Demographic and clinical profile of idiopathic pulmonary fibrosis patients in Spain: the SEPAR National Registry

BackgroundLittle is known on the characteristics of patients diagnosed with idiopathic pulmonary fibrosis (IPF) in Spain. We aimed to characterize the demographic and clinical profile of IPF patients included in the IPF National Registry of the Spanish Respiratory Society (SEPAR).MethodsThis is a prospective, observational, multicentre and nationwide study that involved 608 IPF patients included in the SEPAR IPF Registry up to June 27th, 2017, and who received any treatment for their disease. IPF patients were predominantly males, ex-smokers, and aged in their 70s, similar to other registries.ResultsUpon inclusion, meanSD predicted forced vital capacity was 77.6%+/- 19.4, diffusing capacity for carbon monoxide was 48.5%+/- 17.7, and the 6-min walk distance was 423.5m +/- 110.4. The diagnosis was mainly established on results from the high-resolution computed tomography in the proper clinical context (55.0% of patients), while 21.2% of patients required invasive procedures (surgical lung biopsy) for definitive diagnosis. Anti-fibrotic treatment was prescribed in 69.4% of cases, 51.5% pirfenidone and 17.9% nintedanib, overall with a good safety profile.Conclusions The SEPAR IPF Registry should help to further characterize current characteristics and future trends of IPF patients in Spain and compare/pool them with other registries and cohorts

Çédille, revista de estudios franceses

Presentació

Phlebovirus-associated diseases transmitted by phlebotominae in Spain: Are we at risk?

[ES] Los virus del género Phlebovirus, transmitidos por dípteros de la familia Psychodidae, son una causa de síndrome febril autolimitado durante el verano-otoño en los países mediterráneos. En el caso del virus Toscana, pueden ser causa de meningitis y meningoencefalitis. En España se ha detectado la presencia de los virus Toscana, Granada, Nápoles, Sicilia, Arbia y Arrabida-like. La presencia casi generalizada de vectores del género Phlebotomus, especialmente de Phlebotomus perniciosus, en los que se han detectado varios de estos virus, hace muy probable que aparezcan de manera regular infecciones en humanos en nuestro país, siendo este riesgo moderado para el virus Toscana y bajo para el resto, en las zonas con mayor actividad del vector. La mayor parte de las enfermedades pasarían inadvertidas y solo el virus Toscana puede tener un mayor impacto por la aparición de casos graves.[EN] The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness

RING1B contributes to Ewing sarcoma development by repressing the NaV1.6 sodium channel and the NF-κB pathway, independently of the fusion oncoprotein.

Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as an oncogene. Here we demonstrate that RING1B is highly expressed in primary ES tumors, and its expression is independent of the fusion oncogene. RING1B-depleted ES cells display an expression profile enriched in genes functionally involved in hematological development but RING1B depletion does not induce cellular differentiation. In ES cells, RING1B directly binds the SCN8A sodium channel promoter and its depletion results in enhanced Nav1.6 expression and function. The signaling pathway most significantly modulated by RING1B is NF-κB. RING1B depletion results in enhanced p105/p50 expression, which sensitizes ES cells to apoptosis by FGFR/SHP2/STAT3 blockade. Reduced NaV1.6 function protects ES cells from apoptotic cell death by maintaining low NF-κB levels. Our findings identify RING1B as a trait of the cell-of-origin and provide a potential targetable vulnerability.This work was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncologia de Catalunya and by grants from ISCIII-FEDER (PS09/00973; RIC RD12/0042/0014, Red HERACLES), Ministerio de Economía y Competitividad (MEC) (SAF2012-31089 and SAF2015-69762-R), FEDER Funds and by the Asociación Española Contra el Cáncer (AECC). E.Á.’s lab is supported by the AECC, MECFEDER (RD12/0036/0017, PT13/0010/0056, RTC-2014- 2102-1, ISCIII Sara Borrell CD06/00001, PI12/03102, PI14/01466), the European FP7 Projects EuroSARC (FP7- HEALTH-2011-two-stage, Project 278742 EUROSARC), Euroewing (FP7-HEALTH.2013.2.4.1-1, Project 602856), Fundación Memoria de DM Solorzano Barruso, Fundación Cris contra el Cáncer, Pablo Ugarte Foundation, and Fundación M. García Estrada. O.M.T. is funded by ISCIIIFEDER (CES12/021) and the AECC. AMC is funded by the European FP7 projects (FP7/2007-2013) under a Marie Curie International Reintegration Grant (PIRG- 08- GA-2010-276998) and ISCIII-FEDER (CP13/00189). The Ewing group at the Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, is supported by the AECC and the generous donations from Pablo Ugarte Foundation

RING1B contributes to Ewing sarcoma development by repressing the NaV1.6 sodium channel and the NF-κB pathway, independently of the fusion oncoprotein.

Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as an oncogene. Here we demonstrate that RING1B is highly expressed in primary ES tumors, and its expression is independent of the fusion oncogene. RING1B-depleted ES cells display an expression profile enriched in genes functionally involved in hematological development but RING1B depletion does not induce cellular differentiation. In ES cells, RING1B directly binds the SCN8A sodium channel promoter and its depletion results in enhanced Nav1.6 expression and function. The signaling pathway most significantly modulated by RING1B is NF-κB. RING1B depletion results in enhanced p105/p50 expression, which sensitizes ES cells to apoptosis by FGFR/SHP2/STAT3 blockade. Reduced NaV1.6 function protects ES cells from apoptotic cell death by maintaining low NF-κB levels. Our findings identify RING1B as a trait of the cell-of-origin and provide a potential targetable vulnerability.This work was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncologia de Catalunya and by grants from ISCIII-FEDER (PS09/00973; RIC RD12/0042/0014, Red HERACLES), Ministerio de Economía y Competitividad (MEC) (SAF2012-31089 and SAF2015-69762-R), FEDER Funds and by the Asociación Española Contra el Cáncer (AECC). E.Á.’s lab is supported by the AECC, MECFEDER (RD12/0036/0017, PT13/0010/0056, RTC-2014- 2102-1, ISCIII Sara Borrell CD06/00001, PI12/03102, PI14/01466), the European FP7 Projects EuroSARC (FP7- HEALTH-2011-two-stage, Project 278742 EUROSARC), Euroewing (FP7-HEALTH.2013.2.4.1-1, Project 602856), Fundación Memoria de DM Solorzano Barruso, Fundación Cris contra el Cáncer, Pablo Ugarte Foundation, and Fundación M. García Estrada. O.M.T. is funded by ISCIIIFEDER (CES12/021) and the AECC. AMC is funded by the European FP7 projects (FP7/2007-2013) under a Marie Curie International Reintegration Grant (PIRG- 08- GA-2010-276998) and ISCIII-FEDER (CP13/00189). The Ewing group at the Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, is supported by the AECC and the generous donations from Pablo Ugarte Foundation

Demographic and clinical profile of idiopathic pulmonary fibrosis patients in Spain : The SEPAR National Registry

Little is known on the characteristics of patients diagnosed with idiopathic pulmonary fibrosis (IPF) in Spain. We aimed to characterize the demographic and clinical profile of IPF patients included in the IPF National Registry of the Spanish Respiratory Society (SEPAR). This is a prospective, observational, multicentre and nationwide study that involved 608 IPF patients included in the SEPAR IPF Registry up to June 27th, 2017, and who received any treatment for their disease. IPF patients were predominantly males, ex-smokers, and aged in their 70s, similar to other registries. Upon inclusion, mean ± SD predicted forced vital capacity was 77.6% ± 19.4, diffusing capacity for carbon monoxide was 48.5% ± 17.7, and the 6-min walk distance was 423.5 m ± 110.4. The diagnosis was mainly established on results from the high-resolution computed tomography in the proper clinical context (55.0% of patients), while 21.2% of patients required invasive procedures (surgical lung biopsy) for definitive diagnosis. Anti-fibrotic treatment was prescribed in 69.4% of cases, 51.5% pirfenidone and 17.9% nintedanib, overall with a good safety profile. The SEPAR IPF Registry should help to further characterize current characteristics and future trends of IPF patients in Spain and compare/pool them with other registries and cohorts