Barkerolsson1571

Primary membranous nephropathy (MN) is a frequent cause of nephrotic syndrome (NS) in adults. In untreated patients, the outcome is variable, with one-third of the patients entering remission while the remaining ones show persisting proteinuria or progression to end-stage renal disease. Randomized clinical trials reported the efficacy of a 6-month regimen alternating intravenous and oral glucocorticoids with an alkylating agent every other month. The potential side effects of this regimen were limited by the fact that the use of glucocorticoids and alkylating agent did not exceed 3 months each. Two randomized trials with follow-ups (FU) up to 10 years provided assurance about the long-term efficacy and safety of this cyclical therapy. Calcineurin inhibitors have also been used successfully. However, in most responders, NS relapsed after the drug was withdrawn. Conflicting results have been reported with mycophenolate salts and adrenocorticotropic hormone. Observational studies reported good results with rituximab (RTX). Two controlled trials demonstrated the superiority of RTX over antiproteinuric therapy alone and cyclosporine. However, the FUs were relatively short and no randomized trial has been published against cyclical therapy. The available results, together with the discovery that most patients with MN have circulating antibodies against the phospholipase A2 receptor 1, support the use of cytotoxic drugs or RTX in MN. It is difficult to choose between these two different treatments. RTX is easier to use, but the FUs of the available studies are short, thus doubts remain about the long-term risk of relapses and the safety of repeated administrations of RTX. © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.Erythropoiesis-stimulating agents (ESAs) are effective drugs to correct and maintain haemoglobin (Hb) levels, however, their use at doses to reach high Hb targets has been associated with an increased risk of cardiovascular adverse events, mortality and cancer. Presently used ESAs have a common mechanism of action but different pharmacokinetic and pharmacodynamic characteristics. Accordingly, the mode of activation of the erythropoietin (EPO) receptor can exert marked differences in downstream events. It is unknown whether the various ESA molecules have different efficacy/safety profiles. The relative mortality and morbidity risks associated with the use of different types of ESAs remains poorly evaluated. Recently an observational study and a randomized clinical trial provided conflicting results regarding this matter. However, these two studies displayed several differences in patient characteristics and ESA molecules used. More importantly, by definition, randomized clinical trials avoid bias by indicationblished by Oxford University Press on behalf of ERA-EDTA. All rights reserved.Amyotrophic lateral sclerosis is the most common degenerative disorder of motor neurons in adults. As there is no cure, thousands of individuals who are alive at present will succumb to the disease. In recent years, numerous causative genes and risk factors for amyotrophic lateral sclerosis have been identified. Several of the recently identified genes encode kinases. In addition, the hypothesis that (de)phosphorylation processes drive the disease process resulting in selective motor neuron degeneration in different disease variants has been postulated. We re-evaluate the evidence for this hypothesis based on recent findings and discuss the multiple roles of kinases in amyotrophic lateral sclerosis pathogenesis. We propose that kinases could represent promising therapeutic targets. Mainly due to the comprehensive regulation of kinases, however, a better understanding of the disturbances in the kinome network in amyotrophic lateral sclerosis is needed to properly target specific kinases in the clinic. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.OBJECTIVES This study aimed to evaluate the outcomes and feasibility of different techniques of reconstruction of the right ventricular outflow tract (RVOT) in surgical repair of truncus arteriosus. METHODS We retrospectively reviewed all consecutive patients with truncus arteriosus who underwent successful surgical repair in our centre between 1994 and 2017. We analysed late results according to the type of RVOT repair. RESULTS We collected data from 29 survivors after truncus arteriosus repair. Six (20%) of them were affected by DiGeorge syndrome. The RVOT reconstruction was achieved using a valved conduit in 58.6%, while a direct right ventricle-pulmonary artery (RV-PA) anastomosis, with or without the interposition of the left atrial appendage, was performed in the remaining. At a median follow-up time of 7.9 years (interquartile range 1.8-13.1), 6 patients (3 affected by DiGeorge syndrome) died. Between the 2 groups, there were no differences in terms of the late mortality and onset of adverse events. However, the use of a conduit seemed more prone to reintervention and onset of adverse events. CONCLUSIONS Different RVOT reconstruction techniques are safe and have similar late outcomes. However, use of a direct RV-PA anastomosis and left atrial appendage interposition may reduce the need for reoperation in the long term. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.Stress is a biological adaptive response to restore homeostasis, and occurs in every animal production system, due to the multitude of stressors present in every farm. Heat stress is one of the most common environmental challenges to poultry worldwide. It has been extensively demonstrated that heat stress negatively impacts the health, welfare and productivity of broilers and laying hens. However, basic mechanisms associated with the reported effects of heat stress are still not fully understood. The adaptive response of poultry to a heat stress situation is complex and intricate in nature, and it includes effects on the intestinal tract. This review offers an objective overview of the scientific evidence available on the effects of the heat stress response on different facets of the intestinal tract of poultry, including its physiology, integrity, immunology and microbiota. Although a lot of knowledge has been generated, many gaps persist. The development of standardized models is crucial to be able to better compare and extrapolate results. By better understanding how the intestinal tract is affected in birds subjected to heat stress conditions, more targeted interventions can be developed and applied. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.In order to further increase the stability of the cannula behind the ribs and to facilitate cannula exteriorization in growing pigs, the present study aimed to evaluate whether elongation of the cannula flange could increase the stability of the cannula behind the ribs and to develop a tool to improve the exteriorization of the cannula through the ribs. Moreover, it was assessed whether a special skin protection paste and soft polyurethane foam material used in daily skin care could prevent erythema around the fistula. The feasibility of both, the modified simple T-cannula and daily skin care procedure, was evaluated in a digestibility experiment. Simple T-cannulae were made of high-molecular-weight polyethylene and inserted into the distal ileum of eight growing pigs (average body weight at surgery 30 kg). Modifications in the cannula design included a longer flange (11 cm) that was narrowed from the center to the ends and a bending of the flange to adapt it to the curve of the costal arch. In order to reducail journals.permissions@oup.com.Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood hematologic disorder characterized by lymphadenopathy, systemic inflammation, cytopenias, and life-threatening multi-organ dysfunction. Interleukin-6 (IL-6) inhibition effectively treats approximately one-third of patients. Limited options exist for non-responders, because the etiology, dysregulated cell types, and signaling pathways are unknown. We previously reported three anti-IL-6 non-responders with increased mTOR activation who responded to mTOR inhibition with sirolimus. We investigated mTOR signaling in tissue and serum proteomes from iMCD patients and controls. mTOR activation was increased in the interfollicular space of iMCD lymph nodes (N=26) compared to control lymph nodes by immunohistochemistry (IHC) for pS6, p4EBP1, and p70S6K, known effectors and read-outs of mTORC1 activation. IHC for pS6 also revealed increased mTOR activation in iMCD compared to Hodgkin lymphoma, systemic lupus erythematosus, and reactive lymph nodes, suggesting that the mTOR activation in iMCD is not just a product of lymphoproliferation/inflammatory lymphadenopathy. Further, the degree of mTOR activation in iMCD was comparable to autoimmune lymphoproliferative syndrome, a disease driven by mTOR hyperactivation that responds to sirolimus treatment. Geneset enrichment analysis of serum proteomic data from iMCD patients (n=88) and controls (n=42) showed significantly enriched mTORC1 signaling. Finally, functional studies revealed increased baseline mTOR pathway activation in peripheral monocytes and T-cells from iMCD remission samples compared to healthy controls. IL-6 stimulation augmented mTOR activation in iMCD patients, which was abrogated with JAK1/2 inhibition. These findings support mTOR activation as a novel therapeutic target for iMCD, which is being investigated through a trial of sirolimus (NCT03933904). Copyright © 2020 American Society of Hematology.OBJECTIVES The technique of simultaneously visualizing pulmonary nodules and the intersegmental plane using fluorescent images was developed to measure the distance between them intraoperatively. METHODS Patients who underwent pulmonary segmentectomy were consecutively included in this study between March 2016 and July 2019. Computed tomography or electromagnetic bronchoscopy-guided localization with indocyanine green-lipiodol emulsion was performed on the day of surgery. In the middle of the surgery, after dividing the segmental artery, vein and bronchus to a targeted segment, 0.3-0.5 mg/kg of indocyanine green was injected intravenously. RESULTS In total, 31 patients (17 men and 14 women with a mean age of 63.2 ± 9.8 years) were included in this study. The mean size and depth of the nodules were 1.2 ± 0.5 (range 0.3-2.5) cm and 16.4 ± 9.9 (range 1.0-42.0) mm, respectively. Pulmonary nodules and intersegmental plane of all the patients were visualized using a fluorescent thoracoscope. The resection margins were more than the size of the tumour or were 2 (mean 2.4 ± 1.2) cm in size in all patients except one. The resection margin of this patient looked sufficient on the intraoperative view. However, adenocarcinoma in situ at the resection margin was identified based on the pathological report. GSK467 in vitro The mean duration of the operation was 168.7 ± 53.3 min, and the chest tube was removed on an average of 4.7 ± 1.8 days after surgery in all patients. CONCLUSIONS The dual visualization technique using indocyanine green could facilitate an easier measurement of the distance between pulmonary nodules and the intersegmental plane during pulmonary segmentectomy. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.