IMIB - Instituto Murciano de Investigación Biosanitaria Pascual Parrilla (Murcia)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16981

El Instituto Murciano de Investigación Biosanitaria (IMIB) es la unión de investigadores del ámbito biosanitario adscritos a cada una de las entidades que lo forman. El IMIB es el resultado de un convenio de colaboración suscrito entre los siguientes organismos: La Consejería de Salud, La Consejería de Empleo, Investigación y Universidades, El Servicio Murciano de Salud (SMS), Universidad de Murcia (UMU) y la Fundación para la Formación e Investigación Sanitarias de la Región de Murcia. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2015, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.

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Calibration of Toenail Metal Concentrations for Sample Mass Heterogeneity and Between-Batch Variability: The COMET Approach
(National Institute of Environmental Health Sciences (NIEHS), 2025-04) Pastor-Barriuso, Roberto; Gutiérrez-González, Enrique; Varea-Jiménez, Elena; Gómez-Ariza, José Luis; Castaño-Vinyals, Gemma; Aragonés, Nuria; Molina, Antonio José; Dierssen-Sotos, Trinidad; Fernández-Tardón, Guillermo; Amiano, Pilar; Ederra-Sanz, María; Moreno, Victor; Jiménez-Moleón, José Juan; Molina-Barceló, Ana; Marcos-Gragera, Rafael; Casabonne, Delphine; Alguacil, Juan; Gómez-Gómez, Jesús Humberto; García-Barrera, Tamara; Kogevinas, Manolis; Pollan-Santamaria, Marina; Perez-Gomez, Beatriz; Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Scientific Foundation
Background: Toenails are promising biomarkers of long-term metal exposure in epidemiological studies, but their accuracy may be compromised by systematic and random errors associated with heterogeneous toenail sample masses, as well as by substantial variability across laboratory batches. Objectives: We propose a novel modeling approach to calibrate toenail metal concentrations for the heterogeneity in sample masses and the variability between batches. Methods: We developed a heteroscedastic spline mixed model relating sample mass and laboratory batch with measured concentrations, allowing for an average bias in measurements over all batches as a smooth function of sample mass, random variation in mass-related biases across batches, and mass-related heterogeneity in within-batch error variance. The model allowed partitioning the total variance of measured concentrations into the extraneous variances (due to different sample masses and laboratory batches) and the intrinsic variance (resulting from distinct metal exposures). We derived calibrated metal concentrations from the model by removing both sources of extraneous variation and estimating the predicted concentrations had all toenail samples been analyzed in a single batch and of the same mass. We provide the R script COMET (COrrected METals) to fit the proposed model, extract variance components, and calibrate metal concentrations. Results: In a multicase-control study in Spain (MCC-Spain) with toenail determinations for 16 metals in 4,473 incident cases of five common cancers and 3,450 population controls, sample mass and batch accounted for 26%-60% of the total variance of measured concentrations for most metals. In comparison with calibrated concentrations, odds ratios for measured concentrations were biased by > 10% toward or away from the null in one-quarter of the estimated metal-cancer associations. Discussion: The proposed model allows correcting toenail metal concentrations for sample mass heterogeneity and between-batch variability and could be applied to other biological specimens of heterogeneous size, distinct laboratory techniques, and different study designs.
Epidemiological and Clinical Insights into the Enterovirus D68 Upsurge in Europe 2021-2022 and Emergence of Novel B3-Derived Lineages, ENPEN Multicentre Study
(Oxford University Press, 2024-10-16) Pires Simoes, Margarida; Hodcroft, Emma B; Simmonds, Peter; Albert, Jan; Alidjinou, Enagnon K; Ambert-Balay, Katia; Andrés, Cristina; Antón, Andrés; Auvray, Christelle; Bailly, Jean-Luc; Baldanti, Fausto; Bastings, Capser; Beard, Stuart; Berengua, Carla; Berginc, Natasa; Bloemen, Mandy; Blomqvist, Soile; Bosma, Froukje; Böttcher, Sindy; Bubba, Laura; Buderus, Stafan; Cabrerizo, Maria; Calvo, Cristina; Celma, Cristina; Ceriotti, Ferruccio; Clark, Gemma; Costa, Inës; Coste-Burel, Marianne; Couderé, Karen; Cremer, Jeroen; Del Cuerpo Casas, Margarita; Daehne, Theo; de Beer, Jessica; de Ceano-Vivas, Maria; De Gascun, Cillian; de Rougemont, Alexis; Dean, Jonathan; Dembinski, Jennifer L; Diedrich, Sabine; Diez-Domingo, Javier; Dillner, Lena; Dorenberg, Dagny H; Ducancelle, Alexandra; Dudman, Susanne; Dyrdak, Robert; Eis-Huebinger, Anna-Maria; Falces-Romero, Iker; Farkas, Agnes; Feeney, Susan; Fernandez-Garcia, Maria Dolores; Flipse, Jacky; Franck, Kristina T; Galli, Cristina; Garrigue, Isabelle; Geeraedts, Felix; Georgieva, Irina; Giardina, Federica; Guiomar, Raquel; Hauzenberger, Elenor; Heikens, Esther; Henquell, Cécille; Hober, Didier; Hönemann, Mario; Howson-Wells, Hannah; Hruškar, Željka; Ikonen, Niina; Imbert, Berthemarie; Jansz, Arjan R; Jeannoël, Marion; Jiřincová, Helena; Josset, Laurence; Keeren, Kathrin; Kramer-Lindhout, Naomie; Krokstad, Sidsel; Lazrek, Mouna; Le Guillou-Guillemette, Hélène; Lefeuvre, Caroline; Lind, Andreas; Lunar, Maja M; Maier, Melanie; Marque-Juillet, Stéphanie; McClure, C Patrick; McKenna, James; Meijer, Adam; Menasalvas Ruiz, Ana; Mengual-Chuliá, Beatriz; Midgley, Sofie; Mirand, Audrey; Molenkamp, Richard; Montes, Milagrosa; Moreno-Docón, Antonio; Morley, Ursula; Murk, Jean-Luc; Navascués-Ortega, Ana; Nijhuis, Roel; Nikolaeva-Glomb, Lubomira; Nordbø, Svein A; Numanovic, Sanela; Oggioni, Massimo; Oñate Vergara, Eider; Pacaud, Jordi; Pacreau, Marie L; Panning, Marcus; Pariani, Elena; Pekova, Lili; Pellegrinelli, Laura; Petrovec, Miroslav; Pietsch, Corinna; Pilorge, Léa; Piñeiro, Luis; Piralla, Antonio; Poljak, Mario; Prochazka, Birgit; Rabella, Nuria; Rahamat-Langendoen, Janette C; Rainetova, Petra; Reynders, Marijke; Riezebos-Brilman, Annelies; Roorda, Lieuwe; Savolainen-Kopra, Carita; Schuffenecker, Isabelle; Smeets, Leo C; Stoyanova, Asya; Stefic, Karl; Swanink, Caroline; Tabain, Irena; Tjhie, Jeroen; Thouault, Luc; Tumiotto, Camille; Uceda Renteria, Sara; Uršič, Tina; Vallet, Sophie; Van Ranst, Marc; Van Wunnik, Peter; Verweij, Jaco J; Vila, Jorgina; Wintermans, Bas; Wollants, Elke; Wolthers, Katja C; Xavier López-Labrador, F; Fischer, Thea Kølsen; Harvala, Heli; Benschop, Kimberley SM; Austrian Federal Ministry of Health (Austria); Ministry of Health (República Checa); Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Santé Publique France; Unión Europea. Comisión Europea. NextGenerationEU; Ministry of Health Welfare and Sport (Países Bajos); National Institutes of Health (Estados Unidos); Slovenian Research Agency; Swiss National Science Foundation
Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021-2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0-5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages.
Particulate Matter Exposure during Pregnancy and Childhood Leukemia Incidence
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-06-24) Sanz Olea, Enrique; Ojeda Sánchez, Carlos; Guxens, Mònica; Cañete, Adela; Pardo Romaguera, Elena; Gomez-Barroso, Diana; García-Pérez, Javier; Nuñez-Corcuera, Beatriz; Ortega-García, Juan Antonio; Ramis, Rebeca; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)
Leukemia is the most common childhood cancer and its etiology could be related to various environmental contaminants such as particulate matter (PM). The objective of our study is to evaluate the potential association between exposure to PM during pregnancy and the incidence of childhood leukemia. We established a population-based nationwide cohort using the Spanish Birth Registry Statistics database of the National Statistics Institute. We used spatiotemporal land use random forest models to estimate the concentrations of PM10 and PM2.5 for the entire pregnancy and by trimesters. We conducted logistic regression analyses adjusted for various covariates. In addition, we fitted generalized additive models (GAMs) to estimate the non-linear relationship between PM levels and leukemia incidence. The study included 3,112,123 children and 1066 cases of leukemia. The results for the continuous variable of PM10 exposure levels suggested an increased risk of childhood leukemia to be associated with higher exposure. The results for the categorized PM10 variable suggest an increased risk of childhood leukemia among pregnant women whose exposure levels were higher than the median (third and fourth quartiles). The results for PM2.5 were weaker. We found association between exposure to PM10 during pregnancy and an increased risk of childhood leukemia. Our findings indicate that public health interventions should aim to reduce air pollution to lower the incidence of childhood leukemia.
Novel risk loci for COVID-19 hospitalization among admixed American populations
(eLife Sciences Publications, 2024-10-03) Diz-de Almeida, Silvia; Cruz, Raquel; Luchessi, Andre D; Lorenzo-Salazar, José M; López de Heredia, Miguel; Quintela, Inés; González-Montelongo, Rafaela; Nogueira Silbiger, Vivian; Porras, Marta Sevilla; Tenorio Castaño, Jair Antonio; Nevado, Julián; Aguado, José María; Aguilar, Carlos; Aguilera-Albesa, Sergio; Almadana, Virginia; Almoguera, Berta; Alvarez, Nuria; Andreu-Bernabeu, Álvaro; Arana-Arri, Eunate; Arango, Celso; Arranz, María J; Artiga, Maria-Jesus; Baptista-Rosas, Raúl C; Barreda-Sánchez, María; Belhassen-García, Moncef; Bezerra, Joao F; Bezerra, Marcos A C; Boix-Palop, Lucía; Brion, María; Brugada, Ramón; Bustos, Matilde; Calderón, Enrique J; Carbonell, Cristina; Castano, Luis; Castelao, Jose E; Conde-Vicente, Rosa; Cordero-Lorenzana, M Lourdes; Cortes-Sanchez, Jose L; Corton, Marta; Darnaude, M Teresa; De Martino-Rodríguez, Alba; Del Campo-Pérez, Victor; Diaz de Bustamante, Aranzazu; Domínguez-Garrido, Elena; Eirós, Rocío; Fariñas, María Carmen; Fernandez-Nestosa, María J; Fernández-Robelo, Uxía; Fernandez-Rodriguez, Amanda; Fernández-Villa, Tania; Gago-Dominguez, Manuela; Gil-Fournier, Belén; Gómez-Arrue, Javier; González Álvarez, Beatriz; González Bernaldo de Quirós, Fernan; González-Neira, Anna; González-Peñas, Javier; Gutiérrez-Bautista, Juan F; Herrero, María José; Herrero-Gonzalez, Antonio; Jimenez-Sousa, Maria Angeles; Lattig, María Claudia; Liger Borja, Anabel; Lopez-Rodriguez, Rosario; Mancebo, Esther; Martín-López, Caridad; Martín, Vicente; Martinez-Nieto, Oscar; Martinez-Lopez, Iciar; Martinez-Resendez, Michel F; Martinez-Perez, Angel; Mazzeu, Juliana F; Merayo Macías, Eleuterio; Minguez, Pablo; Moreno Cuerda, Victor; Oliveira, Silviene F; Ortega-Paino, Eva; Pompa-Mera, Ericka N; Parellada, Mara; Paz-Artal, Estela; Santos, Ney PC; Pérez-Matute, Patricia; Perez, Patricia; Pérez-Tomás, M Elena; Perucho, Teresa; Pinsach-Abuin, Mel·lina; Pita, Guillermo; Porras-Hurtado, Gloria L; Pujol, Aurora; Ramiro León, Soraya; Resino, Salvador; Fernandes, Marianne R; Rodríguez-Ruiz, Emilio; Rodríguez-Artalejo, Fernando; Rodriguez-Garcia, José A; Ruiz-Cabello, Francisco; Ruiz-Hornillos, Javier; Ryan, Pablo; Soria, José Manuel; Souto, Juan Carlos; Tamayo, Eduardo; Tamayo-Velasco, Álvaro; Taracido-Fernandez, Juan Carlos; Teper, Alejandro; Torres-Tobar, Lilian; Urioste, Miguel; Valencia-Ramos, Juan; Yáñez, Zuleima; Zarate, Ruth; de Rojas, Itziar; Ruiz, Agustín; Sánchez, Pascual; Real, Luis Miguel; SCOURGE Cohort Group; Guillén-Navarro, Encarna; Ayuso, Carmen; Parra, Esteban; Riancho, José A; Rojas-Martinez, Augusto; Flores, Carlos; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Banco Santander; Fundación La Caixa; Agencia Estatal de Investigación (España); Gobierno de Canarias (España); Fundación Canaria de Investigación Sanitaria; Xunta de Galicia (España); Fundación Amancio Ortega; Estrella de Levante; Colabora Mujer
The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations ( and ). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in . Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.
Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-09-25) Marcos-Delgado, Alba; Martín-Sánchez, Vicente; Molina-Barceló, Ana; Alonso-Molero, Jéssica; Perez-Gomez, Beatriz; Pollán, Marina; Aragones, Nuria; Ederra-Sanz, María; Fernández-Tardón, Guillermo; Binefa, Gemma; Moreno, Victor; Barrios-Rodríguez, Rocío; Amiano, Pilar; Huerta, José María; Teso, Enrique Pastor; Alguacil, Juan; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Molina de la Torre, Antonio José; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Junta de Castilla y León (España); Regional Government of Andalusia (España)
The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). Methods: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. Results: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1-8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). Conclusions: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.
The efficacy of nursing interventions on sleep quality in hospitalized patients: A systematic review of randomized controlled trials
(Elsevier, 2021-03) Bellon, Filip; Mora-Noya, Veronica; Pastells-Peiró, Roland; Abad-Corpa, Eva; Gea-Sánchez, Montserrat; Moreno-Casbas, Teresa
Objective: To determine the effect of interventions that could be performed by nurses to improve the sleep quality of hospitalized patients in acute and semi-acute units. Design: A systematic review of randomized controlled trials and narrative synthesis. Data sources: Seven electronic databases (PubMed, CINAHL Plus, Scopus, ISI WoS, CENTRAL, PsycInfo, and Embase) were accessed on 20 May 2019 with a temporal limit of 10 years prior. Review methods: Original research studies of interventions that could be delivered by nurses to improve sleep quality during hospitalization in acute and semi-acute units were included. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Results: Seventeen studies met the inclusion criteria and were included in this review. The interventions carried out in the trials were classified into four categories of measurement: environmental, physical, behavioural, and combined. Fourteen studies obtained statistically significant improvements; two showed a blend of significant and non-significant improvements; and one reported non-significant results. However, only four trials of the seventeen were judged as having a low risk of bias. Conclusions: Overall evidence about interventions that could be performed by nurses to improve perceived sleep quality in hospitalized patients was found to be positive, and no negative effects were reported. However, higher quality research using both subjective and objective measures is needed, in order to strengthen the evidence.
Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
(Wiley, 2020-01) Palencia-Campos, Adrián; Martinez-Fernandez, Maria Luisa; Altunoglu, Umut; Soto-Bielicka, Patricia; Torres, Antonio; Marín, Purificación; Aller, Elena; Şentürk, Leyli; Berköz, Ömer; Yıldıran, Mehmet; Kayserili, Hülya; Gil-Camarero, Elena; Colli-Lista, Gloria; Sanchís-Calvo, Amparo; Carretero, Alba; ECEMC Working Group on Polydactyly; Guillén-Navarro, Encarna; López-González, Vanesa; Ballesta-Martínez, María; Rosell, Jordi; Aglan, Mona S; Temtamy, Samia; Otaify, Ghada A; Cuevas Catalina, María Lourdes; Torres-Saavedra, María-Nieves; Nevado, Julián; Tenorio, Jair; Lapunzina, Pablo; Bermejo-Sanchez, Eva; Ruiz-Pérez, Víctor L; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Fundación 1000 sobre Defectos Congénitos
Postaxial polydactyly (PAP) is a frequent limb malformation consisting in the duplication of the fifth digit of the hand or foot. Morphologically, this condition is divided into type A and B, with PAP-B corresponding to a more rudimentary extra-digit. Recently, biallelic truncating variants in the transcription factor GLI1 were reported to be associated with a recessive disorder, which in addition to PAP-A, may include syndromic features. Moreover, two heterozygous subjects carrying only one inactive copy of GLI1 were also identified with PAP. Herein, we aimed to determine the level of involvement of GLI1 in isolated PAP, a condition previously established to be autosomal dominantly inherited with incomplete penetrance. We analyzed the coding region of GLI1 in 95 independent probands with nonsyndromic PAP and found 11.57% of these subjects with single heterozygous pathogenic variants in this gene. The detected variants lead to premature termination codons or result in amino acid changes in the DNA-binding domain of GLI1 that diminish its transactivation activity. Family segregation analysis of these variants was consistent with dominant inheritance with incomplete penetrance. We conclude that heterozygous changes in GLI1 underlie a significant proportion of sporadic or familial cases of isolated PAP-A/B.
Enhanced echovirus 11 genomic surveillance in neonatal infections in Spain following a European alert reveals new recombinant forms linked to severe cases, 2019 to 2023
(European Centre for Disease Prevention and Control (ECDC), 2024-10) Fernandez-Garcia, Maria Dolores; Garcia-Ibañez, Nerea; Camacho, Juan; Gutiérrez, Almudena; Sánchez García, Laura; Calvo, Cristina; Moreno-Docón, Antonio; Menasalvas, Ana Isabel; Medina, Antonio; Pérez-Ruiz, Mercedes; Nieto Toboso, Maria Carmen; Muñoz-Almagro, Carmen; Launes, Cristian; Berengua, Carla; Cabrerizo, Maria; Instituto de Salud Carlos III
Background: In 2023, a European alert was issued regarding an increase in severe enterovirus (EV) neonatal infections associated with echovirus 11 (E11) new lineage 1. Aim: To analyse E11-positive cases between 2019 and 2023 to investigate whether the new lineage 1 circulated in Spain causing severe neonatal infections. Methods: EV-positive samples from hospitalised cases are sent for typing to the National Reference Enterovirus Laboratory. Available samples from 2022-23 were subjected to metagenomic next-generation sequencing.ResultsOf 1,288 samples genotyped, 103 were E11-positive (98 patients: 6 adults, 33 neonates, 89 children under 6 years; male to female ratio 1.9). E11 detection rate was similar before and after detection of the new lineage 1 in Spain in June 2022 (9.7% in 2019 vs 10.6% in 2023). The proportion of E11-infected ICU-admitted neonates in 2019-2022 (2/7) vs 2022-2023 (5/12) did not significantly differ (p = 0.65). In severe neonatal infections, 4/7 E11 strains were not linked to the new lineage 1. The three novel E11 recombinant genomes were associated with severe (n = 2) and non-severe (n = 1) cases from 2022-2023 and clustered outside the new lineage 1. Coinfecting pathogenic viruses were present in four of 10 E11-positive samples. Conclusion: The emergence of the new lineage 1 is not linked with an increase in incidence or severity of neonatal E11 infections in Spain. The detection of two novel E11 recombinants associated with severe disease warrants enhancing genomic and clinical surveillance.
New insights of polyamine metabolism in testicular physiology: A role of ornithine decarboxylase antizyme inhibitor 2 (AZIN2) in the modulation of testosterone levels and sperm motility.
(2018-12-19) Lambertos, Ana; Ramos-Molina, Bruno; López-Contreras, Andrés J; Cremades, Asunción; Peñafiel, Rafael
The specific role of polyamines in the testis physiology is not fully understood. Antizymes (OAZs) and antizyme inhibitors (AZINs) are modulators of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis and polyamine uptake. Although the three known OAZs are expressed in the testis, only OAZ3 is testis specific and has been proven to have an essential role in male fertility. Regarding the two existing AZINs, AZIN2 is the most abundantly expressed member in this gonad. Whereas previous studies suggested that AZIN2 might participate in mouse spermatogenesis, immunohistological analysis of human testicular sections revealed that AZIN2 is also detected in the steroidogenic Leydig cells but not in the germinal epithelium. In the present study, we found a close ontogenic similarity in the mRNA levels of OAZs and AZINs between mice and rats, but an opposite expression pattern of ODC activity. Further analysis of AZIN2 and OAZ3 in the testis of mice with different alterations in spermatogenesis and fertility, induced either genetically or pharmacologically, corroborated that both AZIN2 and OAZ3 are mainly expressed in the haploid germinal cells. Finally, by using transgenic mice with a truncated Azin2 gene fused to the bacterial lacZ gene, we studied the expression of Azin2 in testes, epididymides and spermatozoa. AZIN2 was detected in spermatids and spermatozoa, as well as in Leydig cells, and in epithelial epidydimal cells. Azin2 knock-out male mice were fertile; however, they showed marked decreases in testicular putrescine and plasma and testicular testosterone levels, and a dramatic reduction in the sperm motility. These results suggest an important role for AZIN2 in testicular cells by modulating polyamine concentrations, testosterone synthesis and sperm function. Overall, our data corroborate the relevance of polyamine regulation in testis functions, where both AZIN2 and OAZ3 play fundamental roles.
SEOM clinical guidelines for the management of germ cell testicular cancer (2016)
(2016-11-04) Aparicio, J; Terrasa, J; Durán, I; Germà-Lluch, J R; Gironés, R; González-Billalabeitia, E; Gumà, J; Maroto, P; Pinto, A; García-Del-Muro, X
Testicular cancer represents the most common malignancy in males aged 15-34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3-4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.
Learning, internalisation and integration of the COVID-19 pandemic in healthcare workers: A qualitative document analysis
(Wiley, 2024-09-19) Abad-Corpa, Eva; Rich-Ruiz, Manuel; Sánchez-López, Dolores; Solano Ruiz, Carmen; Casado-Ramirez, Elvira; Arregui-Gallego, Beatriz; Moreno-Casbas, Teresa; Muñoz-Jiménez, Daniel; Vidal-Thomàs, María Clara; Company-Sancho, María Consuelo; Orts-Cortes, Maria Isabel; Fundación BBVA
The COVID-19 pandemic triggered an unprecedented health crisis that impacted healthcare systems worldwide. This study explores how Spanish healthcare workers learned, internalised and integrated values and work behaviours during the COVID-19 pandemic and their impact on the personal sphere. This documentary research, using images, narratives and audiovisual content, was framed within the interpretative hermeneutic paradigm. Categories and subcategories emerged after a final theoretical sampling that focused on the analysis. Data triangulation between researchers favoured theoretical saturation. A total of 117 images and 27 texts were selected. The analysis identified three stages: bewilderment, seeking functionality in the chaos and integrating chaos into care. The data reflects how the need for security and knowledge, and the exhaustion and frustration caused by the initial working conditions, prompted adaptive responses. These responses involved focusing on problem-solving and strengthening group sentiments and solidarity. Subsequently, the data indicates the acceptance of new structural, organisational and communication aspects. The findings of the analysis will contribute towards finding a framework that can help understand community health crisis events.
Efficacy of the Otago-Exercise-Programme to reduce falls in community-dwelling adults aged 65-80 when delivered as group or individual training: Non-inferiority-clinical-trial
(BioMed Central (BMC), 2024-10-01) Albornos-Muñoz, Laura; Blanco-Blanco, Joan; Cidoncha-Moreno, María Ángeles; Abad-Corpa, Eva; Rivera-Álvarez, Araceli; López-Pisa, Rosa María; Caperos, José-Manuel; Otago Project Working Group Consortium; Moreno-Casbas, Teresa; Rich-Ruiz, Manuel; Rodriguez Baz; Agencia Estatal de Investigación (España); Instituto de Salud Carlos III; Fundación para la Formación e Investigación Sanitarias de la Región de Murcia; Basque Foundation for Health Innovation and Research
Background: The Otago Exercise Programme is an effective intervention for falls prevention. However, there is limited evidence in relation to studies that compare efficacy for falls prevention when delivered Otago Exercise Programme in a group or individual format in a primary care context. Objective: To compare the Otago Exercise Programme delivered as a group vs. individual format for community dwelling older adults, over a one year period. The hypothesis was that neither format would be inferior to the other. Methods: DESIGN: A four-year multicentre, randomized, non-inferiority clinical trial, with two arms- Otago Exercise Programme group training and individual Otago exercise training. Setting(s): 21 primary healthcare centers. Participants: A sample size of 728 participants was established. Participants were aged between 65 and 80 years; living in the community; able to walk independently; and agreed to take part in the study and provided signed informed consent. Intervention: The Otago Exercise Programme was delivered mainly by nurses in primary care, with five face to face sessions, and a reinforcement 6 months later. Participants were encouraged to exercise at home between face to face sessions. Data collection: at baseline and after 6 and 12 months from October 2017 to 2020. Primary outcome: people who reported at least one fall. Secondary outcomes: number of falls, cause of falls, consequences and assistance, adherence and satisfaction. Group allocation was blinded to the researchers involved in analysis. Reporting: Consolidated Standards of Reporting Trials recommendations for the Statement for Randomized Trials of Nonpharmacologic Treatments. Results: Eight hundred twenty-seven participants were randomized (226 were allocated in group training and 272 in individual training). The analysis of the proportion of people who reported at least one fall and number of falls showed no differences between individual and group training. Assessment of the equivalence between the interventions at 12 months showed that the confidence interval for the difference of people who reported at least one fall was found to be within the equivalence limit of 10% considered. However, in those participants with a previous history of falls, group format showed potentially greater benefit. The participants in individual training presented higher scores on the Exercise Adherence Rating Scale test. No differences were found in satisfaction between the groups. Conclusions: The group Otago Exercise Programme is equivalent to individually delivered Otago Exercise Programme in terms of prevention of falls over a 12-month follow up. Adherence was higher in individual training. Implications: Healthcare professionals could offer either Otago Exercise Programme format dependent on patient preference and be confident that that standardized intervention provides patient benefit. Trial registration: ClinicalTrials.gov (NCT03320668). Data registration 31/10/2017.
Marked increase in cryptosporidiosis cases, Spain, 2023
(European Centre for Disease Prevention and Control (ECDC), 2024-07) Peñuelas, Marina; Carmena, David; Guzmán Herrador, Bernardo R; Palau Miguel, Margarita; Saravia Campelli, Gabriela; García Álvarez, Rosa María; Guerrero-Vadillo, María; Dashti, Alejandro; Köster, Pamela Carolina; Guevara Alemany, Esperanza; Simón Soria, Fernando; Fuentes Corripio, Isabel; Varela Martinez, Maria del Carmen; Sierra Moros, María José; Working group for the National Surveillance Network
Background: By mid-September 2023, several event notifications related to cryptosporidiosis had been identified from different regions in Spain. Therefore, a request for urgent notification of cryptosporidiosis cases to the National Surveillance Network was launched. Aim: We aimed at assessing the extent of the increase in cases, the epidemiological characteristics and the transmission modes and compared to previous years. Methods: We analysed data on case notifications, outbreak reports and genotypes focusing on June-October 2023 and compared the results to 2016-2022. Results: In 2023, 4,061 cryptosporidiosis cases were notified in Spain, which is an increase compared to 2016-2022. The cumulative incidence was 8.3 cases per 100,000 inhabitants in 2023, sixfold higher than the median of 1.4 cases per 100,000 inhabitants 2016-2022. Almost 80% of the cases were notified between June and October. The largest outbreaks were related to contaminated drinking water or swimming pools. was the most common species in the characterised samples (115/122), and the IfA12G1R5 subtype, previously unusual in Spain, was detected from 76 (62.3%) of the 122 characterised samples. Conclusions: A substantial increase in cryptosporidiosis cases was observed in 2023. Strengthening surveillance of is essential for prevention of cases, to better understand trends and subtypes circulating and the impact of adverse meteorological events.
The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018)
(Frontiers Media, 2023) Gracia-Ahufinger, Irene; López-González, Laura; Vasallo, Francisco José; Galar, Alicia; Siller, María; Pitart, Cristina; Bloise, Iván; Torrecillas, Miriam; Gijón-Cordero, Desirée; Viñado, Belén; Castillo-García, Javier; Campo, Rainer; Mulet, Xavier; Madueño-Alonso, Ana; Chamizo-López, Francisco Javier; Arrastia-Erviti, Maitane; Galán-Sánchez, Fátima; Fernández-Quejo, Melisa; Rodríguez-Díaz, Juan Carlos; Gutiérrez-Zufiaurre, María Nieves; Rodríguez-Maresca, Manuel Angel; Ortega-Lafont, María Del Pilar; Yague-Guirao, Genoveva; Chaves-Blanco, Lucía; Colomina-Rodríguez, Javier; Vidal-Acuña, María Reyes; Portillo, María Eugenia; Franco-Álvarez de Luna, Francisco; Centelles-Serrano, María José; Azcona-Gutiérrez, José Manuel; Delgado-Iribarren García Campero, Alberto; Rey-Cao, Sonia; Muñoz, Patricia; Calvo-Montes, Jorge; Zboromyrska, Yuliya; Grandioso, David; Càmara, Jordi; Cantón, Rafael; Larrosa-Escartín, Nieves; Díaz-Regañón, Jazmín; Martínez-Martínez, Luis
Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.
Clinical Heterogeneity and Different Phenotypes in Patients with SETD2 Variants: 18 New Patients and Review of the Literature
(Multidisciplinary Digital Publishing Institute (MDPI), 2023-05-29) Parra, Alejandro; Rabin, Rachel; Pappas, John; Pascual, Patricia; Cazalla, Mario; Arias, Pedro; Gallego-Zazo, Natalia; Santana, Alfredo; Arroyo, Ignacio; Artigas, Mercè; Pachajoa, Harry; Alanay, Yasemin; Akgun-Dogan, Ozlem; Ruaud, Lyse; Couque, Nathalie; Levy, Jonathan; Porras-Hurtado, Gloria Liliana; Santos-Simarro, Fernando; Ballesta-Martinez, Maria Juliana; Guillén-Navarro, Encarna; Muñoz-Hernández, Hugo; Nevado, Julián; Spanish OverGrowth Registry Initiative; Tenorio-Castano, Jair; Lapunzina, Pablo
SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan-Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin-Pappas syndrome (RAPAS). LLS [MIM #616831] is an overgrowth disorder with multisystem involvement including intellectual disability, speech delay, autism spectrum disorder (ASD), macrocephaly, tall stature, and motor delay. RAPAS [MIM #6201551] is a recently reported multisystemic disorder characterized by severely impaired global and intellectual development, hypotonia, feeding difficulties with failure to thrive, microcephaly, and dysmorphic facial features. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and potentially endocrine. Three patients who carried the missense variant p.Arg1740Gln in SETD2 were reported with a moderately impaired intellectual disability, speech difficulties, and behavioral abnormalities. More variable findings included hypotonia and dysmorphic features. Due to the differences with the two previous phenotypes, this association was then named intellectual developmental disorder, autosomal dominant 70 [MIM 620157]. These three disorders seem to be allelic and are caused either by loss-of-function, gain-of-function, or missense variants in the SETD2 gene. Here we describe 18 new patients with variants in SETD2, most of them with the LLS phenotype, and reviewed 33 additional patients with variants in SETD2 that have been previously reported in the scientific literature. This article offers an expansion of the number of reported individuals with LLS and highlights the clinical features and the similarities and differences among the three phenotypes associated with SETD2.
International Consensus Document on Obstructive Sleep Apnea
(Elsevier, 2022-01) Mediano San Andres, Olga; Gonzalez Mangado, Nicolas; Montserrat, Josep M; Luz Alonso-Alvarez, M; Almendros, Isaac; Alonso-Fernandez, Alberto; Barbe, Ferran; Borsini, Eduardo; Caballero-Eraso, Candelaria; Cano-Pumarega, Irene; de Carlos Villafranca, Felix; Carmona-Bernal, Carmen; Carrillo Alduenda, Jose Luis; Chiner, Eusebi; Cordero Guevara, Jose Aurelio; de Manuel, Luis; Duran Cantolla, Joaquin; Farre, Ramon; Franceschini, Carlos; Gaig, Carles; Garcia Ramos, Pedro; Garcia-Rio, Francisco; Garmendia, Onintza; Gomez Garcia, Teresa; Gonzalez Pondal, Silvia; Hoyo Rodrigo, M. Blanca; Lecube, Albert; Antonio Madrid, Juan; Maniegas Lozano, Lourdes; Martinez Carrasco, Jose Luis; Fernando Masa, Juan; Masdeu Margalef, Maria Jose; Mayos Perez, Merce; Mirabet Lis, Enrique; Monasterio, Carmen; Navarro Soriano, Nieves; Olea de la Fuente, Erika; Plaza, Guillermo; Puertas Cuesta, Francisco Javier; Rabec, Claudio; Resano, Pilar; Rigau, David; Roncero, Alejandra; Ruiz, Concepcion; Salord, Neus; Saltijeral, Adriana; Sampol Rubio, Gabriel; Sanchez Quiroga, M. Angeles; Sans Capdevila, Oscar; Teixeira, Carlos; Tinahones, Francisco J; Maria Togeiro, Sonia; Troncoso Acevedo, Maria Fernanda; Vargas Ramirez, Leslie Katherine; Winck, Joao; Zabala Urionaguena, Nerea; Egea Santaolalla, Carlos; Spanish Sleep Network
The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a document a list from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).
Documento de consenso para el manejo de la esquistosomiasis en atención primaria
(Elsevier, 2022-08) Salas-Coronas, Joaquin; Pérez Pérez, Alejandra; Roure, Silvia; Sánchez Peinador, Carmen; Santos Larrégola, Laura; Arranz Izquierdo, Javier; Bocanegra, Cristina; García López Hortelano, Milagros; Garcia Vazquez, Elisa; Moza Moriñigo, Helena; Azkune Galparsoro, Harkaitz
Human schistosomiasis is the parasitic disease with the highest morbidity and mortality worldwide after malaria. It is endemic in more than 78 tropical and subtropical countries, especially in sub-Saharan Africa, and it is estimated that 236 million people are infected. It can cause serious health complications at the genitourinary and hepatosplenic level, leading to the death of 300,000 people each year. The number of imported cases in Western countries has increased in recent years due to the arrival of a significant number of migrants from endemic regions and a growing number of travelers who have visited them. On the other hand, outbreaks of autochthonous transmission have recently been reported in Corsica (France) and Almería (Spain). For all these reasons, the European health authorities have recommended serological screening for the disease in all migrants from endemic areas who have been living in Europe for less than 5 years. Since Primary Care is usually the first point of contact for these people with the Health System, doctors must know the main aspects of the disease, and be provided with the necessary means for its diagnosis and treatment. This document has been prepared by professionals belonging to five scientific societies of Primary Care (SEMFyC, SEMG, SEMERGEN), Pediatrics (SEIP) and Tropical Medicine and International Health (SEMTSI), in order to establish clear recommendations for the diagnosis and management of schistosomiasis in Primary Care.
Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
(Nature Publishing Group, 2023-05-23) Capdevila, J; Hernando, J; Teule, A; Lopez, C; Garcia-Carbonero, R; Benavent, M; Custodio, A; Garcia-Alvarez, A; Cubillo, A; Alonso, V; Carmona-Bayonas, A; Alonso-Gordoa, T; Crespo, G; Jimenez-Fonseca, P; Blanco, M; Viudez, A; La Casta, A; Sevilla, I; Segura, A; Llanos, M; Landolfi, S; Nuciforo, P; Manzano, J L; García-Carbonero, Rocio; Grupo Espanol de Tumores Neuroendocrinos y Endocrinos (GETNE); AstraZeneca
Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.
National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio: a pooled analysis of 458 population-based studies in Asian and Western countries
(Oxford University Press, 2020-02) NCD Risk Factor Collaboration
Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.
Recommendations for follow-up of colorectal cancer survivors (vol 21, pg 1302, 2019)
(Springer, 2019-10) Vera, R; Aparicio, J; Carballo, F; Esteva, Magdalena; Gonzalez-Flores, E; Santianes, J; Santolaya, F; Fernandez-Cebrian, JM

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