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1. Endomyocardial involvement in asymptomatic Latin American migrants with eosinophilia related to helminth infection: A pilot study.

Author

Abiu Sempere, Fernando Salvador, Laia Milà, Guillem Casas, Xavier Durà-Miralles, Elena Sulleiro, Rosa Vila-Olives, Pau Bosch-Nicolau, Maria Luisa Aznar, Juan Espinosa-Pereiro, Begoña Treviño, Adrián Sánchez-Montalvá, Núria Serre-Delcor, Inés Oliveira-Souto, Diana Pou, José Rodríguez-Palomares, and Israel Molina

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BackgroundHypereosinophilic syndrome can produce cardiac involvement and endomyocardial fibrosis, which have a poor prognosis. However, there is limited information regarding cardiac involvement among migrants from Latin America with eosinophilia related to helminthiasis.MethodsWe conducted a pilot observational study where an echocardiography was performed on migrants from Latin America with both eosinophilia (>450 cells/μL) and a diagnosis of helminth infection, and on migrants from Latin America without eosinophilia or helminth infection. Microbiological techniques included a stool microscopic examination using the Ritchie's formalin-ether technique, and a specific serology to detect Strongyloides stercoralis antibodies.Results37 participants were included, 20 with eosinophilia and 17 without eosinophilia. Twenty (54.1%) were men with a mean age of 41.3 (SD 14.3) years. Helminthic infections diagnosed in the group with eosinophilia were: 17 cases of S. stercoralis infection, 1 case of hookworm infection, and 2 cases of S. stercoralis and hookworm coinfection. Among participants with eosinophilia, echocardiographic findings revealed a greater right ventricle thickness (p = 0.001) and left atrial area and volume index (p = 0.003 and p = 0.004, respectively), while showing a lower left atrial strain (p = 0.006) and E-wave deceleration time (p = 0.008). An increase was shown in both posterior and anterior mitral leaflet thickness (p = 0.0014 and p = 0.004, respectively) when compared with participants without eosinophilia.ConclusionsMigrants from Latin America with eosinophilia related to helminthic infections might present incipient echocardiographic alterations suggestive of early diastolic dysfunction, that could be related to eosinophilia-induced changes in the endomyocardium.

Published
2024
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2. Imported schistosomiasis in travelers: Experience from a referral tropical medicine unit in Barcelona, Spain

Author

Fernando Salvador, Cristina Bocanegra, Begoña Treviño, Elena Sulleiro, Adrián Sánchez-Montalvá, Núria Serre-Delcor, Pau Bosch-Nicolau, Ma Luisa Aznar, Lidia Goterris, Diana Pou, María Espiau, Joan Martínez-Campreciós, Juan Espinosa-Pereiro, Inés Oliveira, Francesc Zarzuela, Patricia Martínez-Vallejo, and Israel Molina

Subjects
schistosomiasis, Travelers, Katayama, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Background: Acute schistosomiasis occurs most often in travelers to endemic regions. The aim of the study is to describe the epidemiological, clinical and parasitological characteristics of patients with schistosomiasis acquired during an international travel. Methods: Observational retrospective study including all travel-related schistosomiasis cases seen at the International Health Unit Vall d’Hebron-Drassanes (Barcelona, Spain) from 2009 to 2022. Diagnosis of schistosomiasis was defined by the presence of Schistosoma eggs in stools or urine or the positivity of a serological test. We collected demographic, epidemiological, clinical, parasitological, and therapeutic information. Results: 917 cases of schistosomiasis were diagnosed, from whom 96 (10.5 %) were travel-related. Mean age of the patients was 34.9 years, and 53.1 % were women. Median duration of the travel was 72 days, and geographical areas where travelers had contact with fresh water were Africa (82.3 %), Asia (12.5 %), and South America (5.2 %). Twenty (20.8 %) patients reported having had some clinical symptom, being gastrointestinal symptoms the most frequent. Two patients developed the classical Katayama syndrome. In eleven (11.5 %) cases eggs were observed in urine or feces samples, and 85 (88.5 %) cases were diagnosed by a positive serology. Ninety-one (94.8 %) patients received treatment with praziquantel with different therapeutic schemes. The two patients with Katayama syndrome received concomitant treatment with corticosteroids. Conclusions: Schistosomiasis in travelers represented 10 % of the overall schistosomiasis cases in our center. Increasing the awareness in the pre-travel advice and implementing specific screening in those travelers at risk (long travelers, contact with fresh water) could reduce the incidence and associated morbidity in this group.

Published
2024
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3. Epidemiological and clinical trends of imported strongyloidiasis in a referral international health unit, Barcelona, Spain: A 12-year period experience

Author

Fernando Salvador, Begoña Treviño, Elena Sulleiro, Pau Bosch-Nicolau, Ma Luisa Aznar, Lidia Goterris, Juan Espinosa-Pereiro, Diana Pou, Adrián Sánchez-Montalvá, Inés Oliveira, Joan Martínez-Campreciós, Núria Serre-Delcor, Augusto Sao-Avilés, and Israel Molina

Subjects
Strongyloidiasis, Strongyloides stercoralis, Imported, Screening, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Background: Imported strongyloidiasis in non-endemic countries has increasingly been diagnosed. The aim of the present study is to describe the main epidemiological and clinical characteristics of patients with imported strongyloidiasis attended in a referral International Health Unit and to detect trend changes over a 12-year period. Methods: This is an observational retrospective study including all imported strongyloidiasis cases seen at the International Health Unit Vall d’Hebron-Drassanes (Barcelona, Spain) from January 2009 to December 2020. Epidemiological and clinical characteristics from included patients were collected. Results: Overall, 865 cases of imported strongyloidiasis were diagnosed, of whom 472 (54.6 %) were men and mean age was 38.7 (SD 13.4) years. Most cases were diagnosed in migrants (830, 96 %). The distribution of the geographic origin was: Latin America (561, 67.6 %), Sub-Saharan Africa (148, 17.8 %), Asia (113, 13.6 %), North Africa (5, 0.6 %), Eastern Europe (2, 0.2 %), and North America (1, 0.1 %). The main reasons for consultation at the Unit were screening of health status (371, 42.9 %), laboratory test alteration (367, 42.4 %), gastrointestinal symptoms (56, 6.5 %), cutaneous symptoms (26, 3 %), and other clinical symptoms (45, 5.2 %). An increase in the number of cases was observed in the last years of the study period. Conclusions: Imported strongyloidiasis has increasingly been diagnosed in our referral unit, mostly due to screening strategies implementation. Most of the patients were young migrants coming from Latin America, with no symptoms at the time of diagnosis. The optimization of screening strategies will increase the detection and treatment of cases, reducing potential complications.

Published
2024
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4. Corrigendum to 'Epidemiological and clinical profile of adult patients with diarrhoea after international travel attended in an International Health referral center' [Trav Med Infect Dis 45 (2022) 102216]

Author

Sergio España-Cueto, Fernando Salvador, Inés Oliveira, Lidia Goterris, Begoña Treviño, Adrián Sánchez-Montalvá, Núria Serre-Delcor, Elena Sulleiro, Virginia Rodríguez, María Luisa Aznar, Pau Bosch-Nicolau, Juan Espinosa-Pereiro, Diana Pou, and Israel Molina

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Published
2023
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5. Community engagement in tuberculosis research: the EU-Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) experience

Author

Francesca Saluzzo, Juan Espinosa-Pereiro, Stephan Dressler, Ezio Tàvora Dos Santos Filho, Stephanie Seidel, Jesus Gonzalez Moreno, Norbert Heinrich, Adrian Sanchez-Montalva, and Daniela Maria Cirillo

Subjects
Community engagement, Tuberculosis research, Clinical trials, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Community representatives are key to ensuring that tuberculosis (TB) research is relevant, culturally sensitive, and appropriate. For all trials (new drugs or treatment regimens, diagnostics, or vaccines) this can result in improvement of recruitment, retention, and adherence to the trial schedule. The early engagement of the community will, later in time, support the process of implementation of new policies designed for successful products. We aim at developing a structured protocol for the early engagement of TB community representatives developed in the context of the EU-Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Design: The EU-PEARL Innovative Medicine Initiative 2 (IMI2) project TB work package has developed a community engagement (CE) framework to ensure fair and efficient participation of the community in the design and implementation of TB clinical platform trials. Results: We showed that early engagement of the EU-PEARL community advisory board highly contributes to the process of development of a community-acceptable Master Protocol Trial and Intervention-Specific Appendixes. We identified capacity building and training as major gaps in advancing CE in the TB field. Conclusion: Developing strategies to address these needs can contribute to preventing tokenism and increase the acceptability and appropriateness of TB research.

Published
2023
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6. Exposing and Overcoming Limitations of Clinical Laboratory Tests in COVID-19 by Adding Immunological Parameters; A Retrospective Cohort Analysis and Pilot Study

Author

Adrián Sánchez-Montalvá, Daniel Álvarez-Sierra, Mónica Martínez-Gallo, Janire Perurena-Prieto, Iria Arrese-Muñoz, Juan Carlos Ruiz-Rodríguez, Juan Espinosa-Pereiro, Pau Bosch-Nicolau, Xavier Martínez-Gómez, Andrés Antón, Ferran Martínez-Valle, Mar Riveiro-Barciela, Albert Blanco-Grau, Francisco Rodríguez-Frias, Pol Castellano-Escuder, Elisabet Poyatos-Canton, Jordi Bas-Minguet, Eva Martínez-Cáceres, Alex Sánchez-Pla, Coral Zurera-Egea, Aina Teniente-Serra, Manuel Hernández-González, Ricardo Pujol-Borrell, the “Hospital Vall d’Hebron Group for the study of COVID-19 immune profile”, Artur Llobell Uriel, Romina Dieli, Roger Colobran, Gemma Codina, Tomas Pumarola, Roser Ferrer, Vicente Cortina, Magda Campins, Isabel Ruiz, Nuria Fernaíndez, Esteban Ribera, Joan Roig, Ricardo Ferrer, Adolfo Ruiz-Sanmartín, Albert Selva, Moises Labrador, María José Soler Romeo, Jaume Ferrer, Eva Polverino, Antonio Alvarez, María Queralt Gorgas, Marta Miarons, Pere Soler-Palacin, Andrea Martin, Anna Suy, Maria Jose Buzón, Meritxell Genescà, Santiago Perez-Hoyos, and Miriam Mota-Foix

Subjects
SARS-CoV-2 infection, predictive risk-profile, clinical laboratory tests, cytokines, chemokines, acute phase reactants, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundTwo years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited.ObjectivesTo measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively.Findings1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests.ConclusionsLaboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.

Published
2022
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7. Association Between Trypanosoma cruzi DNA in Peripheral Blood and Chronic Chagasic Cardiomyopathy: A Systematic Review

Author

Pau Bosch-Nicolau, Juan Espinosa-Pereiro, Fernando Salvador, Adrián Sánchez-Montalvá, and Israel Molina

Subjects
Chagas disease, Chagas cardiomyopathy, T. cruzi, polymerase chain reaction, PCR, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Chronic chagasic cardiomyopathy (CCC) is the most important complication of patients with Chagas disease (CD). The role of persistent detection of DNA in peripheral blood and its association to CCC is unknown. We performed a systematic review up to July 2021, including studies that reported ratios of CCC and PCR positivity among non-treated adult patients. We identified 749 records and selected 12 for inclusion corresponding to 1,686 patients. Eight studies were performed in endemic countries and 4 in non-endemic countries. Only two studies showed an association between CCC and Trypanosoma cruzi parasitemia by means of PCR detection. Six studies reported greater positive PCR ratios among patients with CCC than in the patients with indeterminate chagas disease (ICD) with no statistical significance. A significant risk of bias has been detected among most of the studies. Therefore, while we performed a meta-analysis, wide inter-study heterogeneity impeded its interpretation.ConclusionsWith the available information, we could not establish a correlation between PCR-detectable parasitemia and CCC.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216072, identifier: CRD42020216072.

Published
2022
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8. Evaluation of Two Different Strategies for Schistosomiasis Screening in High-Risk Groups in a Non-Endemic Setting

Author

Luisa Roade, Elena Sulleiro, Cristina Bocanegra, Fernando Salvador, Begoña Treviño, Francesc Zarzuela, Lidia Goterris, Nuria Serre-Delcor, Inés Oliveira-Souto, Maria Luisa Aznar, Diana Pou, Adrián Sánchez-Montalvà, Pau Bosch-Nicolau, Juan Espinosa-Pereiro, and Israel Molina

Subjects
schistosomiasis, non-endemic, diagnosis, Medicine
Abstract

A consensus on the recommended screening algorithms for schistosomiasis in asymptomatic high-risk subjects in non-endemic areas is lacking. The objective of this study was to evaluate the real-life performance of direct microscopy and ELISA serology for schistosomiasis screening in a high-risk population in a non-endemic setting. A retrospective cohort study was conducted in two out-patient Tropical Medicine units in Barcelona (Spain) from 2014 to 2017. Asymptomatic adults arriving from the Sub-Saharan region were included. Schistosomiasis screening was conducted according to clinical practice following a different strategy in each setting: (A) feces and urine direct examination plus S. mansoni serology if non-explained eosinophilia was present and (B) S. mansoni serology plus uroparasitological examination as the second step in case of a positive serology. Demographic, clinical and laboratory features were collected. Schistosomiasis cases, clinical management and a 24 month follow-up were recorded for each group. Four-hundred forty individuals were included. The patients were mainly from West African countries. Fifty schistosomiasis cases were detected (11.5% group A vs. 4 % group B, p = 0.733). When both microscopic and serological techniques were performed, discordant results were recorded in 18.4% (16/88). Schistosomiasis cases were younger (p < 0.001) and presented eosinophilia and elevated IgE (p < 0.001) more frequently. Schistosomiasis is a frequent diagnosis among high-risk populations. Serology achieves a similar performance to direct diagnosis for the screening of schistosomiasis in a high-risk population.

Published
2023
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9. Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial

Author

Juan Espinosa-Pereiro, Samiksha Ghimire, Marieke G. G. Sturkenboom, Jan-Willem C. Alffenaar, Margarida Tavares, Sarita Aguirre, Arturo Battaglia, Gladys Molinas, Teresa Tórtola, Onno W. Akkerman, Adrian Sanchez-Montalva, and Cecile Magis-Escurra

Subjects
tuberculosis, rifampicin, clinical trial, vulnerable population, Pharmacy and materia medica, RS1-441
Abstract

Previous clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231.

Published
2022
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10. Risk of Trypanosoma cruzi infection among travellers visiting friends and relatives to continental Latin America.

Author

Adrián Sánchez-Montalvá, Catalina Salinas, Elena Sullerio, Fernando Salvador, Pau Bosch-Nicolau, Clara Crespillo-Andújar, Elena Trigo, Sílvia Roure, Lluís Valerio, Juan Espinosa-Pereiro, and Israel Molina

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BackgroundChagas disease (CD) is regarded as a possible risk for travellers to endemic areas of continental Latin America (LA). The aim of the study is to determine the risk of Trypanosoma cruzi (TC) infection among travellers to CD endemic areas and to identify risk factors for acquiring TC infection.Methods/principal findingWe designed a multicenter cross-sectional study among travellers in Spain (Badalona, Barcelona and Madrid). All available adults with laboratory confirmed proof of absence of TC infection from January 2012 to December 2015 were contacted. Participants referring a trip to LA after the negative TC screening were offered to participate. We performed a standardized questionnaire of travel related factors and measurement of TC antibodies in serum. A total of 971 participants with baseline negative TC serology were selected from the microbiology records. After excluding participants not meeting inclusion criteria, eighty participants were selected. Sixty three (78.8%) were female, and the median age was 38 (IQR 34-47) years. The reason to travel was visiting friends and relatives in 98.8% of the participants. The median duration of travel was 40 (IQR 30-60) days, with 4911 participants-day of exposure. Seventy seven cases (96.25%) participants had two negative TC serology tests after the travel, two cases (2.5%) had discordant serology results (considered false positive results) and one case was infected before travelling to LA. According to our data, the upper limit of the 95% confidence interval of the incidence rate of TC acquisition in travellers is 0.8 per 1000 participant-days.Conclusions/significanceAmong 79 non-CD travellers to TC endemic areas, we found no cases of newly acquired TC infection. The incidence rate of TC acquisition in travellers to endemic countries is less than or equal to 0.8 per 1000 traveller-days.

Published
2021
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11. A retrospective study on the influence of siblings’ relatedness in Bolivian patients with chronic Chagas disease

Author

Juan Espinosa-Pereiro, Adrián Sánchez-Montalvá, Fernando Salvador, Augusto Sao-Avilés, Elena Sulleiro, and Israel Molina

Subjects
Chagas disease, Siblings, Brotherhood, Cardiomyopathy, Gastrointestinal disease, Delayed type hypersensitivity, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Chagas disease is a protozoan infection caused by Trypanosoma cruzi. The disease has a chronic course in which 20–30% of the patients would develop progressive damage to the cardiovascular system and the gastrointestinal tube. We are still unable to predict who will develop end-organ damage but there are some acquired and genetic risk factors already known. Results We reviewed data from 833 patients with serologically confirmed Chagas disease in this retrospective study. Patients were classified as siblings or non-siblings (controls) and the results of pre-treatment blood PCR assay, end-organ damage (cardiac and/or gastrointestinal), and the presence of delayed type hypersensitivity (DTH) skin involvement in patients treated with benznidazole were analyzed. Siblings were grouped by family and we randomly generated groups of 2 or 3 persons with the remaining controls. We classified the results of each variable as concordant or discordant and compared the concordance in these results among the sibling groups with that among control groups. We identified 71 groups of siblings and randomly generated 299 groups of non-related patients. Pre-treatment blood PCR concordance was significantly higher (19%) among siblings compared to controls (P = 0.02), probably due to a higher frequency in pre-treatment positive results. No other statistically significant differences were found. Conclusions A significant difference was found in the concordance of pre-treatment blood PCR for T. cruzi among siblings compared to non-related controls.

Published
2019
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12. MDR Tuberculosis Treatment

Author

Juan Espinosa-Pereiro, Adrian Sánchez-Montalvá, Maria Luisa Aznar, and Maria Espiau

Subjects
tuberculosis, MDR, treatment, Medicine (General), R5-920
Abstract

Multidrug-resistant (MDR) tuberculosis (TB), resistant to isoniazid and rifampicin, continues to be one of the most important threats to controlling the TB epidemic. Over the last few years, there have been promising pharmacological advances in the paradigm of MDR TB treatment: new and repurposed drugs have shown excellent bactericidal and sterilizing activity against Mycobacterium tuberculosis and several all-oral short regimens to treat MDR TB have shown promising results. The purpose of this comprehensive review is to summarize the most important drugs currently used to treat MDR TB, the recommended regimens to treat MDR TB, and we also summarize new insights into the treatment of patients with MDR TB.

Published
2022
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13. Usefulness of FDG PET/CT in the management of tuberculosis.

Author

Adrián Sánchez-Montalvá, Marta Barios, Fernando Salvador, Ana Villar, Teresa Tórtola, Daniel Molina-Morant, Carles Lorenzo-Bosquet, Juan Espinosa-Pereiro, and Israel Molina

Subjects
Medicine, Science
Abstract

BackgroundThe aim of our study is to describe the FDG-PET/CT findings in patients with tuberculosis and to correlate them with the patient's prognosis.MethodsWe retrospectively collected data from patients with tuberculosis, who had an FDG-PET/CT performed prior to treatment initiation from 2010 to 2015.ResultsForty-seven out of 504 patients with active tuberculosis diagnosis (9.33%) underwent an FDG-PET/CT. The reasons for performing the FDG-PET/CT were: characterization of a pulmonary nodule (24; 51.1%), study of fever of unknown origin (12; 25.5%), study of lymph node enlargement (5; 10.6%) and others (6; 12.8%). Median age was 64 (IQR 50-74) years and 31 (66%) patients were male. Twenty-six (55.3%) patients had an immunosuppressant condition. According to the FDG-PET/CT, 48.6% of the patients had more than 1 organ affected and 46.8% had lymph node involvement. Median SUVmax of the main lesion was 5 (IQR 0.28-11.85). We found an association between the FDG accumulation and the size of the main lesion with a correlation coefficient of 0.54 (pConclusionsIn our cohort, almost half of the patients had more than 1 organ affected and 46.8% of them had lymph node involvement. FDG uptake was associated with the size of the main lesion and seems to be related to the treatment outcome. The extent of its potential to be used as an early predictor of treatment success still needs to be defined.

Published
2019
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14. Blastocystis sp. Carriage and Irritable Bowel Syndrome: Is the Association Already Established?

Author

Fernando Salvador, Beatriz Lobo, Lidia Goterris, Carmen Alonso-Cotoner, Javier Santos, Elena Sulleiro, Begoña Bailo, David Carmena, Adrián Sánchez-Montalvá, Pau Bosch-Nicolau, Juan Espinosa-Pereiro, Isabel Fuentes, and Israel Molina

Subjects
Blastocystis sp., irritable bowel syndrome, pathogenesis, Biology (General), QH301-705.5
Abstract

Background: The aim of the present study is to describe the occurrence of Blastocystis sp. detection among asymptomatic subjects and patients with irritable bowel syndrome in order to evaluate the potential association between irritable bowel syndrome and the parasitic infection. Methods: Cross-sectional study where adult patients with irritable bowel syndrome diagnosed according to Rome IV criteria were included. A control group was formed by asymptomatic subjects older than 18 years. Exclusion criteria were: immunosuppressive condition or having received any drug with demonstrated activity against Blastocystis sp. within the last 6 months before study inclusion. Epidemiological and clinical information was collected from all included participants. Two stool samples were obtained from all participants: one sample for microscopic examination and one sample for Blastocystis sp. PCR detection. Blastocystis sp. infection was defined by the positivity of any of the diagnostic techniques. Results: Seventy-two participants were included (36 asymptomatic subjects and 36 patients with irritable bowel syndrome). Thirty-five (48.6%) were men, and median age of participants was 34 (IQR 29–49) years. The overall rate of Blastocystis sp. carriage was 27.8% (20/72). The prevalence assessed through microscopic examination was 22.2% (16/72), while the prevalence measured by PCR was 15.3% (11/72). When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, we did not find any statistically significant difference (36.1% vs. 19.4% respectively, p = 0.114). Conclusions: regarding the occurrence of Blastocystis sp., no differences were found between asymptomatic participants and patients with irritable bowel disease irrespective of the diagnostic technique performed.

Published
2021
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16. Early outcomes in adults hospitalized with severe SARS-CoV-2 infection receiving tocilizumab

Author

Nuria Fernández-Hidalgo, Arnau Monforte-Pallarés, Fernando Salvador, Simeón Eremiev-Eremiev, Marta Miarons, Benito Almirante, Santiago Pérez-Hoyos, Júlia Sellarès-Nadal, Adrián Sánchez-Montalvá, Xavier Durà, Salvador Augustin, Júlia Sampol, Juan Espinosa-Pereiro, Alfredo Guillén-Del-Castillo, Abiu Sempere-González, Andrés Antón, and Pau Bosch-Nicolau

Subjects
Adult, Male, ARDS, medicine.medical_specialty, COVID19, Viral pneumonia, Lung injury, Antibodies, Monoclonal, Humanized, law.invention, Cohort Studies, chemistry.chemical_compound, Tocilizumab, law, Internal medicine, Inmunomodulación, Clinical endpoint, Humans, Medicine, Respiratory Distress Syndrome, SARS-CoV-2, business.industry, Hazard ratio, COVID-19, General Medicine, Middle Aged, medicine.disease, Intensive care unit, IL6, COVID-19 Drug Treatment, Neumonía viral, Treatment Outcome, chemistry, Respiratory failure, Original Article, Female, Immonomodulation, Respiratory Insufficiency, business, Cohort study
Abstract

Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19). The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.We report the preliminary results from the Vall d'Hebron cohort study at Vall d'Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed SARS-CoV-2 infection and who were treated with tocilizumab until March 25th.82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3-8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8-5.8) if tocilizumab was administered after the onset of ARDS.Early administration of tocilizumab in patients needing oxygen supplementation may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data regarding the precise timing in of initiation of the treatment with tocilizumab.Los tratamientos inmunomoduladores para la prevención del daño pulmonar están siendo ampliamente estudiados contra la COVID-19. El objetivo primario es evaluar la mortalidad a los 7 días después de la administración de tocilizumab. El objetivo secundario es el ingreso en UCI, el desarrollo de distrés respiratorio agudo e insuficiencia respiratoria aguda entre otros.Informamos sobre los resultados preliminares de la cohorte del Hospital Universitario Vall d’Hebron en Barcelona (España), que incluye todos los pacientes consecutivos con infección confirmada por SARS-CoV-2 y que recibieron tratamiento con tocilizumab hasta el 25 de marzo 2020.Ochenta y dos pacientes con COVID-19 recibieron al menos una dosis de tocilizumab. La edad media (±DE) fue de 59,1 (±19,8) años, el 63% eran hombres, 22% correspondía a paciente nacidos fuera de España, y la mediana (RIC) del índice de Charlson ajustado por edad en el momento basal fue de 3 (1-4) puntos. Sesenta y dos pacientes (75,6%) y 45 pacientes (54,9%) desarrollaron insuficiencia respiratoria y distrés respiratorio agudo respectivamente. La mediana de tiempo desde el inicio de los síntomas hasta el desarrollo de ditrés fue de 8 días (5-11). La mortalidad a los 7 días fue del 26,8% La hazard ratio de mortalidad fue del 3,3; IC 95% 1,3-8,5 (la hazard ratio de mortalidad ajustada por edad fue de 2,1; IC 95% 0,8-5,8) si el tocilizumab se administraba después del inicio del distrés respiratorio.La administración precoz de tocilizumab en pacientes con suplementos de oxígeno podría ser crítica para la recuperación de los pacientes. Nuestros datos podrían ayudar a tomar decisiones clínicas hasta que se disponga de más información sobre el momento adecuado para iniciar el tratamiento con tocilizumab.

Published
2022

17. Post-infectious irritable bowel syndrome following a diagnosis of traveller’s diarrhoea: a comprehensive characterization of clinical and laboratory parameters

Author

Sergio España-Cueto, Inés Oliveira-Souto, Fernando Salvador, Lidia Goterris, Begoña Treviño, Adrián Sánchez-Montalvá, Núria Serre-Delcor, Elena Sulleiro, Virginia Rodríguez, Maria Luisa Aznar, Pau Bosch-Nicolau, Juan Espinosa-Pereiro, Diana Pou, and Israel Molina

Subjects
General Medicine
Abstract

Background Prolonged or recurrent gastrointestinal symptoms may persist after acute traveller’s diarrhoea (TD), even after adequate treatment of the primary cause. This study aims to describe the epidemiological, clinical and microbiological characteristics of patients with post-infectious irritable bowel syndrome (PI-IBS) after returning from tropical or subtropical areas. Methods We conducted a retrospective study of patients presenting between 2009 and 2018 at the International Health referral centre in Barcelona with persistent gastrointestinal symptoms following a diagnosis of TD. PI-IBS was defined as the presence of persistent or recurrent gastrointestinal manifestations for at least 6 months after the diagnosis of TD, a negative stool culture for bacterial pathogens and a negative ova and parasite exam after targeted treatment. Epidemiological, clinical and microbiological variables were collected. Results We identified 669 travellers with a diagnosis of TD. Sixty-eight (10.2%) of these travellers, mean age 33 years and 36 (52.9%) women, developed PI-IBS. The most frequently visited geographical areas were Latin America (29.4%) and the Middle East (17.6%), with a median trip duration of 30 days (IQR 14–96). A microbiological diagnosis of TD was made in 32 of these 68 (47%) patients, 24 (75%) of whom had a parasitic infection, Giardia duodenalis being the most commonly detected parasite (n = 20, 83.3%). The symptoms persisted for a mean of 15 months after diagnosis and treatment of TD. The multivariate analysis revealed that parasitic infections were independent risk factors for PI-IBS (OR 3.0, 95%CI 1.2–7.8). Pre-travel counselling reduced the risk of PI-IBS (OR 0.4, 95%CI 0.2–0.9). Conclusions In our cohort, almost 10% of patients with travellers’ diarrhoea developed persistent symptoms compatible with PI-IBS. Parasitic infections, mainly giardiasis, seem to be associated with PI-IBS.

Published
2023

18. Case Report: Leishmaniasis in a 33-Year-Old Man with Multiple Sclerosis

Author

Alvaro Guerra-Amor, Ane Lopez-Gonzalez, Pau Bosch-Nicolau, Breogan Rodriguez-Acevedo, Ana Zabalza, Elena Sulleiro, Juan Espinosa-Pereiro, Maria Luisa Aznar, Fernando Salvador, Adrián Sánchez-Montalvá, and Israel Molina

Subjects
Infectious Diseases, Virology, Parasitology
Abstract

Leishmaniasis is a protozoan disease caused by species of genus Leishmania. Immunosuppression increases the risk of severe clinical forms and impairs response to treatment. The expansion of the use of immunomodulatory drugs for different conditions has raised the number of these cases. In this report, we present a case of visceral leishmaniasis in a patient with multiple sclerosis (MS) under fingolimod treatment. He presented with the triad of fever, visceromegaly, and pancytopenia and was diagnosed by the presence of amastigotes in a bone marrow sample. Furthermore, we discuss the previous published cases of MS patients under different immunosuppressant therapies to highlight its risk in endemic areas and suggest a therapeutic approach.

Published
2022

19. Imported cystic echinococcosis in Spain: a systematic review

Author

Laura Escolà-Vergé, Pau Bosch-Nicolau, Adrián Sánchez-Montalvá, Fernando Salvador, Andrea Zabala, Juan Espinosa-Pereiro, and Israel Molina

Subjects
Adult, 030231 tropical medicine, Hydatid cyst, 03 medical and health sciences, 0302 clinical medicine, Echinococcosis, Zoonoses, Environmental health, medicine, Animals, Humans, 030212 general & internal medicine, Echinococcus granulosus, biology, Cystic echinococcosis, Zoonosis, Public Health, Environmental and Occupational Health, Neglected Diseases, Tropical disease, General Medicine, medicine.disease, biology.organism_classification, Country of origin, Infectious Diseases, Geography, Spain, Global distribution, Parasitology, Reporting system
Abstract

BackgroundCystic echinococcosis (CE) is a zoonosis caused by Echinococcus granulosus (sensu lato). It is a neglected tropical disease with a global distribution, affecting an estimated 2–3 million people globally. Official reporting systems in Spain lack information concerning imported cases and their country of origin.MethodsThis is a systematic review of the literature that was performed to obtain published cases of immigrant patients diagnosed with CE in Spain.ResultsFrom the 21 included articles, a total of 84 cases of CE imported into Spain were documented from 1995 to 2018, with an average age of 33.2 years. The main countries of origin of the patients were Morocco with 30 cases (35.7%), Romania with 12 cases (14.3%) and Peru with 8 cases (9.5%). The most involved organ was the liver (28 cases [33.3%]). We found discrepancies between the published cases of imported CE in Spain and those reported by official authorities.ConclusionsThis review of the literature shows the lack of information and clarity in the mechanisms of CE notification in Spain. The disparity between these systems and the cases documented in the literature highlights a failure or shortcoming of the current reporting system.

Published
2021

20. Exposing Limitations of Clinical Laboratory Tests in COVID-19 and the Promise of Immunological Biomarkers

Author

Juan Espinosa-Pereiro, JORDI BAS, Andrés Antón Pagarolas, Juan Carlos Ruiz-Rodriguez, Marta Miarons, Alex Sánchez-Pla, Mónica Martínez Gallo, Iria Arrese-Muñoz, Eva Martínez-Cáceres, Pau Bosch-Nicolau, Janire Perurena-Prieto, and Daniel Álvarez de la Sierra

Abstract

BackgroundAlmost two years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted, nor new tests identified to improve the prediction and management of SARS-CoV-2 infection.MethodsRetrospective observational analysis of the predictive performance of clinical parameters and laboratory tests in hospitalised patients with COVID-19. Outcomes were 28-day survival and maximal severity in a cohort of 1,579 patients and two validation cohorts of 598 and 434 patients. A pilot study conducted in a patient subgroup measured 17 cytokines and 27 lymphocyte phenotypes to explore additional predictive laboratory tests.Findings1) Despite a strong association of 22 clinical and laboratory variables with the outcomes, their joint prediction power was limited due to redundancy. 2) Eight variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the statistical predictive power. 3) The interpretation of clinical and laboratory variables was improved by grouping them in categories. 4) Age and organ damage-related tests were the best predictors of survival, and inflammatory-related tests were the best predictors of severity. 5) The pilot study identified several immunological tests (including chemokine ligand 10, chemokine ligand 2, and interleukin 1 receptor antagonist), that performed better than currently used tests.ConclusionsCurrently used tests for clinical management of COVID-19 patients are of limited predictive value due to redundancy, as all measure aspects of two major processes: inflammation, and organ damage. There are no independent predictors based on the quality of the nascent adaptive immune response. Understanding the limitations of current tests would improve their interpretation and simplify clinical management protocols. A systematic search for better biomarkers is urgent and feasible.This study was funded by Instituto de Salud Carlos III, Madrid, Spain, grants COV20/00416, Cov20/00654 and COV20/00388 to R.P–B, ATS and JBM respectively and co–financed by the European Regional Development Fund (ERDF). DÁ–S is recipient of a doctoral fellowship from the Vall d’Hebron Research Institute, Barcelona, Spain. ASM was supported by a postdoctoral grant “Juan Rodés” (JR18/00022) from Instituto de Salud Carlos III through the Ministry of Economy and Competitiveness, Spain

Published
2022

21. Usefulness of the FDG PET/CT in the management of cystic echinococcosis: A pilot study

Author

Fernando Salvador, Laura Escolà-Vergé, Marta Barios, Moncef Belhassen-Garcia, Pilar Tamayo-Alonso, Adrián Sánchez-Montalvá, Ángela Romero-Alegría, Marc Simó, Paloma Garcia-Talavera, Pau Bosch-Nicolau, Juan Espinosa-Pereiro, and Israel Molina

Subjects
Adult, Aged, 80 and over, Male, Echinococcosis, Hepatic, Adolescent, Veterinary (miscellaneous), Pilot Projects, Middle Aged, Young Adult, Infectious Diseases, Echinococcosis, Fluorodeoxyglucose F18, Insect Science, Positron Emission Tomography Computed Tomography, Zoonoses, Animals, Humans, Parasitology, Aged
Abstract

Cystic echinococcosis is a zoonotic disease caused by the cestode Echinococcus granulosus. The activity of the cysts is assessed through the WHO-IWGE standardized classification based on ultrasound features. However, viability of the cysts is not always concordant with the activity assessed by ultrasound. The aim of the present study is to describe the metabolic activity of cysts in patients with cystic echinococcosis through FDG-PET.Prospective observational study where adult patients diagnosed of cystic echinococcosis were offered to undergo FDG PET/CT before treatment onset. Demographic, clinical, radiological, and histopathological information was collected from all patients.Sixteen patients were included, 50% were male, and age ranged from 18 to 85 years. Most of the patients had liver involvement, and all patients had CE3, CE4 or CE5 stage of the WHO-IWGE classification. Only one patient (CE5) had an increasedIn our pilot study, we did not find the correlation between the FDG PET/CT imaging and the cystic echinococcosis cyst bioactivity.

Published
2021

22. Impact of the COVID-19 pandemic on tuberculosis management in Spain

Author

M. A. Jimenez-Fuentes, R. Zules, J.V. San Martin, Iris García, I. Sanjoaquin, J. F. Garcia Rodriguez, N. Jove, V. Pomar, Teresa Tórtola, J. Cacho, María Luisa Aznar, Nuria Saborit, F. Sanchez Martinez, Juan Espinosa-Pereiro, Adrián Sánchez-Montalvá, Lisbeth Goncalves De Freitas, M.L. De Souza-Galvao, J. Llenas-Garcia, A. Vitoria, S. Perez-Recio, Eugenia Gallardo, Israel Molina, Institut Català de la Salut, [Aznar ML, Sánchez-Montalvá A] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Mycobacteria Infection Study Group (GEIM, Spanish acronym) from Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, Spanish acronym), Spain. [Espinosa-Pereiro J, Saborit N, Molina I] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Jové N, Sánchez Martinez F] Unitat Clínica de Tuberculosis, Hospital del Mar, Barcelona, Spain. [Pérez-Recio S] Tuberculosis Unit, Service of Infectious Diseases, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L’Hospitalet de Llobregat, Spain. [Jiménez-Fuentes MÁ, De Souza-Galvao ML] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Tórtola T] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Zules R] Servei de Medicina Preventiva i Epidemiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, Pediatrics, medicine.medical_treatment, España, Infectious and parasitic diseases, RC109-216, 0302 clinical medicine, Pandemic, Other subheadings::/diagnosis [Other subheadings], virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 030212 general & internal medicine, Child, Transmission (medicine), Household contact screening, Tuberculosi - Diagnòstic - Espanya, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], General Medicine, Geographic Locations::Europe::Spain [GEOGRAPHICALS], Infectious Diseases, Impact, Pandèmia de COVID-19, 2020- - Espanya, Tuberculosis management, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Coronavirus disease 2019 (COVID-19), Tuberculosi, Infecciones por coronavirus, 030106 microbiology, Otros calificadores::/diagnóstico [Otros calificadores], Article, 03 medical and health sciences, Tuberculosis diagnosis, Epidemia, medicine, Humans, Transmission, Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Actinomycetales Infections::Mycobacterium Infections::Tuberculosis [DISEASES], Pandemics, Retrospective Studies, localizaciones geográficas::Europa (continente)::España [DENOMINACIONES GEOGRÁFICAS], business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, medicine.disease, infecciones bacterianas y micosis::infecciones bacterianas::infecciones por bacterias grampositivas::infecciones por Actinomycetales::micobacteriosis::tuberculosis [ENFERMEDADES], Spain, Contact Tracing, business, Contact tracing
Abstract

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacte; Tuberculosi Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacto; Tuberculosis Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impact; Tuberculosis Background The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. Methods Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. Results A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 ( P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 ( P = 0.001). Conclusions The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. MLA was supported by a postdoctoral grant “Rio Hortega” and ASM was supported by a postdoctoral grant “Juan Rodés” (JE18/00022) from the Instituto de Salud Carlos III through the Spanish Ministry of economy and competitiveness.

Published
2021

23. Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study

Author

Jaime Fernández-Bujarrabal Villoslada, Beatriz Dietl Gómez-Luengo, Daniel Ortiz-Sánchez, José Ramón Blanco Ramos, Bartolomé Gómez-Arroyo, Martín Sebastián Ruiz Grinspan, Ester Sáez de Adana Arróniz, Daniel Daniel López, Judit Villar-García, Begoña De Dios García, Josefina García García, Nuria Rabella García, Ana Rodríguez-Revillas, Lydia Martín González, Mercedes San Franco, Elena Martinez Robles, Teresa González Alegre, Elena Morcillo Rodríguez, Oriol Gasch Blasi, Laura Prieto Pérez, Isabel Jiménez Martínez, Elena Isaba Ares, Ricardo Deza-Palacios, Helena Mendez del Sol, Melchor Riera Jaume, Mercedes Rodriguez-Gutiérrez, Daniel Podzamczer, Mikel Urroz, Luis Ramos Ruperto, María Paniagua, Sergio Alcolea-Batres, Mar Masiá Canuto, Rubén Soriano-Arroyo, Paloma Merino Amador, Berta Antón-Huguet, Gabriela Alcaraz, Pablo Ryan, Carlos Franco, Leyre Díez-Porres, Juan Carlos Figueiras, Sara Lidia Kamal, Mónica Hernández, Lorena Barrera-López, Germán Ramírez-Olivencia, Kapil Laxman Nanwani Nanwani, Alberto Oreja, Montserrat Laguno, José Javier Castrodeza Sanz, Belén Loeches Yagüe, Maria Vargas, Luis Eduardo López-Cortés, Isabel Gutiérrez, Sara Vela Berna, P. Martín, Miguel Pedromingo Kus, Jesús Sanz Sanz, Mº Antonia Sepúlveda Berrocal, Carmen Yera Bergua, Juan Cuadros González, Julen Cadiñanos Loidi, Josefa Serralta Buades, María Concepción Prados Sánchez, Francesca Gioia, Iris Pedrola Gorrea, Francisco Arnaiz de las Revillas, Xabier Kortajarena Urkola, Laia Lorenzo-Esteller, Ruth Bravo-Lizcano, Angel Iniesta, Sofía González-García, Belén Martínez López, Agustín Rojas-Vieyra, Concepción García García, Raquel Cavallé-Pulla, Lucía Gómez García, Alicia Herrero, Carlos Jesús Dueñas Gutiérrez, Loreto Vidaur Tello, Carmen Fernández-Capitán, Victoria Lo-Iacono García, Cecilia Gómez-Domínguez, Adalgisa Falcone, María José Ruiz Rodríguez, Arancha Castellano, Miquel Hortos Alsina, María Concepción Nuñez, María Luisa Fernández Vidal, Jésica Abadia Otero, Natalia Moya-González, Albert Sabater Gil, Pedro de la Oliva, Ylenia María Conde-Alonso, Laura Castelo Corral, José Mº García de Lomas Guerrero, Verónica Pérez-Blanco, Isabel San Juan, Martina Archinà, Júlia Sellarés, Juan Carlos Ramos, Cintia María Martínez Mateu, Belén Fernández-Puntero, Andrea Torrecillas-Mainez, Luis Falgueras López, Carlos Carpio-Segura, María Gandullo-Moro, Francisco Abellán Martínez, Cristina Díez, Pilar Martín Dávila, Silvia Gómez-Zorrilla, María Pilar García García, Renzo Tejada-Sorados, María Dolores del Toro, E. Álvarez-Rojas, Gema Muñiz, Lucía Cajuela, María Novella Mena, Estel Pons Viñas, Andrea Pérez Rodríguez, Benito Almirante, Mónica Gozalo, Patricia Girón De Velasco-Sada, Camilo Sanz Zamudio, Ángeles García Flores, Joaquín López-Contreras González, Blanca Fabre-Estremera, Pelayo Fernández Cidón, María Martínez-Redondo, Paula Alejandra Hernández-Liebo, Juan Herrero, Marta Duque-Alcorta, María Teresa García Morales, Concepción Amador Prous, Alex Soriano, Raquel Hernando Nieto, Raquel Álvarez Franco, Alfonso Cabello Úbeda, Luis Force Sanmartín, Laura Mao Martín, Daniel Prieto-Arribas, Mario Pérez-Butragueño, Pere Domingo Pedrol, Henar Serrano-Martín, Mónica Zubimendi, M. Rodríguez-Rubio, David Pujol-Pocull, Manuel García-Gutiérrez, Carlos Manrique de Lara, Lucy Abella Vázquez, Marta Navarro Vilasaró, Carlota Cascajares-Sanz, Berta Torres, Daniel Ceniza-Pena, Isidro Moreno Gómez-Limón, María Rodríguez Mahía, Alí Martakoush, Antonio Buño-Soto, Patricia Serrano de la Fuente, Claudia González Rico, Teresa Pedraz, Conchita Pérez-Jorge Peremarch, Elena Trigo Esteban, Rosana Rouco Esteves Marques, Juan Mora Delgado, Inés Pérez Zapata, Sandra Pérez-Recio, María Ángeles Domínguez, Manuel Cervantes García, Francisco Reinoso-Lozano, M. Martí De Gracia, Carmina Oltra, Beatriz Pérez-Monte Mínguez, Guillermina Bejarano-Redondo, Sara Heili Frades, María Paz García Butenegro, Miguel Torralba González de Suso, Elena Álvaro-Alonso, Víctor J Moreno Cuerda, Gonzalo Garzón, Marcelo Daltro-Lage, Alberto Serrano Martínez, José María Aguado, Mar Mosquera, Ruth Figueroa Cerón, Juan Carlos Martin Gutiérrez, Javier Oliver Ortega, Esteban Martínez, Cristina Gómez-Ayerbe, Nerea Carrasco Antón, María Carmen Fariñas Álvarez, José Antonio Ruiz, Justo Menéndez, Lucía Díaz, José L. Casado, Pilar Vizcarra, Javier Veganzones, Miguel Ángel Moran Rodríguez, Mercedes López-Martinez, Emilio Letang, Paloma Romero Gallego-Acho, Julia Vasquez-Manau, Alexander Rombauts, Marta Robledo del Prado, Luis Puente, Beatriz Alvarez, Juan Emilio Losa García, José Tomas Algado Rabasa, Rafael Torres Perea, Angélica Rivera-Núñez, Esther Expósito Palomo, Antonio J. Carcas, Lucía Platero-Dueñas, Irene Martín Rubio, Miguel Salavert Lletí, Claudia García-Vaz, Antonio Martínez-Verdasco, Jorge Díaz-Garzón, Javier Nieto Arana, Fernando Cadenas-Gota, Richard Rojas, Abelardo García de Lorenzo, Juan Carlos López, Pedro Luis Martinez Hernández, Manuela de Pablos-Gómez, Pablo Alonso, Enrique Seco, María García-López, Lorena López-Corcuer, Celia Blasco-Andres, Delia Romera-Cano, José M. Azcona Gutiérrez, Almudena Gutiérrez-Arroyo, Paula Mendoza Roy, Ignacio De los Santos Gil, Miguel Angel Sánchez-Castellano, Sara Medrano Pardo, Mikel del Álamo Martínez de Lagos, Rocío Martínez Avilés, Elisabet Martínez-Cerón, José Manuel Vázquez Comendador, Marta Virgós-Varela, Alejandra Álvarez Brandt, Carmen Herrero Rodríguez, Jorge Martínez Jordán, Antonio Rezusta López, Marta Vizcaíno Callejón, Manuela Simon-Velasco, Jorge Ignacio Alonso-Eiras, Elisa García Vázquez, Mercè Gurguí Ferrer, Mónica González Bardanca, Nataly Cancelliere-Fernández, José Luis Díaz de Tuesta del Arco, María Larrosa, Alejandro García García, Carmen Román-Hernández, Elena Calvin-García, José Sanz Moreno, Miguel Silvestre-Niño, Nieves Valcarce Pardeiro, Maria Teresa Corcuera-Pindado, Enrique Monteoliva, Aina Gabarrell Pascuet, Elena María Aranda Rife, Aina Gomila Grange, Alba Alastrué Violeta, Daniel Roger Zapata, Jaime Montserrat, Eduardo Malmierca Corral, Marco Palma, Blanca Martínez Cifre, Gema Domínguez de Pablos, Emilio Cuesta, Eva Perales, Silvia Hernáez Crespo, Juan Torres-Macho, Adrián Sánchez Montalvá, Rocío Montejano Sánchez, Eva Van den Eynde Otero, Silvia Castañeda Espinosa, Virginia Pérez Doñate, Adriana Hernández Belmonte, Laura Iglesias Llorente, María Sanz de Pedro, Juan Espinosa Pereiro, Lubna Dani Ben-Abdellah, Raquel Barrós González, Iván Piñero, Araceli López-Tofiño, Ana Such-Diaz, Karim Mohamed Ramírez, Pilar Toledano Sierra, Rebeca Izquierdo, Guillermo Cuevas, Andrés Felipe Cardona Arias, Ileana Gabriela-Tomoiu, David Vinuesa García, Ander González Sarria, Stephan Stuart, José María Fernández, Javier Torres-Cortés, Elisabet Delgado Sánchez, María Varela-Cerdeira, Gemma Bassani, Berta Román Bernal, Isabel García, Paula Betancort de la Torre, Yolanda Martínez-Abad, Beatriz Arizcun, Juan José Cabanillas-Martín, Guillermo Estrada Fernández, Oscar del Río Pérez, Inmaculada Martín Pérez, Andony García, Luis Gómez-Carrera, Alexander Agrifoglio, Alberto M. Borobia, Jordi Niubó, Vanessa Alende Castro, Lara Montes Andújar, Alexandra De la Vega, Efrén Sánchez Vidal, Isabel A. Pérez Hernández, Laura Frade-Pardo, Ana Josefa Tebar-Martinez, Silvia Álvarez Kaelis, Sara De la Fuente Moral, Luz Martin Carbonero, Juan Cantón De Seoane, María Dolores Montero-Vega, Juan Carlos Gainzarain Arana, Sergio España Cueto, Rocío Nuñez-Cabetas, María Sánchez-Martín, Constanza Muñoz Hornero, Ana Gómez-Zamora, Javier Díaz Luperena, Patricia González-Donapetry, José Miguel Cisneros, Lucía Hernández-Rivas, Patricia González Ruano, Andrea Espigares Correa, Rocío González-León, Nicolás García-Arenzana, Omar Cervera, Andrés Canut Blasco, Ana Isabel Cañabate, Mercedes Villarreal García-Lomas, Melania Íñigo Pestaña, Maria Álvarez de Castro, Ana Correa Ruiz, Belén Civantos, Lydia Pascual-García, Paula Villares Fernández, Mikel Rico-Briñas, María José Alcaide-Martín, Adoración Valiente, Victoria Arnalich-Montiel, Pilar Retamar, Jesús Mingorance, Eva María Romay Lema, Pablo Galindo-Ballesteros, M. Teresa Pérez-Rodríguez, Rosario Maria Torres Santos-Olmo, Inmaculada Pinilla, Elie Dahdouh, Beatriz Tejero-Soriano, Cristina Pizarro-Sanchez, Félix Gutiérrez Rodero, Luis Jara-Palomares, María Hernández-Gancedo, Cristina Chico Chumillas, Sergio Gilaberte Reyzábal, Manuel González-Viñolis, Ana Martínez Sapiña, Francisco Parras, Teresa Rubio Obanos, Iker Falces-Romero, Adriana Sánchez Serrano, Teresa Álvarez de Espejo Montiel, Jorge Valencia, Miquel Pujol, José Luis Velasco Garrido, Belén Calderón-Llopis, Álvaro Varela Plaza, Abel Caro, Juan José González-Garcia, Miguel Sampedro Núñez, María Fernández-Velilla, Emilio Cendejas-Bueno, María Cecilia Cánepa, José Luis Santiago Blanco, Alicia Rico-Nieto, Mónica Liébana Gómez, Sarah Caro Bragado, Susana Sánchez-Rico, José María Marimón Ortiz de Zárate, Paloma Dorao, Cristina Plaza-Moreno, Isabel Valbuena, Natividad Benito Hernández, Ginger Giorgiana Cabrera Tejada, Jordi Carratalà, Sara Fernández Rodríguez, Vicente Ferrer Díaz De Brito Fernández, Pilar Catalán, Pablo Mariscal-Aguilar, Germán Daroca-Bengoa, Rafael Fernandez, Raquel Casitas-Mateo, Ester Zamarrón de Lucas, Úrsula Quesada, Julio Yagüe, María Isabel Quijano Contreras, Trinidad Baselga-Puente, Lourdes Herrera Pacheco, Carlota Gudiol, Alazne Lartategi Iraurgi, Estefanía Martinez-Chavez, Silvia Valero Rovira, Alba Bergas, Zaida Ruiz de Azua, Teresa Prim, Cristina García-Quero, Pilar Hernández Machín, Rubén Gomez-Rioja, María Pavón-Masa, María de las Mercedes Valentín-Pastrana Aguilar, Ilduara Pintos Pascual, Lucía Brieba-Plata, María Jesús Domínguez Santalla, Francisco Javier Membrillo de Novales, Raúl Galera-Martínez, Ana Lérida Urteaga, Miguel Cervero, Alberto Mangas-Moro, José Hernández Quero, Teresa Sancho Bueso, María Angustias Quesada Simón, Luz Parra-Gordo, Sofía Díaz-Carrasco, Juan Carlos Abad Almendro, Andrés Javier Ruiz Fernández, Estíbaliz Molina Iturritza, Aurea Díez-Tascón, Yale Tung-Chen, Marta Rava, Carlos Villasante, Gabriel Gaspar Alonso-Vega, Clara Cabré-Verdiell Surribas, Esther Fraile Villarejo, Aida Gutiérrez García, Ana Robustillo-Rodela, Rafael Padrós Selma, Jesús Rodríguez-Baño, Frank Perdomo-García, Lydia de la Fuente Regaño, María del Mar Arenas-Miras, Cristina Rodríguez Roca, Blanca Montero-San Martín, Gema Crespo-Sánchez, Miguel Ramírez-Verdyguer, Alberto Diaz de Santiago, Marta Díaz Menéndez, María de la Luz Padilla Salazar, Silvia Arribas-Terradillos, Sadaf Zafar Iqubal-Mirza, Isabel Rábago Lorite, Belén Estébanez, Maite Ganchegui Aguirre, André Barbosa Ventura, Estefanía Fernandez-Cerezo, Maria Eulalia Valencia, Zaira R. Palacios-Baena, Beatriz Diaz Pollan, Lidia Martín, Sara Fabra-Cadenas, José Miguel Cantero-Escribano, Carmen Busca Arenzana, Emilia Guasch-Arévalo, Virginia Fernández Espinilla, Ainhoa Urrutia Losada, Oscar Noya González, Raquel Aranega, Alejandro Rodríguez Saenz de Urturi, María Jesús Jaras Hernandez, Charbel Maroun Eid, Marta Mora Rillo, Antonio Ramos Martínez, Meritxell Ortega Montoliu, Jose María Mostaza, Sonia García Calvo, Cristina Verdú, Celia Salamanca, Cristina Cervera Acedo, Mónica Martínez, Miren Urrestarazu Larrañag, Carmen Barroso Castro, Ivo Vives-Beltrán, Lorea Arteche Eguizabal, Ana Montero, Javier Balsa Vázquez, Amparo Perez-Garcia Morillón, Alejandra Pérez García, Isabel Pérez-Tamayo, Rafael Cantón Moreno, Antonio Marín-García, Inmaculada Jarrín, Núria Trullen, Ines Fernandez-Jimenez, Guillermo Ruiz-Carrascosa, Almudena Villa Martí, Jamil Cedeño, Marcos Díez Martínez, Carlos Lahoz, Lorena De la Mora, Javier Sánchez-Lora, Ana María Martínez-Virto, Irene Sanjosé Muñiz, Adrian Peña-Hidalgo, Cristina López Mestanza, Carola Gutiérrez, Ana Laila Qasem-Moreno, Irene Salvo García, Lucía Fernández de Orueta, Jorge Parra Ruiz, Sergio Pérez Pinto, Carlos García-Mochales Fortún, Esteban García de las Heras, Patricia González Muñiz, Mario Fernández-Ruiz, Anna Ferrer Santolaria, Olga Sánchez Pernaute, Julieta Latorre, Jesús Manzanares, Miguel Angel Martinez Gallego, Helena Notario, Ángel Rodríguez-Villodres, Eva Fernández-Bretón, Encarnación Moral Escudero, Mónica Sánchez-Santiuste, Carmen Martínez Cilleros, Ricardo Fernández Roblas, María Yllescas, Eva Soria-Alcaide, Marta Arsuaga Vicente, Marta Gómez-López, Regina Cabrera-Gamero, Natalia Carrasco Fons, Diana Piñar Cabezos, Begoña Sánchez-Sánchez, Francisca Garcia-Iglesias, Raquel Marín-Baselga, Alberto Arranz Caso, Virginia Guedez-López, Lucia Boix Palop, Íñigo Gredilla Zubiría, María Hidalgo-Sánchez, Laura López-Tappero Irazábal, José Ignacio Bernardino de la Serna, Javier Queiruga, Natalia Guadalupe Barrera-López, María López-Jodar, Jorge Calderón Parra, Diego Rodríguez-Álvarez, José Molina, María Luisa Montes, Beatriz Rodríguez-Alonso, Daniel Useros Brañas, Maria Gracia Liras-Hernández, Lucía Romero-Imaz, Nieves Jaén Sánchez, Marta Segovia-Amaro, Marta Vara, Maribel Zamora Cintas, Montaña Jiménez Álvaro, Alberto Moreno Fernandez, Asunción Díaz, Jordi Mancebo Cortés, Francisco Javier De Castro Vega, Álvaro Navarro Batet, Francisco Javier Sagra, Alexandre Pérez González, Luis Castro, Isabel Barrio López, Marta Ruiz-Alguero, Silvia Ossaba-Vélez, Alberto Martín-Vega, Maria Jesus Bustinduy Odriozola, Sivia Pastor-Yvorra, Nuria Espinosa, Elena Múñez Rubio, María E García-Leoni, Sandra Rosillo, Cristina Carbonell, Iván Navas Clemente, Paula Arriola Martínez, Marta Peña, Lucía Martínez de Soto, Roberto Mora-Corcovado, Alberto Iglesias-Sigüenza, Rocío Ruíz-Hueso, Elena Alvar, Pedro Camacho, Jesús Sojo-Dorado, Remedios Alemán Valls, Ines Ponz, Esmeralda Palmier Peláez, María Arcos Rueda, Guillermo Maestro de la Calle, Ramón Pérez Tanoira, Ana Martínez Vidal, Cristina Amodeo, Marina Pacheco Martínez-Atienza, Clara Muñoz Aguirre, Felipe Villar Álvarez, Giorgina Salgueiro, Xavier Sanz Salvador, César Pérez-Romero, Beatriz Álvarez Zapatero, Nelsa González-Aguado, Robert Torres Sánchez del Arco, Enrique Míguez Rey, Merce Sirisi, Xavier Bonfill Cosp, Marta Yagüe-Barrado, Elena Pérez-Costa, Sandra Casares, Eva Estirado, Jorge Alvarez Troncoso, Cristina Martín-Carrasco, Diana Sande Llovo, Melchor Álvarez de Mon Soto, Arantzazu Mera Fidalgo, Francisco Marqués-González, Agustín Valido-Morales, Luis Alberto Nieto Fernández del Campo, Helem Haydee Vilchez, María Rivas-Carmenado, Francisco Moreno, Ignacio Fernández-Fernández, Henar Calvo Sánchez, Ana González-Cordón, Isabel Fernández-Navarro, María Simón Sacristán, Eva Jiménez-González de Buitrago, M. Muñoz, María Laplaza-González, Rosa de Miguel Buckley, Marta Redondo-Gutierrez, Paula Santibáñez Sáenz, Raquel Martínez Goñi, Marta Rico Rodríguez, Carlos Toro-Rueda, Francisco Arnalich, Ana Santiago-Recuerda, Clara Soto Abanedes, María Dolores Herrero Mendoza, Aquilino Sanchez Purificación, Diego Franch Llasat, María Velasco Arribas, Alejandro Martín-Quirós, Jorge Alba Fernández, Elena Ramírez, Amparo López-Bernus, Marta Alvarado, María Rexach Fumaña, Martín Pilares-Barco, Carmen Liébana Martos, Yolanda Martínez Martínez, Nicolas Merchante Gutiérrez, Maria José Asensio, Ianire Virto Peña, Lucía Mejuto-Illade, María Angeles Martinez-López, Pilar López-Pirez, Alejandro Suárez, Cristóbal Manuel Rodríguez Leal, Sara Garcia-Bellido Ruiz, Jorge Guisández Martín, Lucia Cachafeiro, Pedro Gil Divasson, Almudena Quintás-Viqueira, Laura Currás-Sánchez, Alverio Seiz-Martinez, Mario Ruiz-Bastián, Juan José Menéndez, Jorge Orihuela Martín, María Dolores Nieto Martín, Cristina Arévalo, Rebeca Marinas, Susana Casas Rodríguez, Zuriñe Ortiz de Zárate Ibarra, Yolanda Posada Franco, Joan Gómez-Junyent, Ana María Garijo Saiz, Marina Alguacil-Guillén, Ana Alguacil, Esther Aznar Muñoz, Sara Bañón Escandell, Juan Salillas Hernando, Chiara Fanciulli, Rosa Gómez-Gil, Francisco García-Río, Moncef Belhassen-García, Belén Gutierrez Sancerni, Sonia Vega Molpeceres, Inés Suárez-García, Leire Pérez-Latorre, Elena Chamarro Martí, Carmen Rosario Herrero Gil, Belén Gutiérrez-Gutiérrez, Tatiana Mata Forte, Francesca Sánchez Martínez, Lucía Ramos Merino, Santiago Yus, Mº Ángeles Marcos, Susana Martínez-Álvarez, Alexy Inciarte, Manuel Quintana-Díaz, Lucía Serrá, Belén Alejos, Guillem Policarpo Torres, José Román Muñoz del Rey, Irene Blanco-Bartolomé, Alberto Bahamonde Carrasco, Victoria Hernando, Jhon Rojas, David Roa, María Ángeles Garcinuño, Aránzazu Villasante de la Puente, Patricia Pérez-Palacios, Jesús Ruiz Aragón, Valvanera Ibarra Cucalón, Lucía Ortega Enciso, Ismail Zakariya-Yousef Breval, Jorge Navarro López, Gema Barbeito Castiñeiras, Clara Sala Jofre, Nora Molina Torres, Manuel Poyato, Inmaculada Poquet Catala, Virginia Pomar Solchaga, María Pilar Romero-Gómez, Clara Hernández, Helena Mozas Moriñigo, Mercedes Guillamón Sánchez, Zineb Karroud, Arianna Catino, Violeta Ramos Sesma, Santos del Campo, Pilar Fernández-Calle, Ana Fernández Cruz, Fernando Salvador, Rosa Mayayo-Alvira, Pilar Barco Núñez, Ana Isabel Peláez Ballesta, Silvia Suárez Diaz, Beatriz María Sanjuan, Nora Izko Gartzia, Teresa Aldámiz-Echevarría, Cecilia Tortajada Alamilla, Pau Bosch-Nicolau, María del Mar Alonso Socas, Sonia Calzado Isbert, Jose R. Arribas, Juan Fernández-Lahera, Elizabet Petkova Saiz, Eva Jiménez, Gabriela Abelenda-Alonso, Alba Ribera Puig, Pascual Sanabria-Carretero, Sara Rodrigo González, Irene Díaz de la Torre, Tamara Manso Gómez, Carmen Sáez Barberá, Roi Suárez Gil, Paloma García-Clemente, Héctor Meijide Míguez, Elsa Izquierdo-García, Josune Goikoetxea Agirre, Olalla Martínez Macia, Jesús Santos González, Guillermo Jiménez Álvarez, Cristina Marcelo-Calvo, Javier Coy Coy, Isabel Arenas-Berenguer, Julio García Rodríguez, Natalia Yustas-Benitez, Sarai Quirós-Fernández, Marina Noguerol-Gutiérrez, María Adalid Moll, Iván Bloise-Sánchez, Mario José Rodriguez Dominguez, Elena Salamanca, Francisco Mora Gómez, Lucio García-Fraile, Pablo Millán, C Gutiérrez, Montserrat Rodríguez, José Antonio Oteo Revuelta, Joseba Portu Zapirain, Cristina Moreno, Irene Carrillo Acosta, Jorge Calvo, Ana Mariño Callejo, David Romero-Ribate, Blanca Alonso, Elena Muñoz del Val, Elena Resino Foz, Olaia Rodriguez-Fraga, Miguel Villamarín, Irene Amores-Hernández, Laura Muñoz López, Esther García Almodóvar, Ismael Casares Guerrero, Angélica Villanueva-Freije, Nuria Parra Arribas, Montserrat Sanmarti Vilamala, Macarena Lerín-Baratas, Mercedes Castro-Martínez, Melissa Carreres Candela, Lucia Suárez Pérez, Jose Manuel Iturzaeta-Sánchez, Thamires Silva-Freire, José Antonio Peregrina, María Luisa Machado Sicilia, Sergio Zurita, Daniel Molina Morant, Olga González-Peña, Fernando Lázaro-Perona, Paloma Oliver-Saez, Beatriz Mestre-Gómez, Luis Díaz Díez Picazo, Silvia García-Bujalance, Francisco Rodríguez Gómez, Pere Comas Casanova, Carlos Ruiz Martínez, Alberto Delgado-Iribarren, Berta Alonso-González, Isabel Moreno-Parra, Teresa Gómez-Ballesteros, Araceli Menéndez, Jose Manuel Añón, Ruth Jorge García, Jonathan Cámara Fernández, Miguel Górgolas Hernández-Mora, Itziar Diego Yagüe, Miriam Latorre-Millán, Covadonga Morcate Fernández, M. Río-García, Elisabet Lerma-Chippirraz, Carmen Yllera Gutiérrez, Francesc Albertí, Eva Flores, Carmen R. Uña Orejón, Patricio González-Pizarro, Neila Rodriguez-Roca, Miguel Fernández-Huerta, Inés Ferrer Ortiz, María José Blanco Vidal, Juan Pablo Avilés, Alicia Lorenzo Hernández, Mireia Puig Campmany, José Bravo-Ferrer, Gonzalo Martínez-Alés, Pablo Marguenda Contreras, M. Sánchez, Antonio García Pardo, Yolanda Meije, Francisco Tejerina, Carolina Hernández Carballo, Victoria Moreno, Daniel Laorden-Escudero, Ana Barrios Blandino, Alexia Costanza Espiño Álvarez, Ana Milagro Beamonte, Jerónimo Pachón, S San José-Villar, Marta Morando, María del Carmen Navarro Sáez, Rodolfo Álvarez-Sala Walther, Jon Ugalde Espiñeira, Fernando De la Calle Prieto, Nuria Fernández, Iván Pelegrín Senent, Alba Rueda López, Cristina Schüffelmann, Marcelino Hayek Peraza, Laura Labajo-Montero, Angel Robles Marhuenda, Pilar Durán, Ana Esteban-Romero, María Rosa Oltra Sempere, Ana Cosmen Sánchez, Alex Smithson Amat, Margarita Ramírez-Schacke, Marco Antonio Sempere Alcocer, Paloma Carrera-Vázquez, M Miarons, Teresa García Delange, Amelia Rodriguez-Mariblanca, Eva Talavera García, Roberto Vates Gómez, Óscar Sanz Peláez, José María Muñoz-Ramón, José Luis García Fogeda, Isabel Arroyo-Rico, Verónica Cano Llorente, Fernando González-Romo, Alberto Alonso-Babarro, Fátima Brañas, Fabricio Iannuccelli, Pilar Álvarez Padín, Luis Metola Sacristán, Vicente Boix, Víctor Hontañón, Juan Berenguer, José Luís Del Pozo León, Patricia Sorní Moreno, Maria Isabel Torres, Rafael Mican Rivera, Amparo Blasco Claramunt, Carmen Ardanuy, Aychel Elena Roura Piloto, María Ángeles Molina, Isabel Asschert Agüero, Julía Alvárez del Vayo, Consuelo García-Sánchez, Begoña Reche-Martínez, Guillermo Cuervo, Carlos Iniesta, María Antonia Gómez-Mendieta, Ana María Noblejas Mozo, Andres Bartrina-Tarrio, Carmen De la Higuera Arranz, Yeray Untoria Tabares, Andrés Enrique Suárez-Plaza, Jesús Frías, Paloma López-Arévalo, Irene María Llorente-Cortijo, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), and Fundación SEIMC-GESIDA

Subjects
Male, Prognostic variable, medicine.medical_specialty, Databases, Factual, Coronavirus disease 2019 (COVID-19), 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Aged, Retrospective Studies, Models, Statistical, SARS-CoV-2, business.industry, Mortality rate, COVID-19, Retrospective cohort study, Articles, Middle Aged, Prognosis, medicine.disease, Phenotype, Hospitals, Hospitalization, Logistic Models, Infectious Diseases, Spain, Cohort, Female, Lymphocytopenia, business, Cohort study
Abstract

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Published
2021

24. Risk of Trypanosoma cruzi infection among travellers visiting friends and relatives to continental Latin America

Author

Elena Sullerio, Pau Bosch-Nicolau, Sílvia Roure, Adrián Sánchez-Montalvá, Fernando Salvador, Clara Crespillo-Andújar, Elena Trigo, Israel Molina, Lluís Valerio, Juan Espinosa-Pereiro, Catalina Salinas, Institut Català de la Salut, [Sánchez-Montalvá A, Salvador F, Bosch-Nicolau P, Espinosa-Pereiro J, Molina I] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. PROSICS Barcelona, Barcelona, Spain. [Salinas C] Màster Oficial en Zoonosi i Una Sola Salut, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sullerio E] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, Barcelona, Spain. [Crespillo-Andújar C] National Referral Centre for Tropical Diseases, Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Latin Americans, Epidemiology, RC955-962, Antibodies, Protozoan, 030204 cardiovascular system & hematology, Pathology and Laboratory Medicine, Serology, Chagas, Malaltia, enfermedades parasitarias::infecciones por protozoos::infecciones por Euglenozoa::tripanosomiasis::enfermedad de Chagas [ENFERMEDADES], 0302 clinical medicine, Medical Conditions, Risk Factors, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Enzyme-Linked Immunoassays, Protozoans, Travel, biology, Incidence, Eukaryota, Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Trypanosoma::Trypanosoma cruzi [ORGANISMS], Middle Aged, Infectious Diseases, Otros calificadores::Otros calificadores::/parasitología [Otros calificadores], Female, Public aspects of medicine, RA1-1270, Travel-Related Illness, Parasitic Diseases::Protozoan Infections::Euglenozoa Infections::Trypanosomiasis::Chagas Disease [DISEASES], afecciones patológicas, signos y síntomas::signos y síntomas::enfermedades relacionadas con los viajes [ENFERMEDADES], Research Article, Neglected Tropical Diseases, Chagas disease, Adult, Trypanosoma, Visiting friends and relatives, Viatges, Trypanosoma cruzi, Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Travel-Related Illness [DISEASES], Research and Analysis Methods, Beverages, 03 medical and health sciences, parasitic diseases, Other subheadings::Other subheadings::/parasitology [Other subheadings], Parasitic Diseases, Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Trypanosoma::Trypanosoma cruzi [ORGANISMOS], Humans, Malalties transmissibles, Chagas Disease, Immunoassays, Nutrition, Related factors, Protozoan Infections, business.industry, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, biology.organism_classification, medicine.disease, Tropical Diseases, Confidence interval, Parasitic Protozoans, Diet, Cross-Sectional Studies, Latin America, Spain, Medical Risk Factors, Immunologic Techniques, business, human activities, Demography
Abstract

Background Chagas disease (CD) is regarded as a possible risk for travellers to endemic areas of continental Latin America (LA). The aim of the study is to determine the risk of Trypanosoma cruzi (TC) infection among travellers to CD endemic areas and to identify risk factors for acquiring TC infection. Methods/Principal finding We designed a multicenter cross-sectional study among travellers in Spain (Badalona, Barcelona and Madrid). All available adults with laboratory confirmed proof of absence of TC infection from January 2012 to December 2015 were contacted. Participants referring a trip to LA after the negative TC screening were offered to participate. We performed a standardized questionnaire of travel related factors and measurement of TC antibodies in serum. A total of 971 participants with baseline negative TC serology were selected from the microbiology records. After excluding participants not meeting inclusion criteria, eighty participants were selected. Sixty three (78.8%) were female, and the median age was 38 (IQR 34–47) years. The reason to travel was visiting friends and relatives in 98.8% of the participants. The median duration of travel was 40 (IQR 30–60) days, with 4911 participants-day of exposure. Seventy seven cases (96.25%) participants had two negative TC serology tests after the travel, two cases (2.5%) had discordant serology results (considered false positive results) and one case was infected before travelling to LA. According to our data, the upper limit of the 95% confidence interval of the incidence rate of TC acquisition in travellers is 0.8 per 1000 participant-days. Conclusions/Significance Among 79 non-CD travellers to TC endemic areas, we found no cases of newly acquired TC infection. The incidence rate of TC acquisition in travellers to endemic countries is less than or equal to 0.8 per 1000 traveller-days., Author summary Chagas disease is caused by the protozoan parasite T. cruzi. It is endemic in certain areas of continental Latin America. Few cases of T. cruzi infection have been described in travellers. However, there is little information regarding the incidence rate of T. cruzi infection during a trip to continental Latin America. In this study we aim to study the incidence of T. cruzi infection among migrants from Latin America living in Spain travelling to visit friends and relatives. In this study we found no cases of newly acquired T. cruzi infection among 79 previously uninfected travellers and calculate that the upper limit of the 95% CI of the incidence rate of T. cruzi acquisition in travellers is 0.8 per 1000 participants-day.

Published
2021

25. Blastocystis sp. Carriage and Irritable Bowel Syndrome: Is the Association Already Established?

Author

Carmen Alonso-Cotoner, Elena Sulleiro, Adrián Sánchez-Montalvá, Begoña Bailo, Fernando Salvador, Lidia Goterris, Isabel Fuentes, Beatriz Lobo, David Carmena, Javier Santos, Pau Bosch-Nicolau, Israel Molina, Juan Espinosa-Pereiro, Red de Investigación Cooperativa en Enfermedades Tropicales (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), European Regional Development Fund (ERDF/FEDER), Institut Català de la Salut, [Salvador F, Montalvá A, Bosch-Nicolau P, Espinosa-Pereiro J, Fuentes I, Molina I] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. PROSICS, Barcelona, Spain. [Lobo B, Alonso-Cotoner C, Santos J] Unitat de Recerca en l’Aparell Digestiu, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Goterris L, Sulleiro E] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. PROSICS, Barcelona, Spain. [Bailo B, Carmena D, Fuentes I] National Centre of Microbiology, Instituto de Salud Carlos III, 28220 Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, medicine.medical_specialty, Blastocystis sp, QH301-705.5, 030231 tropical medicine, Pathogenesis, Asymptomatic, Parasitic infection, Article, General Biochemistry, Genetics and Molecular Biology, Irritable Bowel Syndrome, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Biology (General), Helmints, Irritable bowel syndrome, irritable bowel syndrome, Blastocystis, Còlon irritable, General Immunology and Microbiology, biology, enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable [ENFERMEDADES], pathogenesis, Significant difference, Parasitic Diseases::Intestinal Diseases, Parasitic::Blastocystis Infections [DISEASES], medicine.disease, biology.organism_classification, Infeccions, 030104 developmental biology, Carriage, Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome [DISEASES], enfermedades parasitarias::parasitosis intestinales::infecciones por Blastocystis [ENFERMEDADES], medicine.symptom, General Agricultural and Biological Sciences
Abstract

Simple Summary The intestinal protist Blastocystis sp. is one of the most common intestinal parasites observed in humans, and has a worldwide distribution, being more prevalent in developing countries. Although this parasite has been described decades ago, the pathogenic potential it is still not understood completely. It has been suggested that Blastocystis sp. could be related with irritable bowel syndrome, a functional gastrointestinal disorder characterized by abdominal pain, discomfort with defecation, and changes in the frequency or form of stool. In our study, we compare a group of patients with irritable bowel syndrome with a group of healthy volunteers; no differences regarding the occurrence of Blastocystis sp. detection was found between both groups. Abstract Background: The aim of the present study is to describe the occurrence of Blastocystis sp. detection among asymptomatic subjects and patients with irritable bowel syndrome in order to evaluate the potential association between irritable bowel syndrome and the parasitic infection. Methods: Cross-sectional study where adult patients with irritable bowel syndrome diagnosed according to Rome IV criteria were included. A control group was formed by asymptomatic subjects older than 18 years. Exclusion criteria were: immunosuppressive condition or having received any drug with demonstrated activity against Blastocystis sp. within the last 6 months before study inclusion. Epidemiological and clinical information was collected from all included participants. Two stool samples were obtained from all participants: one sample for microscopic examination and one sample for Blastocystis sp. PCR detection. Blastocystis sp. infection was defined by the positivity of any of the diagnostic techniques. Results: Seventy-two participants were included (36 asymptomatic subjects and 36 patients with irritable bowel syndrome). Thirty-five (48.6%) were men, and median age of participants was 34 (IQR 29–49) years. The overall rate of Blastocystis sp. carriage was 27.8% (20/72). The prevalence assessed through microscopic examination was 22.2% (16/72), while the prevalence measured by PCR was 15.3% (11/72). When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, we did not find any statistically significant difference (36.1% vs. 19.4% respectively, p = 0.114). Conclusions: regarding the occurrence of Blastocystis sp., no differences were found between asymptomatic participants and patients with irritable bowel disease irrespective of the diagnostic technique performed.

Published
2021

26. Early outcomes of tocilizumab in adults hospitalized with severe COVID-19 - The Vall d’Hebron COVID-19 prospective cohort study

Author

Andrés Antón, Arnau Monforte-Pallares, Abiu Sempere-Gonzalez, Pau Bosch-Nicolau, Juan Espinosa-Pereiro, Salvador Augustin, Benito Almirante, Marta Miarons, Xavier Dura-Miralles, Fernando Salvador, Simeon Eremiev, Alfredo Guillén-Del-Castillo, Adrián Sánchez-Montalvá, Julia Sampol, Julia Selares-Nadal, Nuria Fernández-Hidalgo, and Santiago Pérez-Hoyos

Subjects
medicine.medical_specialty, ARDS, business.industry, Hazard ratio, Lung injury, medicine.disease, Intensive care unit, law.invention, chemistry.chemical_compound, Tocilizumab, Respiratory failure, chemistry, law, Internal medicine, medicine, Clinical endpoint, Prospective cohort study, business
Abstract

BackgroundModulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19) despite the scarcity of evidence.MethodsWe report the preliminary results from the Vall d’Hebron prospective cohort study at Vall d’Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and who were treated with tocilizumab until March 25th. The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.Results82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. The median time from symptom onset to the first dose of tocilizumab was 9 (7-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3 to 8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8 to 5.8) if tocilizumab was administered after the onset of ARDS.ConclusionTime from lung injury onset to tocilizumab administration may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data from clinical trials becomes available.Summary of the article’s main pointIn patient with COVID-19 and lung injury, time from lung injury onset to tocilizumab administration may be critical to patient recovery. Early administration of host-directed therapies may improve patient outcome.

Published
2020

28. Tigecycline-associated hypofibrinogenemia in a real-world setting

Author

Lucas Rivera-Sánchez, Maria Larrosa-Garcia, Carles Pigrau-Serrallach, David Campany-Herrero, Jaume Mestre-Torres, Juan Espinosa-Pereiro, and Pilar Lalueza-Broto

Subjects
Male, medicine.medical_specialty, Time Factors, medicine.drug_class, Antibiotics, Pharmaceutical Science, Pharmacy, Tigecycline, Toxicology, Logistic regression, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, Aged, Retrospective Studies, Pharmacology, Aged, 80 and over, Dose-Response Relationship, Drug, business.industry, Retrospective cohort study, Hypofibrinogenemia, Middle Aged, Afibrinogenemia, Anti-Bacterial Agents, Clinical trial, Spain, Observational study, Female, business, medicine.drug
Abstract

Background Tigecycline is a broad-spectrum antibiotic used to treat infections that do not respond to first-line treatments. High-doses and extended treatments are common; therefore, adverse events might be more frequent and severe than those observed in clinical trials. Several case-reports have referred hypofibrinogenemia in patients who received tigecycline. Objective To analyse the impact of tigecycline use on coagulation parameters, and identify which variables could be related with this. Setting The study was performed at Hospital Universitari Vall Hebron, in Barcelona, Spain. Method Observational, retrospective study. All patients older than 18, who received tigecycline for 72 h from January 2016 to March 2018 were included. Clinical and laboratory data from before, during and at the end of tigecycline treatment were retrospectively collected. Differences between means were analyzed using the paired-sample Student's t-test. Binary logistic regression was performed to identify risk factors for hypofibrinogenemia. Main outcome measure Mean difference in fibrinogen plasma concentration and INR, before and at the end of tigecycline treatment. Results 78 patients (mean age 65; SD ± 15.5 years) were identified. The most common indications for tigecycline treatment were abdominal (66%), respiratory tract (16%) and skinsoft tissue (10%) infections. High-dose tigecycline was used in 62% of cases and the median duration of treatment was 12 days. Hypofibrinogenemia occurred in 12 patients, 5 bleeding events were observed and 4 of them required fibrinogen administration. Tigecycline caused significant alterations in fibrinogen plasma concentration (mean decrease 1.76 g/L; IC 95% 1.36 to 2.15) as well as INR (mean increase 0.11; IC 95% 0.05 to 0.17). Both were recovered after treatment cessation. We identified duration of treatment 4 weeks (OR = 6.6), high-dose tigecycline (OR = 4.75) and high protein C levels (OR = 4.2) as independent variables associated with fibrinogen decrease, but not renal impairment. Conclusions Tigecycline administration has been related with hypofibrinogenemia, especially when high-doses of tigecycline are used. Health professionals should be aware of the potentially severe tigecycline-associated hypofibrinogenemia and monitor coagulation during treatment, especially when high-doses of tigecycline are used.

Published
2019

29. Ulcers on psoriatic plaques in a patient with advanced Human Immunodeficiency Virus infection

Author

Juan Espinosa Pereiro, Carlos González-Cruz, Vicenç Falcó Ferrer, and Gloria Aparicio Español

Subjects
0301 basic medicine, business.industry, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, Middle Aged, medicine.disease_cause, Virology, 030207 dermatology & venereal diseases, 03 medical and health sciences, Necrosis, 0302 clinical medicine, Fatal Outcome, Skin Ulcer, Medicine, Humans, Psoriasis, Female, business, Skin
Published
2016

32. Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial

Author

Juan Espinosa-Pereiro, Samiksha Ghimire, Marieke G. G. Sturkenboom, Jan-Willem C. Alffenaar, Margarida Tavares, Sarita Aguirre, Arturo Battaglia, Gladys Molinas, Teresa Tórtola, Onno W. Akkerman, Adrian Sanchez-Montalva, Cecile Magis-Escurra, Institut Català de la Salut, [Espinosa-Pereiro J] Unitat de Medicina Tropical i Salut Internacional Drassanes-Vall d'Hebron Hospital Universitari, Barcelona, Spain. Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. [Ghimire S, Sturkenboom MGG] Department Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [Alffenaar JC] Department Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. Westmead Hospital, Sydney, Australia. Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, Australia. [Tavares M] Infectious Diseases Service, Centro Hospitalar de São João, Porto, Portugal. [Aguirre S] National Program for Tuberculosis, Ministry of Health, Asunción, Paraguay. [Tórtola T] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Sanchez-Montalva A] Unitat de Medicina Tropical i Salut Internacional Drassanes-Vall d'Hebron Hospital Universitari, Barcelona, Spain. Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. Grupo de Estudio de Infecciones por Micobacterias, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GEIM-SEIMC), Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
infecciones bacterianas y micosis::infecciones bacterianas::infecciones por bacterias grampositivas::infecciones por Actinomycetales::micobacteriosis::tuberculosis [ENFERMEDADES], Tuberculosi - Tractament, Otros calificadores::/uso terapéutico [Otros calificadores], Pharmaceutical Science, Medicaments antibacterians - Ús terapèutic, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [CHEMICALS AND DRUGS], Other subheadings::/therapeutic use [Other subheadings], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antibacterianos [COMPUESTOS QUÍMICOS Y DROGAS], Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Actinomycetales Infections::Mycobacterium Infections::Tuberculosis [DISEASES]
Abstract

Rifampicin; Tuberculosis; Vulnerable population Rifampicina; Tuberculosis; Población vulnerable Rifampicina; Tuberculosi; Població vulnerable Previous clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231. This study is part of the European South American TB Research Collaborative Network (EUSAT-RCS), a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 823890. A.S.M. is supported by a Juan Rodés (JR18/00022) postdoctoral fellowship from ISCIII.

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33. Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain

Author

Juan David Puyana Ortiz, Andrea Carolina Garcés Rodríguez, María Luisa Aznar, Juan Espinosa Pereiro, Adrián Sánchez-Montalvá, Joan Martínez-Campreciós, Nuria Saborit, José Ángel Rodrigo-Pendás, Guadalupe García Salgado, Claudia Broto Cortes, Nuria Serre Delcor, Inés Oliveira, Begoña Treviño Maruri, Diana Pou Ciruelo, Fernando Salvador, Pau Bosch-Nicolau, Irene Torrecilla-Martínez, Ricardo Zules-Oña, María Teresa Tórtola Fernández, and Israel Molina

Subjects
Mycobacterium tuberculosis, tuberculosis screening, latent tuberculosis infection, adverse events, toxicity, adherence, Medicine
Abstract

The screening and treatment of latent tuberculosis infection (LTBI) in countries with a low incidence of TB is a key strategy for the elimination of tuberculosis (TB). However, treatment can result in adverse events (AEs) and have poor adherence. This study aimed to describe treatment outcomes and AEs for LTBI patients at two departments in Vall d’Hebron University Hospital in Barcelona, Spain. A retrospective study was conducted on all persons treated for LTBI between January 2018 and December 2020. Variables collected included demographics, the reason for LTBI screening and treatment initiation, AEs related to treatment, and treatment outcome. Out of 261 persons who initiated LTBI treatment, 145 (55.6%) were men, with a median age of 42.1 years. The indications for LTBI screening were household contact of a TB case in 96 (36.8%) persons, immunosuppressive treatment in 84 (32.2%), and recently arrived migrants from a country with high TB incidence in 81 (31.0%). Sixty-three (24.1%) persons presented at least one AE during treatment, and seven (2.7%) required definitive discontinuation of treatment. In the multivariate analysis, AE development was more frequent in those who started LTBI treatment due to immunosuppression. Overall, 226 (86.6%) completed treatment successfully. We concluded that LTBI screening and treatment groups had different risks for adverse events and treatment outcomes. Persons receiving immunosuppressive treatment were at higher risk of developing AEs, and recently arrived immigrants from countries with a high incidence of TB had greater LTFU. A person-centered adherence and AE management plan is recommended.

Published
2023
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