Everolimus Rescue Treatment for Chronic Rejection After Pediatric Living Donor Liver Transplantation: 2 Case Reports

Ueno T., Hiwatashi S., Saka R., et al. Everolimus Rescue Treatment for Chronic Rejection After Pediatric Living Donor Liver Transplantation: 2 Case Reports. Transplantation Proceedings 50, 2872 (2018); https://doi.org/10.1016/J.TRANSPROCEED.2018.03.079.Chronic rejection (CR) remains a challenging complication after liver transplantation. Everolimus, which is a mammalian target of rapamycin inhibitor, has an anti-fibrosis effect. We report here the effect of everolimus on CR. Case 1 was a 7-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 10 months of age. Liver function tests (LFTs) did not improve after transplantation despite treatment with tacrolimus + mycophenolate mofetil (MMF). Antithymoglobulin (ATG) and steroid pulse therapy were also ineffective. The patient was diagnosed with CR, and everolimus was started with a target trough level of about 5 ng/mL. LFTs improved and pathological examination showed no progression of hepatic fibrosis. Case 2 was a 10-year-old girl with Alagille syndrome who underwent LDLT at 1 year of age. She had biopsy-proven acute cellular rejection with prolonged LFT abnormalities beginning 3 years after transplantation. She was treated with steroid pulse therapy, followed by MMF, tacrolimus, and prednisolone. Her condition did not improve, even after subsequent ATG administration. CR was suspected based on liver biopsy in the fourth postoperative year, and everolimus was introduced. The target trough level was around 5 ng/mL, but was reduced to 3 ng/mL due to stomatitis. Four years have passed since the initiation of everolimus, and LFTs are stable with no progression of liver biopsy fibrosis. We describe 2 cases in which everolimus was administered for CR. In both cases, LFTs improved and fibrosis did not progress, suggesting that everolimus is an effective treatment for CR after LDLT

Pulmonary Arterial Pressure Management Based on Oral Medicine for Pediatric Living Donor Liver Transplant With Portopulmonary Hypertension

Ueno T., Hiwatashi S., Saka R., et al. Pulmonary Arterial Pressure Management Based on Oral Medicine for Pediatric Living Donor Liver Transplant With Portopulmonary Hypertension. Transplantation Proceedings 50, 2614 (2018); https://doi.org/10.1016/J.TRANSPROCEED.2018.03.068.Pediatric living donor liver transplantation (LDLT) in patients with advanced portopulmonary hypertension (PoPH) is associated with poor prognoses. Recently, novel oral medications, including endothelin receptor antagonists (ERAs), phosphodiesterase 5 (PDE5) inhibitors, and oral prostacyclin (PGI2) have been used to treat PoPH. Pediatric patients with PoPH who underwent LDLT from 2006 to 2016 were enrolled. Oral pulmonary hypertension (PH) medication was administered to control pulmonary arterial pressure (PAP). Four patients had PoPH. Their ages ranged from 6 to 16 years, and their original diseases were biliary atresia (n = 2), portal vein obstruction (n = 1), and intrahepatic portal systemic shunt (n = 1). For preoperative management, 2 patients received continuous intravenous PGI2 and 2 oral medications (an ERA alone or an ERA and a PDE5 inhibitor), and 2 received only oral drugs (an ERA and a PDE5 inhibitor). One patient managed only with intravenous PGI2 died. In the remaining 3 cases, intravenous PGI2 or NO was discontinued before the end of the first postoperative week. Postoperative medications were oral PGI2 alone (n = 1), an ERA alone (n = 1), or the combination of an ERA and a PDE5 inhibitor (n = 1). An ERA was the first-line therapy, and a PDE5 inhibitor was added if there was no effect. New oral PH medications were effective and safe for use in pediatric patients following LDLT. In particular, these new oral drugs prevent the need for central catheter access to infuse PGI2

The Selaginella Genome Identifies Genetic Changes Associated with the Evolution of Vascular Plants

Vascular plants appeared ~410 million years ago then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes (1). We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first non-seed vascular plant genome reported. By comparing gene content in evolutionary diverse taxa, we found that the transition from a gametophyte- to sporophyte- dominated life cycle required far fewer new genes than the transition from a non-seed vascular to a flowering plant, while secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in post- transcriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the tasiRNA pathway and extensive RNA editing of organellar genes

Investigation of the effect of temper rolling on the texture evolution and mechanical behavior of IF steels using multiscale simulation

The main objective of this study is to simulate texture and deformation during the temper-rolling process. To this end, a rate-independent crystal plasticity model, based on the self-consistent scale-transition scheme, is adopted to predict texture evolution and deformation heterogeneity during temper-rolling process. For computational efficiency, a decoupled analysis is considered between the polycrystalline plasticity model and the finite element analysis for the temper rolling. The elasto-plastic finite element analysis is first carried out to determine the history of velocity gradient during the numerical simulation of temper rolling. The thus calculated velocity gradient history is subsequently applied to the polycrystalline plasticity model. By following some appropriately selected strain paths (i.e., streamlines) along the rolling process, one can predict the texture evolution of the material at the half thickness of the sheet metal as well as other parameters related to its microstructure. The numerical results obtained by the proposed strategy are compared with experimental data in the case of IF steels.French program “Investment in the future” operated by the National Research Agency (ANR)-11-LABX-0008-01, LabEx DAMAS (LST)