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Mathiasen Refsgaard posted an update 5 hours, 15 minutes ago
Delayed methotrexate (MTX) elimination after treatment with high-dose (HD) MTX may result in life-threatening toxicities as well as acute kidney injury. Treatment includes administration of glucarpidase, an enzyme that rapidly inactivates MTX. Dosing of glucarpidase is based on body weight; however, recommendations for dosage adjustments in obese patients are lacking. We describe three obese adult patients (BMI range 31-43 kg/m2 ) who received HD-MTX following all precautions for the treatment of HD-MTX. Although peak MTX concentrations were within the expected range (308-368 µmol/L), MTX concentrations after 24 hours or later were markedly increased (97, 52, and 19 µmol/L). Two patients experienced acute kidney failure. After a single intravenous dose of glucarpidase 4000 units (50 units/kg on the basis of ideal body weight (IBW)) was administered to each patient 38, 46, and 60 hours, respectively, after the start of MTX, MTX concentrations dropped quickly to 1.37, 0.07, and 0.03 µmol/L, respectively, and further decreased steadily. Over time, clinical status and renal function improved in all patients. Glucarpidase is a highly hydrophilic molecule with a volume of distribution of 3.6 L, representing the intravascular volume of an adult. Therefore, we used IBW for glucarpidase dose calculations, which allowed us to reduce the dose by half of the dose that would have been determined by using total body weight. This approach resulted in a rapid decrease of MTX serum concentrations and may reduce treatment costs of this highly expensive drug. This article is protected by copyright. All rights reserved.Vancomycin is a recommended therapy in multiple national guidelines. Despite the common use, there is a poor understanding of the mechanistic drivers and potential modifiers of vancomycin-mediated kidney injury. In this review, historic and contemporary rates of vancomycin-induced kidney injury (VIKI) are described, and toxicodynamic models and mechanisms of toxicity from preclinical studies are reviewed. Aside from known clinical covariates that worsen VIKI, preclinical models have demonstrated that various factors impact VIKI, including dose, route of administration, and thresholds for pharmacokinetic parameters. The degree of acute kidney injury (AKI) is greatest with the intravenous route and higher doses that produce larger maximal concentrations and areas under the concentration curve. Troughs (i.e., minimum concentrations) have less of an impact. Mechanistically, preclinical studies have identified that VIKI is a result of drug accumulation in proximal tubule cells, which triggers cellular oxidative stress and apoptosis. Yet, there are several gaps in the knowledge which may represent viable targets to make vancomycin therapy less toxic. Potential strategies include prolonging infusions and lowering maximal concentrations, administration of antioxidants, administering agents that decrease cellular accumulation, and reformulating vancomycin to alter the renal clearance mechanism. Based on preclinical models and mechanisms of toxicity, we propose potential strategies to lessen VIKI. This article is protected by copyright. All rights reserved.PURPOSE We present a new framework for theoretical analysis of the noise power spectrum (NPS) of photon-counting x-ray detectors, including simple photon-counting detectors (SPCDs) and spectroscopic x-ray detectors (SXDs), the latter of which use multiple energy thresholds to discriminate photon energies. METHODS We show that the NPS of SPCDs and SXDs, including spatio-energetic noise correlations, is determined by the joint probability density function (PDF) of deposited photon energies, which describes the probability of recording two photons of two different energies in two different elements following a single photon interaction. We present an analytic expression for this joint PDF and calculate the pre-sampling and digital NPS of CdTe SPCDs and SXDs. We calibrate our charge sharing model using the energy response of a cadmium zinc telluride (CZT) spectroscopic x-ray detector and compare theoretical results with Monte Carlo simulations. RESULTS Our analysis shows that charge sharing increases pixel signalserved.Testing of ecological, biogeographic and phylogenetic hypotheses of mycorrhizal traits requires a comprehensive reference data set about plant mycorrhizal associations. Here we present a database, FungalRoot, which summarizes publicly available data about vascular plant mycorrhizal type and intensity of root colonization by mycorrhizal fungi, accompanied with rich meta-data. We compiled and digitized data about plant mycorrhizal colonization in nine wide-spread languages. The present version of the FungalRoot database contains 36,303 species-by-site observations for 14,870 plant species, tripling the previously available compiled information about plant mycorrhizal associations. Based on these data, we provide a recommended list of genus-level plant mycorrhizal associations, based on the majority of data for species and careful analysis of conflicting data. The majority of ectomycorrhizal and ericoid mycorrhizal plants are trees (92%) and shrubs (85%), respectively. The majority of arbuscular and non-mycorrhizal plant species are herbaceous (50% and 70%, respectively). Our publicly available database is a powerful resource for mycorrhizal scientists and ecologists. It features possibilities for dynamic updating and addition of data about plant mycorrhizal associations. The new database will promote research on plant and fungal biogeography and evolution, and on links between above- and belowground biodiversity and ecosystem functioning. This article is protected by copyright. All rights reserved.AIM To evaluate the shaping ability of the single-file XP-endo Shaper system (XP-S; FKG Dentaire, La Chaux-de-Fonds, Switzerland) employing a different working time and of the multiple-file ProTaper Next system (Dentsply Sirona, Ballaigues, Switzerland) using micro-computed tomography (micro-CT) technology. METHODOLOGY Twenty long oval-shaped canals in mandibular incisors were matched anatomically and scanned by micro-CT (SkyScan 1172; Bruker microCT, Kontich, Belgium). The canals were divided into two groups (n=10) according to the canal preparation protocol XP-endo Shaper (XP-S) with an extra 45 seconds of instrumentation and ProTaper Next (PTN X4). Ferrostatin-1 clinical trial The images recorded before and after preparation were evaluated for morphometric measures of volume, surface area, structure model index, and untouched walls. The data were compared statistically (Student t-test for homogenous variances and Mann-Whitney test) between the two groups (XP-S and PTN X4) at α = 5%. RESULTS Root canal preparation significantly increased all parameters (volume, surface area, structure model index and untouched walls) tested in each group (p 0.