Poliangeitis amb Granulomatosis eosinofílica i asma al·lèrgica; dues monedes amb una mateixa cara?

La síndrome de Churg-Strauss o Poliangeitis amb Granulomatosis eosinofílica (EGPA), clàssicament s'ha vinculat a un substrat asmàtic d'origen al·lèrgic. No obstant, l'evidència en aquest sentit és equívoca. L'objectiu d'aquest treball és identificar diferències clíniques i serològiques entre pacients amb EGPA i pacients asmàtics al·lèrgics, i determinar el perfil al·lèrgic d'un grup de pacients diagnosticats d'EGPA. Es comparen dos grups de pacients: un grup de diagnosticats d'EGPA, i un altre amb asma al·lèrgic. Malgrat les similituds clíniques entre els dos grups, les reaccions immunoal·lèrgiques no semblen intervenir en la fisiopatologia de la majoria dels casos d'EGPA

Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy

A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment.This work has been supported by grants from Fundación científica AECC -Asociación Española contra el Cáncer- (GCAEC20030CERV) to A.Ce., from Instituto de Salud Carlos III (ISCIII) co-funded by the European Union (CP16/00151, PI17/00211, PI20/00011; Spanish Ministry of Economy and Competitiveness) to A.Ca. and PI20/00625 to P.N., from la Caixa Foundation (LCF/PR/HR19/52160018) and MICINN (PID2020- 119917RB-I00) to E.B., from Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (PID2019-104948RB-I00) to R.R.G. This work was supported by Grant PT20/00023, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, and the Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC). A.Ca. is the recipient of funding from the Instituto de Salud Carlos III co-funded by the European Union (MS16/00151; CPII21/00012). J.L. is the recipient of a Junior Clinician fellowship from Fundación científica AECC (CLJUN19004LINA)

Influence of the IL17A locus in giant cell arteritis susceptibility

Objective: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. Methods: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. Results: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E−03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10−05). Conclusions: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology

Model d’atenció a la salut de les persones trans*

Persones trans; Atenció a la salut; Identitat de gènerePersonas trans; Atención a la salud; Identidad de géneroTrans people; Health care; Gender identityL'objectiu d'aquest document és l'ordenació de la cartera de serveis de l’atenció a la salut de les persones trans en el seu procés de transició en la identitat de gènere sentida a càrrec del sistema sanitari públic de Catalunya a partir d’un model consensuat i d’un protocol clínic marc per a l’atenció de la salut

Protocol d'actuació davant de casos de febre vírica de Zika en l'àmbit obstètric i pediàtric de Catalunya

Virus del Zika; Obstetrícia; PediatriaZika virus; Obstetrics; PediatricsObstetricia; PediatríaAquest document dóna recomanacions d'actuació per a la prevenció, detecció i tractament del virus del Zika a Catalunya

A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA

INTRODUCTION: Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. METHODS: A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays. RESULTS: A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P(MH) = 0.041, OR = 0.88, CI 95% 0.78-0.99) and recessive (P(MH) = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis. CONCLUSIONS: Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA

Model d’atenció a l’endometriosi a Catalunya

Endometriosi; Planificació sanitària; Model d'atencióEndometriosis; Planificación sanitaria; Modelo de atenciónEndometriosis; Health planning; Attention modelEl Model d’atenció a l’endometriosi a Catalunya estableix les bases per a l’ordenació dels serveis assistencials que intervenen en el procés integral d’atenció a les dones afectades amb endometriosi, inclou aspectes clínics, aspectes assistencials i aspectes d’ordenació de circuits assistencials, que venen determinats per les actuacions necessàries per donar una atenció integral a les dones afectades

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6,809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus