334 research outputs found
Organellar division and vesicular transport during cell division in the marine pennate diatom <i>Phaeodactylum tricornutum</i>
Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up
Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term
Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply
Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediateârelease tacrolimus (IRâTAC) is not available. Alternative options explored include extendedârelease tacrolimus (ERâTAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ERâTAC formulations are of nonâinferior efficacy compared to IRâTAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsyâproven rejection, but improved tolerance from classic adverse effects of IRâTAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via thirdâparty payors is an obstacle in nonâKTRs. In the setting of IRâTAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/2/ctr13903.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/1/ctr13903_am.pd
Primary Hepatic Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study.
Primary hepatic lymphoma (PHL) is a rare malignancy. We aimed to assess the clinical profile, outcome and prognostic factors in PHL through the Rare Cancer Network (RCN). A retrospective analysis of 41 patients was performed. Median age was 62 years (range, 23-86 years) with a male-to-female ratio of 1.9:1.0. Abdominal pain or discomfort was the most common presenting symptom. Regarding B-symptoms, 19.5% of patients had fever, 17.1% weight loss, and 9.8% night sweats. The most common radiological presentation was multiple lesions. Liver function tests were elevated in 56.1% of patients. The most common histopathological diagnosis was diffuse large B-cell lymphoma (65.9%). Most of the patients received Chop-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens; 4 patients received radiotherapy (dose range, 30.6-40.0 Gy). Median survival was 163 months, and 5- and 10-year overall survival rates were 77 and 59%, respectively. The 5- and 10-year disease-free and lymphoma-specific survival rates were 69, 56, 87 and 70%, respectively. Multivariate analysis revealed that fever, weight loss, and normal hemoglobin level were the independent factors influencing the outcome. In this retrospective multicenter RCN study, patients with PHL had a relatively better prognosis than that reported elsewhere. Multicenter prospective studies are still warranted to establish treatment guidelines, outcome, and prognostic factors
Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies
Abstract View references (47)
The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P <.001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35). \ua9 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeon
Mortality Prediction after the First Year of Kidney Transplantation: An Observational Study on Two European Cohorts.
After the first year post transplantation, prognostic mortality scores in kidney transplant recipients can be useful for personalizing medical management. We developed a new prognostic score based on 5 parameters and computable at 1-year post transplantation. The outcome was the time between the first anniversary of the transplantation and the patient's death with a functioning graft. Afterwards, we appraised the prognostic capacities of this score by estimating time-dependent Receiver Operating Characteristic (ROC) curves from two prospective and multicentric European cohorts: the DIVAT (Données Informatisées et VAlidées en Transplantation) cohort composed of patients transplanted between 2000 and 2012 in 6 French centers; and the STCS (Swiss Transplant Cohort Study) cohort composed of patients transplanted between 2008 and 2012 in 6 Swiss centers. We also compared the results with those of two existing scoring systems: one from Spain (Hernandez et al.) and one from the United States (the Recipient Risk Score, RRS, Baskin-Bey et al.). From the DIVAT validation cohort and for a prognostic time at 10 years, the new prognostic score (AUC = 0.78, 95%CI = [0.69, 0.85]) seemed to present significantly higher prognostic capacities than the scoring system proposed by Hernandez et al. (p = 0.04) and tended to perform better than the initial RRS (p = 0.10). By using the Swiss cohort, the RRS and the the new prognostic score had comparable prognostic capacities at 4 years (AUC = 0.77 and 0.76 respectively, p = 0.31). In addition to the current available scores related to the risk to return in dialysis, we recommend to further study the use of the score we propose or the RRS for a more efficient personalized follow-up of kidney transplant recipients
Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation.
BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes
Establishment of a community managed marine reserve in the Bay of Ranobe, southwest Madagascar
The Bay of Ranobe, in southwest Madagascar, once noted for its high biodiversity and fish abundance, is under increasing pressure from overfishing, pollution, sedimentation and tourism. The declining health of the coral reef is reflected in fishery productivity and survey data on biological diversity. Sustainable conservation requires the engagement of all interested parties and the integration of their needs into resource management. The British NGO ReefDoctor has adopted this approach in establishing the first community-protected site in the Bay of Ranobe, the Massif des Roses. This is a large coral patch with a high percentage of live coral cover (38%) and important fish diversity compared to other sites surveyed in the lagoon. Since 25 May 2007 it has been legally recognised as a community managed marine reserve under temporary protection where fishing is banned. Tourists must now pay an entry fee to visit the site, with the proceeds contributing to the funding of community projects. In conjunction with the protection of this site, ReefDoctor has worked with local people, regional and local government, tour operators and hotels, and conservation organisations to set up âFIMIHARAâ, an association representative of local people responsible for the management of this site and the development of sustainable conservation initiatives in the Bay of Ranobe. This paper explains the approach taken by ReefDoctor, by setting up and working with FIMIHARA, to protect the Massif des Roses site and develop other conservation initiatives and community projects in the Bay of Ranobe. RĂSUMĂ La baie de Ranobe, au sud-ouest de Madagascar, autrefois remarquable pour sa biodiversitĂ© et lâabondance de la pĂȘche, est de plus en plus menacĂ©e par la surpĂȘche, la sĂ©dimentation, la pollution et le tourisme. Le dĂ©clin de lâĂ©tat de santĂ© du rĂ©cif corallien se reflĂšte dans la diminution de la productivitĂ© des pĂȘcheries et dans les suivis de la biodiversitĂ© marine. La situation est Ă prĂ©sent critique car les ressources marines associĂ©es au rĂ©cif assurent la subsistance des populations cĂŽtiĂšres vivant le long de la baie. Nous considĂ©rons ici quâune protection pĂ©renne nĂ©cessite un engagement concret de toutes les parties prenantes - en particulier des communautĂ©s locales - et que leurs besoins soient intĂ©grĂ©s dans la gestion des ressources. LâONG ReefDoctor a mis en oeuvre cette approche lors de la crĂ©ation de la premiĂšre rĂ©serve marine dans la baie de Ranobe gĂ©rĂ©e par la communautĂ© locale, le Massif des Roses. Cette rĂ©serve est constituĂ©e dâun grand massif de corail largement couvert de coraux et abritant une importante diversitĂ© de poissons par rapport au reste du lagon. Depuis le 25 mai 2007, ce site est lĂ©galement reconnu comme rĂ©serve marine communautaire avec un statut de protection temporaire ; la pĂȘche et les pratiques destructrices associĂ©es au tourisme y sont interdites. De plus, les touristes doivent dĂ©sormais payer un droit dâentrĂ©e pour visiter le site, qui contribue au financement de projets communautaires. En parallĂšle avec la protection du site, ReefDoctor a travaillĂ© avec les communautĂ©s locales, les responsables nationaux et rĂ©gionaux du gouvernement, les opĂ©rateurs touristiques et diverses organisations de protection de la nature pour crĂ©er lâassociation FIMIHARA, reprĂ©sentative de la population locale. Cette association, qui a un statut lĂ©gal depuis le 11 avril 2007, a pour but dâamĂ©liorer la qualitĂ© de vie de ceux qui vivent le long de la baie de Ranobe et de mettre en oeuvre des projets de conservation des ressources marines et terrestres dans la rĂ©gion de la baie de Ranobe. La crĂ©ation de la rĂ©serve marine communautaire du Massif des Roses a rapidement connu le succĂšs qui sâest traduit par la vente de plus dâun millier de tickets, mais lâassociation FIMIHARA doit encore faire face Ă de nombreux dĂ©fis. Lâobjectif principal de lâassociation Ă long terme est de dĂ©velopper son indĂ©pendance par rapport Ă lâONG ReefDoctor et sa capacitĂ© Ă gĂ©rer indĂ©pendamment les ressources marines de la baie de Ranobe dont les communautĂ©s locales dĂ©pendent pour leur survie
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