Les mirades en el territori: les fortificacions al massís de l’Albera, el vessant més oriental dels Pirineus

L’Albera admet una doble mirada: és una barrera física natural, que ha estat límit i frontera, i és la serralada més baixa dels Pirineus, la més important zona de pas terrestre de la serralada pirinenca, la que permet el pas entre l’Europa central-oriental i la península Ibèrica i Àfrica. Aquest pas ha afavorit el desenvolupament de la mateixa cultura identitària catalana a les dues bandes del massís. Territoris culturalment units, administrativament diferents, fet que ha portat a vigilar i defensar els seus passos d’accés. S’han construït fortificacions per salvaguardar i protegir. Unes construccions que han evolucionat segons les tècniques de la guerra per ser el màxim d’eficients i útils. El que dóna com a resultat una tipologia de fortificacions des de fa més de dos mil anys.The Albera mountain range allows a double interpretation: it is a natural physical barrier that has been limit and border, and it is the lowest range of the Pyrenees, the most important overland pass of the Pyrenees range, that connects central and eastern Europe with the Iberian Peninsula and Africa. This crossroad has led to the development of the same Catalan culture and identity on both sides of the range. Culturally united territories, but under different administrations which why their access points had to be controlled and defended. Fortifications have been built to safeguard and to protect. Constructions which have evolved according to the techniques of war to be most efficient and useful. The result is a typology of fortifications from over two thousand years of history

Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer

Colorectal cancer (CRC) shows aggregation in some families but no alterations in the known hereditary CRC genes. We aimed to identify new candidate genes which are potentially involved in germline predisposition to familial CRC. An integrated analysis of germline and tumor whole-exome sequencing data was performed in 18 unrelated CRC families. Deleterious single nucleotide variants (SNV), short insertions and deletions (indels), copy number variants (CNVs) and loss of heterozygosity (LOH) were assessed as candidates for first germline or second somatic hits. Candidate tumor suppressor genes were selected when alterations were detected in both germline and somatic DNA, fulfilling Knudson's two-hit hypothesis. Somatic mutational profiling and signature analysis were also performed. A series of germline-somatic variant pairs were detected. In all cases, the first hit was presented as a rare SNV/indel, whereas the second hit was either a different SNV (3 genes) or LOH affecting the same gene (141 genes). BRCA2, BLM, ERCC2, RECQL, REV3L and RIF1 were among the most promising candidate genes for germline CRC predisposition. The identification of new candidate genes involved in familial CRC could be achieved by our integrated analysis. Further functional studies and replication in additional cohorts are required to confirm the selected candidates

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis

Background: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team.Methods: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up.Results: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE.Conclusions: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team

Late gadolinium enhancement distribution patterns in non-ischemic dilated cardiomyopathy: Genotype-phenotype correlation.

AIMS Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM), there is little information about its frequency and distribution pattern according to underlying genetic substrate. We sought to describe LGE patterns according to genotype and to analyze the risk of major ventricular arrhythmias (MVA) according to patterns. METHODS AND RESULTS Cardiac magnetic resonance findings and LGE distribution according to genetics was performed in a cohort of 600 DCM patients followed at 20 Spanish centers. After exclusion of individuals with multiple causative gene variants or with variants in infrequent DCM-causing genes, 577 patients (34% females, mean age 53.5 years, LVEF 36.9 ± 13.9%) conformed the final cohort. A causative genetic variant was identified in 219 (38%) patients and 147 (25.5%) had LGE. Significant differences were found comparing LGE patterns between genes (P < 0.001). LGE was absent or rare in patients with variants in TNNT2, RBM20 and MYH7 (0%, 5% and 20%, respectively). Patients with variants in DMD, DSP and FLNC showed predominance of LGE subepicardial pattern (50%, 41% and 18%, respectively) whereas patients with variants in TTN, BAG3, LMNA and MYBPC3 showed unspecific LGE patterns. Genetic yield differed according to LGE pattern. Patients with subepicardial, lineal midwall, transmural, right ventricular insertion points or with combination of LGE patterns showed increased risk of MVA compared with patients without LGE. CONCLUSION LGE patterns in DCM has a specific distribution according to the affected gene. Certain LGE patterns are associated with increased risk of MVA and with increased yield of genetic testing.This study has been funded by Instituto Salud Carlos III (ISCIII) through the projects ‘PI18/0004, PI19/01283, and PI20/0320’ (co-funded by the European Regional Development Fund/European Social Fund ‘A way to make Europe’/‘Investing in your future’). The Hospital Universitario Puerta de Hierro, the Hospital Universitario Vall Hebrón, the Hospital General Universitario Gregorio Marañón, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart). F.d.F. receives grant support from ISCIII (CM20/00101). R.B. receives funding from the Obra Social la Caixa Foundation. M.B. receives funding from ISCIII (PI19/01283). The CNIC is supported by the ISCIII, Ministerio de Ciencia e Innovación of the Spanish Government (MCIN), and Pro CNIC Foundation.S

Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases

Altres ajuts: Generalitat de Catalunya, Departament de Salut; Generalitat de Catalunya, Departament d'Empresa i Coneixement i CERCA Program; Ministerio de Ciencia e Innovación; Instituto Nacional de Bioinformática; ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa; European Regional Development Fund (FEDER).Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%)