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Recent advances in videolaparoscopic surgery have made this method the treatment of choice for many biliary diseases. However, it has not been used in certain cases, such as primary intrahepatic lithiasis. The authors report a case of a 62-year-old woman with a history of several episodes of cholangitis. Investigation revealed dilated intra- and extrahepatic bile ducts with intrahepatic stones. The patient underwent laparoscopy, and intraoperative cholangiography disclosed an enlarged common duct with absence of stones and the presence of multiple calculi in the intrahepatic biliary tree. A choledochotomy followed by choledochoscopy was performed, which revealed several intrahepatic pigmented stones that were completely retrieved, followed by a laterolateral choledochoduodenostomy to decompress the biliary tree and to allow the migration of residual or recurrent stones. The patient had an uneventful recovery and was discharged on the fourth postoperative day. After 15 months of follow-up the patient is asymptomatic with normal results of liver function tests. Late postoperative upper digestive endoscopy showed a patent choledochoduodenostomy.

BackgroundMost rheumatoid arthritis (RA) patients initiate therapy with methotrexate (MTX), but only 1/3 will have low disease activity with this agent alone. Several therapeutic options are available for patients with MTX-resistant RA, including new Janus kinase (JAK) inhibitors (eg.: tofacitinib).ObjectivesTo compare the effectiveness of traditional disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs and tofacitinib for RA patients with inadequate response to MTX.MethodsWe used MarketScan® databases (2011–2014) to study adult RA individuals previously treated with methotrexate (oral or SQ) and newly prescribed one of the medications under study. The date of first filled prescription or infusion drug was defined as the cohort entry and a 12-month pre-period was used to exclude prior users of biologics or tofacitinib. We required subjects to be continuously enrolled in the medical and pharmacy plan 12 months before and after the cohort entry. Effectiveness was access through an algorithm previously validated1, based on the following criteria: 1) non-adherence; 2) switching/adding a new biologic or tofacitinib; 3) switching/adding a new DMARD; 4) increasing of the dose of the starting therapy; 5) use of glucocorticoid joint injections; and 6) increasing the dose of oral glucocorticoid. A patient's therapy was defined as not effective if at least one of the criterion occurred during the first year of follow-up.Results16,305 RA patients were included; 2,879 began therapy with DMARD, 13,345 with biologics and 81 with tofacitinib. Among all patients, 77.5% were female and the mean age was 56.2 years (standard deviation 12.6). Table 1 shows the proportion of patients that meet the individual criterion and that achieved effectiveness at the end of one-year follow-up.Table 1.Proportion and 95% confidence interval (CI) of patients who achieved therapy effectiveness and the individual criteriaEffectiveness criteriaDMARDBiologicsTofacitinib %95% CI%95% CI%95% CI Non-adherence75.173.5; 76.754.553.6; 55.369.159.1; 79.2Switch/add biologic or tofacitinib16.114.8; 17.534.633.8; 35.418.510.1; 27.0Switch/add DMARD13.011.7; 14.216.616.0; 17.316.08.1; 24.0Increase in dose or frequency8.67.6;9.76.96.5; 7.300Glucocorticoid joint injection7.86.9; 8.914.013.4; 14.69.63.4; 16.4Increase in dose of oral glucocorticoid19.017.6;20.517.617.0;18.222.213.2;31.3Effective therapy (none of the criteria)15.514.2; 16.817.917.2; 18.514.87.1; 22.6ConclusionsSimilar rates of therapy effectiveness were observed among groups, although the rates for the individual criteria differed. Fewer patients initiating biologic agents were non-adherent compared to DMARD and tofacitinib therapy, but switch/adding and injections tended to be higher in this group.References Curtis JR et al. Derivation and preliminary validation of an administrative claims-based algorithm for the effectiveness of medications for rheumatoid arthritis. Arthritis Res Ther. 2011;13(5). Disclosure of InterestNone declared

27Currently, eight Phyllosticta species are known to be associated with Citrus hosts, 28 incorporating endophytic and pathogenic lifestyles. As sexual reproduction is a key factor 29 involved in host-interaction, it could be related to the differences in lifestyle. To evaluate this 30 hypothesis, we characterized the mating-type loci of six Citrus-associated Phyllosticta species 31 from whole genome assemblies. Mating-type genes are highly variable in their sequence 32 content, but the genomic locations and organization of the mating-type loci are conserved. 33Phyllosticta citriasiana, P. citribraziliensis and P. paracitricarpa are heterothallic, and P. 34 citrichinaensis was confirmed to be homothallic. In addition, the P. citrichinaensis MAT1-2 35 idiomorph occurs in a separate location from the mating-type locus. Ancestral state 36 reconstruction suggests that homothallism is the ancestral thallism state in Phyllosticta, with a 37 shift to heterothallism in Phyllosticta species that are pathogenic to Citrus. Moreover, the 38 homothallic strategies of P. capitalensis and P. citrichinaensis result from independent 39 evolutionary events. As the pathogenic species P. citriasiana, P. citricarpa and P. 40 paracitricarpa are heterothallic and incapable of selfing, disease management practices 41 focused in preventing the occurrence of sexual reproduction could assist in the control of 42Citrus Black Spot and Citrus Tan Spot diseases. This study emphasizes the importance of 43 studying Citrus-Phyllosticta interactions under evolutionary and genomic perspectives, as 44 these approaches can provide valuable information about the association between Phyllosticta 45 species and their hosts, and also serve as guidance for the improvement of disease 46 management practices. 47 48