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Purpose: Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF-V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce.Methods: To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients.Results: Of the 74 patients, 30 (40.5 %) were AKI-, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48-14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation.Conclusions: We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months. [ABSTRACT FROM AUTHOR]

Abstract: The mid-Cretaceous amber of France contains thousands of protist-like inclusions similar in shape to some ciliates, flagellates and amoebae. The sheer abundance of these inclusions and their size variation within a single amber piece are not concordant with true fossil protists. French amber is coniferous in origin, which generally does not preserve well protists without cell walls. Thus, it would be surprising if French Cretaceous amber had preserved millions of protists. Here, we present a survey of the protist-like inclusions from French amber and attempt to elucidate their origins. Diverse Cretaceous ambers (from Spain, Germany and Lebanon), also derived from conifer resins, contain thousands of protist-like inclusions. In contrast, Tertiary ambers and modern resins are poor in protist-like fossils. This suggests these inclusions originated from early Cretaceous plant resins, probably secreted with the resin by trees that did not survive after the Cretaceous (such as the Cheirolepidiaceae). A review of the recent literature on amber microfossils indicates several protist-like inclusions that are unlikely to have a biological origin have already been described as real fossil protists. This is problematic in that it will bias our understanding of protist evolution. [Copyright &y& Elsevier]

Abstract: Over the past decade, the mid-Cretaceous amber deposits of Charentes (SW France) have been intensively studied. The fossils investigated were not only limited to arthropods preserved in amber, but also included microorganisms, plant debris and vertebrate remains. This plethora of analyses provided important data about the ecology of the overall system, including sources of litter input into the soil and of the above-ground ecology. More precisely, they showed that most of the microfossils were those of soil organisms or organisms that participated in the ecology of the forest soil. This new discovery provided the opportunity to study the ecology of the soil as preserved in the 100 million years old Charentes amber. Indeed, the trophic links of the fossil forest soil have been reconstructed on the basis of the fossil assemblage discovered in amber outcrops and overlayed on a model ecological forest soil food web. We relied on existing phylogenetic information to discuss the absence of certain taxonomic groups in the fossilized specimens. Our synthesis shows that although the organisms of this ancient forest of Charentes were different from those of modern soils, the soil food web was organized functionally the same as modern soils. It also demonstrated that trophic links of the soil community were already diverse, including various means of predation, parasitism and organic matter decomposition. The most obvious differences are the absence of evidence for symbiotic root nitrogen fixation and mycorrhizae. [Copyright &y& Elsevier]