OBJECTIVE:To evaluate comprehensively the association of cytotoxic T-lymphocyte antigen 4 (CTLA-4) +49A/G polymorphism with susceptibility to primary biliary cirrhosis (PBC). METHODS:PubMed was used to search for the relevant published articles. The risk of PBC association with the CTLA-4 +49A/G polymorphism was estimated for each study in a random-effects model. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each study. Risks to PBC were estimated by stratified analysis in patients with different ethnicity and antimitochondrial antibody (AMA) status, as well as histological stages. RESULTS:A total of 12 articles were included in the study. An association between PBC and CTLA-4 G allele was found, overall OR = 1.20, 95% CI 1.03-1.41 (P = 0.02). However, stratification by ethnicity indicated a significant association between the G allele and PBC in Asians (OR = 1.36, 95% CI 1.12-1.65, P = 0.002), but not in Caucasians (OR = 1.15, 95% CI 0.95-1.39, P = 0.15). Moreover, AMA positive patients carrying G allele were more susceptible to PBC compared with AMA negative patients (OR = 1.23, 95% CI 1.06-1.43, P = 0.007; OR = 0.98, 95% CI 0.71-1.34, P = 0.88, respectively). CONCLUSIONS:Polymorphism in exon 1 of CTLA-4 gene at position 49 may act as a candidate of susceptibility locus to PBC. However, larger studies with participants of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings.KEY WORDS: cytotoxic T-lymphocyte antigen 4, single nucleotide polymorphism, primary biliary cirrhosis, meta-analysis. INTRODUCTIONPrimary biliary cirrhosis (PBC) is an autoimmune disease characterized by female preponderance and destruction of intrahepatic bile ducts that often results in cirrhosis and hepatic failure. [1][2][3][4] Twin and family aggregated data suggest that there is a significant genetic predisposition for PBC, and the complex features in etiology are thought to be resulted from the interaction between multiple genetic and environmental factors. 2011; 12; 428-435 doi: 10.1111/j.1751-2980.2011.00537.x 428 Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative regulator of T-cell immune response and is expressed predominantly in activated regulatory T-cells. [6][7][8] The absence of gene in knockout or CTLA-4-deficient mice leads to massive lymphoproliferative disorders, fatal multi-organ destruction and early death. Journal of Digestive Diseases2,3 The apparent association between pathological T-cell response and the development of PBC 9,10 suggests that CTLA-4 might be an attractive and candidate facilitator of the PBC susceptibility gene. Variants in the gene encoding immunoregulatory CTLA-4 were examined for the candidate susceptibility loci for PBC.CTLA-4 gene is located on chromosome 2q33; the adjacent gene encoding another two immunoregulatory proteins: inducible co-stimulator and its stimulatory counterpart (CD28).11 Significant amino-acid replacement resulted from single nucleotide polymorphisms (SNPs) has been described. For ...

Left atrial appendage occlusion is not inferior to oral anticoagulants in the prevention of stroke in several randomized controlled trials. However, the clinical efficacy and safety comparison of the Watchman and amplatzer cardiac plug (ACP)/Amulet devices for percutaneous left atrial appendage closure (LAAC) in patients with non‐valvular atrial fibrillation was controversial. A database search was conducted using PubMed, EMBASE, Cochrane Library, and http://Clinicaltrials.gov for trials that compared Watchman device vs ACP/Amulet device. The effective outcomes were stroke and systemic embolism. Safety outcomes were all‐cause death, cardiovascular death, and major bleeding. Device‐related complications included device‐related thrombus (DRT), peri‐device leaks (PDL > 5 mm). A total of 19 articles involving 6224 patients were included in the present study. The Watchman and ACP/Amulet groups comprised 3267 and 2957 patients, respectively. No statistically significant differences were detected in the stroke (odd ratio [OR]:1.24, 95% confidence interval [CI]: 0.92−1.67, p = .17, I2 = 0), systemic embolism (OR:1.10, 95% CI: 0.51−2.35, p = .81, I2 = 0%), all‐cause death (OR:0.97, 95% CI: 0.80−1.18, p = .77, I2 = 1%), cardiogenic death (OR:0.99, 95% CI: 0.77−1.29, p = .96, I2 = 0%), major bleeding (OR:1.18, 95% CI: 0.98−1.43, p = .08, I2 = 25%). DRT (OR:1.48, 95% CI: 1.06−2.06, p = .02, I2 = 0%) and PDL > 5 mm (OR:2.57, 95% CI: 1.63−4.04, p < .0001, I2 = 0%) were significantly lower in ACP/Amulet group compared to Watchman group. The effective and safety outcomes were comparable between two groups. ACP/Amulet group had significantly lower rates of DRT and PDL > 5 mm than Watchman group.

AimTo compare the clinical efficacy of ultrasound-assisted thrombolysis (USAT) vs. standard catheter-directed thrombolysis (SCDT) in patients with acute pulmonary embolism (aPE).MethodsThis study analyzed the clinical outcomes of patients with non-low-risk aPE who received USAT or SCDT. The primary outcomes were all-cause death, total bleeding, and major bleeding. Secondary outcomes included pulmonary thrombotic load score (Miller), improvement in right ventricular-to-left ventricular ratio (RV/LV), dose and duration of the thrombolytic drug tissue plasminogen activator (tPA), length of stay (LOS) in the ICU, and total LOS in the hospital.ResultsA total of seven articles and 451 patients were included in this study. 241 patients were in the USAT group and 210 patients were in the SCDT group. There were no significant differences in all-cause mortality, total bleeding, and major bleeding between the two groups. Miller scores for pulmonary thrombus also showed no difference between the two groups, but pulmonary artery systolic pressure (PASP) was lower in the SCDT group after-treatment. The reduction of RV/LV from baseline was more pronounced in the SCDT group than in the USAT group (OR: −0.14, 95%CI: −0.20 to 0.07, P &lt; 0.0001, I2 = 0%). Total dose of tPA and duration of infusion in the USAT group were lower than those in the SCDT group, but there was no significant statistical difference. LOS in the ICU was similar between the two groups, while LOS in the hospital was lower in the SCDT group.ConclusionThis study did not detect any differences in all-cause mortality, total bleeding, and major bleeding between non-low-risk aPE patients treated with USAT or SCDT. Improvement in right ventricular function was better in the SCDT group, and hospital LOS was lower in the SCDT group.