Intoxicaciones por setas ¿todavía existen hoy?

Presentamos el caso de una paciente de 55 años vegana, que ingresa por presentar cuadro de nauseas, vómitos y deterioro general secundario a la ingesta de Amanita próxima. La paciente sufrió un síndrome norleucínico con fracaso renal agudo oligoanúrico, que requirió tratamiento con hemodiálisis urgente. La evolución de la paciente fue satisfactoria con recuperación completa de la función renal al cabo de 3 semanas. A propósito de este caso revisamos los efectos tóxicos de las principales setas y su tratamiento.We treated a 55-year old patient with nausea, vomiting and general malaise secondary to the ingestion of Amanita proxima. Our patient suffered from a norleucinic syndrome, with oligoanuric acute kidney failure; she was treated with urgent hemodialysis. The clinical outcome of our patient was satisfactory and complete recovery of kidney function was observed after three weeks. We review of the main toxic effects of mushrooms and their treatment

Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial

[EN]Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235

Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23

Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression

New treatment options offering enhanced activity in elderly, newly diagnosed patients with multiple myeloma are required. One strategy is to combine melphalan and prednisone with novel agents. We previously reported an 89% response rate, including 32% complete responses and 11% near complete responses, in our phase 1/2 study of bortezomib plus melphalan and prednisone (VMP) in 60 newly diagnosed multiple myeloma patients with a median age of 75 years. Here, we report updated time-to-events data and the impact of poor prognosis factors on outcome

Immunogenetic characterization of clonal plasma cells in systemic light-chain amyloidosis

This study was supported by the Centro de Investigación Biomédica en Red—Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369; and CB16/12/00489), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI13/02196), Asociación Española Contra el Cáncer (GCB120981SAN and the Accelerator Award), CRIS against Cancer foundation grant 2014/0120, and the Black Swan Research Initiative of the International Myeloma Foundation.Peer reviewe

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice

Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance

Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) is associated with inferior survival in multiple myeloma (MM). Thus, characterization of the minor MRD subclone may represent a unique model to understand chemoresistance, but to our knowledge, the phenotypic and genetic features of the MRD subclone have never been investigated. Here, we compared the antigenic profile of MRD vs diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study and showed that the MRD subclone is enriched in cells overexpressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4), and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs diagnostic PCs was performed in 12 patients; 3 of them showed identical copy number alterations (CNAs), in another 3 cases, MRD clonal PCs displayed all genetic alterations detected at diagnosis plus additional CNAs that emerged at the MRD stage, whereas in the remaining 6 patients, there were CNAs present at diagnosis that were undetectable in MRD clonal PCs, but also a selected number of genetic alterations that became apparent only at the MRD stage. The MRD subclone showed significant downregulation of genes related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and may identify chemoresistant PCs in vitro. Altogether, our results suggest that therapy-induced clonal selection could be already present at the MRD stage, where chemoresistant PCs show a singular phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles. This trial was registered at www.clinicaltrials.gov as #NCT01237249

Construction progress of WEAVE: the next generation wide-field spectroscopy facility for the William Herschel Telescope

We present an update on the overall construction progress of the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT), now that all the major fabrication contracts are in place. We also present a summary of the current planning behind the 5-year initial phase of survey operations, and some detailed end-to-end science simulations that have been effected to evaluate the final on-sky performance after data processing. WEAVE will provide optical ground-based follow up of ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 integral field units, or a single large IFU for each observation. The fibres are fed to a single (dual-beam) spectrograph, with total of 16k spectral pixels, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R 5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R 20000. The project has experienced some delays in procurement and now has first light expected for the middle of 2019

On the selectivity to ethylene during ethane ODH over M1-based catalysts. A surface and electrochemical study

[EN] MoVO, MoVTeO and MoVTeNbO mixed oxides, prepared hydrothermally and heat-treated in N2 at 400, 500 or 600 degrees C, are active and selective catalysts in the oxidative dehydrogenation (ODH) of ethane, although their catalytic behaviour strongly depends on the composition and the activation temperature of the material. Thus, the selectivity to ethylene over samples heat-treated at 400 or 600 degrees C, decreases according to the following trend: MoVTeNb-600 > MoV-400 > MoVTe-600 > MoVTe-400 > MoVTeNb-400 >> MoV-600 (with catalysts heat -treated at 500 degrees C presenting an intermediate performance). This catalytic performance can be explained to a high extent by the presence of the M1 phase in the best catalysts. Interestingly, the temperature of formation and decomposition of the M1 phase strongly depends on the chemical composition of the catalysts, leading to different trends depending on the heat-treatment temperature. Not only the presence of the M1 phase determines the catalytic performance but also the V4+/V5+ ratio in the surface of catalysts. Additionally, a comprehensive brand-new electrochemical characterization of the catalysts has been carried out for MoV-based samples with M1 phase. Accordingly, the best catalytic behaviour in terms of selectivity to ethylene in the ethane ODH was observed in those materials presenting higher charge-transfer resistances at the interfacial active parts and n-type semiconductivity with few O-vacancies. Besides, lower current densities obtained in cyclic voltammetries (related to low electrochemical activity) has been associated with higher selectivity in the ODH reaction.The funding received from the Ministerio de Ciencia e Innovación of Spain, MINECO/FEDER (Projects: PID2021-126235OB-C31, PID2021-126235OB-C33, TED2021-130756B-C32 and TED2021-129555B-I00), for this study is acknowledged. A.A. acknowledges Severo Ochoa Excellence Program for his fellowship (BES-2017-080329).De Arriba-Mateos, A.; Sánchez, G.; Sánchez-Tovar, R.; Concepción Heydorn, P.; Fernández-Domene, R.; Solsona, B.; López Nieto, JM. (2023). On the selectivity to ethylene during ethane ODH over M1-based catalysts. A surface and electrochemical study. Catalysis Today. 418:1-13. https://doi.org/10.1016/j.cattod.2023.11412211341