Nonreferral of Possible Soft Tissue Sarcomas in Adults: A Dangerous Omission in Policy

Introduction. The aim of this study is to compare outcomes in three groups of STS patients treated in our specialist centre: patients referred immediately after an inadequate initial treatment, patients referred after a local recurrence, and patients referred directly, prior to any treatment. Patients and methods. We reviewed all our nonmetastatic extremity-STS patients with a minimum follow-up of 2 years. We compared three patient groups: those referred directly to our centre (group A), those referred after an inadequate initial excision (group B), and patients with local recurrence (group C). Results. The study included 174 patients. Disease-free survival was 73%, 76%, and 28% in groups A, B, and C, respectively (P < .001). Depth, size, and histologic grade influenced the outcome in groups A and B, but not in C. Conclusion. Initial wide surgical treatment is the main factor that determines local control, being even more important than the known intrinsic prognostic factors of tumour size, depth, and histologic grade. The influence on outcome of initial wide local excision (WLE), which is made possible by referral to a specialist centre, is paramount

Derivados de 1,3-dioxoperhidropirido[1,2-c]pirimidinas como antagonistas de colecistoquinina

Referencia OEPM: P9501857.-- Fecha de solicitud: 26/09/1995.-- Titulares: Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Navarra.Derivados de 1,3-dioxoperhidropirido[1,2-c]pirimidinas como antagonistas de colecistoquinina (ver figura en archivo de texto adjunto). La presente invención se refiere a derivados de 1,3- dioxoperhidropirido [1,2,-c] piriminas, e intermedios para su preparación de fórmula general (I). Dichos derivados son útiles como antagonistas de colecistoquinina (CCK) y por lo tanto como agentes activos sobre el sistema nervioso central y el periférico.Peer reviewe

Influence of Tartrate Ligand Coordination over Luminescence Properties of Chiral Lanthanide-Based Metal–Organic Frameworks

The present work reports on a detailed discussion about the synthesis, characterization, and luminescence properties of three pairs of enantiopure 3D metal–organic frameworks (MOFs) with general formula {[Ln2(L/D-tart)3(H2O)2]·3H2O}n (3D_Ln-L/D, where Ln = Sm(III), Eu(III) or Gd(III), and L/D-tart = L- or D-tartrate), and ten pairs of enantiopure 2D coordination polymers (CPs) with general formula [Ln(L/D-Htart)2(OH)(H2O)2]n (2D_Ln-L/D, where Ln = Y(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III), Tm(III) or Yb(III), and L/D-Htart = hydrogen L- or D-tartrate) based on single-crystal X-ray structures. Enantiopure nature of the samples has been further corroborated by Root Mean Square Deviation (RMSD) as well as by circular dichroism (CD) spectra. Solid-state emission spectra of Eu(III), Tb(III), and Dy(III)-based compounds confirm the occurrence of ligand-to-metal charge transfers in view of the characteristic emissions for these lanthanide ions, and emission decay curves were also recorded to estimate the emission lifetimes for the reported compounds. A complete theoretical study was accomplished to better understand the energy transfers occurring in the Eu-based counterparts, which allows for explaining the different performances of 3D-MOFs and 2D-layered compounds. As inferred from the colorimetric diagrams, emission characteristics of Eu-based 2D CPs depend on the temperature, so their luminescent thermometry has been determined on the basis of a ratiometric analysis between the ligand-centered and Eu-centered emission. Finally, a detailed study of the polarized luminescence intensity emitted by the samples is also accomplished to support the occurrence of chiro-optical activity.This work has been funded by the University of the Basque Country (GIU20/028), Gobierno Vasco/Eusko Jaurlaritza (IT1755-22, IT1500-22), Junta de Andalucía (FQM-394, B-FQM-734-UGR20 and ProyExcel_00386), and the Spanish Ministry of Economy and Competitiveness (MCIU/AEI/FEDER, UE) (PGC2018-102052-A-C22, PGC2018-102052-B-C21)

Caracterización de un recuperador entálpico de placas de flujo cruzado

Mantener una ventilación adecuada precisa recuperar la energía contenida en el aire expulsado para evitar un consumo excesivo de energía. Utilizar recuperadores entálpicos permite recuperar calor (energía sensible) y humedad (energía latente) y su caracterización se basa en medir eficiencias de recuperación. Sin embargo, no se tiene en cuenta el riesgo de recirculación del aire procedente del local hacia la corriente de ventilación, que provoca la contaminación cruzada de corrientes, siendo especialmente crítico en el caso del SARS CoV2, ya que puede provocar una dispersión que incrementará el número de contagios. El trabajo presenta los resultados experimentales de la caracterización de un recuperador entálpico de placas en flujo cruzado. donde se han medido la temperatura, humedad relativa y concentración de CO2 de las corrientes que circulan por el mismo, utilizando Data Loggers de la marca testo con un intervalo de medida de 10 segundos

COVID-19 mRNA Based Vaccine Immune-Response Assessment in Nursing Home Residents for Public Health Decision

Nursing home residents (NHR) have been targeted as a vaccination priority due to their higher risk of worse outcome after COVID-19 infection. The mRNA-based vaccine BTN2b2 was first approved in Europe for NHRs. The assessment of the specific vaccine immune response (both humoral and cellular) at long term in NHRs has not been addressed yet. A representative sample of 624 NHR subjects in Northern region of Spain was studied to assess immune response against full vaccination with BTN2b2. The anti-S1 antibody levels and specific T cells were measured at two and six months after vaccination. 24.4% of NHR had a previous infection prior to vaccination. The remaining NHR were included in the full vaccination assessment group (FVA). After two months, a 94.9% of the FVA presented anti-S1 antibodies, whereas those seronegative without specific cellular response were 2.54%. At long-term, the frequency of NHR within the FVA group with anti-S1 antibodies at six months were 88.12% and the seronegative subjects without specific cellular response was 8.07%. The cellular immune assays complement the humoral test in the immune vaccine response assessment. Therefore, the cellular immune assessment in NHRs allows for the fine tuning of those seronegative subjects with potential competent immune responses against the vaccine

Impact of the “Law on promotion of personal autonomy and care for people dependent” in population with severe mental disorder

Law 39/2006, known as Dependence Law, has generated skepticism since its approval, for being focused on dependancy and barely promoting personal autonomy, treating it as a secondary issue. As it relates to people with severe mental disorder, a major concern to mental health professional organizations and family associations has been the compatibility of the law with the services provided by the National health service and whether the established selection criteria for qualifying for the service fits the needs of this group. This article reflects the work done across several Spanish autonomous regions by different professionals in an attempt to convince the administration to make the necessary adjustment to suit the characteristics of people with serious mental disorders. After discussing its strengths and weaknesses, it outlines three different ways to offset their risks in three different regions, Extremadura, Andalucia and Madrid. Finally it addresses the key aspects of the law which need to be worked on, in order to become a benefit for people with severe mental disorder, and not a barrierLa Ley 39/2006, conocida como Ley de Dependencia, ha generado, desde su aprobación, desconfianza por estar enfocada a la atención a la dependencia, siendo la promoción de la autonomía personal un elemento apenas desarrollado y secundario. En el caso de las personas con trastorno mental grave, lo que mayor preocupación ha causado a las organizaciones de profesionales de la salud mental y a las asociaciones de familiares ha sido la compatibilidad de dicha Ley con las prestaciones del Sistema Nacional de Salud y si el baremo establecido se ajustaba a las necesidades de este colectivo. Este artículo recoge el trabajo realizado desde diferentes comunidades autónomas por diferentes profesionales en un intento de, tras un análisis de la Ley, plantear a la administración responsable de la misma el necesario ajuste para adaptarla a las características de las personas con trastorno mental grave. Se analizan, en primer lugar, sus fortalezas y debilidades. Posteriormente se exponen tres formas diferentes de contrarrestar sus riesgos, en tres comunidades autónomas diferentes, Extremadura, Andalucía y Madrid. Finalmente se dan las claves de los aspectos de la Ley sobre los que hay que seguir trabajando para que sea una oportunidad para las personas con trastorno mental grave, y no una barrer

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiplemyeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes werecompared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admittedat six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients weremale; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity wasmoderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was requiredby 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasiveventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients,inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM athospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independentprognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifiespredictors of inpatient mortality among MM patients hospitalized with COVID-19

Validation of the International Myeloma Working Group standard response criteria in the PETHEMA/GEM2012MENOS65 study: are these times of change?

Induction and consolidation based on proteasome inhibitors, immunomodulatory drugs, and corticoids integrated with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), are showing complete response (CR) rates >50% in multiple myeloma (MM).1-3 The addition of anti-CD38 monoclonal antibodies may increase these unprecedented CR rates.4-6 When more than half of transplant-eligible patients with MM achieve CR with frontline therapy, it is reasonable to ask, what other tests are clinically relevant after negative immunofixation. The achievement of deep responses with modern therapy led the International Myeloma Working Group (IMWG) to propose new guidelines that included definitions of negative minimal residual disease (MRD) for standard response criteria.7 Indeed, recent studies have reported nearly 50% MRD− rates,5,8,9 and, more importantly, the prognostic value of MRD criteria was validated in clinical trials8,10-12 and routine practice...

MM, SARS-CoV-2 infection, and inpatient mortality

There is limited information on the characteristics, pre-admission prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with coronavirus disease 2019 (COVID-19). This retrospective case series investigated characteristics and outcomes of 167 MM patients hospitalized with COVID-19 reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in Spain between March 1 and April 30, 2020. Outcomes were compared with a randomly selected contemporary cohort of 167 age-/sex-matched non-cancer patients with COVID-19 admitted at 6 participating hospitals. Common demographic, clinical, laboratory, treatment, and outcome variables were collected; specific disease status and treatment data were collected for MM patients. Among the MM and non-cancer patients, median age was 71 years and 57% of patients were male in each series, and 75% and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77% and 89% of patients and critical in 8% and 4%, respectively. Supplemental oxygen was required by 47% and 55% of MM and non-cancer patients, respectively, and 21%/9% vs 8%/6% required non-invasive/invasive ventilation. Inpatient mortality was 34% and 23% in MM and non-cancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors of inpatient mortality on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.This study was supported by PETHEMA FoundationN

CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response