Pharmacokinetic analysis after implantation of everolimus-eluting self-expanding stents in the peripheral vasculature

Background: A novel self-expanding drug-eluting stent was designed to release everolimus 225 mu g/cm(2) to prevent restenosis following peripheral arterial intervention. The purpose of this study was to measure the pharmacokinetic profile of everolimus following stent implantation. Methods: One hundred four patients with symptomatic peripheral arterial disease underwent implantation of everolimus-eluting stents in the femoropopliteal arteries. In a prespecified subset of 26 patients, blood samples for assay of everolimus content were collected prior to stent implantation, at 1, 4, and 8 hours postprocedure, prior to discharge, and at 1 month postproccdure. Results: A total of 39 stents, ranging from 28 mm to 100 mm in length, were implanted in 26 patients, resulting in a total delivered everolimus dose range of 3.0 to 7.6 mg. Following the procedure, the maximum observed everolimus blood concentrations (C-max) varied from 1.83 +/- 0.05 ng/mL after implantation of a single 80-mm stent to 4.66 +/- 1.78 ng/mL after implantation of two 100-mm stents. The mean time to peak concentration (T-max) varied from 6.8 hours to 35 hours. The pharmacokinetics of everolimus were dose-proportional in that dose-normalized C-max and area under the curve values were constant over the studied dose range. Conclusions: After implantation of everolimus-eluting self-expanding stents in the femoropopliteal arteries, systemic blood concentrations of everolimus are predictable and considerably lower than blood concentrations observed following safe oral administration of everolimus

PTA and stenting after previous aortoiliac endarterectomy

Objectives: to evaluate the feasibility and long-term results of angioplasty and stenting in the treatment of restenosis following aortoiliac endarterectomy. Materials and Methods: between 1991 and 1999 19 patients underwent angioplasty with selective stenting for recurrent stenosis after previous aortoiliac endarterectomy. Aortic lesions were treated five times in four patients. At the iliac level 28 lesions (25 stenosis and three occlusions) were treated in 16 patients (one patient had a stenosis at the aortic as well as iliac level). All patients were followed clinically and by ultrasound. In the second half of 1999, an angiogram or spiral CT-angiography was performed in all patients to determine long-term outcome. Results: technical success was obtained In all patients and clinical succes was achieved in 18 of the 19 patients, Angio,graphic cumulative primary patency for aortoiliac lesions was 96% at 1 year and 76% at 3 years, Conclusions: angioplasty with selective stenting of recurrent aortoiliac disease after previous aortoiliac endarterectomy is feasable and safe. Long-term clinical and angiographic patency rates are in accordance with results of aortoiliac angioplasty in general

Tumor-Infiltrating Lymphocytes in Head and Neck Cancer : Ready for Prime Time?

The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof of their significance was first shown in breast cancer, where TILs are now recommended in the classification of breast tumors. Emerging evidence indicates that the significance of TILs extends to other cancer types, including head and neck cancer. In the era of immunotherapy as a treatment choice for head and neck cancer, assessment of TILs and immune checkpoints is of high clinical relevance. The availability of the standardized method from the International Immuno-oncology Biomarker Working Group (IIBWG) is an important cornerstone toward standardized assessment. The aim of the current article is to summarize the accumulated evidence and to establish a clear premise for future research toward the implementation of TILs in the personalized management of head and neck squamous cell carcinoma patients

Tumor-Infiltrating Lymphocytes in Head and Neck Cancer : Ready for Prime Time?

Simple Summary The immune response has been shown to be a promising indicator to predict the clinical behavior of many cancers, including head and neck cancer. Tumor-infiltrating lymphocytes (TILs) were widely introduced as an important tool to reveal the status of the immune response. This review discusses the significance of TILs in head and neck cancers. The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof of their significance was first shown in breast cancer, where TILs are now recommended in the classification of breast tumors. Emerging evidence indicates that the significance of TILs extends to other cancer types, including head and neck cancer. In the era of immunotherapy as a treatment choice for head and neck cancer, assessment of TILs and immune checkpoints is of high clinical relevance. The availability of the standardized method from the International Immuno-oncology Biomarker Working Group (IIBWG) is an important cornerstone toward standardized assessment. The aim of the current article is to summarize the accumulated evidence and to establish a clear premise for future research toward the implementation of TILs in the personalized management of head and neck squamous cell carcinoma patients.Peer reviewe

Inositol 1,4,5-trisphosphate receptor 1, a widespread Ca2+ channel, is a novel substrate of polo-like kinase 1 in eggs

AbstractTo initiate embryo development, the sperm induces in the egg release of intracellular calcium ([Ca2+]i). During oocyte maturation, the inositol 1,4,5-trisphosphate receptor (IP3R1), the channel implicated, undergoes modifications that enhance its function. We found that IP3R1 becomes phosphorylated during maturation at an MPM-2 epitope and that this persists until the fertilization-associated [Ca2+]i responses cease. We also reported that maturation without ERK activity diminishes IP3R1 MPM-2 reactivity and [Ca2+]i responses. Here, we show that IP3R1 is a novel target for Polo-like kinase1 (Plk1), a conserved M-phase kinase, which phosphorylates it at an MPM-2 epitope. Plk1 and IP3R1 interact in an M-phase preferential manner, and they exhibit close co-localization in the spindle/spindle poles area. This co-localization is reduced in the absence of ERK activity, as the ERK pathway regulates spindle organization and IP3R1 cortical re-distribution. We propose that IP3R1 phosphorylation by Plk1, and possibly by other M-phase kinases, underlies the delivery of spatially and temporally regulated [Ca2+]i signals during meiosis/mitosis and cytokinesis

Editor's choice : European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of acute limb ischaemia

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Search for MSSM Higgs bosons decaying to μ+μ-in proton-proton collisions at √s=13TeV

A search is performed for neutral non-standard-model Higgs bosons decaying to two muons in the context of the minimal supersymmetric standard model (MSSM). Proton-proton collision data recorded by the CMS experiment at the CERN Large Hadron Collider at a center-of-mass energy of 13TeVwere used, corresponding to an integrated luminosity of 35.9fb-1. The search is sensitive to neutral Higgs bosons produced via the gluon fusion process or in association with a bbquark pair. No significant deviations from the standard model expectation are observed. Upper limits at 95% confidence level are set in the context of the mmod+hand phenomenological MSSM scenarios on the parameter tanβas a function of the mass of the pseudoscalar Aboson, in the range from 130 to 600GeV. The results are also used to set a model-independent limit on the product of the branching fraction for the decay into a muon pair and the cross section for the production of a scalar neutral boson, either via gluon fusion, or in association with bquarks, in the mass range from 130 to 1000GeV