Experiencia clínica en el manejo de pacientes con leucemia linfática crónica en tratamiento con IBRUTINIB

Poster [PC-225] Introducción: Analizar la respuesta y la tolerancia a Ibrutinib en pacientes con Leucemia Linfática Crónica (LLC) en un hospital de tercer nivel. Material y Métodos: Estudio descriptivo, observacional, retrospectivo y unicéntrico en pacientes con LLC en tratamiento con Ibrutinib en un período comprendido entre Marzo 2015 a Abril 2018. Variables recogidas: demográficas (sexo y edad), citogenética, número de líneas previas de tratamiento, tiempo de evolución (desde el diagnóstico hasta inicio de Ibrutinib), linfocitos totales (al inicio y a los 6 meses de Ibrutinib), tiempo en el que se objetiva el recuento linfocitario menor, durabilidad del tratamiento, tipo de respuesta según criterios de la National Comprehensive Cancer Network (NCCN), motivo de suspensión y eventos adversos (EA) reportados. Resultados: 9 pacientes (mujeres 44.4 %) recibieron tratamiento con Ibrutinib. Con una mediana de edad al diagnóstico de 65 años (49 – 76). Al inicio del tratamiento, 2 pacientes presentaron delección 11q, 6 delección 13q, 4 delección 17p (mutación TP53) y 1 trisomía del 12. La mediana de líneas de tratamiento recibidas previo a ibrutinib fue de 1 (0-4), administrándose en primera línea a un paciente con delección 17p (mutación TP53). El tiempo medio de evolución fue de 83 meses. La media de linfocitosis al inicio y a los 6 meses fue 186 y 41 mil/mm3 respectivamente. La mediana de tiempo en alcanzar el recuento linfocitario menor fue de 6 meses (4-24). La media de duración de dicho tratamiento fue de 280 días. Tras > 6 meses de tratamiento la respuesta fue: 5 pacientes respuesta parcial, 3 completa y 1 progresión (transformación a síndrome de Ritcher). Suspendieron el tratamiento 6 pacientes. Los motivos fueron: 3 por eventos adversos (2 cambiaron a Idelalisib), 2 por éxitus (infección y problema cardiovascular) y 1 por progresión clínica. Los EA registrados en las historias clínicas fueron: 3 eventos hemorrágicos, 2 gastrointestinales, 2 cardiovasculares (fibrilación auricular e insuficiencia cardíaca congestiva) y 1 astenia. Conclusiones: En nuestra experiencia clínica Ibrutinib es un fármaco eficaz en el tratamiento de LLC. A pesar de su buena tolerancia, el principal motivo de discontinuación fue la aparición de efectos adversos moderados/ graves de tipo hemorrágicos y cardiovasculares. Lo que nos indica la necesidad de realizar una minuciosa selección del paciente más idóneo y una estrecha monitorización durante el tratamiento con Ibrutinib

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Dome patterns in pelagic size spectra reveal strong trophic cascades

In ecological communities, especially the pelagic zones of aquatic ecosystems, certain bodysize ranges are often over-represented compared to others. Community size spectra, the distributions of community biomass over the logarithmic body-mass axis, tend to exhibit regularly spaced local maxima, called "domes", separated by steep troughs. Contrasting established theory, we explain these dome patterns as manifestations of top-down trophic cascades along aquatic food chains. Compiling high quality size-spectrum data and comparing these with a size-spectrum model introduced in this study, we test this theory and develop a detailed picture of the mechanisms by which bottom-up and top-down effects interact to generate dome patterns. Results imply that strong top-down trophic cascades are common in freshwater communities, much more than hitherto demonstrated, and may arise in nutrient rich marine systems as well. Transferring insights from the general theory of nonlinear pattern formation to domes patterns, we provide new interpretations of past lake-manipulation experiments

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

Bacterial iron homeostasis

Iron is essential to virtually all organisms, but poses problems of toxicity and poor solubility. Bacteria have evolved various mechanisms to counter the problems imposed by their iron dependence, allowing them to achieve effective iron homeostasis under a range of iron regimes. Highly efficient iron acquisition systems are used to scavenge iron from the environment under iron-restricted conditions. In many cases, this involves the secretion and internalisation of extracellular ferric chelators called siderophores. Ferrous iron can also be directly imported by the G protein-like transporter, FcoB. For pathogens, host-iron complexes (transferrin, lactoferrin, haem, haemoglobin) are directly used as iron sources. Bacterial iron storage proteins (ferritin, bacterioferritin) provide intracellular iron reserves for use when external supplies are restricted, and iron detoxification proteins (Dps) are employed to protect the chromosome from iron-induced free radical damage. There is evidence that bacteria control their iron requirements in response to iron availability by downregulating the expression of iron proteins during iron-restricted growth. And finally, the expression of the iron homeostatic machinery is subject to iron-dependent global control ensuring that iron acquisition, storage and consumption are geared to iron availability and that intracellular levels of free iron do not reach toxic levels. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved