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everolimus and transplantation

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https://read.qxmd.com/read/30747620/host-and-pathogen-factors-in-klebsiella-pneumoniae-upper-urinary-tract-infections-in-renal-transplant-patients
#1
Justyna E Gołębiewska, Beata Krawczyk, Magdalena Wysocka, Aleksandra Ewiak, Jolanta Komarnicka, Marek Bronk, Bolesław Rutkowski, Alicja Dębska-Ślizień
PURPOSE: To analyse the role of virulence factors (VFs) and host in Klebsiella pneumoniae upper urinary tract infections (UTIs) in renal transplant (RTx) recipients. METHODOLOGY: Clinical and demographic data were registered prospectively. Phylogenetic background of K. pneumoniae isolates was analysed by PCR melting profiles (MP) and the following VFs genes: fimH-1, uge, kpn, ycfM, mrkD, rmpA, magA, hlyA, cnf-1, irp-1, irp-2, fyuA, entB, iutA, iroN by PCR. RESULTS: We studied urine cultures and clinical data from 61 episodes of K...
February 12, 2019: Journal of Medical Microbiology
https://read.qxmd.com/read/30740294/immunosuppression-for-lung-transplantation-current-and-future
#2
Satish Chandrashekaran, Stacy A Crow Pharm, Sadia Z Shah, Chris J Arendt Pharm, Cassie C Kennedy
Purpose of the review: The number of lung transplantations performed worldwide continues to increase. There is a growing need in these patients for more effective immunosuppressive medications with less toxicity. Recent findings: This review article summarizes the recent studies and developments in lung transplant immunosuppression. Novel immunosuppressive medications and strategies used in other solid organ transplantations are being trialed in lung transplantation...
September 2018: Current Transplantation Reports
https://read.qxmd.com/read/30739121/anti-diabetogenic-properties-of-mineralocorticoid-receptor-antagonists-implications-for-enhanced-safety-and-efficacy-of-post-transplantation-pharmacotherapies
#3
EDITORIAL
Yingzi Ming, George B Stefano, Richard M Kream, Quan Zhuang
Widespread usage of the calcineurin inhibitors tacrolimus and cyclosporine A as post-transplantation immunosuppressive agents is fraught with severe nephrotoxic and diabetogenic side effects. More recently, tapering of calcineurin inhibitor-based immunotherapies with concurrent administration of the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been employed within pharmacological regimens designed to achieve better safety and efficacy for preservation of allograft kidney function...
February 10, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://read.qxmd.com/read/30733891/mantle-cell-lymphoma-and-its-management-where-are-we-now
#4
REVIEW
Abdullah Ladha, Jianzhi Zhao, Elliot M Epner, Jeffrey J Pu
Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology. Overexpression of cyclin D1 and chromosome t(11,14) translocation are the known molecular biomarkers of this disease. Mantle cell international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation are emerging as the prognostic biomarkers...
2019: Experimental Hematology & Oncology
https://read.qxmd.com/read/30706940/synergism-of-imatinib-vatalanib-and-everolimus-in-the-prevention-of-chronic-lung-allograft-rejection-after-lung-transplantation-ltx-in-rats
#5
Laura Keil, Anna-Lena Schaub, Stephan W Hirt, Christof Schmid, Karla Lehle, Marietta von Suesskind-Schwendi
Chronic lung allograft dysfunction (CLAD) still remains a major drawback in the outcome following lung transplantation (LTx). New therapeutic strategies are warranted. Growth factors and their receptors like platelet-derived growth factor-receptor (PDGFR) and vascular endothelial growth factor-receptor (VEGFR), may play a crucial role in the development of CLAD, especially bronchiolitis obliterans (BO) and vasculopathy. In this study, we used an orthotopic left lung transplantation model from Fischer (F344) to Wystar Kyoto (WKY) rats to investigate the effect of vatalanib alone, the dual combination of vatalanib and imatinib and a triple therapy consisting of vatalanib, imatinib and the mammalian target of rapamycin inhibitor (mTORI) everolimus on the development of CLAD after LTx in rats...
February 1, 2019: Histology and Histopathology
https://read.qxmd.com/read/30692422/-a-case-of-pancreatic-head-neuroendocrine-tumor-with-multiple-liver-metastases-successfully-treated-with-multimodality-therapy-includingrepeat-hepatectomy
#6
Yoko Inaba, Maiko Hongo, Riki Ninomiya, Akiko Nakazawa, Daijyo Hashimoto
A 68-year-old man who had a history of bone marrow transplantation for acute myeloid leukemia was referred to our hospital due to an abnormal liver function test. Based on the clinical diagnosis of P-NET G2 with multiple livermetastases, pylorus-preserving pancreaticoduodenectomy with combined resection of the portal vein and liver sampling were performed (R2 resection). The resected specimen revealed NET-G2 tumorof the pancreatic head(Ki-67 proliferation index 5.0%)and hepatic metastasis(Ki-67 index 2.2%)...
December 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://read.qxmd.com/read/30615259/a-randomized-trial-of-everolimus-based-quadruple-therapy-versus-standard-triple-therapy-early-after-lung-transplantation
#7
Jens Gottlieb, Claus Neurohr, Joachim Müller-Quernheim, Hubert Wirtz, Bjoern Sill, Heinrike Wilkens, Vasiliki Bessa, Christoph Knosalla, Martina Porstner, Carmen Capusan, Martin Strüber
Calcineurin inhibitor (CNI) therapy after lung transplantation increases risk of kidney failure. Early everolimus-based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open-label, 12-month multicenter trial was conducted at eight German sites. Patients 3-18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate (eGFR). In the quadruple low CNI regimen, patients received everolimus (target trough level 3-5 ng/ml) with reduced CNI (tacrolimus 3-5 ng/ml or cyclosporine 25-75 ng/ml) and a cell cycle inhibitor plus prednisone...
January 7, 2019: American Journal of Transplantation
https://read.qxmd.com/read/30592371/very-early-introduction-of-everolimus-in-de-novo-liver-transplantation-results-of-a-multicenter-prospective-randomized-trial-epocal
#8
Umberto Cillo, Laura Saracino, Alessandro Vitale, Alessandra Bertacco, Mauro Salizzoni, Francesco Lupo, Michele Colledan, Vittorio Corno, Giorgio Rossi, Paolo Reggiani, Umberto Baccarani, Vittorio Bresàdola, Luciano De Carlis, Iacopo Mangoni, Raphael Ramirez Morales, Salvatore Agnes, Erida Nure
Early everolimus introduction and tacrolimus minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated safety and efficacy of early everolimus initiation. Patients treated with corticosteroids, tacrolimus, and basiliximab, were randomized (2:1) to receive everolimus (1.5 mg bid) in day 8 and gradually minimize or withdraw tacrolimus when everolimus was stable >5 ng/mL, or to continue tacrolimus at 6-12 ng/mL...
December 28, 2018: Liver Transplantation
https://read.qxmd.com/read/30577313/terminal-ileac-ulcers-mimicked-post-transplantation-lymphoproliferative-disorder-in-a-heart-recipient-treated-with-everolimus-a-case-report
#9
K Iwasaki, O Seguchi, H Mochizuki, Y Kimura, K Toda, Y Kumai, K Kuroda, S Nakajima, T Watanabe, M Yanase, Y Matsumoto, S Fukushima, T Fujita, J Kobayashi, N Fukushima
Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized and potentially fatal complication of cardiac transplantation that commonly involves the gastrointestinal tract. Herein, we report a case of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers mimicking PTLD in a heart recipient treated with everolimus (EVL). A 40-year-old man underwent heart transplantation for dilated cardiomyopathy 3 years prior to the current admission and was treated with tacrolimus and EVL...
December 2018: Transplantation Proceedings
https://read.qxmd.com/read/30577246/everolimus-vs-mycophenolate-mofetil-in-combination-with-tacrolimus-a-propensity-score-matched-analysis-in-liver-transplantation
#10
P De Simone, P Carrai, L Coletti, D Ghinolfi, S Petruccelli, A Precisi, D Campani, P Marchetti, F Filipponi
BACKGROUND: No trial has investigated the long-term outcome of everolimus (EVR)-incorporating immunosuppression vs tacrolimus (TAC) and mycophenolate mofetil (MMF) after liver transplantation. MATERIALS AND METHODS: With a propensity score methodology, 178 recipients on TAC and MMF were compared to 178 patients on TAC and EVR. RESULTS: At a median (interquartile range) follow-up of 45 (46.3) months, the probability of treated biopsy-proven acute rejection, graft loss, and death was 36...
December 2018: Transplantation Proceedings
https://read.qxmd.com/read/30561097/evaluation-of-the-impact-of-conventional-immunosuppressant-on-the-establishment-of-murine-transplantation-tolerance-an-experimental-study
#11
Haruki Katsumata, Satoshi Miyairi, Masako Ikemiyagi, Toshihito Hirai, Hironori Fukuda, Taichi Kanzawa, Rumi Ishii, Kan Saiga, Yasuyuki Ishii, Kazuya Omoto, Masayoshi Okumi, Takashi Yokoo, Kazunari Tanabe
Regulatory T cells (Tregs) play a significant role in immune tolerance. Since Treg function deeply depends on Interleukin-2 signaling, calcineurin inhibitors could affect their suppressive potentials, whereas mammalian target of rapamycin (mTOR) inhibitors may have less impact, as mTOR signaling is not fundamental to Treg proliferation. We previously reported a novel mixed hematopoietic chimerism induction regimen that promotes Treg proliferation by stimulating invariant natural killer T cells under CD40 blockade...
December 17, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
https://read.qxmd.com/read/30543830/everolimus-delayed-and-suppressed-cytomegalovirus-dna-synthesis-spread-of-the-infection-and-alleviated-cytomegalovirus-infection
#12
Long Tan, Noriaki Sato, Atsuko Shiraki, Motoko Yanagita, Yoshihiro Yoshida, Yoshinori Takemura, Kimiyasu Shiraki
Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and reduces the risk of cytomegalovirus (CMV) infection in transplant recipients. Everolimus inhibits mTOR complex 1, which regulates factors involved in several crucial cellular functions and is required for CMV replication. However, it is not clear how everolimus regulates CMV replication and prevents and alleviates CMV infection. Effects of everolimus on CMV infection, spread, and DNA synthesis and release from infected cells were assessed by plaque formation, infectious centre assay, real-time PCR of infected cells, and culture supernatant in CMV-infected cultures with and without everolimus...
December 10, 2018: Antiviral Research
https://read.qxmd.com/read/30528864/mtor-inhibitors-in-pediatric-liver-transplant-recipients
#13
Jérôme Dumortier, Eduardo Couchonnal, Florence Lacaille, Christine Rivet, Dominique Debray, Olivier Boillot, Alain Lachaux, Oanez Ackermann, Emmanuel Gonzales, Barbara E Wildhaber, Emmanuel Jacquemin, Valérie McLin
BACKGROUND: During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). The aim of the present study was to describe the use of mTORi in pediatric LT recipients. METHODS: All pediatric LT recipients who received mTORi before December 2017 from 4 European pediatric LT centers were included and analyzed. RESULTS: The present retrospective study included 30 patients; 21 were male (70%), median age was 9...
December 6, 2018: Clinics and Research in Hepatology and Gastroenterology
https://read.qxmd.com/read/30526503/early-onset-of-graft-glomerulopathy-in-a-patient-with-post-transplant-diabetes-mellitus-after-renal-transplantation-a-case-report
#14
Marilena Gregorini, Vincenzo Sepe, Francesca Eleonora Pattonieri, Anna Allesina, Teresa Rampino
BACKGROUND: Post-transplant diabetes mellitus (PTDM) is an emerging problem in kidney transplantation, representing an important risk factor for kidney function loss. Diabetic nephropathy (DN) occurrence in transplanted kidneys is poorly investigated. Current knowledge describes DN recurrence in graft 5.9 years from kidney transplantation however there is little data about PTDM and DN. Here, we report a clinical case peculiar for an early appearance of advanced glomerular diabetic lesions, after kidney transplantation...
December 7, 2018: BMC Nephrology
https://read.qxmd.com/read/30510930/pantoprazole-does-not-affect-serum-trough-levels-of-tacrolimus-and-everolimus-in-liver-transplant-recipients
#15
Sebastian C B Bremer, Lars Reinhardt, Michael Sobotta, Marie C Hasselluhn, Thomas Lorf, Volker Ellenrieder, Harald Schwörer
Background: Liver transplant recipients are frequently treated with proton pump inhibitors. Drug interactions have been described especially with respect to omeprazole. Due to the lower binding capacity of pantoprazole to CYP2C19 this drug became preferred and became the most used proton pump inhibitor in Germany. The data on the influence of pantoprazole on immunosuppressive drugs in liver transplant recipients a very scarce. Methods: The authors performed a single center analysis in liver transplant recipients on the effect of pantoprazole on the serum trough levels of different immunosuppressants...
2018: Frontiers in Medicine
https://read.qxmd.com/read/30510618/therapeutic-use-of-mtor-inhibitors-in-renal-diseases-advances-drawbacks-and-challenges
#16
REVIEW
Sofia D Viana, Flávio Reis, Rui Alves
The mammalian (or mechanistic) target of rapamycin (mTOR) pathway has a key role in the regulation of a variety of biological processes pivotal for cellular life, aging, and death. Impaired activity of mTOR complexes (mTORC1/mTORC2), particularly mTORC1 overactivation, has been implicated in a plethora of age-related disorders, including human renal diseases. Since the discovery of rapamycin (or sirolimus), more than four decades ago, advances in our understanding of how mTOR participates in renal physiological and pathological mechanisms have grown exponentially, due to both preclinical studies in animal models with genetic modification of some mTOR components as well as due to evidence coming from the clinical experience...
2018: Oxidative Medicine and Cellular Longevity
https://read.qxmd.com/read/30487748/polymorphisms-in-mtor-and-calcineurin-signaling-pathways-are-associated-with-long-term-clinical-outcomes-in-kidney-transplant-recipients
#17
Antony Brayan Campos-Salazar, Fabiana Dalla Vecchia Genvigir, Claudia Rosso Felipe, Helio Tedesco-Silva, José Medina-Pestana, Gabriela Vieira Monteiro, Rodrigo de Gouveia Basso, Alvaro Cerda, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata
Monitoring of immunosuppressive drugs, such as calcineurin and mTOR inhibitors, is essential to avoid undesirable kidney transplant outcomes. Polymorphisms in pharmacokinetics-related genes have been associated with variability in blood levels of immunosuppressive drugs and adverse effects, but influence of pharmacodynamics-related genes remains to be elucidated. The influence of polymorphisms in genes of the mTOR and calcineurin signaling pathways on long-term clinical outcomes was investigated in Brazilian kidney transplant recipients within the 1-year post-transplant...
2018: Frontiers in Pharmacology
https://read.qxmd.com/read/30472777/ureaplasma-urealyticum-pyelonephritis-presenting-with-progressive-dysuria-renal-failure-and-neurologic-symptoms-in-an-immunocompromised-patient
#18
Drew J Schwartz, Alexis Elward, Gregory A Storch, David A Rosen
Ureaplasma urealyticum is a bacterial species correlated with urethritis in healthy individuals and invasive infections in immunocompromised patients. We describe a 20-year-old female with a history of remote heart transplant on everolimus, mycophenolate, and rituximab presenting with progressive urinary tract symptoms, renal failure, and neurologic symptoms. An extensive workup ultimately identified U urealyticum infection, and the patient successfully recovered after a course of azithromycin and doxycycline...
November 25, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://read.qxmd.com/read/30451741/mtor-inhibitor-everolimus-in-regulatory-t-cell-expansion-for-clinical-application-in-transplantation
#19
Roberto Gedaly, Felice De Stefano, Lilia Turcios, Marita Hill, Giovanna Hidalgo, Mihail I Mitov, Michael C Alstott, D Allan Butterfield, Hunter C Mitchell, Jeremy Hart, Ahmad Al-Attar, Chester D Jennings, Francesc Marti
BACKGROUND: Experimental and pre-clinical evidence suggest that adoptive transfer of regulatory T cells (Tregs) could be an appropriate therapeutic strategy to induce tolerance and improve graft survival in transplanted patients. The University of Kentucky Transplant Service Line is developing a novel Phase I/II clinical trial with ex vivo expanded autologous Tregs as an adoptive cellular therapy in renal transplant recipients who are using everolimus (EVR)-based immunosuppressive regimen...
November 16, 2018: Transplantation
https://read.qxmd.com/read/30401391/renal-function-changes-under-everolimus-plus-cyclosporine-or-everolimus-plus-tacrolimus-after-heart-transplantation
#20
T-Y Chiang, C-I Tsao, S-S Wang
Everolimus (EVR) can be used with calcineurin inhibitors to reduce the risk of renal dysfunction, with similar immunosuppressive effect. In this study, we compared renal function after heart transplantation (HT) under EVR with cyclosporine (CSA) or tacrolimus (TAC). Between 2004 and 2014, EVR with CSA or TAC was used in 117 HT at the National Taiwan University Hospital. After HT, all patients received corticosteroid, EVR (C0 target 3-8 ng/mL) and CSA (C0 blood level 100-200 ng/mL), or TAC (Co blood level 5-10 ng/mL)...
November 2018: Transplantation Proceedings
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