMDs) and odds ratios (ORs) were performed with the random-effects model and interpreted with 95% confidence intervals (CIs). RESULTS: A total of 18 RCTs were included in the quantitative synthesis. MP medications administered preventively reduced the number of mucosal erosions (WMD = -1.24, CI: -2.15 to -0.34) and lead to a significantly lower chance of developing mucosal breaks after treatment (OR = 0.38, CI: 0.16-0.93). MP therapy was associated with a higher rate of complete healing of mucosal breaks (OR = 5.39, CI: 2.79-10.42). In the qualitative synthesis, there were tendencies for a lower increase in the mean number of mucosal breaks and reddened lesions with prophylactic and a higher decrease in mucosal breaks with therapeutic MP drug administration. CONCLUSION: MP treatment administered with NSAIDs can prevent and reduce small intestinal mucosal lesions.

Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Angiotensin-Converting Enzyme 2 Levels: A Comprehensive Analysis Based on Animal Studies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), caused the outbreak escalated to pandemic. Reports suggested that near 1-3% of COVID-19 cases have a fatal outcome. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in hypertension, heart failure and chronic kidney disease. These drugs have been reported to upregulate angiotensin converting enzyme 2 (ACE2) which produces Ang (1-7), the main counter-regulatory mediator of angiotensin II. This enzyme is also known as the receptor of SARS-CoV-2 promoting the cellular uptake of the virus in the airways, however, ACE2 itself proved to be protective in several experimental models of lung injury. The present study aimed to systematically review the relationship between ACEI/ARB administration and ACE2 expression in experimental models. After a comprehensive search and selection, 27 animal studies investigating ACE2 expression in the context of ACEI and ARB were identified. The majority of these papers reported increased ACE2 levels in response to ACEI/ARB treatment. This result should be interpreted in the light of the dual role of ACE2 being a promoter of viral entry to cells and a protective factor against oxidative damage in the lungs.