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Irene Belmonte,1 Alexa Nuñez,1,2 Miriam Barrecheguren,1 Cristina Esquinas,1 Mònica Pons,3 Rosa M López-Martínez,4 Gerard Ruiz,4 Albert Blanco-Grau,4 Roser Ferrer,4 Joan Genescà,3,5 Marc Miravitlles,1,6 Francisco Rodríguez-Frías4 1Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 2Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès). Barcelona, Spain; 3Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron; Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 4Department of Clinical Biochemistry, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 5Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain; 6CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, SpainCorrespondence: Marc MiravitllesPneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, P. Vall d’Hebron 119-129, Barcelona 08035, SpainEmail marcm@separ.esBackground: Alpha-1 antitrypsin deficiency (AATD) remains largely underdiagnosed despite recommendations of healthcare institutions and programmes designed to increase awareness. The objective was to analyse the trends in AATD diagnosis during the last 5 years in a Spanish AATD reference laboratory.Methods: This was a retrospective revision of all alpha-1 antitrypsin (AAT) determinations undertaken in our laboratory from 2015 to 2019. We analysed the number of AAT determinations performed and described the characteristics of the individuals tested, as well as the medical specialties and the reasons for requesting AAT determination.Results: A total of 3507 determinations were performed, of which 5.5% corresponded to children. A significant increase in the number of AAT determinations was observed from 349 in 2015 to 872 in 2019. Among the samples, 57.6% carried an intermediate AATD (50– 119 mg/dL) and 2.4% severe deficiency (< 50 mg/dL). The most frequent phenotype in severe AATD individuals was PI*ZZ (78.5%), and aminotransferase levels were above normal in around 43% of children and 30% of adults. Respiratory specialists requested the highest number of AAT determinations (31.5%) followed by digestive diseases and internal medicine (27.5%) and primary care physicians (19.7%). The main reason for AAT determination in severe AATD adults was chronic obstructive pulmonary disease (41.7%), but reasons for requesting AAT determination were not reported in up to 41.7% of adults and 58.3% of children.Conclusion: There is an increase in the frequency of AATD testing despite the rate of AAT determination remaining low. Awareness about AAT is probably increasing, but the reason for testing is not always clear.Keywords: alpha-1 antitrypsin deficiency, diagnosis, screening, lung disease

Cristina Esquinas,1,2 Sabina Janciauskiene,3 Ricardo Gonzalo,4 Gemma Mas de Xaxars,4 Beata Olejnicka,5 Irene Belmonte,6 Miriam Barrecheguren,1 Esther Rodriguez,1 Alexa Nuñez,1 Francisco Rodriguez-Frias,6 Marc Miravitlles1 1Pneumology Department, University Hospital Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, 2Public Health, Mental, Maternal and Child Health Nursing Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 3Department of Respiratory Medicine, Hannover Medical School, BREATH, German Center for Lung Research (DZL), Hannover, Germany; 4Statistics and Bioinformatics Unit (UEB), Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 5Department of Experimental Medical Science, Lund University, Lund, Sweden; 6Biochemistry Department, University Hospital Vall d’Hebron, Barcelona, Spain Introduction: COPD has complex etiologies involving both genetic and environmental determinants. Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD). Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors. Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD. Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity. Materials and methods: Peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study. We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms. We also integrated the miRNA and the differentially expressed putative target mRNA. For data analyses, we used the R statistical language R Studio (version 3.2.5). Results: The severe and mild COPD–AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy. In severe COPD–AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD–AATD disease. Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients. Conclusions: Despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD–AATD. Nonetheless, our findings warrant further validation in large studies. Keywords: alpha1-antitrypsin deficiency, COPD, gene expression, miRNAs, integrative analysis

Eva Dopico,1,2 Francisco Rodriguez-Frias,3– 5 Itziar Ubillos,6 Ariadna Rando-Segura,3 Damir Garcia-Cehic,4,7 Josep Gregori,4,7 Yolanda Rando-Matos,8,9 Luis Solsona,8,9 Jordi Niubó,1,2 Juan Ignacio Esteban,4,7 Josep Costa,4,10 Miguel J Martínez,10,11 Josep Quer4,5,7 1Microbiology Department, Laboratori Clínic Territorial Metropolitana Sud, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS), Hospitalet de Llobregat, Barcelona, Spain; 2Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; 3Biochemistry Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; 5Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain; 6Laboratory Clínic Territorial Metropolitana Sud, Institut Català de la Salut (ICS), Hospitalet de Llobregat, Barcelona, Spain; 7Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 8Equip d’Atenció Primària Florida Nord, Gerència d’Àmbit d’Atenció Primària Metropolitana Sud, Institut Català de la Salut (ICS), Hospitalet de Llobregat, Barcelona, Spain; 9Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 10Microbiology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain; 11ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainCorrespondence: Josep Quer, Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, Tel +34 934894034, Email josep.quer@vhir.org Miguel J Martínez, Microbiology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain, Email MYOLDI@clinic.catBackground: Hepatitis C virus (HCV) is a major cause of chronic liver infection with 71 million people infected worldwide. Pakistan has the second highest prevalence of HCV infection and more than half (52%) of Pakistani living in Spain reside in Barcelona. The aim of this study was to analyse the seroprevalence and viraemic rate and determine the genotypes and subtypes of HCV among Pakistanis living in the southern metropolitan area of Barcelona.Methods: We included all Pakistani patients seeking primary healthcare in the southern metropolitan area of Barcelona from August 2011 to July 2014. Serum samples were screened for HCV antibodies. HCV viral load was determined by reverse transcription polymerase chain reaction and genotypes and subtypes were performed using Versant HCV Genotype and/or deep-sequencing. Screening for hepatitis B virus (HBV) was also carried out.Results: Among 5877 Pakistani patients, 565 (9.61%) were screened for anti-HCV antibodies, with 68 (12.04%) being positive. The viral load was determined in 65, with 31 presenting active infection and the viraemic rate was 47.69% (95% confidence interval 36.02– 59.62). HCV genotyping and subtyping were performed in 24 individuals. Most infections corresponded to HCV genotype 3 (91.67%), and high resolution HCV subtyping was performed in 18 samples, 16 of which presented subtype 3a. One subject presented HBV coinfection with undetectable HBV DNA. During the study period, we identified a possible case of HCV vertical transmission followed by spontaneous viraemia clearance in a chronically infected mother with a C/T IL28B genetic polymorphism.Conclusion: These results suggest that general HCV screening protocols in patients from high prevalence countries, such as Pakistan, would be helpful to identify and treat active HCV infections. This could avoid further transmission and contribute to building targeted health policies for micro-elimination of HCV infection in specific communities.Keywords: hepatitis C virus, migrants, HCV genotype, HCV subtype

La administración de busulfán es ampliamente utilizada como parte del régimen de acondicionamiento en pacientes que se van a someter a trasplante de células madre hematopoyéticas. Se recomienda monitorizar las concentraciones plasmáticas de busulfán con el fin de optimizar la dosis en cada paciente y minimizar su toxicidad. El objetivo del presente estudio es validar un método analítico sencillo, rápido y costo-efectivo para la cuantificación de busulfán en plasma por cromatografía líquida acoplada a espectrometría de masas en tándem de aplicabilidad en la práctica clínica.

Administration of busulfan is extending rapidly as a part of a conditioning regimen in patients undergoing hematopoietic stem cell transplantation (HSCT). Monitoring blood plasma levels of busulfan is recommended for identifying the optimal dose in patients and for minimizing toxicity. The aim of this research was to validate a simple, rapid, and cost-effective analytical tool for measuring busulfan in human plasma that would be suitable for routine clinical use. This novel tool was based on liquid chromatography coupled to mass spectrometry.

The strain the SARS-COV-2 pandemic is putting on hospitals requires that predictive values are identified for a rapid triage and management of patients at a higher risk of developing severe COVID-19. We developed and validated a prognostic model of COVID-19 severity.

Durante la pandemia causada por el virus SARS-CoV-2 ha surgido la necesidad de identificar variables predictivas que permitan una rápida identificación de aquellos pacientes que desarrollarán la COVID-19 severa para una rápida intervención. Este estudio ha desarrollado y validado un modelo capaz de realizar un pronóstico de severidad de la COVID-19.