- Comparison of efficacy and safety between ultrathin bioresorbable polymer sirolimus-eluting stents and thin durable polymer drug-eluting stents: a systematic review and meta-analysis of the literature. [Journal Article]Coron Artery Dis 2019CA
- CONCLUSIONS: BP SES significantly reduced the risk of any myocardial infarction and target vessel myocardial infarction in comparison with DP EES. There were no differences in cardiac death, STE, TLR, TVR and all-cause death with its follow-up time <2 year between BP SES and DP EES. Following-up ≥2 years, a statistically significant 27% RR increase in the risk of all-case death for patients randomized to BP SES was observed.
- What Now for the Endovascular Community After the Paclitaxel Mortality Meta-Analysis: Can Sirolimus Replace Paclitaxel in the Peripheral Vasculature? [Journal Article]J Endovasc Ther 2019; :1526602819881156JE
- Everolimus: Longer-term CERTITUDE. [Editorial]Liver Transpl 2019LT
- The approval in 2013 by the Federal Drug Administration of everolimus [EVR] for use in liver transplant [LT] recipients was the l arrival of a "new kid on the block" in immunosuppression [IS] therapy. While sirolimus, another mammalian target of rapamycin [mTOR] inhibitor had been used off-label for many years prior to the approval of EVR, the latter's shorter terminal half-life and quicker time …
The approval in 2013 by the Federal Drug Administration of everolimus [EVR] for use in liver transplant [LT] recipients was the l arrival of a "new kid on the block" in immunosuppression [IS] therapy. While sirolimus, another mammalian target of rapamycin [mTOR] inhibitor had been used off-label for many years prior to the approval of EVR, the latter's shorter terminal half-life and quicker time to steady-state trough level resulted in the requirement for no loading dose and easier dosing. EVR was approved for use in de novo LT recipients in conjunction with low dose tacrolimus [TAC] after studies demonstrated significant improvement in renal function compared to standard TAC exposure.[2-4] Because the rate of biopsy-proven acute cellular rejection [BPAR] was significantly higher within the first 12 months in the EVR alone group, EVR was not approved for use as monotherapy.
- Prospective evaluation of an ultrathin strut biodegradable polymer-coated sirolimus-eluting stent: 12 months' results from the S-FLEX UK registry. [Journal Article]BMJ Open 2019; 9(10):e026578BO
- CONCLUSIONS: The S-FLEX UK registry showed that the S-SES is safe with a low incidence of TLF in routine clinical practise in patients with coronary artery disease being treated by PCI.
- Transplantation of PEGylated Islets Enhances Therapeutic Efficacy in a Diabetic Nonhuman Primate Model. [Journal Article]Am J Transplant 2019AJ
- Islet cell transplantation can lead to insulin independence, reduced hypoglycemia, and amelioration of diabetes complications in patients with Type 1 Diabetes. The systemic delivery of anti-inflammatory agents, while considered crucial to limit the early loss of islets associated with intrahepatic infusion, increases the burden of immunosuppression. In an effort to decrease the pharmaceutical loa…
Islet cell transplantation can lead to insulin independence, reduced hypoglycemia, and amelioration of diabetes complications in patients with Type 1 Diabetes. The systemic delivery of anti-inflammatory agents, while considered crucial to limit the early loss of islets associated with intrahepatic infusion, increases the burden of immunosuppression. In an effort to decrease the pharmaceutical load to the patient, we modified the pancreatic islet surface with long-chain poly(ethylene glycol) (PEG) to mitigate detrimental host-implant interactions. The effect of PEGylation on islet engraftment and long-term survival was examined in a robust nonhuman primate model via three paired transplants of dosages 4,300, 8,300. and 10,000 IEQ/kg. A reduced immunosuppressive regimen of anti-thymocyte globulin induction plus tacrolimus in the first post-transplant month followed by maintenance with sirolimus monotherapy, was employed. To limit transplant variability, two of the three pairs were closely MHC matched recipients and received MHC disparate PEGylated or untreated islets isolated from the same donors. Recipients of PEGylated islets exhibited significantly improved early c-peptide levels, reduced exogenous insulin requirements, and superior glycemic control as compared to recipients of untreated islets. These results indicate that this simple islet modification procedure may improve islet engraftment and survival in the setting of reduced immunosuppression.
- Temsirolimus Metabolic Pathways Revisited. [Journal Article]Xenobiotica 2019; :1-30X
- 1. Temsirolimus, a derivative of sirolimus, exhibits potent antitumor properties. It was the goal of this study to identify yet unknown temsirolimus metabolites generated after incubation with human liver microsomes. Previously, 23-hydroxy-, 24-hydroxy, 12-hydroxy, hydroxy-piperidine and 27-O-desmethyl temsirolimus had been described. 2. Metabolite strutures were identified using high-resolution …
1. Temsirolimus, a derivative of sirolimus, exhibits potent antitumor properties. It was the goal of this study to identify yet unknown temsirolimus metabolites generated after incubation with human liver microsomes. Previously, 23-hydroxy-, 24-hydroxy, 12-hydroxy, hydroxy-piperidine and 27-O-desmethyl temsirolimus had been described. 2. Metabolite strutures were identified using high-resolution mass spectrometry, MS/iontrap (MSn) and comparison of fragmentation patterns of the metabolites with those of temsirolimus and other known sirolimus derivatives. Moreover, enzyme kinetic parameters of temsirolimus metabolite formation as well as the contribution of individual recombinant cytochrome P450 (CYP) enzymes to temsirolimus metabolism were investigated. 3. Human liver microsomes mainly hydroxylated and/or demethylated temsirolimus. The structures of the following metabolites were identified: O-demethylated metabolites: 39-O-desmethyl, 16-O-desmethyl, and 27-O-desmethyl temsirolimus; hydroxylated metabolites: hydroxy piperidine temsirolimus, 11-hydroxy, 12-hydroxy, 14-hydroxy, 23-hydroxy, 24-hydroxy, 25-hydroxy, 45/46-hydroxy, and 49-hydroxy temsirolimus; demethylated-hydroxylated metabolites: 16-O-desmethyl, 24-hydroxy; 16-O-desmethyl, 23-hydroxy and 16-O-desmethyl 46-hydroxy temsirolimus; didemethylated metabolite: 27,39-O-didesmethyl temsirolimus; and dihydroxylated metabolite: 12,24-dihydroxy temsirolimus. It was confirmed that CYP3A4 represents the predominant enzyme responsible for temsirolimus metabolism. Moreover, CYP3A5 as well as CYP2C8 also showed significant activities especially resulting in the formation of 27-O-desmethyl, 25-hydroxy and hydroxy-piperidine temsirolimus. 4. It is concluded that temsirolimus is metabolized to more than 20 metabolites, not counting metabolism via the sirolimus pathway. Eighteen of these metabolites could be structurally identified using ion trap MSn and high-resolution mass spectrometry. Moreover, the present study showed that, in addition to CYP3A4, metabolism via CYP3A5 and CYP2C8 also represent significant metabolic pathways.
- Approaching treatment of transplant-associated thrombotic Microangiopathy from two directions with Eculizumab and transitioning from Tacrolimus to Sirolimus. [Journal Article]Transfusion 2019T
- CONCLUSIONS: Response rates and survival were improved for patients who were transitioned to sirolimus, so a two-pronged approach of inhibiting complement along with providing an alternative effective immunosuppressive agent may be beneficial in the treatment of early onset TA-TMA.
- Single Nucleotide Polymorphisms of Ubiquitin-Related Genes were Associated with Allograft Fibrosis of Renal Transplant Fibrosis. [Journal Article]Ann Transplant 2019; 24:553-568AT
- CONCLUSIONS: We are the first to reveal that mutations of rs644731 in the PIAS2 gene were significantly correlated with the progression of IF/TA in kidney transplant recipients.
- Use of mammalian target of rapamycin inhibitors in patient with autosomal dominant polycystic kidney disease: an updated meta-analysis. [Journal Article]Int Urol Nephrol 2019IU
- CONCLUSIONS: mTOR inhibitors did not significantly influence renal progression in patients with ADPKD, but were associated with a higher risk of complications. Whether mTOR inhibitors can be an add-on option or second-line agents remain undetermined.
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- Randomized Sirolimus-based early calcineurin inhibitor reduction in liver transplantation: impact on renal function. [Journal Article]Transplantation 2019T
- CONCLUSIONS: Prevention of CNI nephrotoxicity by Sirolimus-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and Sirolimus maintenance achieved better long-term renal outcomes compared to real-world practice.