The objective of this study was to assess the effects of rituximab on bone mineral density (BMD) in women with systemic lupus erythematosus (SLE) 1 year after treatment. Thirty active female SLE patients treated with rituximab were compared with 43 SLE women not treated with rituximab. BMD was measured using dual energy X-ray absorptiometry (DEXA) before initiating biologic therapy and after 1 year. The mean age was 38.5 ± 2.1 years; median disease duration was 7 years. In the rituximab group, after 1 year of follow-up, BMD at the femoral neck (FN) decreased from 0.980 ± 0.130 g/cm(2) to 0.809 ± 0.139 g/cm(2) (-17.4%; p=0.001). Similarly, BMD at the lumbar spine (LS) decreased from 1.062 ± 0.137 g/cm(2) to 0.893 ± 0.194 g/cm(2) (-15.8%; p=0.001). In control subjects, BMD at the FN decreased from 0.914 ± 0.193 g/cm(2) to 0.890 ± 0.135 g/cm(2) (-2.6%; p=0.001), and BMD at the LS decreased from 0.926 ± 0.128 g/cm(2) to 0.867 ± 0.139 g/cm(2) (-6.2%; p=0.09). After 1 year, SLE patients had lower BMD at both the FN and LS, but the loss was greater in postmenopausal patients who had received rituximab therapy.
Despite wide-ranging implications of selfish mitochondrial DNA (mtDNA) elements for human disease and topics in evolutionary biology (e.g., speciation), the forces controlling their formation, age-related accumulation, and offspring transmission remain largely unknown. Selfish mtDNA poses a significant challenge to genome integrity, mitochondrial function, and organismal fitness. For instance, numerous human diseases are associated with mtDNA mutations; however, few genetic systems can simultaneously represent pathogenic mitochondrial genome evolution and inheritance. The nematode Caenorhabditis briggsae is one such system. Natural C. briggsae isolates harbor varying levels of a large-scale deletion affecting the mitochondrial nduo-5 gene, termed nad5Δ. A subset of these isolates contains putative compensatory mutations that may reduce the risk of deletion formation. We studied the dynamics of nad5Δ heteroplasmy levels during animal development and transmission from mothers to offspring in genetically diverse C. briggsae natural isolates. Results support previous work demonstrating that nad5Δ is a selfish element and that heteroplasmy levels of this deletion can be quite plastic, exhibiting high degrees of inter-family variability and divergence between generations. The latter is consistent with a mitochondrial bottleneck effect, and contrasts with previous findings from a laboratory-derived model uaDf5 mtDNA deletion in C. elegans. However, we also found evidence for among-isolate differences in the ability to limit nad5Δ accumulation, the pattern of which suggested that forces other than the compensatory mutations are important in protecting individuals and populations from rampant mtDNA deletion expansion over short time scales.
Aim: To compare gallstones removal rate and incidence of bleeding, pancreatitis, use of mechanical lithotripsy, cholangitis and perforation between isolated sphincterotomy versus sphincterotomy associated with balloon dilation of papilla in choledocholithiasis through the meta-analysis of randomized clinical trials. Methods: We conducted a systematic review according to the PRISMA guidelines. Literature search was restricted to randomized controlled trials (RCTs) on MedLine, Cochrane Library, LILACS, and EMBASE database platforms in July 2017. Eligibility criteria: Participants: patients with choledocholithiasis, older than 18 years. Interventions and comparisons: to compare endoscopic isolated sphincterotomy vs endoscopic sphincterotomy associated with balloon dilation. All relevant articles were accessed in full text. The manual search included references of retrieved articles. We extracted data focusing on outcomes: The primary endpoint was the stones removal rate; Secondary endpoints were rates of pancreatitis, bleeding, use of mechanical lithotripsy (ML), perforation and cholangitis. We analyzed the data and reported the results in tables and text. Results: Nine RCTs with a total of 1230 patients were included. Data analysis of the included studies showed that there was no statistical difference in safety between the two methods, since the incidence of pancreatitis (FE RD -0.01, CI [-0.03, 0.02], I 2 Z 0, p Z 0.5), bleeding (FE RD -0.01, CI [-0.03, 0.01], I 2 Z 32%, p Z 0.25), cholangitis (FE RD 0.00, CI[-0.01, 0.01], I 2 Z0, p Z 0.98) and perforation (FE RD -0.01, CI [-0.02, 0.01], I 2 Z0, p Z 0.37) was similar between the groups, but it was evident that there was a difference in efficacy, not quantitatively, with similar removal rates of gallstones in general and for subgroups greater than 15mm (FE RD 0.01, CI [-0.02, 0.04], I 2 Z 0, p Z 0.59) and (FE RD 0.02, CI [-0.04, 0.07], I 2 Z 5%, p Z 0.52), respectively, but perhaps qualitative, since there was less need for mechanical lithotripsy in the ESBD group (RE RD -0.14, CI [-0.25, -0.03], I 2 Z 91%, p Z 0.01), with a consequent theoretical decrease in exposure to adverse events resulting from it. Conclusion: There was no difference in the stone removal rate and incidence of bleeding, pancreatitis, cholangitis and perforation between isolated sphincterotomy and sphincterotomy associated with balloon dilation in the approach to remove gallstones. However, there was less use of mechanical lithotripsy in patients with choledocholithiasis submitted to sphincterotomy associated with balloon dilation.
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