An institutional perspective on the impact of recent antibiotic exposure on length of stay and hospital costs for patients with gram-negative sepsis

Carta a Alfonso Sastre Pascual Serrano Pero ¿qué pasa con los intelectuales? (para mi amigo Pascual Serrano) Alfonso Sastre Una reflexión necesaria Pascual Serrano Carta a Alfonso Sastre y a Pascual Serrano, Octavio Rodríguez Araujo. La cobardía de los intelectuales, Carlo Frabetti. Los intelectuales y la apatía, Santiago Alba Ric

Algunos conceptos para la mejora de la rentabilidad en explotaciones cunícolas

La cunicultura no atraviesa por buenos momentos y la rentabilidad de muchas de las explotaciones españolas está cada vez más comprometida. En este trabajo se intenta conocer y razonar sobre algunas cuestiones generales que podrían contribuir a la mejora de la rentabilidad de las explotaciones cunícolas. El conocimiento sobre el origen de los ingresos y costes de nuestra explotación tanto fijos como variables es imprescindible a la hora de adoptar medidas adecuadas que contribuyan a mejorar la situación económica de nuestras explotaciones

Single Cord Blood Combined with HLA-Mismatched Third Party Donor Cells: Comparable Results to Matched Unrelated Donor Transplantation in High-Risk Patients with Hematologic Disorders

AbstractMatched unrelated donor (MUD) transplantation is the first alternative in the absence of a matched sibling donor. For patients without a suitable adult donor, we have adopted the dual stem cell transplantation protocol consisting of cord blood (CB) in combination with CD34+ cells from a third party HLA-mismatched donor. We analyzed the outcomes of patients undergoing both procedures in a single center. Starting in 2004, a total of 20 patients with high-risk disease underwent 22 dual transplants and 25 patients underwent myeloablative MUD transplantation. The 30-day cumulative incidence of neutrophil engraftment was similar in both groups (91% and 95%), with a median time to engraftment of 14 and 16 days, respectively. Grade II-IV acute graft-versus-host disease was more frequent in the MUD group (40% versus 5%). Except for a tendency toward a higher incidence of viral hemorrhagic cystitis in the dual transplantation group, posttransplantation infectious events were comparable in the 2 groups. The 3-year cumulative incidence rates of relapse (41% versus 44%) and nonrelapse mortality (30% versus 25%) were similar in the MUD and dual transplantation cohorts. Estimated 3-year overall survival and disease-free survival were 47% and 41%, respectively, with no survival advantage for either group. In our experience, dual transplantation offers survival rates comparable to those from myeloablative MUD transplantation with similar nonrelapse mortality rates

Service Orchestration and Federation for Verticals

The next generation mobile transport networks shall transform into flexible and agile SDN/NFV-based transport and computing platforms, capable of simultaneously supporting the needs of different vertical industries, e.g., automotive, e-health and media, by meeting a diverse range of networking and computing requirements. Network slicing, has emerged as the most promising approach to address this challenge by enabling per-slice management of virtualized resources and provisioning and managing slices tailored to the needs of different vertical industries. Service orchestration is the key enabler for slicing that allows efficient placement of virtual network functions over the infrastructure as well as optimal allocation of virtual resources among all network slices to deliver guaranteed, reliable and scalable services of different verticals. Besides, due to the limited footprint of infrastructure operators, it is also required to enable the interconnection and federation of multiple administrative domains, to effectively allow services to span across several providers. This paper presents the design of Service Orchestrator (SO) in the 5G- TRANSFORMER system, which deals with service orchestration and federation across multiple domains.This work has been partially funded by the EU H2020 5G-TRANSFORMER Project (grant no. 761536

Supervivencia del injerto tras trasplante hepático: aproximación a un nuevo índice de riesgo español

Introducción: existen diversos indicadores para la valoración de la supervivencia del injerto hepático (DRI americano y ET-DRI europeo, entre otros), pero existen diferencias importantes entre los programas de trasplante de los diferentes países y podría ser que dichos indicadores no sean válidos en nuestro medio. Objetivos: el objetivo de este estudio es describir un nuevo indicador nacional de riesgo del injerto hepático a partir de los resultados del Registro Español de Trasplante Hepático (RETH) y validar el DRI y el ET-DRI. Metodología: el RETH incluye un análisis de Cox de los factores relacionados con la supervivencia del injerto. En base a sus resultados se define el indicador graft risk index (GRI). Las variables que contempla dependen del proceso de donación: edad, causa de muerte, compatibilidad sanguínea y tiempo de isquemia fría; y del receptor: edad, enfermedad de base, virus C, número de trasplante, estado UNOS y técnica quirúrgica. Se obtuvo la curva de la regresión logística y se calcularon las curvas de supervivencia del injerto por estratificación. La precisión se evaluó mediante el área ROC. Resultados: un GRI de 1 se corresponde con una probabilidad de pérdida del injerto del 23, 25%; cada punto de aumento del GRI supone que la probabilidad se multiplica por 1, 33. El GRI mostró la mejor discriminación por estratificación. El área ROC del DRI fue 0, 54 (95% IC, 0, 50-0, 59) y del ET-DRI, 0, 56 (95% IC, 0, 51-0, 61), frente al GRI 0, 70 (95% IC, 0, 65-0, 73) (p < 0, 0001). Conclusiones: el DRI y el ET-DRI no parecen útiles en nuestro medio y sería necesario disponer de un indicador propio. El GRI requiere un estudio nacional que perfile más el indicador y realice una validación más amplia. Introduction: several indicators are available to assess liver graft survival, including the American DRI and the European ET-DRI. However, there are significant differences between transplant programs of different countries, and the previously mentioned indicators might be not valid in our setting. Objectives: the aim of the study was to describe a new national liver graft risk indicator based on the results obtained from the Registro Espanol de Trasplante Hepatico (RETH) and to validate the DRI and ET-DRI indicators. Methods: the RETH includes a Cox analysis of factors associated with graft survival; the graft risk index (GRI) indicator was defined based on these results. The variables considered are dependent upon the donation conditions (age, cause of death, blood compatibility and cold ischemia time) and the transplant recipient (age, underlying disease, hepatitis C virus, transplant number, UNOS status and surgical technique). A logistic regression curve was obtained and graft survival curves were calculated by stratification. Precision was assessed using the ROC analysis. Results: a GRI of 1 represents a probability of graft loss of 23.25%; each point increase in the GRI score multiplies this probability by 1.33. The best discrimination of GRI was obtained by stratification.The DRI ROC area was 0.54 (95% CI, 0.50-0.59) and the ET-DRI ROC area was 0.56 (95% CI, 0.51-0.61), compared to 0.70 (95% CI, 0.65-0.73) (p < 0.0001) for the GRI. Conclusions: both the DRI and ET-DRI do not seem to be useful in our setting. Hence a national indicator is more desirable.The GRI requires a national study in order to further streamline and assess this indicator

Exploiting the potential of autophagy in cisplatin therapy: a new strategy to overcome resistance

Resistance to cisplatin is a major challenge in the current cancer therapy. In order to explore new therapeutic strategies to cisplatin resistance, we evaluated, in a model of lung cancer (H1299 and H460 cell lines), the nature of the pathways leading to cell death. We observed that H1299 displayed a natural resistance to cisplatin due to an inability to trigger an apoptotic response that correlates with the induction of autophagy. However, pharmacological and genetic approaches showed how autophagy was a mechanism associated to cell death rather than to resistance. Indeed, pro-autophagic stimuli such as mTOR or Akt inhibition mediate cell death in both cell lines to a similar extent. We next evaluated the response to a novel platinum compound, monoplatin, able to promote cell death in an exclusive autophagy-dependent manner. In this case, no differences were observed between both cell lines. Furthermore, in response to monoplatin, two molecular hallmarks of cisplatin response (p53 and MAPKs) were not implicated, indicating the ability of this pro-autophagic compound to overcome cisplatin resistance. In summary, our data highlight how induction of autophagy could be used in cisplatin resistant tumours and an alternative treatment for p53 mutated patient in a synthetic lethally approach

Exploiting the potential of autophagy in cisplatin therapy: A new strategy to overcome resistance

Resistance to cisplatin is a major challenge in the current cancer therapy. In order to explore new therapeutic strategies to cisplatin resistance, we evaluated, in a model of lung cancer (H1299 and H460 cell lines), the nature of the pathways leading to cell death. We observed that H1299 displayed a natural resistance to cisplatin due to an inability to trigger an apoptotic response that correlates with the induction of autophagy. However, pharmacological and genetic approaches showed how autophagy was a mechanism associated to cell death rather than to resistance. Indeed, pro-autophagic stimuli such as mTOR or Akt inhibition mediate cell death in both cell lines to a similar extent. We next evaluated the response to a novel platinum compound, monoplatin, able to promote cell death in an exclusive autophagy-dependent manner. In this case, no differences were observed between both cell lines. Furthermore, in response to monoplatin, two molecular hallmarks of cisplatin response (p53 and MAPKs) were not implicated, indicating the ability of this pro-autophagic compound to overcome cisplatin resistance. In summary, our data highlight how induction of autophagy could be used in cisplatin resistant tumours and an alternative treatment for p53 mutated patient in a synthetic lethally approach.This work was supported by grants from Fundación Leticia Castillejo Castillo and Ministerio de Economía y Competitividad (grant SAF2012-30862 to RSP and grant CTQ2011-24434 to FAJ). RSP Research Institute, and the work carried out in his laboratory receive support from the European Community through the regional development funding program (FEDER). JGC received funding from the Regional Ministry of Education and Science of Castilla–La Mancha (FPI-JCCM) and from Fundación Leticia Castillejo Castillo. MCC and RSP have a contract from the INCRECYT progra

Recent advances in gastrointestinal stromal tumors: Where are we going?

Tumores del estroma gastrointestinal; Inhibidores de la tirosina cinasa; LaparoscopiaGastrointestinal stromal tumors; Tyrosine kinase inhibitors; LaparoscopyTumors de l'estroma gastrointestinal; Inhibidors de la tirosina cinasa; LaparoscòpiaLos tumores del estroma gastrointestinal (GIST) suponen el 1-2% de los tumores digestivos, siendo su localización más frecuente el estómago (55-60%) y el intestino delgado (30%). Los avances más importantes sucedidos en los últimos años se centran en cuatro áreas: biología molecular, abordaje quirúrgico laparoscópico, manejo técnico del GIST en localizaciones inusuales y tratamiento e integración de la cirugía en el manejo del GIST avanzado. Los avances en el conocimiento de la biología molecular del GIST han dado lugar a la progresiva identificación de nueva mutaciones oncogénicas que hacen del concepto wild type obsoleto. Estos avances han permitido el desarrollo de dos nuevos fármacos, avapritinib y ripretinib, lo que permite el tratamiento de pacientes con mutaciones resistentes a las tres líneas terapéuticas clásicas. El tratamiento quirúrgico del GIST se rige por unos principios técnicos bien establecidos que el abordaje laparoscópico debe cumplir, abordaje que queda limitado por dos factores clave: localización y tamaño. El GIST de localización infrecuente (esófago, duodeno o recto, o extradigestivo) supone un reto terapéutico. Estos pacientes deben ser manejados en un contexto multidisciplinario. La cirugía queda integrada en el manejo del GIST avanzado, considerándose como adyuvante a los inhibidores de la tirosina cinasa.Gastrointestinal Stromal Sarcomas (GIST) are mesenchymal neoplasms whose incidence accounts for 1-2% of digestive tumors, being located in the stomach (55-60%) and small intestine (30%). The advances in its knowledge and management succeeded in the last years have being spectacular. This review aims to summarize the most important of them for surgeons. We identified four areas of interest: molecular oncology, laparoscopic approach, management of GIST located at unusual locations, and management of advanced GIST. Advances in the field of molecular oncology lead to the discovery of new oncogenic mutations making the term Wil Type GIST obsolete. Moreover, these advances allow for the development of 2 new drugs: Avapritinib and Ripretinib, that added to the previous 3 commercially available drugs (imatinib, sunitinib and regorafenib) make possible the management of GIST with resistant mutations. The principles of the surgical management of primary GIST are well stablished which laparoscopic approach must accomplish. This approach is limited by 2 main factors: location and size. The diagnosis of GIST in unusual locations as esophagus, duodenum, rectum of out of the gastrointestinal tract (EGIST), implies an extraordinary therapeutic challenge, being imperative to manage them by surgeons and oncologist among others in the setting of a multidisciplinary team. The management of advanced/metastatic GIST has changed in a revolutionary fashion because surgery is now part of its treatment as adjuvant to tyrosine kinase inhibitors