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Solid organ transplantation

Michael Ong, Andrea Marie Ibrahim, Samuel Bourassa-Blanchette, Christina Canil, Todd Fairhead, Greg Knoll
BACKGROUND: Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer...
2016: Journal for Immunotherapy of Cancer
Annabelle Pourbaix, Nacera Ouali, Patrick Soussan, Anne Marie Roque Afonso, Marie-Noelle Péraldi, Eric Rondeau, Julie Peltier
Hepatitis E virus (HEV) can cause chronic infection among immunocompromised patients, especially solid organ transplant (SOT) recipients, and can evolve to cirrhosis. Several modes of transmission are known. Here we describe the first 2 cases, to our knowledge, of HEV infection transmitted by a kidney graft from the same infected donor that led to chronic hepatitis. Consequently, systematic screening of donors by HEV serology and HEV RNA detection by polymerase chain reaction, particularly in endemic regions, should be considered...
October 24, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Anke Theil, Carmen Wilhelm, Matthias Kuhn, Andreas Petzold, Sebastian Tuve, Uta Oelschlägel, Andreas Dahl, Martin Bornhäuser, Ezio Bonifacio, Anne Eugster
T regulatory cell (Treg) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GvHD). However, our knowledge on in vivo persistence of transfused Treg is limited. Whether Treg transfusion leads to notable changes in the overall Treg repertoire and or whether longevity of Treg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCRα-NGS) to monitor changes in the repertoire of Treg upon polyclonal expansion and after subsequent adoptive transfer...
October 24, 2016: Clinical and Experimental Immunology
Kathleen O Degnan, Emily A Blumberg
Patients infected with human immunodeficiency virus (HIV) are living longer, healthier lives on highly active antiretroviral therapy and, as a result, interest in kidney transplantation for HIV-infected patients with end-stage renal disease has increased. HIV is no longer considered a contraindication to solid-organ transplantation and the number of kidney transplants performed in HIV-infected patients each year is increasing steadily. HIV-infected kidney transplant recipients have had excellent outcomes overall, but there are still significant challenges, including high rates of acute rejection, drug-drug interactions, and poor outcomes in patients co-infected with hepatitis C virus...
September 2016: Seminars in Nephrology
Cybele Lara Abad, Raymund R Razonable
The α herpes viruses HSV-1, HSV-2, and VZV often reactivate in the setting of immune suppression after solid organ transplantation. Oral or genital mucocutaneous disease is the most common clinical manifestation of HSV disease while VZV manifests as varicella (or chickenpox) or reactivation herpes zoster, characterized by a diffuse rash, or a painful unilateral vesicular eruption in a dermatomal distribution, respectively. The diagnosis of HSV and VZV is primarily based on history and clinical presentation, although diagnostic tests may be necessary for atypical presentations of disease...
September 2016: Seminars in Nephrology
Aaron S Rosenberg, Robin Ruthazer, Jessica K Paulus, David M Kent, Andrew M Evens, Andreas K Klein
BACKGROUND: Multiple myeloma/plasmacytoma-like posttransplantation lymphoproliferative disorder (PTLD-MM) is a rare complication of solid organ transplantation. Case series have shown variable outcomes, and survival data in the modern era are lacking. PATIENTS AND METHODS: A cohort of 212 PTLD-MM patients was identified in the Scientific Registry of Transplant Recipients between 1999 and 2011. Overall survival (OS) was estimated by the Kaplan-Meier method, and the effects of treatment and patient characteristics on OS were evaluated by Cox proportional hazards models...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Péter Farkas, Dorottya Csuka, Bálint Mikes, György Sinkovits, Marienn Réti, Endre Németh, Kristóf Rácz, Krisztina Madách, Mihály Gergely, Judit Demeter, Zoltán Prohászka
BACKGROUND: The secondary forms of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (secondary TMA) emerge as complications of coexisting diseases. OBJECTIVES: We hypothesized that secondary TMA could be characterized by the presence of relative ADAMTS13 deficiency and complement activation, and this relationship may have a prognostic value for outcome. PATIENTS AND METHODS: Fifty-three patients with thrombotic microangiopathy (TMA) and coexisting disease (such as malignancies, sepsis, heart surgery with extracorporeal circulation, solid organ transplantation, systemic autoimmune disorders), 41 patient controls, and 34 healthy controls were enrolled in our case-control study with 30days follow-up...
October 18, 2016: Immunobiology
Niamh M Long, Andrew J Plodkowski, Rachel Schor-Bardach, Alexander I Geyer, Junting Zheng, Chaya S Moskowitz, Michelle S Ginsberg
OBJECTIVE: The aims of this study were to describe the computed tomographic features of organizing pneumonia (OP) in an oncologic patient population and to also identify features associated with lung cancer and patients undergoing hematopoietic stem cell transplant (HSCT). METHODS: In retrospective computed tomographies from 151 patients with pathologically confirmed OP between January 2009 and September 2014, number of lesions, location, size, margin type, and consistency, as well as volume of lymphadenopathy and the presence and size of pleural effusions, were recorded...
October 20, 2016: Journal of Computer Assisted Tomography
Maria A Pérez-Jacoiste Asín, Nerea Carrasco-Antón, Mario Fernández-Ruiz, Rafael San Juan, Rodrigo Alonso-Moralejo, Esther González, Amado Andrés, Francisco López-Medrano, Jose M Aguado
BACKGROUND: The incidence of visceral leishmaniasis (VL) after solid organ transplantation (SOT) is increasing. The optimal therapy for post-transplant VL remains unclear, as relapses after liposomal amphotericin B (L-AmB) are common. Miltefosine has been shown to be effective for treating VL in immunocompetent patients, although data in the specific population of SOT recipients are lacking. METHODS: In the setting of an outbreak of leishmaniasis occurring in Southwest Madrid, we reviewed our experience in 6 SOT recipients with persistent or relapsing VL who received a 28-day course of miltefosine (2...
October 21, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Meghan B Brennan, Barbara L Herwaldt, James J Kazmierczak, John W Weiss, Christina L Klein, Catherine P Leith, Rong He, Matthew J Oberley, Laura Tonnetti, Patricia P Wilkins, Gregory M Gauthier
Babesia microti, an intraerythrocytic parasite, is tickborne in nature. In contrast to transmission by blood transfusion, which has been well documented, transmission associated with solid organ transplantation has not been reported. We describe parasitologically confirmed cases of babesiosis diagnosed ≈8 weeks posttransplantation in 2 recipients of renal allografts from an organ donor who was multiply transfused on the day he died from traumatic injuries. The organ donor and recipients had no identified risk factors for tickborne infection...
November 2016: Emerging Infectious Diseases
Wubing He, Lihong Chen, Lin Zheng, Liuping Luo, Lingyun Gao
BACKGROUND: Dendritic cells (DCs) and regulatory T (Treg) cells are crucial for inducing immune tolerance. However, the suppressive function of infused Treg cells and immature DCs (imDCs) following solid organ transplantation remains unclear. METHODS: ImDCs derived from DA-donor rats and Treg cells isolated from spleens of Lewis rats were prepared. A heterotopic liver transplantation model was established to examine the immune tolerance effects of infusion of Treg-imDCs, imDCs and Treg cells individually...
October 17, 2016: Molecular Immunology
David Shaw, Denie Georgieva, Bernadette Haase, Dale Gardiner, Penney Lewis, Nichon Jansen, Tineke Wind, Undine Samuel, Maryon McDonald, Rutger Ploeg
Millions of people want to donate their organs after they die for transplantation, and many of them have registered their wish to do so or told their family and friends about their decision. For most of them, however, this wish is unlikely to be fulfilled, as only a small number of deaths (1% in the United Kingdom) occur in circumstances where the opportunity to donate organs is possible. Even for those who do die in the 'right' way and have recorded their wishes or live in a jurisdiction with a 'presumed consent' system, donation often does not go ahead because of another issue: their families refuse to allow donation to proceed...
October 19, 2016: Transplantation
Kipp Weiskopf, Peter J Schnorr, Wendy W Pang, Mark P Chao, Akanksha Chhabra, Jun Seita, Mingye Feng, Irving L Weissman
The hematopoietic stem cell (HSC) is a multipotent stem cell that resides in the bone marrow and has the ability to form all of the cells of the blood and immune system. Since its first purification in 1988, additional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: the myeloid and lymphoid arms. The myeloid arm is characterized by the common myeloid progenitor and all of its resulting cell types...
October 2016: Microbiology Spectrum
Arvind U Gowda, Colton H L McNichols, Ishan Asokan, Jamil A Matthews, E Bryan Buckingham, Jennifer Sabino, John S Maddox, Sheri Slezak, Yvonne Rasko, Devinder P Singh
PURPOSE: The purpose of this study was to compare clinical outcomes of incisional hernia repair in solid organ transplant patients using non-cross-linked porcine acellular dermal matrix (PADM), human derived acellular dermal matrix (HADM) and synthetic mesh. METHODS: A retrospective review of patients who underwent hernia repair with PADM after pancreas and/or renal transplant at the University of Maryland Medical Center from 2008 to 2012 was conducted. Repair type, postoperative infection, hernia recurrence, mesh removal, and length of follow-up were recorded...
October 17, 2016: Annals of Plastic Surgery
Megan A Rocchio, James W Schurr, Aaron P Hussey, Paul M Szumita
BACKGROUND: In October 2010, a pharmacist-driven stewardship program was implemented at the Brigham and Women's Hospital to ensure continued adherence to the prescribing guideline, focusing on indications for intravenous immune globulin (IVIG) use and dosing per ideal body weight. OBJECTIVE: The primary objective was to describe an IVIG stewardship program at a tertiary academic medical center. METHODS: This was a prospective, observational study from January 2013 through December 2014...
October 6, 2016: Annals of Pharmacotherapy
Scott N Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J Hunt, John B Schell, Katie Zeleski, Alison Yu, Cindy Giver, Edmund Waller, Jeffrey S Miller, Bruce R Blazar, Leslie S Kean
One of the central challenges of transplantation is the development of alloreactivity despite the use of multi-agent immunoprophylaxis. Effective control of this immune-suppression-resistant T cell activation represents one of the key unmet needs in the fields of both solid organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly-translational non-human primate model to interrogate the transcriptional signature of T cells during Breakthrough Acute GVHD that occurs in the setting of clinically-relevant immune suppression and compared this to the Hyperacute GVHD, that develops in unprophylaxed or sub-optimally prophylaxed transplant recipients...
October 6, 2016: Blood
Abbas Rana, Eileen D Brewer, Brandi B Scully, Michael L Kueht, Matt Goss, Karim J Halazun, Hao Liu, N Thao N Galvan, Ronald T Cotton, Christine A O'Mahony
BACKGROUND: Low case volume has been associated with worse survival outcomes in solid organ transplantation. Our aim was to analyze wait-list outcomes in conjunction with posttransplant outcomes. METHODS: We studied a cohort of 11,488 candidates waitlisted in the Organ Procurement and Transplantation Network (OPTN) for pediatric kidney transplant between 2002 and 2014, including both deceased- and living-donor transplants; 8757 (76 %) candidates received a transplant...
October 18, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Carla C Baan
Over 3000 delegates attended the 26st International Congress of the Transplantation Society in Hong Kong, which marked the 50th anniversary of the society. In his presidential address, Professor Phil O'Connell from the Westmead Hospital in Sydney, Australia, commented that a major challenge for the future is improving long-term outcomes after solid organ transplantation. He highlighted that 40% of transplanted organs are lost within 10 years, and that a high proportion of patients suffer from immunosuppression-related side effects...
October 7, 2016: Transplantation
Christian L Johnson, Yorick Soeder, Marc H Dahlke
PURPOSE OF REVIEW: The current review presents an update on the existing preclinical and human experience of mesenchymal stromal cell (MSC) therapies for post-transplant immunomodulation. RECENT FINDINGS: Although results from early clinical studies have demonstrated that the application of autologous and allogeneic MSC to be both safe and feasible in a solid organ transplantation setting, for example in liver, the efficacy of MSC immunotherapy demonstrated in preclinical models has yet to be replicated in human clinical trials...
October 7, 2016: Current Opinion in Organ Transplantation
Mark W Lowdell, Amy Thomas
Advanced therapy medicinal products (ATMPs) represent the current pinnacle of 'patient-specific medicines' and will change the nature of medicine in the near future. They fall into three categories; somatic cell-therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed 'tissue engineered' products. The term also incorporates 'combination products' where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres...
October 17, 2016: British Journal of Haematology
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