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https://www.readbyqxmd.com/read/29242852/prospective-study-of-nonmyeloablative-hla-mismatched-unrelated-bmt-with-high-dose-posttransplantation-cyclophosphamide
#1
Yvette L Kasamon, Richard F Ambinder, Ephraim J Fuchs, Marianna Zahurak, Gary L Rosner, Javier Bolaños-Meade, Mark J Levis, Douglas E Gladstone, Carol Ann Huff, Lode J Swinnen, William H Matsui, Ivan Borrello, Robert A Brodsky, Richard J Jones, Leo Luznik
Allogeneic blood or marrow transplantation (BMT) candidates may lack HLA-matched, related haploidentical, and unrelated umbilical cord options. Barriers to partially HLA-mismatched, unrelated donor (mMUD) BMT include excess graft-versus-host disease (GVHD), graft failure, and death. We prospectively studied nonmyeloablative (NMA) mMUD BMT with high-dose posttransplantation cyclophosphamide (PTCy) for patients with hematologic malignancies. Three transplants were performed with busulfan/fludarabine conditioning, with subsequent change to fludarabine/Cy/total body irradiation (flu/Cy/TBI)...
2017: Blood Advances
https://www.readbyqxmd.com/read/29242294/in-vivo-il-12-il-23p40-neutralization-blocks-th1-th17-response-after-allogeneic-hematopoietic-cell-transplantation
#2
Joseph Pidala, Francisca Beato, Jongphil Kim, Brian Betts, Heather Jim, Elizabeth Sagatys, John E Levine, James Lm Ferrara, Umut Ozbek, Ernesto Ayala, Marco Davila, Hugo F Fernandez, Teresa Field, Mohamed A Kharfan-Dabaja, Divis Khaira, Farhad Khimani, Frederick L Locke, Asmita Mishra, Michael Nieder, Taiga Nishihori, Lia Perez, Marcie Riches, Claudio Anasetti
T helper 1 and T helper 17 lymphocytes mediate acute graft vs. host disease. Interleukin 12 is critical for T helper 1 differentiation and interleukin 23 for T helper 17 maintenance. Interleukin 12 and 23 are heterodimeric cytokines that share the p40 subunit (IL-12/IL-23p40). In a randomized, blinded, placebo-controlled trial, we examined the biologic impact and clinical outcomes following IL-12/IL-23p40 neutralization using ustekinumab. 30 patients received peripheral blood mobilized hematopoietic cell transplantation from HLA-matched sibling or unrelated donors, received sirolimus plus tacrolimus as graft vs...
December 14, 2017: Haematologica
https://www.readbyqxmd.com/read/29240034/management-of-refractory-pediatric-kaposiform-hemangioendothelioma-with-sirolimus-and-aspirin
#3
Suzanne P MacFarland, Lisa M Sullivan, Lisa J States, L Charles Bailey, Naomi J Balamuth, Richard B Womer, Timothy S Olson
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor characterized by aggressive local invasion and a syndrome of platelet trapping known as Kasabach-Merritt phenomenon that, through deposition of platelet derived growth factors, may perpetuate the growth of the tumor. Although many cases of KHE are successfully treated with local control or low-intensity chemotherapy, some cases are often refractory even to aggressive treatment. Herein, we describe a patient with a refractory, recurrent KHE despite multiple attempts at local control and intensive chemotherapy, that ultimately was successfully treated with rationally designed and low-intensity combination therapy of sirolimus and aspirin...
December 12, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29238469/the-role-of-sirolimus-in-proteinuria-in-diabetic-nephropathy-rats
#4
JinJun Wang, ZiQiang Xu, BiCheng Chen, ShaoLing Zheng, Peng Xia, Yong Cai
Objectives: The aim of this study was to observe the impact of sirolimus on proteinuria in streptozotocin (STZ) induced diabetic rats. Materials and Methods: Rats were given a single injection of STZ to induce diabetic rat model. Rats' 24 hr urine was collected to test, urinary and the kidney tissues were harvested at the 8th and 20th weeks, respectively. Podocyte morphological changes were examined by electron microscopy and the ZO-1, podocin expressions in kidneys were detected by immunohistochemistry; the protein levels of Raptor and pS6 were measured by Western blot assay...
December 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29233209/rapid-regression-of-large-cardiac-rhabdomyomas-in-neonates-after-sirolimus-therapy
#5
M David Weiland, Kristin Bonello, Kevin D Hill
Cardiac rhabdomyomas are the most common tumours in children and are typically seen in association with the tuberous sclerosis complex. Although benign and often associated with spontaneous regression, in rare circumstances surgical resection is indicated to relieve obstruction or other mass-related effects. Recent clinical trials have demonstrated the benefits of mammalian target of rapamycin inhibitors for the treatment of other tumour sub-types associated with tuberous sclerosis. Here we report rapid regression of several massive cardiac rhadomyomas in two neonates with the use of the mammalian target of rapamycin inhibitor sirolimus...
December 13, 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/29228766/the-effects-of-addition-of-coenzyme-q10-to-metformin-on-sirolimus-induced-diabetes-mellitus
#6
In O Sun, Long Jin, Jian Jin, Sun Woo Lim, Byung Ha Chung, Chul Woo Yang
Background/Aims: This study was performed to determine whether adding coenzyme Q10 (CoQ10) to metformin (MET) has a beneficial effect as a treatment for sirolimus (SRL)-induced diabetes mellitus (DM). Methods: DM was induced in rats by daily treatment with SRL (0.3 mg/kg, subcutaneous) for 28 days, and animals were treated with CoQ10 (20 mg/kg, oral) and MET (250 mg/kg, oral) alone or in combination for the latter 14 days of SRL treatment. The effects of CoQ10 and MET on SRL-induced DM were assessed with the intraperitoneal glucose tolerance test (IPGTT) and by determining plasma insulin concentration and the homeostatic model assessment of insulin resistance (HOMA-R) index...
December 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29226570/campath-calcineurin-inhibitor-reduction-and-chronic-allograft-nephropathy-the-3c-study-results-of-a-randomized-controlled-clinical-trial
#7
Richard Haynes, Lisa Blackwell, Natalie Staplin, William G Herrington, Jonathan Emberson, Parminder K Judge, Benjamin C Storey, Martin J Landray, Paul N Harden, Colin Baigent, Peter Friend
Calcineurin inhibitors (CNI e.g. tacrolimus) reduce short-term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin pathway (mTOR e.g. sirolimus) might avoid long-term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial comprising sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6-months post-transplant...
December 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29225777/evaluation-of-electrochemiluminescence-immunoassays-for-immunosuppressive-drugs-on-the-roche-cobas-e411-analyzer
#8
Angela W S Fung, Michael J Knauer, Ivan M Blasutig, David A Colantonio, Vathany Kulasingam
Background:  Therapeutic drug monitoring of immunosuppressant drugs are used to monitor drug efficacy and toxicity and to prevent organ transplantation rejection. This study evaluates the analytical performance of semi-automated electrochemiluminescence immunoassays (ECLIA) for cyclosporine (CSA), tacrolimus (TAC) and sirolimus (SRL) on the Roche cobas e 411 analyzer at a major transplant hospital to identify method suitability and limitations. Methods: Residual whole blood samples from patients undergoing immunosuppressant therapy were used for evaluation...
2017: F1000Research
https://www.readbyqxmd.com/read/29221958/a-comparison-of-the-ultrathin-orsiro-hybrid-sirolimus-eluting-stent-with-contemporary-drug-eluting-stents-a-meta-analysis-of-randomized-controlled-trials
#9
Michael J Lipinski, Brian J Forrestal, Micaela Iantorno, Rebecca Torguson, Ron Waksman
BACKGROUND: Recent studies suggest the Orsiro sirolimus-eluting stent (O-SES), which has ultrathin struts with a biodegradable sirolimus-eluting polymer coating, performed better than contemporary drug-eluting stents (DES). We performed a meta-analysis to compare clinical outcomes for all randomized controlled trials (RCTs) of O-SES vs contemporary DES. METHODS/MATERIALS: PubMed, Cochrane CENTRAL, and meeting abstracts were searched for all RCTs comparing O-SES with contemporary DES...
November 21, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/29217498/sirolimus-induced-hepatitis-in-two-cases-with-hyperinsulinemic-hypoglycemia
#10
Belma Haliloğlu, Heybet Tüzün, Sarah E Flanagan, Muhittin Çelik, Avni Kaya, Sian Ellard, Mehmet Nuri Özbek
BACKGROUND: Sirolimus has been described for the treatment of the diffuse form of congenital hyperinsulinism (CHI) unresponsive to diazoxide and octreotide without severe side effect. CASE REPORT: Two newborns with CHI due to homozygous ABCC8 gene mutations were started sirolimus due to unresponsive to medical treatment on day 21 and 17, and good response was observed. At follow-up, liver enzyme levels increased at 10 and 2 month of therapy in case 1 and 2, respectively (serum sirolimus level 1...
December 8, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29210476/delayed-revascularization-of-islets-after-transplantation-by-il-6-blockade-in-pig-to-non-human-primate-islet-xenotransplantation-model
#11
Byoung-Hoon Min, Jun-Seop Shin, Jong-Min Kim, Seong-Jun Kang, Hyun-Je Kim, Il-Hee Yoon, Su-Kyoung Park, Ji-Won Choi, Min-Suk Lee, Chung-Gyu Park
BACKGROUND: Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model...
December 6, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29210159/safety-of-mtor-inhibitor-continuation-in-pediatric-heart-transplant-recipients-undergoing-surgical-procedures
#12
Ann Heble, Melanie D Everitt, Jane Gralla, Shelley D Miyamoto, Michael Lahart, Jennifer Eshelman
mTOR inhibitors have been associated with SWC when used in the perioperative period. Limited literature is available to guide providers in managing chronic mTOR inhibitor use in the perioperative period, especially in the pediatric setting. The primary aim of this study was to describe the prevalence of SWC with mTOR inhibitor continuation during the perioperative period for major surgeries. Heart transplant recipients ≤25 years old at the time of primary heart transplant receiving sirolimus maintenance therapy during a surgical procedure and within the study period were included...
December 6, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29208258/durability-of-sirolimus-for-lymphangioleiomyomatosis
#13
Alexandra Martirossian, Shiwan Shah, Lola Carrete, Jose Valle, Vincent Valentine
Lymphangioleiomyomatosis (LAM), a rare, multisystem disorder primarily affecting women of reproductive age, is characterized by cystic-appearing lung lesions, progressive loss of lung function, chylous effusions and renal angiomyolipomas. Sirolimus, an mammalian target of rapamycin inhibitor, has been shown to stabilize lung function, reduce symptoms and resolve chylous effusions in the short term for patients with LAM. Herein, we report a premenopausal female with LAM who experienced complete and durable resolution of her chylothoraces with significant and sustained improvement in lung function on sirolimus...
December 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29206642/measurement-of-sirolimus-concentrations-in-human-blood-using-an-automated-electrochemiluminescence-immunoassay-eclia-a-multicenter-evaluation
#14
Veronique Stove, Pedro Alía Ramos, Pierre Wallemacq, Michael Vogeser, Andre Schuetzenmeister, Christian Schmiedel, Maria Shipkova
BACKGROUND: Therapeutic drug monitoring (TDM) of sirolimus is essential in transplant recipients. We evaluated the performance of a new electrochemiluminescence immunoassay (ECLIA) for measuring sirolimus concentrations in whole blood at five European laboratories. METHODS: Study assessments included repeatability, intermediate precision and functional sensitivity (concentration at coefficient of variation [CV] of 20%) experiments. Method comparisons with liquid chromatography-tandem mass spectrometry (LC-MS/MS; reference method) and two immunoassays (chemiluminescent microparticle immunoassay [CMIA] and antibody-conjugated magnetic immunoassay [ACMIA]) were performed using native samples from patients with kidney transplants...
December 5, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29205492/9-month-results-of-polymer-free-sirolimus-eluting-stents-in-young-patients-compared-to-a-septuagenarian-and-octogenarian-all-comer-population
#15
Behrouz Kherad, Matthias Waliszewski, Matthias Leschke, Muhammad Ali Kader, Liew Houng Bang, Fernando Lozano Ruiz-Poveda, Burkert Pieske, Florian Krackhardt
OBJECTIVES: To evaluate the 9-month safety and efficacy of polymer-free sirolimus eluting drug eluting stents in septuagenarians and octogenarians. METHODS: An all-comer, worldwide single armed trial (ClinicalTrials.gov Identifier NCT02629575) was conducted to demonstrate the safety and efficacy of an ultra-thin strut, polymer-free sirolimus eluting stent (PF-SES). The primary endpoint was the 9-month target revascularization rate (TLR). Secondary endpoints included the rates of major adverse cardiac events (MACE), stent thrombosis (ST) and bleeding (BARC) in septuagenarians (≥70 years, <80 years), and in octogenarians (≥80 years) to be compared to the younger patient group (<70 years)...
December 4, 2017: Journal of Interventional Cardiology
https://www.readbyqxmd.com/read/29205157/a-comparison-of-an-ultrathin-strut-biodegradable-polymer-sirolimus-eluting-stent-with-a-durable-polymer-everolimus-eluting-stent-for-patients-with-acute-stsegment-elevation-myocardial-infarction-undergoing-primary-percutaneous-coronary-intervention-rationale
#16
Juan F Iglesias, Olivier Muller, Serge Zaugg, Marco Roffi, David J Kurz, André Vuilliomenet, Daniel Weilenmann, Christoph Kaiser, Maxime Tapponnier, Dik Heg, Marco Valgimigli, Eric Eeckhout, Peter Jüni, Stephan Windecker, Thomas Pilgrim
AIMS: A novel ultrathin-strut biodegradable polymer sirolimus-eluting stent (Orsiro™, Biotronik, Bülach, Switzerland; BP-SES) was shown to be superior to a thin-strut durable polymer everolimus-eluting stent (Xience™ Xpedition/Alpine, Abbott Vascular, Santa Clara, USA; DP-EES) with respect to the primary endpoint of target lesion failure (TLF) at 12 months in the prespecified subgroup of patients with ST-segment elevation myocardial infarction (STEMI) included in the BIOSCIENCE trial...
December 5, 2017: EuroIntervention
https://www.readbyqxmd.com/read/29203070/a-sirolimus-eluting-bioabsorbable-polymer-coated-stent-mistent-versus-an-everolimus-eluting-durable-polymer-stent-xience-after-percutaneous-coronary-intervention-dessolve-iii-a-randomised-single-blind-multicentre-non-inferiority-phase-3-trial
#17
Robbert J de Winter, Yuki Katagiri, Taku Asano, Krzysztof P Milewski, Philipp Lurz, Pawel Buszman, Gillian A J Jessurun, Karel T Koch, Roland P T Troquay, Bas J B Hamer, Ton Oude Ophuis, Jochen Wöhrle, Rafał Wyderka, Guillaume Cayla, Sjoerd H Hofma, Sébastien Levesque, Aleksander Żurakowski, Dieter Fischer, Maciej Kośmider, Pascal Goube, E Karin Arkenbout, Michel Noutsias, Markus W Ferrari, Yoshinobu Onuma, William Wijns, Patrick W Serruys
BACKGROUND: MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population. METHODS: We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland...
December 1, 2017: Lancet
https://www.readbyqxmd.com/read/29198920/impact-of-post-dilatation-on-longitudinal-stent-elongation-an-in-vitro-study
#18
Takuya Sumi, Hideki Ishii, Akihito Tanaka, Susumu Suzuki, Hiroki Kojima, Naoki Iwakawa, Toshijiro Aoki, Kenshi Hirayama, Takayuki Mitsuda, Kazuhiro Harada, Yosuke Negishi, Tomoyuki Ota, Kenji Kada, Toyoaki Murohara
OBJECTIVES: To evaluate whether balloon inflation for post-dilatation causes longitudinal stent deformation (LSD). METHODS AND RESULTS: Two stents, sized 2.5mm×28mm and 3.5mm×28mm (Nobori®, biodegradable polymer biolimus-eluting stent; Ultimaster®, biodegradable polymer sirolimus-eluting stent; Terumo Co., Tokyo, Japan), were deployed at nominal pressure in straight and tapered silicon vessel models. Then, post-dilatation was performed in two ways: dilatation from the distal (D-P group) or proximal (P-D group) side of the stent...
November 30, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29192951/first-in-man-study-of-dedicated-bifurcation-cobalt-chromium-sirolimus-eluting-stent-bioss-lim-c-3-month-results
#19
Robert J Gil, Jacek Bil, Adam Kern, Tomasz Pawłowski
BACKGROUND: The optimal approach to coronary bifurcations treatment by PCI is still a subject of debate and the dedicated bifurcation stents are one of proposed solutions. AIM: The aim of this report was to assess effectiveness and safety profile of a new dedicated bifurcation stent - sirolimus-eluting BiOSS® LIM C (Balton, Poland) at the first 3 months of the 12-month Registry. METHODS: This is the two-center registry, which enrolls patients with NSTE-ACS and stable angina...
December 1, 2017: Kardiologia Polska
https://www.readbyqxmd.com/read/29186990/nanomedicine-approaches-for-sirolimus-delivery-a-review-of-pharmaceutical-properties-and-preclinical-studies
#20
Azadeh Haeri, Mahraz Osouli, Fereshteh Bayat, Sonia Alavi, Simin Dadashzadeh
Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. However, its clinical application is often hampered by poor aqueous solubility, first-pass metabolism, transport by p-glycoprotein efflux pump, limited oral bioavailability and nonspecific distribution in off-target sites. Recently, various formulation strategies have emerged to overcome these limitations. Among these, pharmaceutical nanotechnology with numerous advantages has great potential for sirolimus delivery...
November 29, 2017: Artificial Cells, Nanomedicine, and Biotechnology
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