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https://www.readbyqxmd.com/read/28715589/association-between-visual-function-response-and-reduction-of-inflammation-in-noninfectious-uveitis-of-the-posterior-segment
#1
Benedicte Lescrauwaet, Elisabetta Miserocchi, Stephan Thurau, Bahram Bodaghi, Luc Duchateau, Thomas Verstraeten, Sunil Srivastava
Purpose: To examine the association between visual function response (VFR) and inflammation reduction in active noninfectious uveitis of the posterior segment (NIU-PS). Methods: Phase 3 SAKURA Study 1 randomized 347 subjects in a double-masked fashion to receive injections of intravitreal sirolimus 44 μg (n = 117); 440 μg (n = 114); or 880 μg (n = 116) every other month. Vitreous haze (VH) response, a measure of inflammation reduction, was defined as a VH score of 0 or 0...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28708333/conversion-from-calcineurin-inhibitors-to-mtor-inhibitors-as-primary-immunosuppressive-drugs-in-pediatric-heart-transplantation
#2
Alfred Asante-Korang, Jennifer Carapellucci, Diane Krasnopero, Abigail Doyle, Brian Brown, Ernest Amankwah
There are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995-2015. Nineteen patients were switched from tacrolimus(n=15) or cyclosporin(n=4) to everolimus(n=4) or sirolimus(n=15) due to nephrotoxicity(n=5), malignancy(n=8), EBV viremia/reactive plasmacytic changes(n=5) and immune hemolytic anemia(n=1)...
July 14, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28707379/three-and-6-month-optical-coherence-tomographic-surveillance-following-percutaneous-coronary-intervention-with-the-angiolite%C3%A2-drug-eluting-stent-the-anchor-study
#3
Rishi Puri, Imanol Otaegui, Manel Sabaté, Antonio Serra-Peñaranda, Marti Puigfel, Armando Perez de Prado, Luis Nombela-Franco, Jose M de la Torre Hernandez, Rosario Ortas Nadal, Andres Iniguez-Romo, Gustavo Jiménez, Felipe Fernandez-Vazquez, Carlos Cuellas-Ramon, Nieves Gonzalo, Victor Alfonso Jiménez Diaz, Lluis Duocastella, Maria Molina, Marc Amoros, Isabel Perez, Alberto Barria Perez, Emilie Pelletier Beaumont, Stephen J Nicholls, Bruno Garcia Del Blanco, Josep Rodés-Cabau
BACKGROUND: Pre-clinical results of a novel open-cell, thin strut, durable polymer, laser cut cobalt chromium sirolimus-eluting stent (Angiolite) were promising. Using quantitative optical coherence tomographic (OCT) analyses, we explored the healing characteristics of the Angiolite DES system at 3- and 6-months post implantation. METHODS: A total of 103 patients with de novo coronary lesions underwent percutaneous coronary intervention with the Angiolite DES and were randomized 1:3 into two cohorts for angiographic and OCT follow-up, with 28 and 70 patients returning for 3- or 6-month post-PCI surveillance, respectively...
July 14, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28706985/clinical-utility-of-epstein-barr-virus-viral-load-monitoring-and-risk-factors-for-posttransplant-lymphoproliferative-disorders-after-kidney-transplantation-a-single-center-10-year-observational-cohort-study
#4
Erica Franceschini, Jessica Plessi, Stefano Zona, Antonella Santoro, Margherita Digaetano, Francesco Fontana, Gaetano Alfano, Giovanni Guaraldi, Patrizia Comoli, Francesca Facchini, Leonardo Potenza, William Gennari, Mauro Codeluppi, Mario Luppi, Gianni Cappelli, Inge C Gyssens, Cristina Mussini
BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality in solid organ transplants. Epstein Barr virus (EBV) plays a major role in PTLD development. Guidelines recommend EBV viral load (VL) monitoring in high-risk populations in the first year. METHODS: Retrospective observational study in all adult patients who had at least 1 EBV-VL performed in the postkidney transplant (KT) period from January 2005 to December 2014 at the Policlinico Modena Hospital...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28706981/outcomes-of-liver-transplant-recipients-with-autoimmune-liver-disease-using-long-term-dual-immunosuppression-regimen-without-corticosteroid
#5
Sanjaya K Satapathy, Ollie D Jones, Jason M Vanatta, Faisal Kamal, Satish K Kedia, Yu Jiang, Satheesh P Nair, James D Eason
BACKGROUND: Liver transplant (LT) recipients with autoimmune liver disease (primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis) are at increased risk of developing acute cellular rejection (ACR), and in many cases graft failure due to recurrent disease. We describe our experience with dual immunosuppression without steroid maintenance and analyze its effect on disease recurrence; ACR; patient and graft survivals; and complications, such as sepsis and de novo malignancy...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28706974/sirolimus-increases-t-cell-abundance-in-the-sun-exposed-skin-of-kidney-transplant-recipients
#6
Michael Thomas Burke, Lauren C Sambira Nahum, Nicole M Isbel, Robert P Carroll, Hans Peter Soyer, Ross Francis, Jennifer Anne Bridge, Carmel Hawley, Kimberly Oliver, Christine E Staatz, James William Wells
BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Despite studies investigating the effects of these 2 drug classes on T cells in patient blood, the effect these drugs may have in patient skin is not yet known. METHODS: Fifteen patients with chronic kidney disease (not recipients of immunosuppressive drugs), and 30 KTRs (15 receiving a calcineurin inhibitor, and 15 receiving sirolimus) provided matched samples of blood, sun exposed (SE) and non-SE skin...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28703334/a-case-of-kaposiform-haemangioendothelioma-successfully-and-safely-treated-with-sirolimus
#7
C Wlodek, H Burt, L Shaw
No abstract text is available yet for this article.
July 13, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28701488/comparative-biomechanical-behavior-and-healing-profile-of-a-novel-thinned-wall-ultrahigh-molecular-weight-amorphous-poly-l-lactic-acid-sirolimus-eluting-bioresorbable-coronary-scaffold
#8
Yanping Cheng, Pawel Gasior, Jing-Gang Xia, Kamal Ramzipoor, Chang Lee, Edward A Estrada, Daniell Dokko, Jenn C McGregor, Gerard B Conditt, Thomas McAndrew, Greg L Kaluza, Juan F Granada
BACKGROUND: Mechanical strength of bioresorbable scaffolds (BRS) is highly dependent on strut dimensions and polymer features. To date, the successful development of thin-walled BRS has been challenging. We compared the biomechanical behavior and vascular healing profile of a novel thin-walled (115 µm) sirolimus-eluting ultrahigh molecular weight amorphous poly-l-lactic acid-based BRS (APTITUDE, Amaranth Medical [AMA]) to Absorb (bioresorbable vascular scaffold [BVS]) using different experimental models...
July 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28700521/effect-of-cyp3a4-and-cyp3a5-genetic-polymorphisms-on-the-pharmacokinetics-of-sirolimus-in-healthy-chinese-volunteers
#9
Jing Zhang, Ying Dai, Zhihong Liu, Minxin Zhang, Chen Li, Dingxiong Chen, Hongtao Song
BACKGROUND: Sirolimus is a promising immunosuppressive drug for preventing the rejection of organ transplants. However, inter-individual variability in sirolimus pharmacokinetics causes adverse drug reactions, compromising therapeutic efficacy. Sirolimus is primarily metabolized by cytochrome CYP3A4 and CYP3A5. This study aimed to clarify the effect of CYP3A genetic polymorphisms, including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of sirolimus. METHODS: Thirty-one healthy Chinese volunteers were included in this study...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28695825/tsc2-disruption-in-mesenchymal-progenitors-results-in-tumors-with-vascular-anomalies-overexpressing-lgals3
#10
Peter J Klover, Rajesh L Thangapazham, Jiro Kato, Ji-An Wang, Stasia A Anderson, Victoria Hoffmann, Wendy K Steagall, Shaowei Li, Elizabeth McCart, Neera Nathan, Joshua D Bernstock, Matthew D Wilkerson, Clifton L Dalgard, Joel Moss, Thomas N Darling
Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud mesenchymal progenitors. Tsc2cKO(Prrx1-cre) mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with TSC1/TSC2 mutations in the TCGA database...
July 11, 2017: ELife
https://www.readbyqxmd.com/read/28693498/sirolimus-alters-lung-pathology-and-viral-load-following-influenza-a-virus-infection
#11
Ahmed R Alsuwaidi, Junu A George, Saeeda Almarzooqi, Stacey M Hartwig, Steven M Varga, Abdul-Kader Souid
BACKGROUND: Inhibitors of mTOR, such as sirolimus, have been shown to induce thymus involution and inflammatory lung disease in mice. The latter effect supports the role of this serine/threonine kinase in ameliorating lung inflammation. Other studies have shown sirolimus reduces/delays lung disease associated with various strains of influenza A virus (IAV). Thus, the effects of mTOR inhibitors on influenza infection deserve further studies. METHODS: Here, we examined the changes in lung viral copies, pathology and pulmonary function associated with IAV (A/PR/8/34) infection in mice treated with sirolimus...
July 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28692458/angiographic-and-clinical-outcomes-after-recanalization-of-coronary-chronic-total-occlusions-with-the-orsiro-sirolimus-eluting-stent-compared-with-the-resolute-zotarolimus-eluting-stent
#12
Sinisa Markovic, Michael Lützner, Sergiu Dragomir, Wolfgang Rottbauer, Jochen Wöhrle
OBJECTIVE: The third generation drug eluting Orsiro stent had shown already promising results in non-complex lesions. BACKGROUND: We evaluated angiographic and 24 month clinical results of the sirolimus eluting Orsiro stents (O-SES) after recanalization of coronary chronic total occlusions (CTO). Results were compared with the zotarolimus eluting Resolute Integrity (R-ZES). METHODS: In a prospective series 57 patients were treated with a R-ZES followed by 74 patients treated with a O-SES stent...
August 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28685070/pilot-study-of-sirolimus-in-patients-with-pik3ca-mutant-amplified-refractory-solid-cancer
#13
Ki Sun Jung, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Seung Tae Kim
In patients with refractory cancer, the effect of additional chemotherapy is very limited. Targeted agents for molecular pathways associated with cancer cell progression and survival have emerged as attractive options in several cancer types. The current pilot study assessed the efficacy and safety of sirolimus in patients with refractory cancer with PIK3CA mutation/amplification. Refractory cancer patients with PIK3CA mutation/amplification were enrolled, irrespective of tumor-types. Enrolled patients received a daily dose of 1 mg sirolimus and one cycle defined as 28 days...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28676933/association-of-nr1i2-cyp3a5-and-abcb1-genetic-polymorphisms-with-variability-of-temsirolimus-pharmacokinetics-and-toxicity-in-patients-with-metastatic-bladder-cancer
#14
Litaty C Mbatchi, Matthieu Gassiot, Philippe Pourquier, Alejando Goberna, Hakim Mahammedi, Loic Mourey, Florence Joly, Serge Lumbroso, Alexandre Evrard, Nadine Houede
PURPOSE: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor that exhibits antitumor activity in renal cell carcinoma and mantle cell lymphoma. The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Differently from sirolimus, no pharmacogenetic study on temsirolimus has been conducted. Therefore, the aim of this pilot study was to identify genetic determinants of the inter-individual variability in temsirolimus pharmacokinetics and toxicity...
July 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28670871/clinical-practice-patterns-are-relatively-uniform-between-pediatric-heart-transplant-centers-a-survey-based-assessment
#15
Chesney Castleberry, Sonja Ziniel, Christopher Almond, Scott Auerbach, Seth A Hollander, Ashwin K Lal, Matthew Fenton, Elfriede Pahl, Joseph W Rossano, Melanie D Everitt, Kevin P Daly
Clinical practice variations are a barrier to the study of pediatric heart transplants and coordination of multicenter RCTs in this patient population. We surveyed centers to describe practice patterns, understand areas of variation, and willingness to modify protocol. Pediatric heart transplant centers were identified, and one survey was completed per center. Simple descriptive statistics were used. The response rate was 77% (40 responses from 52 contacted centers, 37 with complete responses). Median center volume of respondents was eight transplants/year (IQR 3-19)...
July 3, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28669853/effect-of-sirolimus-on-arteriosclerosis-induced-by-advanced-glycation-end-products-via-inhibition-of-the-ilk-mtor-pathway-in-kidney-transplantation-recipients
#16
Zhen Xu, Xuzhong Liu, Zijie Wang, Jun Tao, Zhijian Han, Min Gu, Wei Zhang, Ruoyun Tan
To investigate the effect and related mechanism of sirolimus (SRL) in arteriosclerosis(AS) induced by advanced glycation end products (AGEs) in kidney transplantation recipients (KTRs).Human kidney tissues from KTRs before and after treatment with SRL were assessed by hematoxylin-eosin and immunohistochemical staining. Rat vascular smooth muscle cells (VSMCs) were treated with AGEs and/or SRL. The expressions of α-smooth muscle actin (α-SMA), osteopontin (OPN), actinin-associated LIM protein (ALP), proliferating cell nuclear antigen (PCNA), integrin-linked kinase (ILK) and the mTOR signaling pathway proteins were examined using western blot assay...
June 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28663780/new-insights-into-the-pathogenesis-and-prevention-of-tuberous-sclerosis-associated-neuropsychiatric-disorders-tand
#17
REVIEW
Tanjala T Gipson, Michael V Johnston
Tuberous sclerosis complex (TSC) is a multi-system disorder resulting from mutations in either the TSC1 or TSC2 genes leading to hyperactivation of mechanistic target of rapamycin (mTOR) signaling. TSC is commonly associated with autism (61%), intellectual disability (45%), and behavioral, psychiatric, intellectual, academic, neuropsychological, and psychosocial difficulties that are collectively referred to as TSC-associated neuropsychiatric disorders (TAND). More than 90% of children with TSC have epilepsy, including infantile spasms, and early onset of seizures, especially infantile spasms, is associated with greater impairment in intellectual development compared with individuals with TSC without seizures...
2017: F1000Research
https://www.readbyqxmd.com/read/28661568/everolimus-induced-nephrotic-syndrome-precipitated-by-interaction-with-voriconazole-in-a-patient-with-hodgkin-s-lymphoma
#18
P N Tran, L C Pinter-Brown
WHAT IS KNOWN AND OBJECTIVES: Everolimus is a small molecule that inhibits the mammalian target of rapamycin (mTOR) and is used for treatment of various solid tumours and renal transplant rejection prophylaxis. Whereas everolimus-induced proteinuria was previously observed in 3%-36% renal transplant recipients, nephrotic syndrome was not reported in cancer patients taking everolimus. However, nephrotic syndrome was reported in patients taking sirolimus. CASE SUMMARY: We report the case of a 32-year-old female with relapsed Hodgkin's lymphoma who was on everolimus for 5 years and developed nephrotic syndrome about 2 months after initiation of voriconazole...
June 29, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28659551/impact-of-stent-type-and-presence-of-vasospastic-angina-on-long-term-prognosis
#19
Reo Hata, Naoki Oka, Shunsuke Kubo, Akimune Kuwayama, Masanobu Ohya, Takenobu Shimada, Katsuya Miura, Hidewo Amano, Yusuke Hyodo, Suguru Otsuru, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazushige Kadota
BACKGROUND: Little is known about the impact of stent type on the prognosis of vasospastic angina (VSA) in patients who undergo stent implantation.Methods and Results:We evaluated consecutive patients undergoing coronary angiography with positive (n=650; VSA) and negative (n=2,872; non-VSA) ergonovine testing. Among them, 304 patients undergoing stent implantation for organic stenosis were classified for comparison into 3 respective VSA and non-VSA groups based on stent type (68 and 78 with bare-metal stent [BMS]; 21 and 49 with sirolimus-eluting stent [SES]; 26 and 62 with newer generation drug-eluting stent [N-DES])...
June 28, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28658478/long-term-safety-and-efficacy-of-new-generation-drug-eluting-stents-in-women-with-acute-myocardial-infarction-from-the-women-in-innovation-and-drug-eluting-stents-win-des-collaboration
#20
Gennaro Giustino, Rafael Harari, Usman Baber, Samantha Sartori, Gregg W Stone, Martin B Leon, Stephan Windecker, Patrick W Serruys, Adnan Kastrati, Clemens Von Birgelen, Takeshi Kimura, Giulio G Stefanini, George D Dangas, William Wijns, P Gabriel Steg, Marie-Claude Morice, Edoardo Camenzind, Giora Weisz, Pieter C Smits, Sabato Sorrentino, Madhav Sharma, Serdar Farhan, Michela Faggioni, David Kandzari, Soren Galatius, Raban V Jeger, Marco Valgimigli, Dipti Itchhaporia, Laxmi Mehta, Hyo-Soo Kim, Alaide Chieffo, Roxana Mehran
Importance: Women with acute myocardial infarction (MI) undergoing mechanical reperfusion remain at increased risk of adverse cardiac events and mortality compared with their male counterparts. Whether the benefits of new-generation drug-eluting stents (DES) are preserved in women with acute MI remains unclear. Objective: To investigate the long-term safety and efficacy of new-generation DES vs early-generation DES in women with acute MI. Design, Setting, and Participants: Collaborative, international, individual patient-level data of women enrolled in 26 randomized clinical trials of DES were analyzed between July and December 2016...
June 28, 2017: JAMA Cardiology
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