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Direct oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice. However, their use in the treatment of acute venous thromboembolism (VTE) in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/m2) guarded. This is due to the scarce data supporting their use in this population. As a result, the International Society on Thrombosis and Haemostasis recommended against their use in this cohort of patients. New data emerged supporting the use of DOACs in these patients. Hence, we aimed to systematically review the literature exploring the efficacy and safety of these agents compared to warfarin in VTE treatment in morbidly obese patients. A systematic review of PubMed and EMBASE since inception until 01/04/2020. Subsequently, a non-inferiority (NI of 1.75) meta-analysis utilizing the random-effects model. Five observational studies (6585 patients) were included in our meta-analysis. DOAC analogs were non-inferior compared to warfarin in reducing the primary efficacy outcome of VTE recurrence (OR 1.07, 95% CI 0.93–1.23) and the primary safety outcome (major bleeding events) (OR 0.80, 95% CI 0.54–1.17). Our meta-analysis comprising real-world observational data concludes that the use of DOAC analogs in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/m2) is non-inferior with regards to efficacy and safety compared to warfarin. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it invites for a confirmatory non-inferiority randomized controlled trial testing DOAC vs. Warfarin in this group of patients.

BackgroundExtreme transaminase elevation > 1000 international units per liter (IU/L) is typically caused by hepatocellular injury due to ischemia, drugs, or viral infection. Acute choledocholithiasis can also present with marked transaminase elevation mimicking severe hepatocellular injury, contrary to the presumed cholestatic pattern. MethodsWe searched PubMed/Medline, EMBASE, Cochrane Library, and Google Scholar for studies reporting the proportion of marked elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1000 IU/L in patients with common bile duct (CBD) stones. A proportion meta-analysis with a corresponding 95% confidence interval (CI) was used to pool the proportion of patients with extreme transaminase elevation. I2 was used to examine heterogeneity. We used CMA software utilizing a random effect model for statistical analysis. ResultsThree studies (n = 1328 patients) were included in our analysis. The reported frequency of ALT or AST > 1000 IU/L in choledocholithiasis patients ranged between 6 and 9.6%, with pooled frequency of 7.8% (95% CI 5.5–10.8%, I2 61%). The frequency of patients with ALT or AST > 500 IU/L was higher, ranging between 28 and 47%, with pooled frequency of 33.1% (95% CI 25.3–42%, I2 88%).ConclusionThis is the first meta-analysis to study prevalence of severe hepatocellular injury in patients with CBD stones. Results revealed that approximately one-third of patients with choledocholithiasis present with ALT or AST > 500 IU/L. Furthermore, levels > 1000 IU/L are not uncommon. An elaborate work-up for alternative etiologies of severe transaminase elevation is likely unwarranted in cases with clear evidence of choledocholithiasis.

INTRODUCTION:Whether dye spray chromoendoscopy (DCE) adds value in surveillance colonoscopy with high-definition (HD) scopes remains controversial. This updated meta-analysis compares dysplasia detection using DCE and high-definition white light endoscopy (HD-WLE) in patients with inflammatory bowel disease (IBD) undergoing surveillance colonoscopy.METHODS:A comprehensive search was performed for randomized controlled trials (RCT) comparing HD-WLE and DCE in patients with IBD. The primary outcome was to compare the proportion of patients with at least 1 dysplastic lesion detected by DCE vs HD-WLE. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using the random-effects model, with I2 > 60% indicating substantial heterogeneity. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence (CoE).RESULTS:Six RCT involving 978 patients were analyzed (DCE = 479 vs HD-WLE = 499 patients). DCE detected significantly more patients with dysplasia than HD-WLE (18.8% vs 9.4%), OR 1.94 (95% CI 1.21-3.11, I2 = 28%, P = 0.006, high CoE). This remained significant after excluding 2 RCT published as abstracts. A sensitivity analysis excluding a noninferiority RCT with a single experienced operator eliminated the results' heterogeneity, OR 2.46 (95% CI 1.56-3.90, I2 = 0%). Although high-grade dysplasia detection was numerically higher in the DCE group (2.8% vs 1.1%), the difference was statistically insignificant, OR 2.21 (95% CI 0.64-7.62, I2 = 0%, low CoE).DISCUSSION:Our updated meta-analysis supports DCE as a superior strategy in overall dysplasia detection in IBD, even with HD scopes. When expertise is available, DCE should be considered for surveillance colonoscopy in patients with high-risk IBD, with the acknowledgment that virtual chromoendoscopy shows equivalence in recent studies. Further multicenter trials with multiple endoscopists with varying expertise levels and longer-term outcome data showing a reduction in cancer or cancer-related death are needed.

Background and AimsEndoscopic retrograde cholangiopancreatography (ERCP) is the standard of care for the management of choledocholithiasis but carries risk of complications which may result in significant morbidity and mortality. While currently available guidelines endorse the use of ERCP for the management of symptomatic common bile duct stones, the need for ERCP in incidentally found asymptomatic choledocholithiasis is more controversial, and practice varies on a geographic and institutional level. This systematic review and meta-analysis is conducted to compare post-ERCP adverse events between asymptomatic and symptomatic choledocholithiasis patients.MethodsWe searched PubMed/Embase/Web of Science databases to include all studies comparing post-ERCP outcomes between asymptomatic and symptomatic choledocholithiasis patients. The primary outcome was post-ERCP pancreatitis (PEP), while secondary outcomes included post-ERCP cholangitis, bleeding, and perforation. We calculated pooled risk ratios (RR) and 95% confidence intervals (CIs) using the Mantel–Haenszel method within a random-effect model.ResultsOur analysis included six observational studies, totaling 2,178 choledocholithiasis patients (392 asymptomatic and 1786 symptomatic); 53% were female. Asymptomatic patients exhibited a higher risk of PEP compared with symptomatic patients (11.7% versus 4.8%; RR 2.59, 95% CI 1.56–4.31, p ≤ 0.001). No significant difference was observed in post-ERCP cholangitis, bleeding, or perforation rates between the two groups.ConclusionsAsymptomatic patients with choledocholithiasis appear to have a higher risk of PEP than symptomatic patients, while the risk of other post-ERCP adverse events is similar between the two groups. Interventional endoscopists should thoroughly discuss potential adverse events (particularly PEP) with asymptomatic patients before performing ERCP and utilize PEP-prevention measures more liberally in this subgroup of patients.

IntroductionPeptic ulcers with adherent clots are associated with a high-risk of rebleeding and mortality. However, the optimal management of bleeding ulcers with adherent clots remains unclear. We conducted this systematic review and meta-analysis to compare endoscopic therapy and conservative therapy to manage bleeding ulcers with adherent clots.MethodsWe systematically searched PubMed, Embase, and Web of Science databases through October 2022 to include all studies comparing the endoscopic and conservative therapeutic approaches for bleeding ulcers with adherent clots. Our primary outcome was rebleeding (overall and 30-day). The secondary outcomes were mortality (overall and 30-day), need for surgery, and length of hospital stay (LOS). The random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding confidence intervals (CI) for proportional and continuous variables, respectively.ResultsEleven studies (9 RCTs) with 833 patients (431 received endoscopic therapy vs. 402 received conservative therapy) were included. Overall, endoscopic therapy was associated with lower overall rebleeding (OR 0.41, 95% CI 0.22–0.79, P = 0.007), 30-day rebleeding (OR 0.43, 95% CI 0.21–0.89, P = 0.002), overall mortality (OR 0.47, 95% CI 0.23–0.95, P = 0.04), 30-day mortality (OR 0.43, 95% CI 0.21–0.89, P = 0.002), need for surgery (OR 0.44, 95% CI 0.21–0.95, P = 0.04), and LOS (MD − 3.17 days, 95% CI − 4.14, − 2.19, P < 0.00001). However, subgroup analysis of randomized controlled trials (RCTs) showed no significant difference in overall mortality (OR 0.78, 95% CI 0.24–2.52, P = 0.68) between the two strategies, with numerically lower but statistically non-significant rates of overall rebleeding (7.2% vs. 18.5%, respectively; OR 0.42, 95% CI 0.17–1.05, P = 0.06), statistically lower rate of need for surgery (OR 0.28, 95% CI 0.08–0.96, P = 0.04) with endoscopic therapy compared to conservative therapy.ConclusionsOur meta-analysis demonstrates that endoscopic therapy was overall associated with lower rates of rebleeding (overall and 30-day), mortality (overall and 30-day), need for surgery, and LOS, compared to conservative therapy for the management of bleeding ulcers with adherent clots. However, subgroup analysis of RCTs showed that endoscopic therapy was associated with numerically lower but statistically non-significant rates of overall rebleeding and a statistically lower rate of need for surgery compared to conservative therapy with similar overall mortality rates. Combined treatment with thermal therapy and injection therapy was the most effective treatment modality in reducing rebleeding risk. Further large-scale RCTs are needed to validate our findings.

Abstract Background and purposeUncertainty remains regarding the impact of enteric-coated aspirin (EC-ASA) on secondary prevention of ischemic stroke compared to plain aspirin (P-ASA). Hence, this study was designed to investigate the effect of EC formulation on ASA response via evaluating thromboxane B2 (TXB2) levels in patients with suspected or newly diagnosed stroke.MethodsA prospective cohort study on suspected or newly diagnosed ischemic stroke patients who are aspirin-naive was conducted. Patients were received either EC aspirin or plain aspirin for at least 3 days. The primary outcome was the proportion of aspirin non-responsiveness between two groups (level of residual serum TXB2 associated with elevated thrombotic risk (< 99.0% inhibition or TXB2 > 3.1 ng/ml) within 72 h after three daily aspirin doses, while secondary outcomes were the incidence of early gastrointestinal tract (GIT) bleeding with the various aspirin preparations. (Trial registration: Clinicaltrials.gov NCT04330872 registered on 02 April 2020).ResultsOf 42 patients, ischemic strokes were confirmed in both P-ASA (81%) and EC-ASA (67%) arms. ASA non-responsiveness showed no significant difference between the two formulations (P-ASA vs. EC-ASA; 28.6% vs 23.8%; P = 0.726). Univariate and multivariate logistic regression analysis showed that patients treated with EC-ASA were more likely to have a lower rate of non-responders compared to P-ASA (unadjusted OR 0.78; 95% CI 0.20, 3.11); with the risk highest in type 2 diabetic patients with HBA1c > 6.5% (adjusted OR 6; 95% CI 1.02, 35.27; P = 0.047). No incidence of GIT bleeding observed throughout the study.ConclusionA significant proportion of ASA non-responsiveness was recorded regardless of ASA formulation administered. The increased risk of ASA non-responsiveness in diabetic patients needs further exploration by larger prospective studies.

Background The prevalence, management, and clinical outcomes of cholangiocarcinoma in Africa are unknown. The aim is to conduct a comprehensive systematic review on the epidemiology, management, and outcomes of cholangiocarcinoma in Africa. Methods We searched PubMed, EMBASE, Web of Science and CINHAL from inception up to November 2019 for studies on cholangiocarcinoma in Africa. The results reported follow PRISMA guidelines. Quality of studies and risk of bias were adapted from a standard quality assessment tool. Descriptive data were expressed as numbers with proportions and Chi-squared test was used to compare proportions. P values < 0.05 were considered significant. Results A total of 201 citations were identified from the four databases. After excluding duplicates, 133 full texts were reviewed for eligibility, and 11 studies were included. The 11 studies are reported from 4 countries only: 8 are from North Africa (Egypt 6 and Tunisia 2), and 3 in Sub-Saharan Africa (2 in South Africa, 1 in Nigeria). Ten studies reported management and outcomes, while one study reported epidemiology and risk factors. Median age for cholangiocarcinoma ranged between 52 and 61 years. Despite the proportion with cholangiocarcinoma being higher among males than females in Egypt, this gender disparity could not be demonstrated in other African countries. Chemotherapy is mainly used for palliative care. Surgical interventions are curative and prevent cancer progression. Statistical analyses were performed with Stata 15.1. Conclusion The known global major risk factors such as primary sclerosing cholangitis, Clonorchis sinensis and Opisthorchis viverrini infestation are rare. Chemotherapy treatment was mainly used for palliative treatment and was reported in three studies. Surgical intervention was described in at least 6 studies as a curative modality of treatment. Diagnostic capabilities such as radiographic imaging and endoscopic are lacking across the continent which most likely plays a role in accurate diagnosis.

INTRODUCTION:Diagnostic paracentesis is recommended for patients with cirrhosis admitted to the hospital, but adherence is suboptimal with unclear impact on clinical outcomes. The aim of this meta-analysis was to assess the outcomes of early vs delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites.METHODS:We searched multiple databases for studies comparing early vs delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites. The pooled odds ratio (OR) and mean difference with confidence intervals (CIs) for proportional and continuous variables were calculated using the random-effects model. Early diagnostic paracentesis was defined as receiving diagnostic paracentesis within 12-24 hours of admission. The primary outcome was in-hospital mortality. Secondary outcomes were length of hospital stay, acute kidney injury, and 30-day readmission.RESULTS:Seven studies (n = 78,744) (n = 45,533 early vs n = 33,211 delayed diagnostic paracentesis) were included. Early diagnostic paracentesis was associated with lower in-hospital mortality (OR 0.61, 95% CI 0.46-0.82, P = 0.001), length of hospital stay (mean difference −4.85 days; 95% CI −6.45 to −3.20; P < 0.001), and acute kidney injury (OR 0.62, 95% CI 0.42-0.92, P = 0.02) compared with delayed diagnostic paracentesis, with similar 30-day readmission (OR 1.11, 95% CI 0.52-2.39, P = 0.79). Subgroup analysis revealed consistent results for in-hospital mortality whether early diagnostic paracentesis performed within 12 hours (OR 0.51, 95% CI 0.32-0.79, P = 0.003, I2 = 0%) or within 24 hours of admission (OR 0.67, 95% CI 0.45-0.98, P = 0.04, I2 = 82%). Notably, the mortality OR was numerically lower when diagnostic paracentesis was performed within 12 hours, and the results were precise and homogenous (I2 = 0%).DISCUSSION:Findings from this meta-analysis suggest that early diagnostic paracentesis is associated with better patient outcomes. Early diagnostic paracentesis within 12 hours of admission may be associated with the greatest mortality benefit. Data from large-scale randomized trials are needed to validate our findings, especially if there is a greater mortality benefit for early diagnostic paracentesis within 12 hours.

INTRODUCTION:Colorectal cancer (CRC) screening is now recommended at the age of 45 years in the United States. However, information regarding the adenomas detection rate (ADR) and sessile serrated lesions (SSLs) in 45- to 49-year-old individuals is limited. In addition, the impact of lowering the screening age to 45 years on the ADR and the detection rate of SSLs is not well elucidated. This systematic review and meta-analysis aims to report the overall ADR and SSL detection rate in 45- to 49-year-old individuals undergoing colonoscopy.METHODS:We searched MEDLINE, EMBASE, SCOPUS, Web of Science, ClinicalTrials.gov, and the Cochrane database from inception through October 2022 to identify studies reporting on ADR and SSL detection rates in 45- to 49-year-old individuals undergoing colonoscopies for all indications. This approach acknowledges the possibility of including individuals undergoing diagnostic colonoscopies or those with increased risk factors for CRC. We also conducted a separate analysis examining ADR in average-risk individuals undergoing screening colonoscopy. The pooled rates with their corresponding 95% confidence intervals (CIs) were generated using the fixed-effects model. I2 was used to adjudicate heterogeneity.RESULTS:Sixteen studies met the inclusion criteria. All studies were retrospective except one; 3 had data from national/local registries. There were 41,709 adenomas detected across 150,436 colonoscopies. The pooled overall ADR was 23.1% (95% CI 19.7%-27.0%, I2 = 98.6%). The pooled ADR in individuals with average risk of CRC from 7 studies was 28.2% (95% CI 24.6%-32.0%, I2 = 96.5%). The pooled overall SSL detection rate from 6 studies was 6.3% (95% CI 3.8%-10.5%, I2 = 97%). The included studies were heterogeneous because of differences in the inclusion and exclusion criteria and patient population.DISCUSSION:In 45- to 49-year-old individuals undergoing a colonoscopy for any indication, the ADR and SSL detection rates were 23.1% and 6.3%, respectively. We conclude that these outcomes in 45- to 49-year-olds are comparable with individuals aged 50-54 years.