A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues

A20 Modulates Lipid Metabolism and Energy Production to Promote Liver Regeneration

Background: Liver Regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-$\kappa$B inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. Methodology and Principal Findings: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.$\beta$galactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-$\kappa$B, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. Conclusion: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation

Finding a Needle in the Virus Metagenome Haystack - Micro-Metagenome Analysis Captures a Snapshot of the Diversity of a Bacteriophage Armoire

Viruses are ubiquitous in the oceans and critical components of marine microbial communities, regulating nutrient transfer to higher trophic levels or to the dissolved organic pool through lysis of host cells. Hydrothermal vent systems are oases of biological activity in the deep oceans, for which knowledge of biodiversity and its impact on global ocean biogeochemical cycling is still in its infancy. In order to gain biological insight into viral communities present in hydrothermal vent systems, we developed a method based on deep-sequencing of pulsed field gel electrophoretic bands representing key viral fractions present in seawater within and surrounding a hydrothermal plume derived from Loki's Castle vent field at the Arctic Mid-Ocean Ridge. The reduction in virus community complexity afforded by this novel approach enabled the near-complete reconstruction of a lambda-like phage genome from the virus fraction of the plume. Phylogenetic examination of distinct gene regions in this lambdoid phage genome unveiled diversity at loci encoding superinfection exclusion- and integrase-like proteins. This suggests the importance of fine-tuning lyosgenic conversion as a viral survival strategy, and provides insights into the nature of host-virus and virus-virus interactions, within hydrothermal plumes. By reducing the complexity of the viral community through targeted sequencing of prominent dsDNA viral fractions, this method has selectively mimicked virus dominance approaching that hitherto achieved only through culturing, thus enabling bioinformatic analysis to locate a lambdoid viral “needle" within the greater viral community “haystack". Such targeted analyses have great potential for accelerating the extraction of biological knowledge from diverse and poorly understood environmental viral communities

Percepciones de continuidad de la atención por parte de los usuarios de los sistemas de salud en Colombia y Brasil: M Luisa Vázquez

Antecedentes La continuidad de la atención (CC) es el grado en que el paciente experimenta la atención con el tiempo como coherente y vinculada. Se identifican tres tipos de CC: relacional, informativo y gerencial. El objetivo es determinar el grado de continuidad de la atención entre la atención primaria (PC) y la atención secundaria (SC) e identificar los factores asociados en Brasil y Colombia, países con diferentes sistemas de salud. Métodos Estudio transversal mediante una encuesta de población en Brasil (Pernambuco, n = 465) y Colombia (Bogotá, n = 609) en 2011. Se analizaron los usuarios de los servicios de salud de los sistemas de salud pública de cada país. Variables de resultado: índices sintéticos en CC relacional, informativo y gerencial. Variables explicativas: características sociodemográficas y salud. Se realizaron análisis descriptivos y modelos de regresión logística multivariante. Resultados El CC relacional fue mayor en Brasil que en Colombia tanto para los médicos de PC (82.2 y 72.9%, respectivamente) como para los médicos de SC (82.4 y 70.1%, respectivamente), pero la percepción de una buena transferencia de información (CC informativo) es menor (56.3 y 67.6%, respectivamente). No se encontraron diferencias en la percepción de consistencia de la atención (CC gerencial) (alrededor del 70%). Entre los factores asociados con CC, se destacan los siguientes: en Brasil, la edad (ancianos) y el área (Caruaru, ciudad remota) se asociaron con cualquier tipo de CC. En ambos países, la mala salud autoevaluada se asoció con niveles más bajos de CC relacional y en Colombia, también, con el control clínico CC. Además, en Colombia, Conclusiones El nivel de continuidad relacional y gerencial percibida es alto, y de continuidad informativa, baja. Los factores asociados con la percepción de la continuidad de la atención difieren según el país y el tipo de continuidad de la atención. Mensajes clave Es el primer intento de evaluar los tres tipos de continuidad de la atención en áreas de Colombia y Brasil. La comprensión de los factores asociados con la continuidad de la atención revelará qué aspectos del sistema de salud pública podrían mejorarse.Background Continuity of care (CC) is the degree to which the patient experiences care over time as coherent and linked. Three types of CC are identified: relational, informational and managerial. The aim is to determine the degree of continuity of care between primary (PC) and secondary care (SC) and to identify the associated factors in Brazil and Colombia, countries with different health systems. Methods Cross-sectional study by means of a population survey in Brazil (Pernambuco, n = 465) and Colombia (Bogota, n = 609) in 2011. Users of health services of public health systems of each country were analyzed. Outcome variables: synthetic indexes on relational, informational and managerial CC. Explanatory variables: sociodemographic characteristics and health. Descriptive analysis and multivariate logistic regression models were performed. Results Relational CC was higher in Brazil than in Colombia both for PC physicians (82.2 and 72.9%, respectively) and for SC physicians (82.4 and 70.1%, respectively), but the perception of a good information transfer (informational CC) is lower (56.3 and 67.6%, respectively). No differences in the perception of consistency of care (managerial CC) were found (around 70%). Among the associated factors with CC, the following stand out: in Brazil, age (elderly) and area (Caruaru, remote town) was associated with any type of CC. In both countries, poor self-rated health was associated with lower levels of relational CC and in Colombia, also, with clinical management CC. In addition, in Colombia, having at least one chronic disease was associated with higher levels of any type of CC and sex (female) with a continuous relationship with PC physicians and informational CC. Conclusions The level of perceived relational and managerial continuity is high, and of informational continuity, low. Factors associated with the perception of continuity of care differ by countries and type of continuity of care. Key messages It is the first attempt to evaluate the three types of continuity of care in areas of Colombia and Brazil The understanding of the factors associated with the continuity of care will reveal which aspects of the public health system could be improve

Validación de la versión brasileña y colombiana de la escala CCAENA (continuidad de la atención en todos los niveles de atención): Irene Garcia-Subirats

Introducción El cuestionario de continuidad de la atención en todos los niveles de atención (CCAENA en español) evalúa los tres tipos de continuidad de la atención (relacional, informativa, gerencial) en todos los niveles de atención desde la perspectiva del paciente. Había sido validado para el contexto sanitario español. Objetivo: evaluar las propiedades psicométricas de la versión abreviada de la escala CCAENA en el contexto colombiano y brasileño. Métodos Estudio transversal mediante encuesta de población en municipios de Colombia (n = 2,163) y Brasil (n = 2,167). Los datos se recopilaron en 2011 mediante un cuestionario que incluía 14 ítems de la escala CCAENA adaptados a ambos contextos (y traducidos). Se evaluaron la validez de constructo (análisis factorial exploratorio), la consistencia interna (alfa de Cronbach) y la multidimensionalidad (coeficientes de correlación de Spearman). Resultados Al igual que en la versión original, el análisis factorial mostró que los ítems se agruparon en tres factores: la continuidad entre los niveles de atención y la relación entre el proveedor de atención primaria y el proveedor de atención secundaria. El alfa de Cronbach indicó una buena consistencia interna (Colombia: 0.87, 0.91, 0.87; Brasil: 0.86, 0.89, 0.86). Los coeficientes de correlación sugieren que los tres factores pueden interpretarse como escalas separadas (<0.70). Conclusión La validez y la confiabilidad de la versión abreviada de CCAENA son adecuadas en ambos países, manteniendo una alta equivalencia con la versión original, por lo tanto, es una herramienta útil para evaluar la continuidad de la atención en estos contextos. Mensajes clave Este estudio demuestra buenas propiedades psicométricas (validez y confiabilidad) de la versión abreviada de la escala CCAENA adaptada al contexto colombiano y brasileño. Esta herramienta será útil para proveedores e investigaciones para evaluar los tres tipos de continuidad de la atención en todos los niveles de atención desde la perspectiva del paciente en Colombia y Brasil. The Author 2014. Publicado por Oxford University Press en nombre de la Asociación Europea de Salud Pública. Todos los derechos reservados.Introduction The questionnaire of continuity of care across care levels (CCAENA in Spanish) assesses the three types of continuity of care (relational, informational, managerial) across care levels from the patient’s perspective. It had been validated for the Spanish health care context. Objective: To evaluate the psychometric properties of shortened version of the CCAENA scale in the Colombian and Brazilian context. Methods Cross-sectional study by means of a population survey in municipalities of Colombia (n = 2,163) and Brazil (n = 2,167). Data were collected in 2011 using a questionnaire that included 14 items of the CCAENA scale adapted to both contexts (and translated). Construct validity (exploratory factor analysis), internal consistency (Cronbach’s alpha) and multidimensionality (Spearman correlation coefficients) were assessed. Results As in the original version, the factor analysis showed that the items grouped into three factors: continuity across care levels and patient-primary care provider and -secondary care provider relationship. Cronbach’s alpha indicated good internal consistency (Colombia: 0.87, 0.91, 0.87; Brazil: 0.86, 0.89, 0.86). The correlation coefficients suggest that the three factors can be interpreted as separated scales (<0.70). Conclusion Validity and reliability of the shortened version of CCAENA are adequate in both countries – maintaining high equivalence with the original version – thus, is a useful tool to assess continuity of care in these contexts. Key messages This study demonstrates good psychometric properties - validity and reliability- of the shortened version of CCAENA scale adapted to the Colombian and Brazilian context. This tool will be useful for providers and researches to assess the three types of continuity of care across care levels from the patient’s perspective in Colombia and Brazil. The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved

Doenças priônicas: avaliação dos riscos envolvidos na utilização de produtos de origem bovina Prionic disease: evaluation of the risks involved in using products of bovine origin

Os príons são proteínas que se mostram capazes de auto-replicação apesar de, para isso, alterar o metabolismo celular. São responsáveis por inúmeras doenças em animais e no ser humano (doenças priônicas), todas elas fatais. Essas moléstias apresentam enorme variabilidade quanto ao período de incubação, de alguns meses a 40 anos. Os príons acumulam-se e destroem os neurônios, provocando quadros conhecidos como encefalopatias espongiosiformes. Discute-se a apresentação clínica, epidemiológica e histórica das doenças priônicas. O foco maior de discussão recai, no entanto, na possibilidade teórica da transmissão iatrogênica dos príons por meio das formulações tópicas que utilizam ceramidas (cerebrosídeos) ou placenta de origem bovina, assim como pelo risco representado por alguns procedimentos dermatológicos, como transplantes da pele e implantes de colágeno.<br>A prion is a protein that is capable of self replication, thereby altering a cell's metabolism. It is responsible for a number of human and animal diseases (prionic diseases), all of which are always lethal. These diseases have enormous variability in their incubation periods, ranging from a few months to forty years. Prions accumulate and destroy nerve cells, causing spongiform encephalopathy. We discuss the clinical picture, epidemiology, and historical background of prionic diseases. The major focus of the discussion lies, however, on the theoretical possibility of iatrogenic transmission of prion infection due to topical formulations using ceramides (cerebrosides) or placenta of bovine origin, as well as the risk represented by some dermatological procedures such as skin grafts and collagen implants

Attitudes of cystic fibrosis patients and parents toward carrier screening and related reproductive issues

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting similar to 1 in 2500-4000 Caucasians. As most CF patients have no family history of the disorder, carrier screening for CF has the potential to prospectively identify couples at risk of conceiving an affected child. At-risk couples may consequently choose to act on the provided information and take steps to avoid the birth of a child with CF. Although carrier screening is widely believed to enhance reproductive autonomy of prospective parents, the practice also raises important ethical questions. A written questionnaire was administered to adult patients and parents of children with CF with the aim to explore participants' attitudes toward CF carrier screening and related reproductive issues. The study population was recruited from a CF patient registry in Belgium and comprised 111 participants (64 parents, 47 patients aged 16 or older). We found that more than 80% of all participants were in favor of preconception carrier screening for CF. However, some were concerned over potential negative consequences of population-wide CF carrier screening. Regarding future reproductive intentions, 43% of the participants indicated a desire to have children. Among these, preimplantation genetic diagnosis was found to be the most preferred reproductive option, closely followed by spontaneous pregnancy and prenatal diagnosis. Although the findings of our study suggest that patients and parents of children with CF support a population-based carrier screening program for CF, they also highlight some issues deserving particular attention when implementing such a program