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https://www.readbyqxmd.com/read/28097735/autoimmune-enteropathy-and-hepatitis-in-pediatric-heart-transplant-recipient
#1
Kimberly Lewis, Ryan Butts, J Antonio Quiros, Michelle Hudspeth, Katherine Twombley, Andrew Savage, Sally Self, Ali Burnette, Shaoli Sun
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis...
January 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28089555/epstein-barr-virus-and-renal-transplantation
#2
REVIEW
Jade Le, Christine M Durand, Irfan Agha, Daniel C Brennan
Epstein-Barr virus (EBV) is a gamma herpesvirus associated with diseases ranging from asymptomatic viremia to post-transplant malignancies in kidney transplant recipients. EBV specifically is associated with post-transplantation lymphoproliferative disorder (PTLD), in kidney transplant recipients, with increased risk in EBV seronegative patients with EBV seropositive donors on intensified immunosuppression. The diagnosis of PTLD relies on clinical suspicion plus tissue biopsy with polymerase chain reaction (PCR) testing of blood currently used for risk determination in high-risk recipients...
December 29, 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/28081041/a-systematic-literature-review-approach-to-estimate-the-therapeutic-index-of-selected-immunosuppressant-drugs-after-renal-transplantation
#3
Jessica E Ericson, Kanecia O Zimmerman, Daniel Gonzalez, Chiara Melloni, Jeffrey T Guptill, Kevin D Hill, Huali Wu, Michael Cohen-Wolkowiez
BACKGROUND: Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence standards for approval of generic formulations. However, many immunosuppressant drugs do not have a well-defined therapeutic index (TI). METHODS: We sought to determine whether safety, efficacy, and pharmacokinetic data obtained from the medical literature through a comprehensive literature search could be used to estimate the TI of cyclosporine, tacrolimus, and sirolimus...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28078989/a-comprehensive-review-of-mtor-inhibiting-pharmacotherapy-for-the-treatment-of-non-infectious-uveitis
#4
Joshua Blair, Robert Barry, David J Moore, Alastair K Denniston
BACKGROUND: Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role. METHODS: A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious uveitis was performed...
January 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28070711/immune-suppression-during-preclinical-drug-development-mitigates-immunogenicity-mediated-impact-on-therapeutic-exposure
#5
Jonathan Herskovitz, Josiah Ryman, Theingi Thway, Stephanie Lee, Lei Zhou, Narendra Chirmule, Bernd Meibohm, Vibha Jawa
In the clinical setting, anti-drug antibodies (ADA) against biotherapeutics can influence patient safety and interfere with product efficacy. High immunogenicity has been addressed in clinic by concomitant immune suppression, such as co-administration of methotrexate with enzyme replacement therapy (ERT) and combination tacrolimus/sirolimus treatment for prophylaxis against organ transplant rejection. This study investigates the use of such immune suppressants in mitigating ADA responses to a fully human monoclonal antibody (mAb1) in preclinical animal studies...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28065691/difference-in-vascular-response-between-sirolimus-eluting-and-everolimus-eluting-stents-in-ostial-left-circumflex-artery-after-unprotected-left-main-as-observed-by-optical-coherence-tomography
#6
Yusuke Fujino, Guilherme F Attizzani, Satoko Tahara, Toru Naganuma, Kensuke Takagi, Hiroto Yabushita, Wei Wang, Kentaro Tanaka, Takahiro Matsumoto, Hiroyoshi Kawamoto, Yuya Yamada, Shinnosuke Amano, Yusuke Watanabe, Takayuki Warisawa, Tomohiko Sato, Satoru Mitomo, Naoyuki Kurita, Hisaaki Ishiguro, Koji Hozawa, Takahiro Tsukahara, Masahiro Motosuke, Hiram G Bezerra, Shotaro Nakamura, Sunao Nakamura
BACKGROUND: Kissing-balloon technique (KBT) is commonly performed during percutaneous coronary intervention of distal unprotected left main coronary artery (ULM) aiming at obtaining optimal opening of the side branch (left circumflex artery; LCX) ostium. Nonetheless, detailed evaluation of vascular response to stents in LCX ostium is lacking. We therefore evaluated the vascular response to different drug-eluting stents (DES) in ostial LCX after ULM by means of optical coherence tomography (OCT)...
December 23, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28062139/efficacy-and-safety-of-everolimus-and-zotarolimus-eluting-stents-versus-first-generation-drug-eluting-stents-in-patients-with-diabetes-a-meta-analysis-of-randomized-trials
#7
Chirag Bavishi, Usman Baber, Sadik Panwar, Stefania Pirrotta, George D Dangas, Pedro Moreno, Jacqueline Tamis-Holland, Annapoorna S Kini, Samin K Sharma
INTRODUCTION: Patients with diabetes and coronary artery disease remain at high risk for adverse cardiovascular events after percutaneous coronary intervention. The efficacy and safety of the various drug-eluting stents (DES) in patients with diabetes is unclear. METHODS: Randomized controlled trials comparing first-generation DES [paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES)] with everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in diabetic patients were systematically searched...
December 27, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28056758/thrombotic-management-of-antiphospholipid-syndrome-towards-novel-targeted-therapies
#8
Md Asiful Islam, Fahmida Alam, Kah Keng Wong, Mohammad Amjad Kamal, Siew Hua Gan
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology...
5, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28054461/comparative-efficacy-of-sirolimus-eluting-stents-and-paclitaxel-eluting-stents-in-east-asian-versus-non-east-asian-patients-a-systematic-review-meta-analysis
#9
Rui Zhao, Qianwei Lu, Rui Yang, Jianlin Du, Songbo Deng, Qiang She
BACKGROUND: First-generation drug-eluting stents - such as the sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) - have become attractive options for percutaneous coronary intervention (PCI) and are still widely used in Asia. However, the effect of East Asian ethnicity on their efficacy remains unclear. METHODS: Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials comparing the efficacy of the Cypher SES and Taxus PES...
January 5, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28053551/genetics-of-tuberous-sclerosis-complex-implications-for-clinical-practice
#10
REVIEW
Carolina Caban, Nubaira Khan, Daphne M Hasbani, Peter B Crino
Tuberous sclerosis complex (TSC) is a multisystem disorder that results from heterozygous mutations in either TSC1 or TSC2. The primary organ systems that are affected include the brain, skin, lung, kidney, and heart, all with variable frequency, penetrance, and severity. Neurological features include epilepsy, autism, and intellectual disability. There are more than 1,500 known pathogenic variants for TSC1 and TSC2, including deletion, nonsense, and missense mutations, and all pathogenic mutations are inactivating, leading to loss of function effects on the encoded proteins TSC1 and TSC2...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28043665/angioscopic-observation-of-extremely-late-arterial-repair-after-intracoronary-implantation-of-the-first-generation-sirolimus-eluting-stents
#11
Minoru Ichikawa, Kazunori Bando, Yoshiyuki Kijima
BACKGROUND: Arterial repair delays after intracoronary implantation of Cypher sirolimus-eluting stents (SES), a representative first-generation drug-eluting stent. It remains unclear whether this delay would catch up with bare metal stents (BMS) during extremely long observation. The aim of this study was angioscopic observation of extremely late arterial repair after Cypher SES implantation. METHODS: Thirty-seven SES and 17 BMS were implanted into 22 and 9 patients with angina pectoris, respectively...
December 21, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28038988/serial-in-vivo-imaging-of-transplanted-allogeneic-neural-stem-cell-survival-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#12
Amit K Srivastava, Sarah K Gross, Akshata A Almad, Camille A Bulte, Nicholas J Maragakis, Jeff W M Bulte
Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc(+)-NSCs) were transplanted bilaterally (100,000 cells/2μl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1(G93A) ALS mice (n=14) and wild-type age-matched littermates (n=14)...
December 28, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28029575/use-of-sirolimus-in-pediatric-heart-transplant-patients-a-multi-institutional-study-from-the-pediatric-heart-transplant-study-group
#13
Joseph W Rossano, John L Jefferies, Elfriede Pahl, David C Naftel, Elizabeth Pruitt, Kathy Lupton, William J Dreyer, Richard Chinnock, Gerard Boyle, William T Mahle
BACKGROUND: Proliferation signal inhibitors, such as sirolimus, are increasingly used in solid-organ transplantation. However, limited data exist on sirolimus-treated pediatric patients. We aimed to describe sirolimus use in pediatric heart transplant patients and test the hypothesis that sirolimus use is associated with improved outcomes. METHODS: A retrospective review and propensity-matched analysis of the Pediatric Heart Transplant Study database was performed on patients undergoing primary heart transplantation from 2004 to 2013 with at least 1 year of follow-up comparing patients treated vs not treated with sirolimus at 1 year after transplant...
October 4, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28028691/sirolimus-therapy-is-associated-with-elevation-in-circulating-pcsk9-levels-in-cardiac-transplant-patients
#14
Vinaya Simha, Sisi Qin, Pankaj Shah, Byron H Smith, Walter K Kremers, Sudhir Kushwaha, Liewei Wang, Naveen L Pereira
Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0...
December 27, 2016: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28025695/efficacy-of-everolimus-eluting-stent-implantation-in-patients-with-small-coronary-arteries-%C3%A2-2-5%C3%A2-mm-outcomes-of-3-year-clinical-follow-up
#15
Hideki Yano, Shigeo Horinaka, Mayuko Ishikawa, Toshihiko Ishimitsu
Previous studies have demonstrated that patients with small coronary artery lesions are at increased risk for late cardiac events after percutaneous coronary intervention. It remains uncertain whether second-generation drug-eluting stents have an advantage over first-generation drug-eluting stents in patients with small vessel lesions. Our aim was to compare in the 3-year clinical impact between second-generation everolimus-eluting stents (EES) and first-generation sirolimus-eluting stents (SES) in small vessel lesions...
December 26, 2016: Heart and Vessels
https://www.readbyqxmd.com/read/28007199/coronary-artery-bypass-surgery-versus%C3%A2-drug-eluting-stent-implantation-for%C3%A2-left%C3%A2-main-or-multivessel-coronary-artery%C3%A2-disease-a-meta-analysis-of-individual-patient-data
#16
Cheol Whan Lee, Jung-Min Ahn, Rafael Cavalcante, Yohei Sotomi, Yoshinobu Onuma, Pannipa Suwannasom, Erhan Tenekecioglu, Sung-Cheol Yun, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Seong-Wook Park, Patrick W Serruys, Seung-Jung Park
OBJECTIVES: The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD). BACKGROUND: The relative efficacy and safety of CABG versus PCI with DES for left main or multivessel CAD remain controversial. METHODS: Data were pooled from the BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery vs...
December 26, 2016: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28006738/biomimetic-apatite-formed-on-cobalt-chromium-alloy-a-polymer-free-carrier-for-drug-eluting-stent
#17
Cen Chen, Chenxue Yao, Jingxin Yang, Dandan Luo, Xiangdong Kong, Sung-Min Chung, In-Seop Lee
In this study, sirolimus (SRL) was loaded within biomimetic apatite formed on cobalt-chromium (Co-Cr) alloy, which has been reported for the first time, to inhibit the in-stent restenosis. Two different groups of loading SRL within biomimetic apatite were prepared: Group A (mono-layer of apatite/SRL) and Group B (bi-layer of apatite/SRL). Group A and Group B showed the biphasic pattern of SRL release up to 40 and 90days, respectively. The attachment of human artery smooth muscle cell (HASMC) for both Group A and Group B was significantly inhibited, and proliferation dramatically decreased with the release of SRL...
December 15, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28000286/population-pharmacokinetics-of-temsirolimus-and-sirolimus-in-children-with-recurrent-solid-tumours-a-report-from-the-children-s-oncology-group
#18
Tomoyuki Mizuno, Tsuyoshi Fukuda, Uwe Christians, John P Perentesis, Maryam Fouladi, Alexander A Vinks
AIMS: Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR). Pharmacokinetic (PK) characterization of temsirolimus in children is limited and there is no paediatric temsirolimus population PK model available. The objective of this study was to simultaneously characterize the PK of temsirolimus and its metabolite sirolimus in paediatric patients with recurrent solid or central nervous system tumours and to develop a population PK model. METHODS: The PK data for temsirolimus and sirolimus were collected as a part of a Children's Oncology Group phase I clinical trial in paediatric patients with recurrent solid tumours...
November 7, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27990590/angiopoietins-as-serum-biomarkers-for-lymphatic-anomalies
#19
Timothy D Le Cras, Paula S Mobberley-Schuman, Mary Broering, Lin Fei, Cameron C Trenor, Denise M Adams
Vascular anomalies can cause significant morbidity and mortality. Advances in diagnosis will be improved if noninvasive biomarkers can be identified, as obtaining a tissue biopsy can worsen the disease and precipitate complications. The goal of this study was to identify biomarkers for vascular anomaly patients to aid diagnosis and potentially give insights into pathogenesis. Blood was collected at baseline and then 6 and 12 months after treatment with the mTOR inhibitor sirolimus. Patients groups included generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA) and kaposiform hemangioendothelioma (KHE) with or without the Kasabach-Merritt phenomenon (KMP) coagulopathy...
December 18, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27987857/effective-attenuation-of-vascular-restenosis-following-local-delivery-of-chitosan-decorated-sirolimus-liposomes
#20
Azadeh Haeri, Saeed Sadeghian, Shahram Rabbani, Maryam Sotoudeh Anvari, Samaneh Ghassemi, Fatemeh Radfar, Simin Dadashzadeh
Assuring the efficient local delivery via biocompatible nanosystems can be considered as a promising therapy for restenosis. The aim of the present study was preparation, in vitro characterization, and in vivo efficacy evaluation of sirolimus containing chitosan decorated liposomes for restenosis treatment. Liposomes were coated with chitosan, leading to ∼38nm increase in the particle size and a positive shift in the zeta potential from -1mV to +21mV. Chitosan modification was also confirmed by TEM, increased stability against detergent solubilization, and FTIR analyses...
February 10, 2017: Carbohydrate Polymers
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