Luxación de rótula en el perro: ¿Vale todo para resolverlo?

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Preclinical studies of toxicity and safety of the AS-48 bacteriocin

The in vitro antimicrobial potency of the bacteriocin AS-48 is well documented, but its clinical application requires investigation, as its toxicity could be different in in vitro (haemolytic and antibacterial activity in blood and cytotoxicity towards normal human cell lines) and in vivo (e.g. mice and zebrafish embryos) models. Overall, the results obtained are promising. They reveal the negligible propensity of AS-48 to cause cell death or impede cell growth at therapeutic concentrations and support the suitability of this peptide as a potential therapeutic agent against several microbial infections, due to its selectivity and potency at low concentrations. In addition, AS-48 exhibits low haemolytic activity in whole blood and does not induce nitrite accumulation in non-stimulated RAW macrophages, indicating a lack of pro-inflammatory effects. The unexpected heightened sensitivity of zebrafish embryos to AS-48 could be due to the low differentiation state of these cells. The low cytotoxicity of AS-48, the absence of lymphocyte proliferation in vivo after skin sensitization in mice, and the lack of toxicity in a murine model support the consideration of the broad spectrum antimicrobial peptideThis research was funded by the Spanish Ministry of Economy and Competitiveness (SAF2013-48971-C2-1-R, CSD2010-00065, and AGL2015-67995-C3-3-R, all including funds from the European Regional Development Funding, ERDF) and by the Research Groups (BIO160, CTS 944 and CTS 164, UGR) from Junta de Andalucía (Spain). The CIBER-EHD is funded by the Instituto de Salud Carlos III. RM-E is grateful for an FPU Grant (FPU14/01537) from the Ministry of Education, (Spain)

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P= 2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those re-ceiving tisa-cel. Efficacy was not significantly different between both products

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P =0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P =0.003, and 42% vs. 16%, P <0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P =0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P =0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P =0.195), 51% and 47% (P =0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality

Synergy of the Bacteriocin AS-48 and Antibiotics against Uropathogenic Enterococci

The genus Enterococcus comprises a ubiquitous group of Gram-positive bacteria that can cause diverse health care-associated infections. Their genome plasticity enables easy acquisition of virulence factors as well as antibiotic resistances. Urinary tract infections (UTIs) and catheter-associated UTIs are common diseases caused by enterococci. In this study, Enterococcus strains isolated from UTIs were characterized, showing that the majority were E. faecalis and contained several virulence factors associated to a better colonization of the urinary tract. Their susceptibility against the bacteriocin AS-48 and several antibiotics was tested. AS-48 is a potent circular bacteriocin that causes bacterial death by pore formation in the cell membrane. The interest of this bacteriocin is based on the potent inhibitory activity, the high stability against environmental conditions, and the low toxicity. AS-48 was active at concentrations below 10 mg/L even against antibiotic-resistant strains, whereas these strains showed resistance to, at least, seven of the 20 antibiotics tested. Moreover, the e ect of AS-48 combined with antibiotics commonly used to treat UTIs was largely synergistic (with up to 100-fold MIC reduction) and only occasionally additive. These data suggest AS-48 as a potential novel drug to deal with or prevent enterococcal infections.Spanish Ministry of Economy and Competitiveness SAF2013-48971-C2-1-REuropean Union (EU)Research Group General (UGR) BIO16

Eficacia de la administración de ácido ascórbico en pacientes con hemodiálisis en tratamiento con darbepoetina y con déficit funcional de hierro

El déficit funcional de hierro es causa bien conocida de hiporrespuesta al tratamiento con estimuladores eritropoyéticos en la anemia del paciente en hemodiálisis. El objetivo de nuestro estudio fue evaluar la eficacia de la administración intravenosa de ácido ascórbico en pacientes con ferropenia funcional que reciben tratamiento con darbepoetina. Incluimos 33 pacientes en hemodiálisis convencional durante más de seis meses, tratados con darbepoetina, que presentan cifras de ferritina mayores de 350 ng/ml e índice de saturación de transferrina menor del 25%. A estos pacientes se les administra ácido ascórbico por vía intravenosa posthemodiálisis (300 mg tres veces por semana) durante 12 semanas. Se realiza control basal, a las 2, 4, 6, 8, 10, 12 semanas y a los 15 días de finalizar el tratamiento, de hemoglobina, hematocrito, ferritina, IST, hierro sérico, transferrina, dosis de darbepoetina, ácido úrico, PCR y vitamina C sérica. Finalizan el estudio 26 pacientes (50% mujeres). La edad media es de 66,81 años (rango2685). Llevan en hemodiálisis 46,19 meses (rango 7-192). Los niveles de hemoglobina aumentan progresivamente a lo largo del estudio, de forma significativa a las 12 semanas de tratamiento (basal 11,72; final 12,75, p 0,005). La dosis administrada de darbepoetina se reduce, pero no de forma significativa (basal 38,27; final 32,70). El estatus del hierro mejora durante el estudio. El hierro sérico y el IST aumentan de forma significativa (p=0,017 y p=0,001, respectivamente). Los niveles de ferritina disminuyen y aumentan los de transferrina, en ambos casos sin significación estadística. Los niveles plasmáticos de vitamina C son indetectables al inicio del estudio, alcanzando niveles máximos a las 6 semanas de tratamiento (0,48 ± 0,31). La administración de ácido ascórbico resulta útil como tratamiento coadyuvante de la anemia, aumentando significativamente los niveles de hemoglobina y la biodisponibilidad del hierro, disminuyendo en parte los depósitos tisulares

Inmigración y cuidados de mayores en la Comunidad de Madrid

Vicente Rodríguez Rodríguez es el editor de la obra.La presente monografía muestra una mirada sobre los cuidados de las personas mayores ofrecidos por cuidadoras inmigrantes en el ámbito familiar en Madrid, en un mercado informal. A ello se llega a través de los discursos proporcionados por los actores que intervienen en ese proceso, las cuidadoras y las personas cuidadas y sus familiares, así como las instituciones y organizaciones que interactúan con ellas. Sus opiniones, obtenidas de entrevistas en profundidad, son analizadas mediante metodología cualitativa y permiten deslindar los factores que condicionan la aproximación de las necesidades de las personas cuidadas y su entorno familiar con las urgencias de las cuidadoras inmigrantes por acceder al mercado laboral. Asimismo, proporcionan interesantes reflexiones sobre los componentes del mercado informal de los cuidados prestados por inmigrantes, esencialmente las relaciones laborales, las condiciones de trabajo y las prácticas y tareas desarrolladas. Un aspecto principal lo constituyen los efectos que tiene este mercado informal en la esfera económica, a través de un estudio exploratorio de su valor económico, y en las relaciones personales. Este libro constituye un esfuerzo por ahondar en el análisis de los cuidados a personas mayores, en un contexto migratorio y una sociedad que están al final de un ciclo expansivo. Sus páginas de información cuantitativa sobre el envejecimiento de la población, sobre la discapacidad y dependencia de muchas personas mayores y sobre la migración en el espacio madrileño sirven de contrapunto acertado a la realidad que subyace a las relaciones entre las personas implicadas en este mercado informal, realidad a la que solo se puede acceder mediante la introspección cualitativa. En su conjunto, se trata de una obra atractiva en sus contenidos y sugerente en sus interpretaciones para la población en general y, especialmente, para los investigadores en la materia y los profesionales de las áreas de servicios sociales, inmigración, relaciones laborales, sanidad y mayores.N

Randomised, double-blind, placebo-controlled clinical trial for evaluating the efficacy of intracoronary injection of autologous bone marrow mononuclear cells in the improvement of the ventricular function in patients with idiopathic dilated myocardiopathy: a study protocol

Background Cellular therapies have been increasingly applied to diverse human diseases. Intracoronary infusion of bone marrow-derived mononuclear cells (BMMNC) has demonstrated to improve ventricular function after acute myocardial infarction. However, less information is available about the role of BMMNC therapy for the treatment of dilated myocardiopathies (DCs) of non-ischemic origin. This article presents the methodological description of a study aimed at investigating the efficacy of intracoronary injection of autologous BMMNCs in the improvement of the ventricular function of patients with DC. Methods This randomised, placebo-controlled, double-blinded phase IIb clinical trial compares the improvement on ventricular function (measured by the changes on the ejection fraction) of patients receiving the conventional treatment for DC in combination with a single dose of an intracoronary infusion of BMMNCs, with the functional recovery of patients receiving placebo plus conventional treatment. Patients assigned to both treatment groups are monitored for 24 months. This clinical trial is powered enough to detect a change in Left Ventricular Ejection Fraction (LVEF) equal to or greater than 9%, although an interim analysis is planned to re-calculate sample size. Discussion The study protocol was approved by the Andalusian Coordinating Ethics Committee for Biomedical Research (Comité Coordinador de Ética en Investigación Biomédica de Andalucia), the Spanish Medicines and Medical Devices Agency (Agencia Española de Medicamentos y Productos Sanitarios), and is registered at the EU Clinical Trials Register (EudraCT: 2013–002015-98). The publication of the trial results in scientific journals will be performed in accordance with the applicable regulations and guidelines to clinical trials. Trial registration ClinicalTrials.gov Identifier NCT02033278 (First Posted January 10, 2014): https://clinicaltrials.gov/ct2/show/NCT02033278; EudraCT number: 2013–002015-98, EU CT Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-002015-98. Trial results will also be published according to the CONSORT statement at conferences and reported peer-reviewed journals.This paper presents an investigator-driven Clinical trial partially funded by research grant provided by the Regional Ministry of Health of Andalusia (Grant Reference Number salud-201600073587-tra).Ye