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1. Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Author

Laura Herrera-Hidalgo, Patricia Muñoz, Ana Álvarez-Uría, David Alonso-Menchén, Rafael Luque-Marquez, Encarnación Gutiérrez-Carretero, María Del Carmen Fariñas, Jose Maria Miró, Miguel Angel Goenaga, Luis Eduardo López-Cortés, Basilio Angulo-Lara, Lucia Boix-Palop, Arístides de Alarcón, Fernando Fernández Sánchez, José Mª García de Lomas, Gabriel Rosas, Javier de la Torre Lima, Elena Bereciartua, María José Blanco Vidal, Roberto Blanco, María Victoria Boado, Marta Campaña Lázaro, Alejandro Crespo, Laura Guio Carrión, Mikel Del Álamo Martínez de Lagos, Gorane Euba Ugarte, Ane Josune Goikoetxea, Marta Ibarrola Hierro, José Ramón Iruretagoyena, Josu Irurzun Zuazabal, Leire López-Soria, Miguel Montejo, Javier Nieto, David Rodrigo, Regino Rodríguez, Yolanda Vitoria, Roberto Voces, Mª Victoria García López, Radka Ivanova Georgieva, Guillermo Ojeda, Isabel Rodríguez Bailón, Josefa Ruiz Morales, Ignacio Álvarez Rodríguez, Harkaitz Azkune Galparsoro, Elisa Berritu Boronat, Mª Jesús Bustinduy Odriozola, Cristina del Bosque Martín, Tomás Echeverría, Alberto Eizaguirre Yarza, Ana Fuentes, Miguel Ángel Goenaga, Muskilda Goyeneche del Río, Ángela Granda Bauza, José Antonio Iribarren, Xabier Kortajarena Urkola, José Ignacio Pérez-Moreiras López, Ainhoa Rengel Jiménez, Karlos Reviejo, Alberto Sáez Berbejillo, Elou Sánchez Haza, Rosa Sebastián Alda, Itziar Solla Ruiz, Irati Unamuno Ugartemendia, Diego Vicente Anza, Iñaki Villanueva Benito, Mar Zabalo Arrieta, Rafael Carrasco, Vicente Climent, Patricio Llamas, Esperanza Merino, Joaquín Plazas, Sergio Reus, Alberto Bouzas, Brais Castelo, José Cuenca, Laura Gutiérrez, Lucía Ramos, María Rodríguez Mayo, Joaquín Manuel Serrano, Dolores Sousa Regueiro, Francisco Javier Martínez, Mª del Mar Alonso, Beatriz Castro, Teresa Delgado Melian, Javier Fernández Sarabia, Dácil García Rosado, Julia González González, Juan Lacalzada, Lissete Lorenzo de la Peña, Alina Pérez Ramírez, Pablo Prada Arrondo, Fermín Rodríguez Moreno, Antonio Plata Ciezar, José Mª Reguera Iglesias, Víctor Asensi Álvarez, Carlos Costas, Jesús de la Hera, Jonnathan Fernández Suárez, Lisardo Iglesias Fraile, Víctor León Arguero, José López Menéndez, Pilar Mencia Bajo, Carlos Morales, Alfonso Moreno Torrico, Carmen Palomo, Begoña Paya Martínez, Ángeles Rodríguez Esteban, Raquel Rodríguez García, Mauricio Telenti Asensio, Manuel Almela, Juan Ambrosioni, Manuel Azqueta, Mercè Brunet, Marta Bodro, Ramón Cartañá, Guillermo Cuervo, Carlos Falces, Mariana J Fernández-Pittol, Guillermina Fita, David Fuster, Cristina García de la Mària, Delia García-Pares, Marta Hernández-Meneses, Jaume Llopis Pérez, Francesc Marco, José M. Miró, Asunción Moreno, David Nicolás, Salvador Ninot, Eduardo Quintana, Carlos Paré, Daniel Pereda, Juan M. Pericás, José L. Pomar, José Ramírez, Mercè Roque, Irene Rovira, Elena Sandoval, Marta Sitges, Dolors Soy, Adrián Téllez, José M. Tolosana, Bárbara Vidal, Jordi Vila, Iván Adán, David Alonso, Juan Carlos Alonso, Javier Bermejo, Emilio Bouza, Gregorio Cuerpo Caballero, Antonia Delgado Montero, Agustín Estévez, Ramón Fortuny Ribas, Esther Gargallo, Mª Eugenia García Leoni, Ana González Mansilla, Francisco Javier González Moraga, Víctor González Ramallo, Martha Kestler Hernández, Amaia Mari Hualde, Marina Machado, Mercedes Marín, Manuel Martínez-Sellés, Rosa Melero, Diego Monzón, María Olmedo, Álvaro Pedraz, Blanca Pinilla, Ángel Pinto, Cristina Rincón, Hugo Rodríguez-Abella, Marta Rodríguez-Créixems, Eduardo Sánchez-Pérez, Antonio Segado, Neera Toledo, Maricela Valerio, Pilar Vázquez, Eduardo Verde Moreno, Sofía de la Villa, Isabel Antorrena, Belén Loeches, Mar Moreno, Ulises Ramírez, Verónica Rial Bastón, María Romero, Sandra Rosillo, Jesús Agüero Balbín, Cristina Amado Fernández, Carlos Armiñanzas Castillo, Francisco Arnaiz de las Revillas, Manuel Cobo Belaustegui, María Carmen Fariñas, Concepción Fariñas-Álvarez, Marta Fernández Sampedro, Iván García, Claudia González Rico, Laura Gutiérrez-Fernández, Manuel Gutiérrez-Cuadra, José Gutiérrez Díez, Marcos Pajarón, José Antonio Parra, Ramón Teira, Jesús Zarauza, Jorge Calderón Parra, Marta Cobo, Fernando Domínguez, Pablo García Pavía, Ana Fernández Cruz, Antonio Ramos-Martínez, Isabel Sánchez Romero, Tomasa Centella, José Manuel Hermida, José Luis Moya, Pilar Martín-Dávila, Enrique Navas, Enrique Oliva, Alejandro del Río, Jorge Rodríguez-Roda Stuart, Soledad Ruiz, Carmen Hidalgo Tenorio, Sergio Sequera, Manuel Almendro Delia, Omar Araji, José Miguel Barquero, Román Calvo Jambrina, Marina de Cueto, Juan Gálvez Acebal, Irene Méndez, Isabel Morales, José Antonio Lepe, José López-Haldón, Rafael Luque-Márquez, Guillermo Marín, Antonio Ortiz-Carrellán, Eladio Sánchez-Domínguez, Luis Javier Alonso, Pedro Azcárate, José Manuel Azcona Gutiérrez, José Ramón Blanco, Estíbaliz Corral Armas, Lara García-Álvarez, José Antonio Oteo, Antonio Barros Membrilla, Antonino Ginel Iglesias, Sara Grillo, Rubén Leta Petracca, Joaquín López-Contreras, María Alba Rivera Martínez, M. Álvarez, A.L. Fernández, Amparo Martínez, A. Prieto, Benito Regueiro, E. Tijeira, Marino Vega, Amaia Aguirre Quiñonero, Ángela Alonso Miñambres, Juan Carlos Gainzarain Arana, Sara González de Alaiza Ortega, Miguel Ángel Morán Rodríguez, Anai Moreno Rodríguez, Zuriñe Ortiz de Zárate, José Joaquín Portu Zapirain, Ester Sáez de Adana Arroniz, Daisy Carolina Sorto Sánchez, Sánchez-Porto Antonio, Úbeda Iglesias Alejandro, José Mª Arribas Leal, Elisa García Vázquez, Alicia Hernández Torres, Ana Blázquez, Gonzalo de la Morena Valenzuela, Ángel Alonso, Javier Aramburu, Felicitas Elena Calvo, Paola Tarabini-Castellani, Eva Heredero Gálvez, Carolina Maicas Bellido, José Largo Pau, Mª Antonia Sepúlveda, Pilar Toledano Sierra, Sadaf Zafar Iqbal-Mirza, Eva Cascales Alcolea, Ivan Keituqwa Yañez, Julián Navarro Martínez, Ana Peláez Ballesta, Eduardo Moreno Escobar, Alejandro Peña Monje, Valme Sánchez Cabrera, David Vinuesa García, María Arrizabalaga Asenjo, Carmen Cifuentes Luna, Juana Núñez Morcillo, Mª Cruz Pérez Seco, Aroa Villoslada Gelabert, Carmen Aured Guallar, Nuria Fernández Abad, Pilar García Mangas, Marta Matamala Adell, Mª Pilar Palacián Ruiz, Juan Carlos Porres, Begoña Alcaraz Vidal, María Jesús Del Amor Espín, Francisco Buendía, Roberto Jiménez Sánchez, Rosario Mármol, Francisco Martínez, Antonio Meseguer, Beatriz Pérez, Leticia Risco, Zoser Saura, Vanina Silva, Mª Belén Villmarín, Mª Ángels Ribas Blanco, Enrique Ruiz de Gopegui Bordes, Laura Vidal Bonet, Miquel Vives Borràs, Mª Carmen Bellón Munera, Elena Escribano Garaizabal, Antonia Tercero Martínez, Juan Carlos Segura Luque, Cristina Badía, Lucía Boix Palop, Mariona Xercavins, Sónia Ibars, Xerach Bosch, Eloy Gómez Nebreda, Ibalia Horcajada Herrera, Irene Menduiña Gallego, Imanol Pulido, Héctor Marrero Santiago, Isabel de Miguel Martínez, Elena Pisos Álamo, Daniel San Román Sánchez, Jorge Boan Pérez, Eva Mª Aguilar Blanco, Mercedes Catalán González, María Angélica Corres Peiretti, Andrea Eixerés Esteve, Laura Domínguez Pérez, Santiago de Cossío Tejido, Francisco Galván Román, José Antonio García Robles, Francisco López Medrano, Mª Jesús López Gude, Mª Ángeles Orellana Miguel, Patrick Pilkington, Yolanda Revilla Ostalaza, Juan Ruiz Morales, Sebastián Ruiz Solís, Ana Sabín Collado, Marcos Sánchez Fernández, Javier Solera Rallo, Jorge Solís Martín, Francesc Escrihuela-Vidal, Jordi Carratalà, Inmaculada Grau, Carmen Ardanuy, Dámaris Berbel, José Carlos Sánchez Salado, Oriol Alegre, Alejandro Ruiz Majoral, Fabrizio Sbraga, Arnau Blasco, Laura Gracia Sánchez, Iván Sánchez-Rodríguez, Gonzalo Aldamiz, Beatriz Álvarez, Marina Bernal Palacios, Alfonso Cabello Úbeda, Ricardo Fernández Roblas, Rafael Hernández, Victoria Andrea Hortigüela Martín, Andrea Kallmeyer, Cristina Landaeta Kancev, Marta Martín, Miguel Morante Ruiz, Miguel Ángel Navas Lobato, Ana María Pello, Laura Prieto, Marta Tomás Mallebrera, Laura Varela, Mireia de la Peña Triguero, Ruth Esther Figueroa Cerón, Lara Ruiz Gómez, Mireia Ble, Juan Pablo Horcajada Gallego, Antonio José Ginel, Inmaculada López, Alexandra Mas, Antoni Mestres, Lluís Molina, Ramón Serrat, Núria Ribas, Francisca Sánchez, Ana Silverio, Marina Suárez, Luisa Sorlí, Lluís Recasens, Manuel Taurón, María Fernández Regueras, María Ángeles Mantecón Vallejo, José Ángel Pérez Rivera, Nuria Sánchez Mata, Antonia Calvo Cano, Miguel Fajardo Olivares, María Victoria Millán Núñez, and Agustín Muñoz Sanz

Subjects
Infective endocarditis, Methicillin-susceptible Staphylococcus aureus, Cefazolin, Antistaphylococcal penicillin, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P

Published
2023
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2. Effects of frailty, geriatric syndromes, and comorbidity on mortality and quality of life in older adults with HIV

Author

Fátima Brañas, Miguel Torralba, Antonio Antela, Jorge Vergas, Margarita Ramírez, Pablo Ryan, Fernando Dronda, María José Galindo, Isabel Machuca, María Jesús Bustinduy, Alfonso Cabello, María Luisa Montes, Matilde Sánchez-Conde, and FUNCFRAIL study group

Subjects
HIV, Frailty, Geriatric syndromes, Mortality, Quality of life, Geriatrics, RC952-954.6
Abstract

Abstract Background To understand the effects of frailty, geriatric syndromes, and comorbidity on quality of life and mortality in older adults with HIV (OAWH). Methods Cross-sectional study of the FUNCFRAIL multicenter cohort. The setting was outpatient HIV-Clinic. OAWH, 50 year or over were included. We recorded sociodemographic data, HIV infection-related data, comorbidity, frailty, geriatric syndromes (depression, cognitive impairment, falls and malnutrition), quality of life (QOL) and the estimated risk of all-cause 5-year mortality by VACS Index. Association of frailty with geriatric syndromes and comorbidity was evaluated using the Cochran-Mantel-Haenszel test. Results Seven hundred ninety six patients were included. 24.7% were women, mean age was 58.2 (6.3). 14.7% were 65 or over. 517 (65%) patients had ≥3 comorbidities, ≥ 1 geriatric syndrome and/or frailty. There were significant differences in the estimated risk of mortality [(frailty 10.8%) vs. (≥ 3 comorbidities 8.2%) vs. (≥ 1 geriatric syndrome 8.2%) vs. (nothing 6.2%); p = 0.01] and in the prevalence of fair or poor QOL [(frailty 71.7%) vs. (≥ 3 comorbidities 52%) vs. (≥ 1 geriatric syndrome 58.4%) vs. (nothing 51%); p = 0.01]. Cognitive impairment was significantly associated to mortality (8.7% vs. 6.2%; p = 0.02) and depression to poor QOL [76.5% vs. 50%; p = 0.01]. Conclusions Frailty, geriatric syndromes, and comorbidity had negative effects on mortality and QOL, but frailty had the greatest negative effect out of the three factors. Our results should be a wake-up call to standardize the screening for frailty and geriatric syndromes in OAWH in the clinical practice. Trial registration NCT03558438.

Published
2023
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3. High frequency of CD8 escape mutations in elite controllers as new obstacle for HIV cure

Author

María A. Navarrete-Muñoz, Ricardo Ramos, África Holguín, Alfonso Cabello, Miguel Górgolas, José M. Benito, and Norma Rallón

Subjects
HIV reservoir, resting memory CD4+ T-cells, elite controllers, CTL response, HIV-Gag proviral DNA, next generation sequencing (NGS), Infectious and parasitic diseases, RC109-216
Abstract

Accumulation of mutations in epitopes of cytolytic-T-lymphocytes immune response (CTL) in HIV-reservoir seems to be one of the reasons for shock-and-kill strategy failure. Ten non-controller patients on successful cART (TX) and seven elite controllers (EC) were included. HIV-Gag gene from purified resting memory CD4+ T-cells was sequenced by Next-Generation-Sequencing. HLA class-I alleles were typed to predict optimal HIV-Gag CTL epitopes. For each subject, the frequency of mutated epitopes in the HIV-Gag gene, the proportion of them considered as CTL-escape variants as well as their effect on antigen recognition by HLA were assessed. The proportion (%) of mutated HIV-Gag CTL epitopes in the reservoir was high and similar in EC and TX (86%[50–100] and 57%[48–82] respectively, p=0.315). Many of them were predicted to negatively impact antigen recognition. Moreover, the proportion of mutated epitopes considered to be CTL-escape variants was also similar in TX and EC (77%[49–92] vs. 50%[33–75] respectively, p=0.117). Thus, the most relevant finding of our study was the high and similar proportions of HIV-Gag CTL-escape mutations in the reservoir of both HIV-noncontroller patients with cART (TX) and patients with spontaneous HIV-control (EC). Our findings suggest that escape mutations of CTL-response may be another obstacle to eliminate the HIV reservoir and constitute a proof of concept that challenges HIV cure strategies focused on the reactivation of reservoirs. Due to the small sample size that could impact the robustness of the study, further studies with larger cohorts of elite controller patients are needed to confirm these results.

Published
2022
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4. Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS eventsResearch in context

Author

Javier Martínez-Sanz, Jorge Díaz-Álvarez, Marta Rosas, Raquel Ron, José Antonio Iribarren, Enrique Bernal, Félix Gutiérrez, Andrés Ruiz Sancho, Noemi Cabello, Julián Olalla, Santiago Moreno, Sergio Serrano-Villar, Inma Jarrín, David Dalmau, M. Luisa Navarro, M. Isabel González, Federico Garcia, Eva Poveda, Jose Antonio Iribarren, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, M. Ángeles Muñoz-Fernández, Inmaculada Jarrín, Cristina Moreno, Marta Rava, Rebeca Izquierdo, Elba Mauleón, Joaquín Portilla, Irene Portilla, Esperanza Merino, Gema García, Iván Agea, José Sánchez-Payá, Juan Carlos Rodríguez, Livia Giner, Sergio Reus, Vicente Boix, Diego Torrus, Verónica Pérez, Julia Portilla, Juan Luís Gómez, Jehovana Hernández, Ana López Lirola, Dácil García, Felicitas Díaz-Flores, M. Mar Alonso, Ricardo Pelazas, M. Remedios Alemán, Víctor Asensi, María Eugenia Rivas Carmenado, Tomás Suarez-Zarracina, Federico Pulido, Otilia Bisbal, M. Asunción Hernando, David Rial, María de Lagarde, Octavio Arce, Adriana Pinto, Laura Bermejo, Mireia Santacreu, Roser Navarro, Candela Gonzalez, M. José Aramburu, Xabier Camino, Miguel Ángel von Wichmann, Miguel Ángel Goenaga, M. Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Xabier Kortajarena, Ignacio Álvarez-Rodriguez, Leire Gil, Lourdes Martínez, Catalina Robledano, Mar Masiá, Sergio Padilla, Araceli Adsuar, Rafael Pascual, Marta Fernández, Antonio Galiana, José Alberto García, Xavier Barber, Vanessa Agullo, Javier Garcia Abellán, Reyes Pascual, Guillermo Telenti, Lucia Guillén, Ángela Botella, Roberto Muga, Arantza Sanvisens, Daniel Fuster, Isabel Gutierrez, Juan Carlos López, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Cristina Diez, Leire Pérez, Chiara Fanciulli, Saray Corral, Anna Martí, Joaquín Peraire, Consuelo Viladés, Montserrat Vargas, Montserrat Olona, Anna Rull, Verónica Alba, Elena Yeregui, Jenifer Masip, Graciano García-Pardo, Frederic Gómez Bertomeu, Sonia Espineira, Marta Montero, Sandra Cuéllar, Marino Blanes, María Tasias, Eva Calabuig, Miguel Salavert, Juan Fernández, Inmaculada Segarra, Juan González-García, Ana Delgado, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino, Juan Miguel Castro, Luis Escosa, Pedro Herranz, Victor Hontañón, Silvia García-Bujalance, Milagros García, Alicia González-Baeza, M. Luz Martín-Carbonero, Mario Mayoral, M. Jose Mellado, Rafael Esteban, Rocío Montejano, M. Luisa Montes, Victoria Moreno, Ignacio Pérez-Valero, Berta Rodés, Guadalupe Rúa, Talía Sainz, Elena Sendagorta, Eulalia Valencia, Carmen Busca, Joanna Cano, Julen Cardiñanos, Rosa de Miguel, Jose Ramón Blanco, Laura Pérez-Martínez, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Piedad Arazo, Gloria Sampériz, Marina Martinez, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Alonso, Francesco Aiello, María Rivero, Beatriz Piérola, Maider Goikoetxea, María Gracia, Carlos Ibero, Estela Moreno, Jesús Repáraz, Gemma Navarro, Manel Cervantes Garcia, Sonia Calzado Isbert, Marta Navarro Vilasaro, Belen Lopez Garcia, Ignacio de los Santos, Alejandro de los Santos, Jesús Sanz, Lucio García-Fraile, Enrique Martín, Ildefonso Sánchez-Cerrillo, Marta Calvet, Ana Barrios, Azucena Bautista, Carmen Sáez, Marianela Ciudad, Ángela Gutiérrez, Santos del Campo, José Luis Casado, Fernando Dronda, Ana Moreno, M. Jesús Pérez, Sergio Serrano, Ma Jesús Vivancos, Alejandro Vallejo, Matilde Sanchez, Jose Antonio Pérez-Molina, José Manuel Hermida, Antonia Alcaraz, Joaquín Bravo, Ángeles Muñoz, Cristina Tomás, Mónica Martínez, M. Carmen Villalba, Federico García, Clara Martínez, José Hernández, Leopoldo Muñoz Medina, Marta Álvarez, Natalia Chueca, David Vinuesa, Adolfo de Salazar, Ana Fuentes, Emilio Guirao, Laura Viñuela, Andrés Ruiz-Sancho, Francisco Anguita, Jorge Del Romero, Montserrat Raposo, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Begoña Baza, Eva Orviz, Antonio Antela, Elena Losada, Melchor Riera, María Peñaranda, M. Angels Ribas, Antoni A. Campins, Mercedes Garcia-Gazalla, Francisco J. Fanjul, Javier Murillas, Francisco Homar, Helem H. Vilchez, Luisa Martin, Antoni Payeras, Jesús Santos, María López, Crisitina Gómez, Isabel Viciana, Rosario Palacios, Luis Fernando López-Cortés, Nuria Espinosa, Cristina Roca, Silvia Llaves, Juan Manuel Tiraboschi, Arkaitz Imaz, Ana Karina Silva, María Saumoy, Sofía Catalina Scévola, Adrián Curran, Vicenç Falcó, Jordi Navarro, Joaquin Burgos, Paula Suanzes, Jorge García, Vicente Descalzo, Patricia Álvarez, Bibiana Planas, Marta Sanchiz, Lucía Rodríguez, M José Sánchez, Javier Pérez, Alfonso del Arco, Javier de la Torre, José Luis Prada, Onofre Juan Martínez, Lorena Martinez, Francisco Jesús Vera, Josefina García, Begoña Alcaraz, Antonio Jesús Sánchez Guirao, Alvaro Mena, Angeles Castro, Berta Pernas, Pilar Vázquez, Soledad López, Sofía Ibarra, Guillermo García, Josu Mirena, Oscar Luis Ferrero, Josefina López, M. Mar Cámara, Mireia de la Peña, Miriam Lopez, Iñigo Lopez, Itxaso Lombide, Victor Polo, Joana de Miguel, Carlos Galera, Marian Fernández, Helena Albendin, Antonia Castillo, Asunción Iborra, Antonio Moreno, M. Angustias Merlos, Asunción Vidal, Concha Amador, Francisco Pasquau, Concepcion Gil, Jose Tomás Algado, Inés Suarez-García, Eduardo Malmierca, Patricia González-Ruano, M. Pilar Ruiz, José Francisco Pascual, Elena Sáez, Luz Balsalobre, M. Villa López, Mohamed Omar, Carmen Herrero, M. Amparo Gómez, Miguel Alberto de Zarraga, Desiré Pérez, Vicente Estrada, Nieves Sanz, Noemí Cabello, Jorge Vergas García, Maria Jose Núñez, Iñigo Sagastagoitia, Miguel Górgolas, Alfonso Cabello, Beatriz Álvarez, Laura Prieto, Irene Carrillo, José Sanz, Alberto Arranz, Cristina Hernández, María Novella, M. José Galindo, Ana Ferrer, Antonio Rivero Román, Inma Ruíz, Antonio Rivero Juárez, Pedro López, Isabel Machuca, Mario Frias, Ángela Camacho, Ignacio Pérez, Diana Corona, Miguel Cervero, Rafael Torres, Juan Antonio Pineda, Pilar Rincón, Juan Macías, Luis Miguel Real, Anais Corma, Alejandro Gonzalez-Serna, Alexandre Pérez, Luis Morano, Celia Miralles, Antonio Ocampo, Guillermo Pousada, Lucía Patiño, Carlos Dueñas, Sara Gutiérrez, Elena Tapia, Cristina Novoa, Xjoylin Egües, and Pablo Telleria

Subjects
HIV, Non-AIDS events, Neoplasia, Cardiovascular event, CD4/CD8 ratio, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Published
2023
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5. HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy

Author

Beatriz Álvarez, María A. Navarrete-Muñoz, Veronica Briz, Susana Olmedillas-López, Sara Nistal, Alfonso Cabello, Laura Prieto, Miguel Górgolas, Mariano García-Arranz, José M. Benito, and Norma Rallón

Subjects
Medicine, Science
Abstract

Abstract The role of HCV on the HIV reservoir is controversial since the reduction on HIV-DNA levels after HCV eradication with IFNα/RBV treatment seems to be the result of drugs instead of HCV clearance. We assessed whether HCV eradication can decrease HIV-DNA content in HIV/HCV-coinfected patients treated with direct-acting antivirals, DAAs (IFNα/RBV-free regimens). Cell-associated HIV-DNA was measured by ddPCR in 25 HIV-monoinfected and 25 HIV/HCV-coinfected patients. There were no differences in HIV-DNA levels between groups neither at baseline nor at 12 weeks after DAAs treatment completion. Our results indicate that HCV does not appear to influence the HIV reservoir size and suggest the lack of an anti-HIV action for DAAs.

Published
2022
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6. Histiocytoid Sweet Syndrome associated with anorectal lymphogranuloma venereum in a patient with HIV infection

Author

Aws Waleed M. Al-Hayani, Iris Martínez Alemany, Carlos Santonja, Alfonso Cabello Úbeda, Laura Prieto Pérez, María Carmen Ceballos-Rodríguez, Irene Carrillo Acosta, Miguel de Górgolas Hernández-Mora, and Beatriz Álvarez Álvarez

Subjects
Sweet Syndrome, Histiocytoid Sweet Syndrome, Chlamydia trachomatis, lymphogranuloma venereum, HIV, Infectious and parasitic diseases, RC109-216
Abstract

ABSTRACT: Sweet Syndrome belongs to a group of diseases known as neutrophilic dermatoses. An uncommon variant named Histiocytoid Sweet Syndrome (HSS) can be associated with a variety of conditions, including cancer, infections, drug toxicity and others. Here we present an instance of HSS in an HIV-positive patient in an infectious disease setting.

Published
2022
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7. Increased risk factors associated with lower BMD in antiretroviral-therapy–naïve HIV-infected adult male

Author

Patricia Atencio, Alfonso Cabello, Francisco M. Conesa-Buendía, Ramón Pérez-Tanoira, Laura Prieto-Pérez, Irene Carrillo, Beatriz Álvarez, Rosa Arboiro-Pinel, Manuel Díaz-Curiel, Gabriel Herrero-Beaumont, Aránzazu Mediero, and Miguel Górgolas

Subjects
HIV, Bone comorbidity, Naïve patients, DXA, BMD, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Low BMD (bone mineral density) has been described as a non–AIDS (Acquired Immune Deficiency Syndrome)-related event in HIV (human immunodeficiency virus)-patients but it is poorly studied in young HIV-infected men who have received no previous antiretroviral therapy. Methods A cross-sectional study of 245 naïve-HIV-infected men over 21 and under 50 years old who voluntary attended the Infectious Disease Division appointment in Hospital Fundación Jimenez Díaz in Madrid, from January 1st, 2014 to September 30th, 2017. All subjects underwent a baseline DXA scan (dual energy x-ray absorptiometry) performed prior to start antiretroviral treatment. Further, all patients who started treatment between May 1st and September 30th, 2017 were invited to participate in a substudy on bone mineral metabolism. All the information was collected through clinical history and complementary questionnaire. Results The mean age was 36.4 years, been 68% Caucasian, 29.3% Latin American and 2.7% African race. At the time of diagnosis, 91% of patients had stage-A (median CD4+ T-cell 481cells/μL, IQR, 320–659). 10% had a count below 200 CD4 cells/μL, and 40% had a CD4/CD8 cell-count-ratio below 0.4. Regarding lifestyle and risk factors, 14.1% presented underweight, 36.1% were not engage in any regular exercise, 51.9% were active smokers and 35.3% reported drug use. Low levels of vitamin D were seen in 87.6% of the study participants. Low BMD (Z-score

Published
2021
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8. Expert Consensus: Main Risk Factors for Poor Prognosis in COVID-19 and the Implications for Targeted Measures against SARS-CoV-2

Author

Francisco Javier Candel, Pablo Barreiro, Miguel Salavert, Alfonso Cabello, Mario Fernández-Ruiz, Pedro Pérez-Segura, Jesús San Román, Juan Berenguer, Raúl Córdoba, Rafael Delgado, Pedro Pablo España, Ignacio Alberto Gómez-Centurión, Juan María González del Castillo, Sarah Béatrice Heili, Francisco Javier Martínez-Peromingo, Rosario Menéndez, Santiago Moreno, José Luís Pablos, Juan Pasquau, José Luis Piñana, and on behalf of the MODUS Investigators (Adenda)

Subjects
COVID, SARS-CoV-2, risk factors, poor prognosis, therapy, Microbiology, QR1-502
Abstract

The clinical evolution of patients infected with the Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) depends on the complex interplay between viral and host factors. The evolution to less aggressive but better-transmitted viral variants, and the presence of immune memory responses in a growing number of vaccinated and/or virus-exposed individuals, has caused the pandemic to slowly wane in virulence. However, there are still patients with risk factors or comorbidities that put them at risk of poor outcomes in the event of having the coronavirus infectious disease 2019 (COVID-19). Among the different treatment options for patients with COVID-19, virus-targeted measures include antiviral drugs or monoclonal antibodies that may be provided in the early days of infection. The present expert consensus is based on a review of all the literature published between 1 July 2021 and 15 February 2022 that was carried out to establish the characteristics of patients, in terms of presence of risk factors or comorbidities, that may make them candidates for receiving any of the virus-targeted measures available in order to prevent a fatal outcome, such as severe disease or death. A total of 119 studies were included from the review of the literature and 159 were from the additional independent review carried out by the panelists a posteriori. Conditions found related to strong recommendation of the use of virus-targeted measures in the first days of COVID-19 were age above 80 years, or above 65 years with another risk factor; antineoplastic chemotherapy or active malignancy; HIV infection with CD4+ cell counts < 200/mm3; and treatment with anti-CD20 immunosuppressive drugs. There is also a strong recommendation against using the studied interventions in HIV-infected patients with a CD4+ nadir 3 or treatment with other immunosuppressants. Indications of therapies against SARS-CoV-2, regardless of vaccination status or history of infection, may still exist for some populations, even after COVID-19 has been declared to no longer be a global health emergency by the WHO.

Published
2023
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9. Increased Prevalence of Symptomatic Human Intestinal Spirochetosis in MSM with High-Risk Sexual Behavior in a Cohort of 165 Individuals

Author

Ramón Pérez-Tanoira, Marta del Palacio Tamarit, Ana María Vicente Montaña, David Carmena, Pamela Köster, Miguel Górgolas, José R. Fortes Alen, Alfonso Cabello-Úbeda, and Laura Prieto-Pérez

Subjects
intestinal spirochetosis, diarrhea, Brachyspira, MSM, chemsex, HIV infection, Medicine
Abstract

Human intestinal spirochetosis (HIS) can cause gastrointestinal symptoms, although asymptomatic infections have been described. Individuals from low-income countries, people living with HIV, and men who have sex with men (MSM) show increased risk. A retrospective review of all patients diagnosed with HIS (n = 165) between January 2013 and October 2020 at a tertiary hospital in Madrid, Spain, was performed to assess risk factors for symptomatic HIS, symptoms, and response to treatment. Most patients were male (n = 156; 94.5%), 86.7% were MSM, and 23.5% practiced chemsex, of whom most were symptomatic (p = 0.039). Most patients (78.4%) reported unprotected oral-anal intercourse. A total of 124 (81.1%) were symptomatic; diarrhea was the most common complaint (68.3%). Multivariable regression showed increased odds of symptoms associated with age under 41 (odds ratio 5.44, 95% CI 1.87–15.88; p = 0.002). Colonoscopy was normal in 153 (92.7%). Furthermore, 66.7% presented previous or concomitant sexually transmitted diseases (STDs). Among the patients, 102 underwent testing for other gastrointestinal pathogens, with positive results in 20 (19.6%). All symptomatic patients without concomitant gastrointestinal infection presenting improvement on follow-up (42 of 53) had received either metronidazole or doxycycline (p = 0.049). HIS should be considered as a cause of chronic diarrhea in MSM with high-risk sexual behavior after other causes have been ruled out; treatment with metronidazole is recommended. Coinfection with other STDs is common.

Published
2023
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10. Compassionate use of tocilizumab in severe SARS-CoV2 pneumonia

Author

Miguel Górgolas Hernández-Mora, Alfonso Cabello Úbeda, Laura Prieto-Pérez, Felipe Villar Álvarez, Beatriz Álvarez Álvarez, María Jesús Rodríguez Nieto, Irene Carrillo Acosta, Itziar Fernández Ormaechea, Aws Waleed Mohammed Al-Hayani, Pilar Carballosa, Silvia Calpena Martínez, Farah Ezzine, Marina Castellanos González, Alba Naya, Marta López De Las Heras, Marcel José Rodríguez Guzmán, Ana Cordero Guijarro, Antonio Broncano Lavado, Alicia Macías Valcayo, Marta Martín García, Javier Bécares Martínez, Ricardo Fernández Roblas, Miguel Ángel Piris Pinilla, José Fortes Alen, Olga Sánchez Pernaute, Fredeswinda Romero Bueno, Sarah Heili-Frades, and Germán Peces-Barba Romero

Subjects
SARS-CoV-2, Covid-19, Tocilizumab, Pneumonia, Treatment, Infectious and parasitic diseases, RC109-216
Abstract

Introduction: Tocilizumab (TCZ) is an interleukin-6 receptor antagonist, which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), which aims to ameliorate the cytokine release syndrome (CRS) induced acute respiratory distress syndrome (ARDS). However, there are no consistent data about who might benefit most from it. Methods: We administered TCZ on a compassionate-use basis to patients with SSP who were hospitalized (excluding intensive care and intubated cases) and who required oxygen support to have a saturation >93%. The primary endpoint was intubation or death after 24 h of its administration. Patients received at least one dose of 400 mg intravenous TCZ from March 8, 2020 to April 20, 2020. Results: A total of 207 patients were studied and 186 analyzed. The mean age was 65 years and 68% were male patients. A coexisting condition was present in 68% of cases. Prognostic factors of death were older age, higher IL-6, d-dimer and high-sensitivity C-reactive protein (HSCRP), lower total lymphocytes, and severe disease that requires additional oxygen support. The primary endpoint (intubation or death) was significantly worst (37% vs 13%, p < 0·001) in those receiving the drug when the oxygen support was high (FiO2 >0.5%). Conclusions: TCZ is well tolerated in patients with SSP, but it has a limited effect on the evolution of cases with high oxygen support needs.

Published
2021
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11. COVID-19 in people living with HIV: A multicenter case-series study

Author

Alfonso Cabello, Belén Zamarro, Sara Nistal, Virginia Victor, Jana Hernández, Laura Prieto-Pérez, Irene Carrillo, Beatriz Álvarez, Ricardo Fernández-Roblas, Marta Hernández-Segurado, Javier Becares, José Miguel Benito, Norma Rallón, Raquel Téllez, Ángel Luis Castaño, Antonio Herrero, and Miguel Górgolas

Subjects
HIV, COVID-19, SARS-CoV-2, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Information on how COVID-19 affects people living with HIV (PLHIV) remains scarce. Methods: An observational study was conducted in four public hospitals in Madrid. All HIV patients with confirmed or suspected COVID-19 were included and compared with COVID-19 patients without HIV infection. Results: Sixty-three patients with HIV infection and confirmed or suspected COVID-19 were analyzed. The median age was 46 years (IQR: 37–56 years), and 88.9% were men. The median duration of HIV infection was 10.8 years (IQR: 6.5–16.8 years), and 96.8% were on antiretroviral therapy. 84.1% had previous comorbidities. The most common symptoms were fever (66.1%), cough (66.1%) and dyspnea (46.8%). Pneumonia was found in 47.5%, 28.6% of patients had severe disease, and 32.3% were admitted to hospital. The ICU admission rate and the mortality rate were both 3.17%. A significant association was observed between age, arterial hypertension, overweight, and diabetes mellitus and the severity of COVID-19. No association was observed between HIV-related factors and the severity of COVID-19. The rate of COVID-19 in HIV-patients was 1.68%. Similar hospitalization (31.74% vs 32.57%) and ICU admission (3.17% vs 2%) rates were observed with non-HIV infected patients. A lower mortality rate during hospitalization (10% vs 21.37%) and a lower global mortality rate (3.17% vs 6.96%) were also observed. Conclusions: Established poor prognostic factors for COVID-19 patients, such as age and comorbidities, remain the main determinants for PLHIV. Neither the HIV severity nor the type of ARV treatment seem to influence the outcome of COVID-19. Large prospective cohorts are needed in order to establish the differences between HIV-positive and HIV-negative patients.

Published
2021
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12. 48-Week effectiveness and tolerability of dolutegravir (DTG) + lamivudine (3TC) in antiretroviral-naïve adults living with HIV: A multicenter real-life cohort.

Author

Alfonso Cabello-Ubeda, Juan Carlos López Bernardo de Quirós, Luz Martín Carbonero, Jesús Sanz, Jorge Vergas, Álvaro Mena, Miguel Torralba, Marta Hernández Segurado, Adriana Pinto, Francisco Tejerina, Esmeralda Palmier, Ángela Gutiérrez, Pilar Vázquez, Federico Pulido, and Miguel Górgolas

Subjects
Medicine, Science
Abstract

BackgroundThe main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use.MethodsA retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL.Results135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic.ConclusionsIn a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

Published
2022
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13. Different profiles among older adults with HIV according to their chronological age and the year of HIV diagnosis: The FUNCFRAIL cohort study (GeSIDA 9817).

Author

Fátima Brañas, Mª José Galindo, Miguel Torralba, Antonio Antela, Jorge Vergas, Margarita Ramírez, Pablo Ryan, Fernando Dronda, Carmen Busca, Isabel Machuca, Mª Jesús Bustinduy, Alfonso Cabello, Matilde Sánchez-Conde, and FUNCFRAIL study group

Subjects
Medicine, Science
Abstract

BackgroundPeople in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group.ObjectiveTo evaluate the differences among older adults with HIV according to their chronological age and the year of HIV diagnosis.MethodsCross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors [LTHS]) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL).ResultsWe evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996. Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis. LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB ConclusionsA LTHS and a 65 or over person are both "older adults with HIV," but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.

Published
2022
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14. First and Second Waves of Coronavirus Disease 2019 in Madrid, Spain: Clinical Characteristics and Hematological Risk Factors Associated With Critical/Fatal Illness

Author

Irene Mollinedo-Gajate, PhD, Felipe Villar-Álvarez, MD, PhD, María de los Ángeles Zambrano-Chacón, MD, Laura Núñez-García, MD, Laura de la Dueña-Muñoz, MD, Carlos López-Chang, MD, Miguel Górgolas, MD, PhD, Alfonso Cabello, MD, PhD, Olga Sánchez-Pernaute, MD, PhD, Fredeswinda Romero-Bueno, MD, PhD, Álvaro Aceña, MD, PhD, Nicolás González-Mangado, MD, PhD, Germán Peces-Barba, MD, PhD, and Faustino Mollinedo, PhD

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Objectives:. This study aims to determine similarities and differences in clinical characteristics between the patients from two waves of severe acute respiratory syndrome coronavirus-2 infection at the time of hospital admission, as well as to identify risk biomarkers of coronavirus disease 2019 severity. Design:. Retrospective observational study. Setting:. A single tertiary-care center in Madrid. Patients:. Coronavirus disease 2019 adult patients admitted to hospital from March 4, 2020, to March 25, 2020 (first infection wave), and during July 18, 2020, and August 20, 2020 (second infection wave). Interventions:. Treatment with a hospital-approved drug cocktail during hospitalization. Measurements and Main Results:. Demographic, clinical, and laboratory data were compared between the patients with moderate and critical/fatal illness across both infection waves. The median age of patients with critical/fatal coronavirus disease 2019 was 67.5 years (interquartile range, 56.75–78.25 yr; 64.5% male) in the first wave and 59.0 years (interquartile range, 48.25–80.50 yr; 70.8% male) in the second wave. Hypertension and dyslipidemia were major comorbidities in both waves. Body mass index over 25 and presence of bilateral pneumonia were common findings. Univariate logistic regression analyses revealed an association of a number of blood parameters with the subsequent illness progression and severity in both waves. However, some remarkable differences were detected between both waves that prevented an accurate extrapolation of prediction models from the first wave into the second wave. Interleukin-6 and d-dimer concentrations at the time of hospital admission were remarkably higher in patients who developed a critical/fatal condition only during the first wave (p < 0.001), although both parameters significantly increased with disease worsening in follow-up studies from both waves. Multivariate analyses from wave 1 rendered a predictive signature for critical/fatal illness upon hospital admission that comprised six blood biomarkers: neutrophil-to-lymphocyte ratio (≥ 5; odds ratio, 2.684 [95% CI, 1.143–6.308]), C-reactive protein (≥ 15.2 mg/dL; odds ratio, 2.412 [95% CI, 1.006–5.786]), lactate dehydrogenase (≥ 411.96 U/L; odds ratio, 2.875 [95% CI, 1.229–6.726]), interleukin-6 (≥ 78.8 pg/mL; odds ratio, 5.737 [95% CI, 2.432–13.535]), urea (≥ 40 mg/dL; odds ratio, 1.701 [95% CI, 0.737–3.928]), and d-dimer (≥ 713 ng/mL; odds ratio, 1.903 [95% CI, 0.832–4.356]). The predictive accuracy of the signature was 84% and the area under the receiver operating characteristic curve was 0.886. When the signature was validated with data from wave 2, the accuracy was 81% and the area under the receiver operating characteristic curve value was 0.874, albeit most biomarkers lost their independent significance. Follow-up studies reassured the importance of monitoring the biomarkers included in the signature, since dramatic increases in the levels of such biomarkers occurred in critical/fatal patients over disease progression. Conclusions:. Most parameters analyzed behaved similarly in the two waves of coronavirus disease 2019. However, univariate logistic regression conducted in both waves revealed differences in some parameters associated with poor prognosis in wave 1 that were not found in wave 2, which may reflect a different disease stage of patients on arrival to hospital. The six-biomarker predictive signature reported here constitutes a helpful tool to classify patient’s prognosis on arrival to hospital.

Published
2021
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15. Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers

Author

José M. Benito, María C. Ortiz, Agathe León, Luis A. Sarabia, José M. Ligos, María Montoya, Marcial Garcia, Ezequiel Ruiz-Mateos, Rosario Palacios, Alfonso Cabello, Clara Restrepo, Carmen Rodriguez, Jorge del Romero, Manuel Leal, María A. Muñoz-Fernández, José Alcamí, Felipe García, Miguel Górgolas, Norma Rallón, and On behalf of ECRIS integrated in the Spanish AIDS Research Network

Subjects
Elite controllers, CD4 T-cell loss, Class modeling, T-cell homeostatic parameters, CD8 exhaustion, Medicine
Abstract

Abstract Background Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. Methods A case–control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares–class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. Results Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. Conclusions These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials.

Published
2018
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16. Diagnosis of cutaneous anthrax in resource-poor settings in West Arsi Province, Ethiopia

Author

Ramón Pérez-Tanoira, Jose Manuel Ramos, Laura Prieto-Pérez, Abraham Tesfamariam, Seble Balcha, Gabre Tissiano, Alfonso Cabello, Juan Cuadros, Natalia Rodríguez-Valero, Pablo Barreiro, Francisco Reyes, and Miguel Górgolas

Subjects
Bacillus anthracis, cutaneous anthrax, Ethiopia, Agriculture, Environmental sciences, GE1-350
Abstract

Introduction Cutaneous anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, which typically presents with ulcers after contact with animals or animal products, and is rarely seen in high-income countries but is common in those with low- and middle-incomes. Objective. The aim of this study is to show the main clinical characteristics of cutaneous anthrax in endemic areas. Material and methods The study describes the main clinical characteristics of cutaneous anthrax in eight patients (six female and two male, age range 1 – 56 years) admitted to the rural General Hospital of Gambo, West Arsi Province of Ethiopia from 2010–2013. Results In all cases, lesions began as an erythematous papule located on exposed sites (n=7 head; n=1 thigh) and subsequently became a necrotic black eschar surrounded by an edematous halo. Two patients presented with painful ipsilateral adenopathy near the black eschar. Four patients developed a malignant pustule on the suborbital region of the face. Patients responded positively to treatment, and the lesions resolved, leaving eschars. However, one patient suffered the loss of an eyeball, and another died 12 hours after starting treatment. Conclusions Physicians working in rural areas of resource-poor settings should be trained in the clinical identification of cutaneous anthrax. Early antibiotic treatment is essential for decreasing morbidity and mortality.

Published
2017
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17. Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression.

Author

Clara Restrepo, Mónica Gutierrez-Rivas, Yolanda M Pacheco, Marcial García, Julià Blanco, Luz M Medrano, María A Navarrete-Muñoz, Félix Gutiérrez, Pilar Miralles, David Dalmau, Juan Luis Gómez, Miguel Górgolas, Alfonso Cabello, Salvador Resino, José M Benito, Norma Rallón, and CoRIS and the HIV Biobank integrated in the Spanish AIDS Research Network Project RIS/EPICLIN 10_

Subjects
Medicine, Science
Abstract

OBJECTIVE:We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts. METHODS:A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count

Published
2019
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18. Drug-related and psychopathological symptoms in HIV-positive men who have sex with men who inject drugs during sex (slamsex): Data from the U-SEX GESIDA 9416 Study.

Author

Helen Dolengevich-Segal, Alicia Gonzalez-Baeza, Jorge Valencia, Eulalia Valencia-Ortega, Alfonso Cabello, Maria Jesus Tellez-Molina, Maria Jesus Perez-Elias, Regino Serrano, Leire Perez-Latorre, Luz Martin-Carbonero, Sari Arponen, Jose Sanz-Moreno, Sara De la Fuente, Otilia Bisbal, Ignacio Santos, Jose Luis Casado, Jesus Troya, Miguel Cervero-Jimenez, Sara Nistal, Guillermo Cuevas, Javier Correas-Lauffer, Marta Torrens, Pablo Ryan, and U-SEX GESIDA 9416 Study

Subjects
Medicine, Science
Abstract

OBJECTIVES:Sexualized intravenous drug use, also known as slamsex, seems to be increasing among HIV-positive men who have sex with men (MSM). Physical and psychopathological symptoms have previously been reported in this population, although research on the subject of slamsex is scarce. The objectives of our study were to describe the psychopathological background of a sample of HIV-positive MSM who engaged in slamsex during the previous year and to compare physical, psychopathological, and drug-related symptoms between these participants and those who engaged in non-injecting sexualized drug use. DESIGN AND METHODS:Participants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional online survey on sexual behavior and recreational drug use. When participants met the inclusion criteria, physicians offered them the opportunity to participate and gave them a card with a unique code and a link to access the online survey. The present analysis is based on HIV-positive MSM who had engaged in slamsex and non-injecting sexualized drug use. RESULTS:The survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) had engaged in chemsex, and of these, 34 (15.7%) had engaged in slamsex. Participants who engaged in slamsex were more likely to have current psychopathology (depression, anxiety, and drug-related disorders) than participants who engaged in non-injecting sexualized drug use. In addition, participants who engaged in slamsex more frequently reported high-risk sexual behaviors and polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with participants who did not inject drugs, participants who engaged in slamsex experienced more severe drug-related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms during or after slamsex (eg, paranoid thoughts and suicidal behaviors). CONCLUSION:Slamsex is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.

Published
2019
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19. Liver Stiffness Hinders Normalization of Systemic Inflammation and Endothelial Activation after Hepatitis C Virus (HCV) Eradication in HIV/HCV Coinfected Patients

Author

Beatriz Álvarez, Clara Restrepo, Marcial García, María A. Navarrete-Muñoz, María A. Jiménez-Sousa, Laura Prieto, Alfonso Cabello, Sara Nistal, Salvador Resino, Miguel Górgolas, Norma Rallón, and José M. Benito

Subjects
systemic inflammation, endothelial activation, HIV/HCV coinfection, liver stiffness, HCV eradication, DAAs, Medicine
Abstract

Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these conditions. However, HCV can be eradicated in most patients with the new direct-acting antivirals (DAAs) therapy. We have analyzed the effect of HCV on systemic inflammation, endothelial activation and coagulopathy in PLWH and its evolution after HCV eradication with DAAs. Twenty-five HIV/HCV coinfected (HIV/HCV group), 25 HIV monoinfected (HIV group) and 20 healthy controls (HC) were included in the study. All patients were on ART and HIV suppressed. Levels of fourteen markers of systemic inflammation, endothelial activation and coagulopathy (IL-1ß, IL-6, IL-12p70, IL-8, TNFα, D-dimer, Eotaxin, IL-18, IP-10, monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), TNFα receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)) were measured on plasma at baseline and after DAAs-mediated HCV eradication. Non-parametric tests were used to establish inter/intra-group differences. At baseline, the HIV/HCV group showed increased levels of IL-18 (p = 0.028), IP-10 (p < 0.0001), VCAM-1 (p < 0.0001) and ICAM-1 (p = 0.045), compared to the HC and HIV groups, with the highest levels for IL18 and IP10 observed in HIV/HCV patients with increased liver stiffness (≥7.1 KPa). Eradication of HCV with DAAs-based therapy restored some but not all the evaluated parameters. VCAM-1 remained significantly increased compared to HC (p = 0.001), regardless of the level of basal liver stiffness in the HIV/HCV group, and IP-10 remained significantly increased only in the HIV/HCV group, with increased level of basal liver stiffness compared to the HC and to the HIV groups (p = 0.006 and p = 0.049, respectively). These data indicate that DAAs therapy in HIV/HCV co-infected patients and HCV eradication does not always lead to the normalization of systemic inflammation and endothelial dysfunction conditions, especially in cases with increased liver stiffness.

Published
2020
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20. Tinea nigra palmaris: a clinical case in a rural Ethiopian hospital

Author

Ramón Perez-Tanoira, Carlos Zarco Olivo, José Fortes Alen, Laura Prieto-Pérez, Alfonso Cabello, Jose Manuel Ramos Rincón, Juan Cuadros, and Miguel Górgolas

Subjects
Tinea nigra, Ethiopia, Hortaea werneckii, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

ABSTRACT Tinea nigra is an infrequent, superficial fungal infection, mainly caused by Hortaea werneckii, which is still underreported in Ethiopia. An asymptomatic 62-year-old male patient sought a rural hospital of Ethiopia, showing dark plaques on the palms of both hands. A superficial mycosis was suspected and a direct light microscopic mycological examination from skin scrapings revealed short brownish hyphae. To our knowledge, this is the first case of tinea nigra from the Ethiopian highlands. This may be due to the actual rarity of the condition or to underreporting.

Published
2018
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21. Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection.

Author

Norma Rallón, Marcial García, Javier García-Samaniego, Alfonso Cabello, Beatriz Álvarez, Clara Restrepo, Sara Nistal, Miguel Górgolas, and José M Benito

Subjects
Medicine, Science
Abstract

T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection.96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored.Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035).Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.

Published
2018
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22. Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study.

Author

Jesús Troya, Rocio Montejano, Pablo Ryan, Cristina Gómez, Mariano Matarranz, Alfonso Cabello, Francisco Vera, María Antonia Sepúlveda, Ignacio Santos, Gloria Samperiz, Pablo Bachiller, Vicente Boix, Pilar Barrufet, Miguel Cervero, José Sanz, Javier Solís, María Yllescas, Eulalia Valencia, and GESIDA-8715 Study Group

Subjects
Medicine, Science
Abstract

BACKGROUND:Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. DESIGN:Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. METHODS:We evaluated effectiveness (defined as maintenance of HIV-1-RNA

Published
2018
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23. HCV coinfection contributes to HIV pathogenesis by increasing immune exhaustion in CD8 T-cells.

Author

Norma Rallón, Marcial García, Javier García-Samaniego, Noelia Rodríguez, Alfonso Cabello, Clara Restrepo, Beatriz Álvarez, Rosa García, Miguel Górgolas, and José M Benito

Subjects
Medicine, Science
Abstract

BACKGROUND:There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS:Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. RESULTS:HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. CONCLUSIONS:We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.

Published
2017
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24. Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Author

Sánchez, Fernando Fernández, de Lomas, José Mª García, Rosas, Gabriel, de la Torre Lima, Javier, Bereciartua, Elena, Vidal, María José Blanco, Blanco, Roberto, Boado, María Victoria, Lázaro, Marta Campaña, Crespo, Alejandro, Carrión, Laura Guio, Del Álamo Martínez de Lagos, Mikel, Ugarte, Gorane Euba, Goikoetxea, Ane Josune, Hierro, Marta Ibarrola, Iruretagoyena, José Ramón, Zuazabal, Josu Irurzun, López-Soria, Leire, Montejo, Miguel, Nieto, Javier, Rodrigo, David, Rodríguez, Regino, Vitoria, Yolanda, Voces, Roberto, López, Mª Victoria García, Georgieva, Radka Ivanova, Ojeda, Guillermo, Bailón, Isabel Rodríguez, Morales, Josefa Ruiz, Rodríguez, Ignacio Álvarez, Galparsoro, Harkaitz Azkune, Boronat, Elisa Berritu, Odriozola, Mª Jesús Bustinduy, del Bosque Martín, Cristina, Echeverría, Tomás, Yarza, Alberto Eizaguirre, Fuentes, Ana, Goenaga, Miguel Ángel, del Río, Muskilda Goyeneche, Bauza, Ángela Granda, Iribarren, José Antonio, Urkola, Xabier Kortajarena, López, José Ignacio Pérez-Moreiras, Jiménez, Ainhoa Rengel, Reviejo, Karlos, Berbejillo, Alberto Sáez, Haza, Elou Sánchez, Alda, Rosa Sebastián, Ruiz, Itziar Solla, Ugartemendia, Irati Unamuno, Anza, Diego Vicente, Benito, Iñaki Villanueva, Arrieta, Mar Zabalo, Carrasco, Rafael, Climent, Vicente, Llamas, Patricio, Merino, Esperanza, Plazas, Joaquín, Reus, Sergio, Bouzas, Alberto, Castelo, Brais, Cuenca, José, Gutiérrez, Laura, Ramos, Lucía, Mayo, María Rodríguez, Serrano, Joaquín Manuel, Regueiro, Dolores Sousa, Martínez, Francisco Javier, del Mar Alonso, Mª, Castro, Beatriz, Melian, Teresa Delgado, Sarabia, Javier Fernández, Rosado, Dácil García, González, Julia González, Lacalzada, Juan, de la Peña, Lissete Lorenzo, Ramírez, Alina Pérez, Arrondo, Pablo Prada, Moreno, Fermín Rodríguez, Ciezar, Antonio Plata, Iglesias, José Mª Reguera, Álvarez, Víctor Asensi, Costas, Carlos, de la Hera, Jesús, Suárez, Jonnathan Fernández, Fraile, Lisardo Iglesias, Arguero, Víctor León, Menéndez, José López, Bajo, Pilar Mencia, Morales, Carlos, Torrico, Alfonso Moreno, Palomo, Carmen, Martínez, Begoña Paya, Esteban, Ángeles Rodríguez, García, Raquel Rodríguez, Asensio, Mauricio Telenti, Almela, Manuel, Ambrosioni, Juan, Azqueta, Manuel, Brunet, Mercè, Bodro, Marta, Cartañá, Ramón, Cuervo, Guillermo, Falces, Carlos, Fernández-Pittol, Mariana J, Fita, Guillermina, Fuster, David, de la Mària, Cristina García, García-Pares, Delia, Hernández-Meneses, Marta, Pérez, Jaume Llopis, Marco, Francesc, Miró, José M., Moreno, Asunción, Nicolás, David, Ninot, Salvador, Quintana, Eduardo, Paré, Carlos, Pereda, Daniel, Pericás, Juan M., Pomar, José L., Ramírez, José, Roque, Mercè, Rovira, Irene, Sandoval, Elena, Sitges, Marta, Soy, Dolors, Téllez, Adrián, Tolosana, José M., Vidal, Bárbara, Vila, Jordi, Adán, Iván, Alonso, David, Alonso, Juan Carlos, Álvarez-Uría, Ana, Bermejo, Javier, Bouza, Emilio, Caballero, Gregorio Cuerpo, Montero, Antonia Delgado, Estévez, Agustín, Ribas, Ramón Fortuny, Gargallo, Esther, Leoni, Mª Eugenia García, Mansilla, Ana González, Moraga, Francisco Javier González, Ramallo, Víctor González, Hernández, Martha Kestler, Hualde, Amaia Mari, Machado, Marina, Marín, Mercedes, Martínez-Sellés, Manuel, Melero, Rosa, Muñoz, Patricia, Monzón, Diego, Olmedo, María, Pedraz, Álvaro, Pinilla, Blanca, Pinto, Ángel, Rincón, Cristina, Rodríguez-Abella, Hugo, Rodríguez-Créixems, Marta, Sánchez-Pérez, Eduardo, Segado, Antonio, Toledo, Neera, Valerio, Maricela, Vázquez, Pilar, Moreno, Eduardo Verde, de la Villa, Sofía, Antorrena, Isabel, Loeches, Belén, Moreno, Mar, Ramírez, Ulises, Bastón, Verónica Rial, Romero, María, Rosillo, Sandra, Balbín, Jesús Agüero, Fernández, Cristina Amado, Castillo, Carlos Armiñanzas, de las Revillas, Francisco Arnaiz, Belaustegui, Manuel Cobo, Fariñas, María Carmen, Fariñas-Álvarez, Concepción, Sampedro, Marta Fernández, García, Iván, Rico, Claudia González, Gutiérrez-Fernández, Laura, Gutiérrez-Cuadra, Manuel, Díez, José Gutiérrez, Pajarón, Marcos, Parra, José Antonio, Teira, Ramón, Zarauza, Jesús, Parra, Jorge Calderón, Cobo, Marta, Domínguez, Fernando, Pavía, Pablo García, Cruz, Ana Fernández, Ramos-Martínez, Antonio, Romero, Isabel Sánchez, Centella, Tomasa, Hermida, José Manuel, Moya, José Luis, Martín-Dávila, Pilar, Navas, Enrique, Oliva, Enrique, del Río, Alejandro, Stuart, Jorge Rodríguez-Roda, Ruiz, Soledad, Tenorio, Carmen Hidalgo, Sequera, Sergio, Delia, Manuel Almendro, Araji, Omar, Barquero, José Miguel, Jambrina, Román Calvo, de Cueto, Marina, Acebal, Juan Gálvez, Méndez, Irene, Morales, Isabel, López-Cortés, Luis Eduardo, de Alarcón, Arístides, Gutiérrez-Carretero, Encarnación, Lepe, José Antonio, López-Haldón, José, Luque-Márquez, Rafael, Marín, Guillermo, Ortiz-Carrellán, Antonio, Sánchez-Domínguez, Eladio, Alonso, Luis Javier, Azcárate, Pedro, Gutiérrez, José Manuel Azcona, Blanco, José Ramón, Armas, Estíbaliz Corral, García-Álvarez, Lara, Oteo, José Antonio, Membrilla, Antonio Barros, Iglesias, Antonino Ginel, Grillo, Sara, Petracca, Rubén Leta, López-Contreras, Joaquín, Martínez, María Alba Rivera, Álvarez, M., Fernández, A.L., Martínez, Amparo, Prieto, A., Regueiro, Benito, Tijeira, E., Vega, Marino, Quiñonero, Amaia Aguirre, Miñambres, Ángela Alonso, Arana, Juan Carlos Gainzarain, de Alaiza Ortega, Sara González, Rodríguez, Miguel Ángel Morán, Rodríguez, Anai Moreno, de Zárate, Zuriñe Ortiz, Zapirain, José Joaquín Portu, de Adana Arroniz, Ester Sáez, Sánchez, Daisy Carolina Sorto, Antonio, Sánchez-Porto, Alejandro, Úbeda Iglesias, Leal, José Mª Arribas, Vázquez, Elisa García, Torres, Alicia Hernández, Blázquez, Ana, de la Morena Valenzuela, Gonzalo, Alonso, Ángel, Aramburu, Javier, Calvo, Felicitas Elena, Tarabini-Castellani, Paola, Gálvez, Eva Heredero, Bellido, Carolina Maicas, Pau, José Largo, Sepúlveda, Mª Antonia, Sierra, Pilar Toledano, Iqbal-Mirza, Sadaf Zafar, Alcolea, Eva Cascales, Yañez, Ivan Keituqwa, Martínez, Julián Navarro, Ballesta, Ana Peláez, Escobar, Eduardo Moreno, Monje, Alejandro Peña, Cabrera, Valme Sánchez, García, David Vinuesa, Asenjo, María Arrizabalaga, Luna, Carmen Cifuentes, Morcillo, Juana Núñez, Seco, Mª Cruz Pérez, Gelabert, Aroa Villoslada, Guallar, Carmen Aured, Abad, Nuria Fernández, Mangas, Pilar García, Adell, Marta Matamala, Ruiz, Mª Pilar Palacián, Porres, Juan Carlos, Vidal, Begoña Alcaraz, Del Amor Espín, María Jesús, Buendía, Francisco, Sánchez, Roberto Jiménez, Mármol, Rosario, Martínez, Francisco, Meseguer, Antonio, Pérez, Beatriz, Risco, Leticia, Saura, Zoser, Silva, Vanina, Villmarín, Mª Belén, Blanco, Mª Ángels Ribas, de Gopegui Bordes, Enrique Ruiz, Bonet, Laura Vidal, Borràs, Miquel Vives, Munera, Mª Carmen Bellón, Garaizabal, Elena Escribano, Martínez, Antonia Tercero, Luque, Juan Carlos Segura, Badía, Cristina, Palop, Lucía Boix, Xercavins, Mariona, Ibars, Sónia, Bosch, Xerach, Nebreda, Eloy Gómez, Herrera, Ibalia Horcajada, Gallego, Irene Menduiña, Pulido, Imanol, Santiago, Héctor Marrero, de Miguel Martínez, Isabel, Álamo, Elena Pisos, Sánchez, Daniel San Román, Pérez, Jorge Boan, Blanco, Eva Mª Aguilar, González, Mercedes Catalán, Peiretti, María Angélica Corres, Esteve, Andrea Eixerés, Pérez, Laura Domínguez, de Cossío Tejido, Santiago, Román, Francisco Galván, Robles, José Antonio García, Medrano, Francisco López, Gude, Mª Jesús López, Miguel, Mª Ángeles Orellana, Pilkington, Patrick, Ostalaza, Yolanda Revilla, Morales, Juan Ruiz, Solís, Sebastián Ruiz, Collado, Ana Sabín, Fernández, Marcos Sánchez, Rallo, Javier Solera, Martín, Jorge Solís, Escrihuela-Vidal, Francesc, Carratalà, Jordi, Grau, Inmaculada, Ardanuy, Carmen, Berbel, Dámaris, Salado, José Carlos Sánchez, Alegre, Oriol, Majoral, Alejandro Ruiz, Sbraga, Fabrizio, Blasco, Arnau, Sánchez, Laura Gracia, Sánchez-Rodríguez, Iván, Aldamiz, Gonzalo, Álvarez, Beatriz, Palacios, Marina Bernal, Úbeda, Alfonso Cabello, Roblas, Ricardo Fernández, Hernández, Rafael, Martín, Victoria Andrea Hortigüela, Kallmeyer, Andrea, Kancev, Cristina Landaeta, Martín, Marta, Ruiz, Miguel Morante, Lobato, Miguel Ángel Navas, Pello, Ana María, Prieto, Laura, Mallebrera, Marta Tomás, Varela, Laura, de la Peña Triguero, Mireia, Cerón, Ruth Esther Figueroa, Gómez, Lara Ruiz, Ble, Mireia, Gallego, Juan Pablo Horcajada, Ginel, Antonio José, López, Inmaculada, Mas, Alexandra, Mestres, Antoni, Molina, Lluís, Serrat, Ramón, Ribas, Núria, Sánchez, Francisca, Silverio, Ana, Suárez, Marina, Sorlí, Luisa, Recasens, Lluís, Taurón, Manuel, Regueras, María Fernández, Vallejo, María Ángeles Mantecón, Rivera, José Ángel Pérez, Mata, Nuria Sánchez, Cano, Antonia Calvo, Olivares, Miguel Fajardo, Núñez, María Victoria Millán, Sanz, Agustín Muñoz, Herrera-Hidalgo, Laura, Alonso-Menchén, David, Luque-Marquez, Rafael, Fariñas, María Del Carmen, Miró, Jose Maria, Goenaga, Miguel Angel, Angulo-Lara, Basilio, and Boix-Palop, Lucia

Published
2023
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26. The Era of DAAs: Assessing the Clinical Impact and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals

Author

Álvarez-Álvarez, Beatriz, primary, Prieto-Pérez, Laura, additional, Cuadra-Grande, Alberto de la, additional, Casado, Miguel Ángel, additional, Úbeda, Alfonso Cabello, additional, Al-Hayani, Aws W., additional, Acosta, Irene Carrillo, additional, Mahillo-Fernández, Ignacio, additional, Hernández-Mora, Miguel Górgolas, additional, Rallón, Norma, additional, and Benito, Jose M., additional

Published
2024
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27. Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Author

Herrera-Hidalgo, Laura, primary, Muñoz, Patricia, additional, Álvarez-Uría, Ana, additional, Alonso-Menchén, David, additional, Luque-Marquez, Rafael, additional, Gutiérrez-Carretero, Encarnación, additional, Fariñas, María Del Carmen, additional, Miró, Jose Maria, additional, Goenaga, Miguel Angel, additional, López-Cortés, Luis Eduardo, additional, Angulo-Lara, Basilio, additional, Boix-Palop, Lucia, additional, de Alarcón, Arístides, additional, Sánchez, Fernando Fernández, additional, de Lomas, José Mª García, additional, Rosas, Gabriel, additional, de la Torre Lima, Javier, additional, Bereciartua, Elena, additional, Vidal, María José Blanco, additional, Blanco, Roberto, additional, Boado, María Victoria, additional, Lázaro, Marta Campaña, additional, Crespo, Alejandro, additional, Carrión, Laura Guio, additional, Del Álamo Martínez de Lagos, Mikel, additional, Ugarte, Gorane Euba, additional, Goikoetxea, Ane Josune, additional, Hierro, Marta Ibarrola, additional, Iruretagoyena, José Ramón, additional, Zuazabal, Josu Irurzun, additional, López-Soria, Leire, additional, Montejo, Miguel, additional, Nieto, Javier, additional, Rodrigo, David, additional, Rodríguez, Regino, additional, Vitoria, Yolanda, additional, Voces, Roberto, additional, López, Mª Victoria García, additional, Georgieva, Radka Ivanova, additional, Ojeda, Guillermo, additional, Bailón, Isabel Rodríguez, additional, Morales, Josefa Ruiz, additional, Rodríguez, Ignacio Álvarez, additional, Galparsoro, Harkaitz Azkune, additional, Boronat, Elisa Berritu, additional, Odriozola, Mª Jesús Bustinduy, additional, del Bosque Martín, Cristina, additional, Echeverría, Tomás, additional, Yarza, Alberto Eizaguirre, additional, Fuentes, Ana, additional, Goenaga, Miguel Ángel, additional, del Río, Muskilda Goyeneche, additional, Bauza, Ángela Granda, additional, Iribarren, José Antonio, additional, Urkola, Xabier Kortajarena, additional, López, José Ignacio Pérez-Moreiras, additional, Jiménez, Ainhoa Rengel, additional, Reviejo, Karlos, additional, Berbejillo, Alberto Sáez, additional, Haza, Elou Sánchez, additional, Alda, Rosa Sebastián, additional, Ruiz, Itziar Solla, additional, Ugartemendia, Irati Unamuno, additional, Anza, Diego Vicente, additional, Benito, Iñaki Villanueva, additional, Arrieta, Mar Zabalo, additional, Carrasco, Rafael, additional, Climent, Vicente, additional, Llamas, Patricio, additional, Merino, Esperanza, additional, Plazas, Joaquín, additional, Reus, Sergio, additional, Bouzas, Alberto, additional, Castelo, Brais, additional, Cuenca, José, additional, Gutiérrez, Laura, additional, Ramos, Lucía, additional, Mayo, María Rodríguez, additional, Serrano, Joaquín Manuel, additional, Regueiro, Dolores Sousa, additional, Martínez, Francisco Javier, additional, del Mar Alonso, Mª, additional, Castro, Beatriz, additional, Melian, Teresa Delgado, additional, Sarabia, Javier Fernández, additional, Rosado, Dácil García, additional, González, Julia González, additional, Lacalzada, Juan, additional, de la Peña, Lissete Lorenzo, additional, Ramírez, Alina Pérez, additional, Arrondo, Pablo Prada, additional, Moreno, Fermín Rodríguez, additional, Ciezar, Antonio Plata, additional, Iglesias, José Mª Reguera, additional, Álvarez, Víctor Asensi, additional, Costas, Carlos, additional, de la Hera, Jesús, additional, Suárez, Jonnathan Fernández, additional, Fraile, Lisardo Iglesias, additional, Arguero, Víctor León, additional, Menéndez, José López, additional, Bajo, Pilar Mencia, additional, Morales, Carlos, additional, Torrico, Alfonso Moreno, additional, Palomo, Carmen, additional, Martínez, Begoña Paya, additional, Esteban, Ángeles Rodríguez, additional, García, Raquel Rodríguez, additional, Asensio, Mauricio Telenti, additional, Almela, Manuel, additional, Ambrosioni, Juan, additional, Azqueta, Manuel, additional, Brunet, Mercè, additional, Bodro, Marta, additional, Cartañá, Ramón, additional, Cuervo, Guillermo, additional, Falces, Carlos, additional, Fernández-Pittol, Mariana J, additional, Fita, Guillermina, additional, Fuster, David, additional, de la Mària, Cristina García, additional, García-Pares, Delia, additional, Hernández-Meneses, Marta, additional, Pérez, Jaume Llopis, additional, Marco, Francesc, additional, Miró, José M., additional, Moreno, Asunción, additional, Nicolás, David, additional, Ninot, Salvador, additional, Quintana, Eduardo, additional, Paré, Carlos, additional, Pereda, Daniel, additional, Pericás, Juan M., additional, Pomar, José L., additional, Ramírez, José, additional, Roque, Mercè, additional, Rovira, Irene, additional, Sandoval, Elena, additional, Sitges, Marta, additional, Soy, Dolors, additional, Téllez, Adrián, additional, Tolosana, José M., additional, Vidal, Bárbara, additional, Vila, Jordi, additional, Adán, Iván, additional, Alonso, David, additional, Alonso, Juan Carlos, additional, Bermejo, Javier, additional, Bouza, Emilio, additional, Caballero, Gregorio Cuerpo, additional, Montero, Antonia Delgado, additional, Estévez, Agustín, additional, Ribas, Ramón Fortuny, additional, Gargallo, Esther, additional, Leoni, Mª Eugenia García, additional, Mansilla, Ana González, additional, Moraga, Francisco Javier González, additional, Ramallo, Víctor González, additional, Hernández, Martha Kestler, additional, Hualde, Amaia Mari, additional, Machado, Marina, additional, Marín, Mercedes, additional, Martínez-Sellés, Manuel, additional, Melero, Rosa, additional, Monzón, Diego, additional, Olmedo, María, additional, Pedraz, Álvaro, additional, Pinilla, Blanca, additional, Pinto, Ángel, additional, Rincón, Cristina, additional, Rodríguez-Abella, Hugo, additional, Rodríguez-Créixems, Marta, additional, Sánchez-Pérez, Eduardo, additional, Segado, Antonio, additional, Toledo, Neera, additional, Valerio, Maricela, additional, Vázquez, Pilar, additional, Moreno, Eduardo Verde, additional, de la Villa, Sofía, additional, Antorrena, Isabel, additional, Loeches, Belén, additional, Moreno, Mar, additional, Ramírez, Ulises, additional, Bastón, Verónica Rial, additional, Romero, María, additional, Rosillo, Sandra, additional, Balbín, Jesús Agüero, additional, Fernández, Cristina Amado, additional, Castillo, Carlos Armiñanzas, additional, de las Revillas, Francisco Arnaiz, additional, Belaustegui, Manuel Cobo, additional, Fariñas, María Carmen, additional, Fariñas-Álvarez, Concepción, additional, Sampedro, Marta Fernández, additional, García, Iván, additional, Rico, Claudia González, additional, Gutiérrez-Fernández, Laura, additional, Gutiérrez-Cuadra, Manuel, additional, Díez, José Gutiérrez, additional, Pajarón, Marcos, additional, Parra, José Antonio, additional, Teira, Ramón, additional, Zarauza, Jesús, additional, Parra, Jorge Calderón, additional, Cobo, Marta, additional, Domínguez, Fernando, additional, Pavía, Pablo García, additional, Cruz, Ana Fernández, additional, Ramos-Martínez, Antonio, additional, Romero, Isabel Sánchez, additional, Centella, Tomasa, additional, Hermida, José Manuel, additional, Moya, José Luis, additional, Martín-Dávila, Pilar, additional, Navas, Enrique, additional, Oliva, Enrique, additional, del Río, Alejandro, additional, Stuart, Jorge Rodríguez-Roda, additional, Ruiz, Soledad, additional, Tenorio, Carmen Hidalgo, additional, Sequera, Sergio, additional, Delia, Manuel Almendro, additional, Araji, Omar, additional, Barquero, José Miguel, additional, Jambrina, Román Calvo, additional, de Cueto, Marina, additional, Acebal, Juan Gálvez, additional, Méndez, Irene, additional, Morales, Isabel, additional, Lepe, José Antonio, additional, López-Haldón, José, additional, Luque-Márquez, Rafael, additional, Marín, Guillermo, additional, Ortiz-Carrellán, Antonio, additional, Sánchez-Domínguez, Eladio, additional, Alonso, Luis Javier, additional, Azcárate, Pedro, additional, Gutiérrez, José Manuel Azcona, additional, Blanco, José Ramón, additional, Armas, Estíbaliz Corral, additional, García-Álvarez, Lara, additional, Oteo, José Antonio, additional, Membrilla, Antonio Barros, additional, Iglesias, Antonino Ginel, additional, Grillo, Sara, additional, Petracca, Rubén Leta, additional, López-Contreras, Joaquín, additional, Martínez, María Alba Rivera, additional, Álvarez, M., additional, Fernández, A.L., additional, Martínez, Amparo, additional, Prieto, A., additional, Regueiro, Benito, additional, Tijeira, E., additional, Vega, Marino, additional, Quiñonero, Amaia Aguirre, additional, Miñambres, Ángela Alonso, additional, Arana, Juan Carlos Gainzarain, additional, de Alaiza Ortega, Sara González, additional, Rodríguez, Miguel Ángel Morán, additional, Rodríguez, Anai Moreno, additional, de Zárate, Zuriñe Ortiz, additional, Zapirain, José Joaquín Portu, additional, de Adana Arroniz, Ester Sáez, additional, Sánchez, Daisy Carolina Sorto, additional, Antonio, Sánchez-Porto, additional, Alejandro, Úbeda Iglesias, additional, Leal, José Mª Arribas, additional, Vázquez, Elisa García, additional, Torres, Alicia Hernández, additional, Blázquez, Ana, additional, de la Morena Valenzuela, Gonzalo, additional, Alonso, Ángel, additional, Aramburu, Javier, additional, Calvo, Felicitas Elena, additional, Tarabini-Castellani, Paola, additional, Gálvez, Eva Heredero, additional, Bellido, Carolina Maicas, additional, Pau, José Largo, additional, Sepúlveda, Mª Antonia, additional, Sierra, Pilar Toledano, additional, Iqbal-Mirza, Sadaf Zafar, additional, Alcolea, Eva Cascales, additional, Yañez, Ivan Keituqwa, additional, Martínez, Julián Navarro, additional, Ballesta, Ana Peláez, additional, Escobar, Eduardo Moreno, additional, Monje, Alejandro Peña, additional, Cabrera, Valme Sánchez, additional, García, David Vinuesa, additional, Asenjo, María Arrizabalaga, additional, Luna, Carmen Cifuentes, additional, Morcillo, Juana Núñez, additional, Seco, Mª Cruz Pérez, additional, Gelabert, Aroa Villoslada, additional, Guallar, Carmen Aured, additional, Abad, Nuria Fernández, additional, Mangas, Pilar García, additional, Adell, Marta Matamala, additional, Ruiz, Mª Pilar Palacián, additional, Porres, Juan Carlos, additional, Vidal, Begoña Alcaraz, additional, Del Amor Espín, María Jesús, additional, Buendía, Francisco, additional, Sánchez, Roberto Jiménez, additional, Mármol, Rosario, additional, Martínez, Francisco, additional, Meseguer, Antonio, additional, Pérez, Beatriz, additional, Risco, Leticia, additional, Saura, Zoser, additional, Silva, Vanina, additional, Villmarín, Mª Belén, additional, Blanco, Mª Ángels Ribas, additional, de Gopegui Bordes, Enrique Ruiz, additional, Bonet, Laura Vidal, additional, Borràs, Miquel Vives, additional, Munera, Mª Carmen Bellón, additional, Garaizabal, Elena Escribano, additional, Martínez, Antonia Tercero, additional, Luque, Juan Carlos Segura, additional, Badía, Cristina, additional, Palop, Lucía Boix, additional, Xercavins, Mariona, additional, Ibars, Sónia, additional, Bosch, Xerach, additional, Nebreda, Eloy Gómez, additional, Herrera, Ibalia Horcajada, additional, Gallego, Irene Menduiña, additional, Pulido, Imanol, additional, Santiago, Héctor Marrero, additional, de Miguel Martínez, Isabel, additional, Álamo, Elena Pisos, additional, Sánchez, Daniel San Román, additional, Pérez, Jorge Boan, additional, Blanco, Eva Mª Aguilar, additional, González, Mercedes Catalán, additional, Peiretti, María Angélica Corres, additional, Esteve, Andrea Eixerés, additional, Pérez, Laura Domínguez, additional, de Cossío Tejido, Santiago, additional, Román, Francisco Galván, additional, Robles, José Antonio García, additional, Medrano, Francisco López, additional, Gude, Mª Jesús López, additional, Miguel, Mª Ángeles Orellana, additional, Pilkington, Patrick, additional, Ostalaza, Yolanda Revilla, additional, Morales, Juan Ruiz, additional, Solís, Sebastián Ruiz, additional, Collado, Ana Sabín, additional, Fernández, Marcos Sánchez, additional, Rallo, Javier Solera, additional, Martín, Jorge Solís, additional, Escrihuela-Vidal, Francesc, additional, Carratalà, Jordi, additional, Grau, Inmaculada, additional, Ardanuy, Carmen, additional, Berbel, Dámaris, additional, Salado, José Carlos Sánchez, additional, Alegre, Oriol, additional, Majoral, Alejandro Ruiz, additional, Sbraga, Fabrizio, additional, Blasco, Arnau, additional, Sánchez, Laura Gracia, additional, Sánchez-Rodríguez, Iván, additional, Aldamiz, Gonzalo, additional, Álvarez, Beatriz, additional, Palacios, Marina Bernal, additional, Úbeda, Alfonso Cabello, additional, Roblas, Ricardo Fernández, additional, Hernández, Rafael, additional, Martín, Victoria Andrea Hortigüela, additional, Kallmeyer, Andrea, additional, Kancev, Cristina Landaeta, additional, Martín, Marta, additional, Ruiz, Miguel Morante, additional, Lobato, Miguel Ángel Navas, additional, Pello, Ana María, additional, Prieto, Laura, additional, Mallebrera, Marta Tomás, additional, Varela, Laura, additional, de la Peña Triguero, Mireia, additional, Cerón, Ruth Esther Figueroa, additional, Gómez, Lara Ruiz, additional, Ble, Mireia, additional, Gallego, Juan Pablo Horcajada, additional, Ginel, Antonio José, additional, López, Inmaculada, additional, Mas, Alexandra, additional, Mestres, Antoni, additional, Molina, Lluís, additional, Serrat, Ramón, additional, Ribas, Núria, additional, Sánchez, Francisca, additional, Silverio, Ana, additional, Suárez, Marina, additional, Sorlí, Luisa, additional, Recasens, Lluís, additional, Taurón, Manuel, additional, Regueras, María Fernández, additional, Vallejo, María Ángeles Mantecón, additional, Rivera, José Ángel Pérez, additional, Mata, Nuria Sánchez, additional, Cano, Antonia Calvo, additional, Olivares, Miguel Fajardo, additional, Núñez, María Victoria Millán, additional, and Sanz, Agustín Muñoz, additional

Published
2023
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28. Incidence of Anal Cancer and Related Risk Factors in HIV-Infected Patients Enrolled in the National Prospective Spanish Cohort CoRIS

Author

Cudós, Elena Sendagorta, primary, De La Piedra, César Sotomayor, additional, Canuto, Mar Masia, additional, Úbeda, Alfonso Cabello, additional, Curran, Adrian, additional, Hermida, Antonio Ocampo, additional, Rava, Marta, additional, Muriel, Alfonso, additional, Macías, Juan, additional, Rial-Crestelo, David, additional, Martínez-Sanz, Javier, additional, Martinez, Lorena, additional, De La Villa López-Sánchez, María, additional, and Perez-Molina, José A., additional

Published
2023
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30. Microbiome-Derived Cobalamin and Succinyl-CoA are Powerful Biomarkers for Improved Screening of Anal Cancer

Author

Sergio Serrano-Villar, Johan S. Saenz, Camilla Tincati, Sajan Raju, Elena Moreno, Rafael Bargiela, Alfonso Cabello, Elena Sendagorta, Amparo Benito, Alina Kurz, Jose A. Perez-Molina, Johannes Hov, Laura Fernández-López, Alfonso Muriel, Rosa del Campo, Santiago Moreno, Marius Troseid, Jana Seifert, and Manuel Ferrer

Abstract

Background. People with HIV (PWH) exhibit a markedly increased risk of anal cancer, especially men who have sex with men (MSM), with specific microbiota signatures possibly contributing to greater human papillomavirus (HPV) oncogenic potential. Low specificity of the current screening strategy for detecting high-grade squamous intraepithelial lesions (HSIL) hinders anal cancer prevention. We investigated microbiome derivatives associated with HSIL in anal cytology samples. Methods. We recruited a discovery and a validation cohort at four clinical sites in Spain and Italy. Study participants were mostly MSM undergoing HSIL screening with high-resolution anoscopy and anal biopsies to confirm HSIL. We extracted the bacterial DNA, proteins, and metabolites from anal cytology samples, and we performed 16SrRNA gene sequencing, mass spectrometry, and targeted metabolite quantification. Results. We included 213 participants, 167 in the discovery cohort (70 with confirmed HSIL) and 46 in the validation cohort (25 with confirmed HSIL). While we did not find clear microbiome composition signatures associated with HSIL, the microbiome associated with HSIL overexpressed proteins involved in the production of succinyl-CoA and cobalamin, with levels consistently increased in subjects with HSIL in the discovery and validation cohorts. Combined measurement of succinyl-CoA and cobalamin overperformed anal cytology, improving sensitivity from 91.2% to 96.6%, specificity from 34.1% to 81.8%, positive predictive value from 48.1% to 77.8%, and negative predictive value from 85.3% to 97.3%. While anal cytology correctly classified only 59.9% of individuals, combined measurement of both metabolites improved the classification to 87.7%. This test overcame internal (adjusted AUC 0.877) and external validation. From 98 false-positive cytologic results, succinyl-CoA and cobalamin level measurement reclassified 49 (50%) to true negatives. Finally, we demonstrate greater in vitro production of succinyl-CoA and cobalamin in bacteria associated with HSIL or cancer vs. those presumably protective. Conclusions. Cobalamin and succinyl-CoA are overexpressed in the anal microbiome of patients with HSIL and show excellent diagnostic capacity. Their measurement overperforms anal cytology to screen for patients with HSIL. Hence, we discovered two powerful biomarkers for which detection methods can readily be established, that could improve the current strategy of anal cancer screening.

Published
2022
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31. Progression Risk in People with HIV and COVID-19: Predictive Performance of Current Risk Scores

Author

Alfonso Cabello, Ana Moreno, Pilar Vizcarra, María J Vivancos, Belen Zamarro, Javier López-Botet, José L. Casado, and Miguel Górgolas

Subjects
Adult, Male, 0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Human immunodeficiency virus (HIV), HIV Infections, Disease, medicine.disease_cause, Risk Assessment, Cohort Studies, Hospitals, University, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Virology, Humans, Medicine, 030212 general & internal medicine, Aged, SARS-CoV-2, business.industry, COVID-19, virus diseases, Middle Aged, Prognosis, CD4 Lymphocyte Count, 030104 developmental biology, Infectious Diseases, Disease Progression, Female, business
Abstract

People with HIV (PWH) might have a higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes. Several scores were developed to predict COVID-19 progression to critical disease and are often used among PWH. We assessed the performance of two commonly used risk equations among PWH and COVID-19. Participants were identified from a multicenter cohort of 6,361 PWH on regular follow-up at 2 university hospitals. Of 99 HIV-infected individuals with confirmed SARS-CoV-2 infection, 63 had complete data and were included in this analysis. CALL and COVID-GRAM scores were calculated and participants were stratified into low-, intermediate-, and high-risk groups for each. Discrimination was assessed using receiver operating characteristic curves. Calibration was evaluated using observed versus expected (O:E) ratios and the Hosmer-Lemeshow χ

Published
2021
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32. Histiocytoid Sweet Syndrome associated with anorectal lymphogranuloma venereum in a patient with HIV infection

Author

María Carmen Ceballos-Rodríguez, Alfonso Cabello Úbeda, Miguel de Górgolas Hernández-Mora, Iris Martínez Alemany, Carlos Santonja, Irene Carrillo Acosta, B. Alvarez, Aws Waleed Mohammed Al-Hayani, and Laura Prieto Pérez

Subjects
Male, Microbiology (medical), medicine.medical_specialty, Human immunodeficiency virus (HIV), Chlamydia trachomatis, HIV Infections, Infectious and parasitic diseases, RC109-216, Histiocytoid Sweet Syndrome, medicine.disease_cause, medicine, Humans, Homosexuality, Male, Drug toxicity, Sweet's syndrome, integumentary system, business.industry, Lymphogranuloma venereum, Sweet Syndrome, HIV, food and beverages, Cancer, General Medicine, medicine.disease, Dermatology, Infectious Diseases, Infectious disease (medical specialty), Chlamydia trachomatis, lymphogranuloma venereum, Lymphogranuloma Venereum, business
Abstract

Sweet Syndrome (SS) belongs to a group of diseases known as neutrophilic dermatoses. An uncommon variant named Histiocytoid Sweet Syndrome (HSS) can be associated with a variety of conditions, including cancer, infections, drug toxicity and others. Here we present an instance of HSS in an HIV-positive patient in the setting of an infectious disease.

Published
2022
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33. Changes in Quality of Sleep, Mood, and Other Neuropsychiatric Symptoms After Switching Dolutegravir/Lamivudine/Abacavir to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Randomized Study of People With Human Immunodeficiency Virus With Poor Sleep Quality: GESIDA 10418

Author

Alfonso Cabello-Úbeda, Alicia González Baeza, Jesús Troya García, Sara de La Fuente Moral, María Novella Mena, Adriana Pinto Martínez, Rafael Micán, Miguel Górgolas, Guillermo Cuevas Tascón, Alberto Díaz de Santiago, José Sanz Morerno, David Rial Crestelo, Carmen Busca Arenzana, José Ignacio Bernardino Serna, Mariana Díaz Almirón, Joanna Cano, Herminia Esteban, and Ignacio Pérez-Valero

Subjects
Infectious Diseases, Oncology, neurotoxicity, clinical trial, darunavir, CNS, dolutegravir
Abstract

Background Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

Published
2022
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34. Increased risk factors associated with lower BMD in antiretroviral-therapy–naïve HIV-infected adult male

Author

Alfonso Cabello, Aránzazu Mediero, Irene Carrillo, B. Alvarez, Miguel Górgolas, Gabriel Herrero-Beaumont, Manuel Díaz-Curiel, Francisco Miguel Conesa-Buendía, Laura Prieto-Pérez, Ramón Pérez-Tanoira, Rosa Arboiro-Pinel, and Patricia Atencio

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adult male, HIV Infections, Infectious and parasitic diseases, RC109-216, Bone comorbidity, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Medical microbiology, Naïve patients, Bone Density, Risk Factors, BMD, Internal medicine, Prevalence, medicine, Vitamin D and neurology, Humans, 030212 general & internal medicine, Life Style, Femoral neck, Bone mineral, DXA, business.industry, Research, HIV, Middle Aged, 030112 virology, Antiretroviral therapy, Bone Diseases, Metabolic, Cross-Sectional Studies, Infectious Diseases, medicine.anatomical_structure, Spain, Tropical medicine, Underweight, medicine.symptom, business
Abstract

Background Low BMD (bone mineral density) has been described as a non–AIDS (Acquired Immune Deficiency Syndrome)-related event in HIV (human immunodeficiency virus)-patients but it is poorly studied in young HIV-infected men who have received no previous antiretroviral therapy. Methods A cross-sectional study of 245 naïve-HIV-infected men over 21 and under 50 years old who voluntary attended the Infectious Disease Division appointment in Hospital Fundación Jimenez Díaz in Madrid, from January 1st, 2014 to September 30th, 2017. All subjects underwent a baseline DXA scan (dual energy x-ray absorptiometry) performed prior to start antiretroviral treatment. Further, all patients who started treatment between May 1st and September 30th, 2017 were invited to participate in a substudy on bone mineral metabolism. All the information was collected through clinical history and complementary questionnaire. Results The mean age was 36.4 years, been 68% Caucasian, 29.3% Latin American and 2.7% African race. At the time of diagnosis, 91% of patients had stage-A (median CD4+ T-cell 481cells/μL, IQR, 320–659). 10% had a count below 200 CD4 cells/μL, and 40% had a CD4/CD8 cell-count-ratio below 0.4. Regarding lifestyle and risk factors, 14.1% presented underweight, 36.1% were not engage in any regular exercise, 51.9% were active smokers and 35.3% reported drug use. Low levels of vitamin D were seen in 87.6% of the study participants. Low BMD (Z-score Conclusions We find prevalence of increased bone involvement among naïve HIV-infected men under 50 years old. Further studies are necessary to evaluate if changes in actual guidelines are needed to assess BMD measurements in HIV-infected adult male patients under 50.

Published
2021

35. Reasons for Choice of Antiretroviral Regimens in HIV Patients Presenting Late for Initial Treatment in Europe

Author

Lisa Hamzah, Philipp de Leuw, Christoph Stephan, Annette Haberl, Gerrit Kann, Aoife G. Cotter, Alfonso Cabello, Álvaro Mena, Eva Herrmann, Miguel Górgolas, Gundolf Schuettfort, and Pavel Khaykin

Subjects
Pediatrics, medicine.medical_specialty, Anti-HIV Agents, Human immunodeficiency virus (HIV), HIV Infections, Disease, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Antiretroviral Therapy, Highly Active, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Child, Selection (genetic algorithm), 030505 public health, Reverse-transcriptase inhibitor, business.industry, Public Health, Environmental and Occupational Health, Europe, Clinical trial, Regimen, Infectious Diseases, Spain, Hiv patients, Female, Late presenters, 0305 other medical science, business, medicine.drug
Abstract

The choice of an optimal antiretroviral therapy (ART) in naive patients presenting late for initial therapy with advanced HIV infection, that is, with a CD4 cell count

Published
2021
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36. Efficacy of Elbasvir/Grazoprevir in Early Chronic G1/G4 Hepatitis C infection in HIV/HCV co-infected patients with mild fibrosis

Author

María Martínez-Rebollar, Ana González-Cordón, Montserrat Laguno Centeno, Josep Mallolas, Berta Torres, Beatriz Alvarez, Miguel Górgolas, Alfonso Cabello, Laura Prieto, Elisa de Lazzari, and Lorena de la Mora

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Elbasvir, Genotype, HIV Infections, Pilot Projects, Hepacivirus, Severity of Illness Index, Men who have sex with men, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, Quinoxalines, Internal medicine, medicine, Humans, Elbasvir, Grazoprevir, Prospective Studies, 030212 general & internal medicine, Homosexuality, Male, Adverse effect, Benzofurans, Hepatology, Coinfection, business.industry, Ribavirin, Imidazoles, Gastroenterology, virus diseases, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Drug Combinations, Treatment Outcome, Grazoprevir, chemistry, 030211 gastroenterology & hepatology, business
Abstract

Background Acute hepatitis C virus (AHC) infection is increasingly common among HIV+ men who have sex with men (MSM). Until 2017, the guidelines recommended therapy with pegylated-interferon plus ribavirin with a mild sustained virological response (SVR). This prompted many patients to reject that treatment, at that time, waiting to be treated with better and safer options with new Direct-Acting-Antivirals (DAA). Objectives Assess the efficacy and safety of Elbasvir/Grazoprevir to treat recent chronic hepatitis C infection, genotype 1 or 4, in HIV+ MSM patients. Methods Prospective, open-labeled, two center, pilot study. SVR is analyzed for treatment with Elbasvir/Grazoprevir (8 weeks in GT1b or 12 in GT1a or GT4) in patients with a recent chronic HCV infection, defined as HCV infection lasting less than 4 years and mild liver fibrosis (liver stiffness Results Forty-eight patients were included (May 2017–March 2018): 2 GT1b, 24 GT1a and 22 GT4. HCV-RNA > 800000 UI in 63% and medium liver stiffness 4.9 kPa. The SVR was 98%, one patient failed due to poor adherence. 67% of patients had adverse effects, but only 16% treatment related. The most frequent side effects were gastrointestinal (19%), related with the central nervous system (18%), respiratory (16%) and systemic symptoms (15%). During one year of follow-up post-therapy, 4 AHC and 18 patients with sexually transmitted diseases (STD) were diagnosed. Conclusions Treatment with Elbasvir/Grazoprevir in this scenario is highly effective and safe. Patients with risky sexual practices must remain linked to the medical care system to detect new STD and HCV reinfection.

Published
2021
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37. Trabecular bone score and 3D-DXA in young, antiretroviral treatment-naïve patients in Madrid

Author

Manuel Díaz-Curiel, Alfonso Cabello, Patricia Atencio, Rosa Arboiro-Pinel, Francisco Miguel Conesa-Buendía, Miguel Górgolas, and Aránzazu Mediero

Subjects
Therapy naive, medicine.medical_specialty, Trabecular bone score, business.industry, Internal medicine, Antiretroviral treatment, Human immunodeficiency virus (HIV), Medicine, General Medicine, business, medicine.disease_cause
Published
2021
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38. COVID-19 in people living with HIV: A multicenter case-series study

Author

Raquel Téllez, Laura Prieto-Pérez, Ángel Luis Castaño, Ricardo Fernández-Roblas, Norma Rallón, Sara Nistal, Miguel Górgolas, Irene Carrillo, B. Alvarez, José Miguel Benito, Alfonso Cabello, A. Herrero, Belen Zamarro, Virginia Victor, Jana Hernández, Marta Hernández-Segurado, and Javier Becares

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, Comorbidity, Overweight, medicine.disease_cause, Article, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Humans, Medicine, lcsh:RC109-216, Prospective Studies, 030212 general & internal medicine, ComputingMethodologies_COMPUTERGRAPHICS, SARS-CoV-2, business.industry, Mortality rate, COVID-19, HIV, General Medicine, Middle Aged, medicine.disease, Hospitalization, Intensive Care Units, Pneumonia, Infectious Diseases, Female, Observational study, medicine.symptom, business, Case series
Abstract

Graphical Abstract, Highlights • Lower mortality rate was observed in HIV patients. • Similar hospitalization and ICU admission rate were observed in HIV patients. • Age and comorbidities also represent the main poor prognostic factors for PLHIV. • HIV severity or the type of antiretroviral does not influence the Covid-19 outcome., Objectives The information of how COVID-19 infection affects people living with HIV (PLHIV) is still scarce. Methods Observational study was conducted in four of public hospitals in Madrid. All HIV patients with confirmed or suspected COVID-19 disease were included and compared with COVID-19 infected patients without HIV infection. Results Sixty-three patients with HIV infection were analysed. The median age was 46 years (IQR: 37-56 years), 88.9% were men. The median time of HIV infection was 10.8 years (IQR: 6.5 - 16.8 years), 96.8% were on antiretroviral therapy. 84.1% had previous comorbidities. The most common symptoms were fever(66.1%), cough(66.1%) and dyspnea(46.8%). Pneumonia was found in 47.5%, 28.6% of patients had severe disease and 32.3% was admitted to hospital. The ICU admission rate and the mortality rate were both 3.17%. Significant association was observed between age, arterial hypertension, overweight, diabetes mellitus and the severity of COVID-19 disease. No association was observed between HIV-related factors. The rate of COVID-19 disease in HIV-patients was 1,68%. A similar hospitalization (31.74% vs 32.57%) and ICU admission rate (3.17% vs 2%) was observed with non-HIV infected patients. A lower mortality rate during hospitalization (10% vs 21.37%) and global mortality rate (3.17% vs 6.96%) were observed. Conclusions Established poor prognostic factors, such as age and comorbidities, represent also the main determinants for PLHIV. Neither the HIV severity, nor the type of ARV treatment seem to influence the outcome of COVID-19 infection. Large prospective cohorts are needed in order to establish the differences between HIV positive and negative patients.

Published
2021
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39. Compassionate use of tocilizumab in severe SARS-CoV2 pneumonia

Author

María Jesús Rodríguez Nieto, Marta Lopez de las Heras, Silvia Calpena Martínez, Sarah Heili-Frades, Irene Carrillo Acosta, Aws Waleed Mohammed Al-Hayani, Laura Prieto-Pérez, Alba Naya, Javier Martinez, Miguel Ángel Piris Pinilla, Alicia Macias Valcayo, Marcel Jose Rodriguez Guzman, Ricardo Fernández Roblas, Miguel de Górgolas Hernández-Mora, Felipe Villar Álvarez, Alfonso Cabello Úbeda, José Fortes Alen, Pilar Carballosa, B. Alvarez, Fredeswinda Romero Bueno, Germán Peces-Barba Romero, Olga Sánchez Pernaute, Itziar Fernández Ormaechea, Marina Castellanos Gonzalez, Farah Ezzine, Antonio Broncano Lavado, Marta Martin Garcia, and Ana Cordero Guijarro

Subjects
Adult, Compassionate Use Trials, Male, 0301 basic medicine, Microbiology (medical), ARDS, medicine.medical_specialty, Critical Care, medicine.medical_treatment, 030106 microbiology, Severe disease, Antibodies, Monoclonal, Humanized, Article, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Intensive care, Internal medicine, medicine, Clinical endpoint, Humans, Immunologic Factors, Intubation, lcsh:RC109-216, 030212 general & internal medicine, ComputingMethodologies_COMPUTERGRAPHICS, Aged, Aged, 80 and over, SARS-CoV-2, Interleukin-6, business.industry, COVID-19, Pneumonia, General Medicine, Middle Aged, medicine.disease, COVID-19 Drug Treatment, Treatment, Cytokine release syndrome, C-Reactive Protein, Infectious Diseases, chemistry, Spain, Female, business
Abstract

Graphical abstract, Highlights • The survival rate is high (94% vs 72%) if tocilizumab is administered with a FiO2 ≤ 0.5%. • There are very limited side effects and secondary infections. • A significant decrease in the median serum ferritin and the median HSCRP was observed., Introduction Tocilizumab is an interleukin 6 receptor antagonist which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), aiming to ameliorate the cytokine release syndrome (CRS) -induced acute respiratory distress syndrome (ARDS). However, there are no consistent data whom might benefit most from it. Methods We provided tocilizumab on a compassionate-use basis to patients with SSP hospitalized (excluding intensive care and intubated cases) who required oxygen support to have a saturation >93%. Primary endpoint was intubation or death after 24 hours of its administration. Patients received at least one dose of 400 mg intravenous tocilizumab during March 8-2020, through April 20-2020. Results A total of 207 patients were studied and 186 analysed. The mean age was 65 years and 68% were male. A co-existing condition was present in 68 % of cases. Death prognostic factors were older age, higher IL-6, D-dimer and high sensitivity C reactive protein (HSCRP), lower total lymphocytes and severe disease requiring higher oxygen support. The primary endpoint (intubation or death) was significantly worst (37% vs 13%, p 0.5%). Conclusions Tocilizumab is well tolerated in patients with severe SARS-CoV-2 pneumonia, but it has a limited effect on the evolution of cases with high oxygen support needs.

Published
2021
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40. Histiocytic hyperplasia with hemophagocytosis and acute alveolar damage in COVID-19 infection

Author

Marcela Valverde-Monge, Soraya de la Fuente, Carlos Soto, Laura Astilleros Blanco de Cordova, Álvaro Trascasa, Miguel Górgolas, Alberto Lazaro-Garcia, Elizabet Petkova, Socorro María Rodríguez-Pinilla, Ánxela Vidal-González, Marina Alonso-Riaño, Itziar Fernández-Ormaechea, Miguel A. Piris, Diana Fresneda, Germán Peces-Barba, María José Cortti, Sheila Recuero, Ignacio Cornejo, Raul Cordoba, Anabel Antonio, Alfonso Cabello, Silvia Calpena, Rafael Rubio-Martín, Marina Castellanos, Andrés M. Silva, B. Alvarez, Laura Prieto-Pérez, María José Díez Medrano, Irene Carrillo, Miguel Lafarga, Oderay Cedeño, José Fortes, Marta Lopez de las Heras, and Ramón Pérez-Tanoira

Subjects
Male, 0301 basic medicine, ARDS, Pathology, medicine.medical_specialty, Pneumonia, Viral, Article, Lymphohistiocytosis, Hemophagocytic, Pathology and Forensic Medicine, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, medicine, Humans, Diffuse alveolar damage, Lung, Pandemics, Histiocyte, Aged, Aged, 80 and over, Respiratory Distress Syndrome, Hyperplasia, SARS-CoV-2, business.industry, COVID-19, Diagnostic markers, Histiocytes, Middle Aged, medicine.disease, Histiocytosis, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Macrophage activation syndrome, Infectious diseases, Female, Bone marrow, Hemophagocytosis, Coronavirus Infections, business
Abstract

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

Published
2020
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41. Transcriptional signature of resting-memory CD4 T cells differentiates spontaneous from treatment-induced HIV control

Author

Manuel L. Fernández-Guerrero, María A Navarrete-Muñoz, Alfonso Cabello, Marcial García, Sara Morón-López, Luis A. López-Fernández, Pablo Minguez, Miguel Górgolas, Javier Martinez-Picado, Francisco Javier de la Hera, Alberto Benguria, Clara Restrepo, Norma Rallón, Carlos Castilho Barros, Vicente Estrada, José M. Benito, María I. García, and Juan Carlos López-Bernaldo

Subjects
CD4-Positive T-Lymphocytes, Systems biology, Cell, HIV Infections, Biology, Virus Replication, Transcriptome, Downregulation and upregulation, Antiretroviral Therapy, Highly Active, Drug Discovery, medicine, Humans, Genetics (clinical), Innate immune system, Gene Expression Profiling, Viral Load, Molecular medicine, Human genetics, CD4 Lymphocyte Count, Cell biology, Treatment Outcome, medicine.anatomical_structure, Viral replication, Host-Pathogen Interactions, Molecular Medicine, Immunologic Memory
Abstract

The HIV reservoir is the main barrier to eradicating HIV infection, and resting memory CD4 T (Trm) cells are one of the most relevant cellular component harboring latent proviruses. This is the first study analyzing the transcriptional profile of Trm cells, in two well-characterized groups of HIV patients with distinct mechanisms of viral replication control (spontaneous versus treatment-induced). We use a systems biology approach to unravel subtle but important differences in the molecular mechanisms operating at the cellular level that could be associated with the host's ability to control virus replication and persistence. Despite the absence of significant differences in the transcriptome of Trm cells between Elite Controllers (ECs) and cART-treated (TX) patients at the single gene level, we found 353 gene ontology (GO) categories upregulated in EC compared with TX. Our results suggest the existence of mechanisms at two different levels: first boosting both adaptive and innate immune responses, and second promoting active viral replication and halting HIV latency in the Trm cell compartment of ECs as compared with TX patients. These differences in the transcriptional profile of Trm cells could be involved in the lower HIV reservoir observed in ECs compared with TX individuals, although mechanistic studies are needed to confirm this hypothesis. Combining transcriptome analysis and systems biology methods is likely to provide important findings to help us in the design of therapeutic strategies aimed at purging the HIV reservoir. KEY MESSAGES: HIV-elite controllers have the lowest HIV-DNA content in resting memory CD4 T cells. HIV-ECs show a particular transcriptional profile in resting memory CD4 T cells. Molecular mechanisms of enhanced adaptative and innate immune response in HIV-ECs. High viral replication and low viral latency establishment associate to the EC status.

Published
2020
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43. HIV Treatment with the Two-Drug Regimen Dolutegravir Plus Lamivudine in Real-world Clinical Practice: A Systematic Literature Review

Author

Rahul Dinesh Kamath, Lee Alexandra Evitt, Clotilde Allavena, Jean van Wyk, Diwakar Jha, Ilias Mariolis, Justin Koteff, José Casado, Tia Vincent, Antonella d'Arminio Monforte, Simona Di Giambenedetto, Alfonso Cabello Úbeda, Rickesh Patel, Rahul Kumar, Laurent Hocqueloux, and Tristan J Barber

Subjects
Microbiology (medical), medicine.medical_specialty, Dual therapy, Settore MED/17 - Malattie Infettive, Review, Cochrane Library, HIV-1 infection, law.invention, chemistry.chemical_compound, Randomized controlled trial, law, Internal medicine, Medicine, Adverse effect, business.industry, Lamivudine, Dolutegravir, Real-world, Discontinuation, Regimen, Infectious Diseases, Systematic review, chemistry, business, medicine.drug
Abstract

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE®, Embase®, PubMed, Cochrane library, and relevant international conference proceedings from 2013 to 2020. Qualitative synthesis of virologic suppression at Week 48, treatment-emergent resistance, discontinuation rates, and comorbidities was undertaken, with no statistical analyses conducted. Linked publications and potential for duplication in reporting of outcomes for cohorts and populations were identified, and the publication reporting the highest number of PWH receiving dolutegravir plus lamivudine was included in the analysis. Thirty-four studies reporting on cohorts of PWH not suspected to be linked or to include duplicate data receiving dolutegravir plus lamivudine were identified (N = 5017). Of 3744 virologically suppressed PWH who switched to dolutegravir plus lamivudine, 603 (16%) reported history of virologic failure. Nineteen studies included effectiveness data (n = 3558), four of which included data from treatment-naive PWH (n = 69). In studies with > 100 PWH, high rates of virologic suppression (Week 48, 97–100%) were maintained with dolutegravir plus lamivudine, with low rates of virologic failure (0–3.3 per 100 person-years of follow-up); one instance of emergent integrase strand transfer inhibitor resistance was reported in a complex treatment-experienced individual. Rates of discontinuation due to adverse events were low and consistent with previously observed trial data. Dolutegravir plus lamivudine minimally impacted renal function and had minimal impact on or improved lipid profiles and bone mineral density. This systematic review demonstrates that effectiveness and safety of dolutegravir plus lamivudine in clinical practice support data from randomized controlled trials with regard to high rates of virologic response, low rates of discontinuation, and a high barrier to resistance. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00522-7.

Published
2021

44. Initiation of antiretroviral therapy in treatment-naive adults with HIV infection at the first specialist appointment

Author

Aws Waleed M. Al-Hayani, Alfonso Cabello-Úbeda, Marta Del Palacio-Tamarit, Blanca Rodríguez-Alonso, Irene Carrillo-Acosta, Beatriz Álvarez-Álvarez, Laura Prieto-Pérez, Laura Fernández Quintela, Gema Fuensalida, Raquel Téllez, Ángel Luis-Castaño, Marta Hernández-Segurado, Javier Becares, José Miguel Benito, Norma Rallón, and Miguel Górgolas

Subjects
Pharmacology, Microbiology (medical), Adult, Infectious Diseases, Cognition, Drug-Related Side Effects and Adverse Reactions, Anti-HIV Agents, Humans, Pharmacology (medical), HIV Infections, Viral Load, CD4 Lymphocyte Count, Retrospective Studies
Abstract

Background Fast initiation of ART has been associated with higher rates of retention in HIV care and viral suppression at 48 weeks and with lower mortality rates. However, scarce evidence exists in our setting, where diagnosis and treatment are carried out in different contexts. Methods An observational retrospective study evaluating efficacy and safety of ART prescribed at the first specialist appointment, without baseline laboratory data, in a tertiary hospital in downtown Madrid. Individuals with a new diagnosis of HIV infection who initiated treatment at their first appointment with an infectious diseases specialist before receiving baseline laboratory results were included, irrespective of the ART regimen chosen. Results One hundred and eight participants were included. The majority (99.1%) were MSM who had acquired infection during sexual intercourse. The efficacy of ART, without baseline laboratory results at the time of initiation, was 85.2% (92/108) in the ITT analysis and 91.7% (99/108) in the treatment-related discontinuation equals failure analysis. All but nine patients presented an undetectable viral load ( Conclusions Initiating ART at the first available opportunity without baseline laboratory data does not reduce efficacy or safety of ART and achieves rapid virological control with high rates of retention in HIV care.

Published
2021

45. Spectrum of Syphilitic Chorioretinitis and Its Evolution Based on Multimodal Imaging

Author

Celia Rodríguez-Olleros Rodríguez, Ester Carreño, Nelida Muñoz, Nuria Estébanez-Corrales, June Artaechevarria Artieda, and Alfonso Cabello Úbeda

Subjects
medicine.medical_specialty, genetic structures, Retinitis, Spectral domain, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ophthalmology, medicine, Immunology and Allergy, In patient, 030203 arthritis & rheumatology, Multimodal imaging, medicine.diagnostic_test, Syphilitic chorioretinitis, business.industry, Retinal, Fluorescein angiography, medicine.disease, eye diseases, Fundus autofluorescence, chemistry, 030221 ophthalmology & optometry, sense organs, business
Abstract

Purpose: To describe the different phenotypes of syphilitic chorioretinitis (SCR) and its clinical features in multimodal imaging (MI).Methods: Complete ophthalmological examination and MI including spectral domain optic coherence tomography (SD-OCT), fundus autofluorescence (FAF) and fluorescein angiography (FA) were performed at diagnosis and during follow-up in patients diagnosed with SCR.Results: 17 eyes of 10 patients were included. Clinical phenotypes included acute syphilitic posterior placoid chorioretinopathy (ASPPC), syphilitic outer retinitis (SOR) and punctate inner retinitis (PIR). Disruption of outer retinal layers were visible in all patients in SD-OCT. Inner retinal layers were only affected in PIR. FAF revealed macular hyperautofluorescence in all patients. FA showed maintained hyperfluorescence in ASPPC and SOR.Conclusions: ASPPC, SOR and PIR are different phenotypes of syphilitic chorioretinitis and present common features in SD-OCT and FAF. MI provides useful information to help the clinician during diagnosis and follow-up of these entities.

Published
2021

46. Bone Deleterious Effects of Different NRTIs in Treatment-naïve HIV Patients After 12 and 48 Weeks of Treatment

Author

Patricia Llamas-Granda, Irene Carrillo Acosta, Manuel Díaz-Curiel, Patricia Atencio, Beatriz Alvarez, Aránzazu Mediero, Alfonso Cabello-Ubeda, Raquel Largo, Laura Prieto-Pérez, Francisco Miguel Conesa-Buendía, Rosa Arboiro-Pinel, Gabriel Herrero-Beaumont, Miguel Górgolas, Ramón Pérez-Tanoira, and UAM. Departamento de Medicina

Subjects
Adult, medicine.medical_specialty, Bone markers, Medicina, Anti-HIV Agents, Osteoporosis, HIV Infections, Tenofovir alafenamide, Gastroenterology, Abacavir, Bone Density, Virology, Internal medicine, Medicine, Humans, Prospective Studies, Prospective cohort study, Tenofovir, Femoral neck, Bone mineral, Osteopenia, business.industry, Nucleotides, HIV, medicine.disease, Resorption, Infectious Diseases, medicine.anatomical_structure, Reverse Transcriptase Inhibitors, business, medicine.drug
Abstract

Background: Bone alterations have been observed in the course of HIV infection, char-acterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibi-tors (NRTIs) in treatment-naïve HIV patients. Methods: We conducted a prospective study in naïve HIV-infected adults (under 50 years), separat-ed into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment. Results: Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/μL. At week 12 after starting treatment, both TDF [increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003)] and TAF [increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049)] presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences. Conclusion: Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks., This research was financially supported by The Carlos III Health Institute through the “Miguel Servet” program (CP15/00053), co-funded by The European Regional Development Fund and research grants from the Spanish Carlos III Health Institute (PI16/00991 and PI19/00744)

Published
2021

47. The relationship between 25(OH) vitamin D levels and COVID-19 onset and disease course in Spanish patients

Author

Rosa Arboiro-Pinel, Ignacio Mahillo-Fernandez, Marjorie Andrade-Poveda, Sarah Heili-Frades, Manuel Díaz-Curiel, Antonio Herrero-González, Alfonso Cabello, and Jose Luis Mansur

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Disease, Biochemistry, vitamin D deficiency, Article, law.invention, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, law, Internal medicine, medicine, Vitamin D and neurology, Humans, Mortality, Vitamin D, Molecular Biology, Intensive Care Unit (ICU), Aged, Retrospective Studies, Aged, 80 and over, business.industry, Incidence (epidemiology), Mortality rate, COVID-19, Retrospective cohort study, Cell Biology, Middle Aged, medicine.disease, Vitamin D Deficiency, Intensive care unit, Intensive Care Units, 030104 developmental biology, Spain, 030220 oncology & carcinogenesis, Molecular Medicine, Female, business, Hospital Admission
Abstract

Objective Currently, there are no definitive data on the relationship between low levels of vitamin D in the blood and a more severe disease course, in terms of the need for hospital admission, intensive care unit (ICU) stay, and mortality, in patients with coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to study the association between levels of circulating 25-hydroxyvitamin D (25(OH)D) and adverse clinical outcomes linked to SARS-CoV-2 infection. We further aimed to observe the incidence of low, below-average, and normal levels of 25(OH)D in patients hospitalized for COVID-19 between March 12, 2020, and May 20, 2020, and assess whether these values differed between these patients and a normal population. Finally, we determined whether the need for transfer to the intensive care unit (ICU) and the mortality rate were related to low levels of 25(OH)D. Study Design Retrospective observational study Setting Quironsalud Hospitals in Madrid, Spain Participants We analyzed 1549 patients (mean age, 70 years; range, 21-104 years); 835 were male (53.9%; mean age, 73.02 years), and 714 were female (46.1%; mean age, 68.05 years). Subsequently, infected patients admitted to the ICU (n = 112) and those with a fatal outcome (n = 324) were analyzed. Procedures Serum concentrations of 25(OH)D were measured by electrochemiluminescence. Results More hospitalized patients (66%, n = 1017) had low baseline levels of 25(OH)D (

Published
2021

48. Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Author

Jesús Rodríguez-Baño, Jerónimo Pachón, Jordi Carratalà, Pablo Ryan, Inmaculada Jarrín, María Yllescas, José Ramón Arribas, Juan Berenguer, Esther Aznar Muñoz, Pedro Gil Divasson, Patricia González Muñiz, Clara Muñoz Aguirre, Marta Díaz Menéndez, Fernando de la Calle Prieto, Marta Arsuaga Vicente, Elena Trigo Esteban, Ignacio Pérez Valero, Rosa de Miguel Buckley, Julen Cadiñaños Loidi, Beatriz Diaz Pollan, Luz Martín Carbonero, Juan Carlos Ramos Ramos, Belén Loeches Yagüe, Rocío Montejano Sánchez, Juan González García, Julio García Rodríguez, Margarita Ramírez, Isabel Gutiérrez, Francisco Tejerina, Teresa Aldámiz-Echevarría, Cristina Díez, Chiara Fanciulli, Leire Pérez-Latorre, Blanca Pinilla, Juan Carlos López, Ana Such Diaz, Elena Álvaro Alonso, Juan Torres Macho, Guillermo Cuevas Tascon, Eva Jiménez González de Buitrago, Fátima Brañas Baztán, Jorge Valencia de la Rosa, Mario Pérez Butragueño, Inés Fernández Jiménez, Gemma Muñiz Nicolás, Antonia Sepúlveda Berrocal, Alberto Gato Díez, María Pilar Toledano Sierra, María Paz García Butenegro, Ana Isabel Peláez Ballesta, Elena Morcillo Rodríguez, Isidoro Fernández Romero, Cristina Peláez Ballesta, María Isabel Guirado Torrecillas, Josune Goikoetxea Agirre, Elena Bereciartua Bastarrica, Laura Guio Carrión, Regino Rodríguez Álvarez, Marta Ibarrola Hierro, Isabel A. Pérez Hernández, Inés Pérez Zapata, Sergio Román Soto, Mohamed Kallouchi, Juan Ramón Domínguez Vicent, Rafae Silvariño Fernández, Jon Ugalde Espiñeira, Ainhoa Sanjuan López, Silvia García Martínez, Mikel Temprano Gogenola, Víctor Asensi, Silvia Suárez, Lucia Suárez, Carmen Yllera, María Rivas-Carmenado, Alberto Romero-Palacios, Jesús Ruiz Aragón, Patricia Jiménez Aguilar, Ma Luisa Fernández Ávila, Rosario Castilla Ortiz, Vanesa Alende Castro, Cristina Pérez García, Marta Fernández Morales, María Lorena María Valle Feijoo Begoña Rodríguez Ferreira, Joan Gómez-Junyent, Judit Villar-García, Inmaculada López-Montesinos, Itziar Arrieta-Aldea, Abora Rial-Villavecchia, Elisa García Vázquez, Aychel Elena Roura Piloto, Encarnación Moral Escudero, Alicia Hernández Torres, Helena Albendín Iglesias, David Vinuesa García, Clara Martínez Montes, Francisco Javier De la Hera Fernández, Francisco Anguita Santos, Andrés Ruiz Sancho, Vicens Díaz de Brito Fernández, Montserrat Sanmarti Vilamala, Sergio España Cueto, Daniel Molina Morant, Araceli González-Cuevas, Joel Elías Chara Cervantes, Guillem Policarpo Torres, Meritxell Ortega Montoliu, Mònica Angerri Nadal, Ariadna De Genover Gil, Eleni Patera, Rita Godoy Lorenzo, Evangelia Anna María Zioga, Virginia Isern Fernández, Carlos Enrique Sabbagh Fajardo, Ana Ferrer Ribera, Carlos Bea Serrano, Rosa Oltra Sempere, Sara Vela Bernal, Paloma Albiol Viñals, Miguel Pedromingo Kus, María Ángeles Garcinuño, Silvana Fiorante, Sergio Pérez Pinto, Alexandra de la Vega, María Carmen Fariñas Álvarez, Claudia González Rico, Francisco Arnaiz de las Revillas, Teresa Giménez, Jorge Calvo, Yolanda Meije Castillo, Alejandra Duarte Borges, Júlia Pareja Coca, Mercedes Clemente Presas, Xavier Sanz Salvador, Ma Teresa Pérez Rodríguez, Adrián Sousa, Alexandre Pérez González, Rebeca Longueira, Alejandro Araujo, Blanca Alonso Martínez, Laura García Escudero, Sara Lidia Kamel Rey, David Roa Alonso, Juan Pablo Avilés Parra, Iván Pelegrín Senent, Rosana Rouco Esteves Marques, Laia Raich Montiu, Jessica Souto Higueras, Manuel Alejandro Gálvez Bobadilla, Jorge Parra Ruiz, Violeta Ramos Sesma, Sara Velasco Fuentes, Laura García Pereña, Alfonso Lluna Carrascosa, Sergio Gilaberte Reyzábal, Mónica Liébana Gómez, Juan Salillas Hernando, Alberto Serrano Martínez, Miguel Torralba González de Suso, Patricia Martínez Martín, Isabel Rábago Lorite, Patricia González-Ruano Pérez, Beatriz Pérez-Monte Mínguez, Ángeles García Flores, Pere Comas Casanova, Andrea Martín Plata, Sergio Manuel Santana Báez, Oscar Sanz Peláez, Karim Mohamed Ramírez, José María Robaina Bordón, Helem Haydeé Vílchez Rueda, Melchor Riera Jaume, Gemma Mut Ramon, Meritxell Gavalda Manso, Lluis Planas Bibiloni, Laura Castelo Corral, Lucía Ramos Merino, Efrén Sánchez Vidal, María Rodríguez Mayo, Enrique Míguez Rey, José M. García de Lomas Guerrero, Javier De la Torre Lima, Ana Correa Ruiz, Fernando Fernández Sánchez, Nicolás Jiménez-García, José Luis Sierra-Monzón, Borja Gracia-Tello, María Hernández-Bonaga, Galadriel Pellejero, Marta Asín-Corrochano, Lucia Boix Palop, Esther Calbo, Cristina Badía, Beatriz Dietl, Gómez Lucía, Ángel Domínguez-Castellano, María José Ríos-Villegas, María D. del Toro, Zaira R. Palacios Baena, Elena Salamanca-Rivera, Elena Marín, Virginia Almadana, Salvador Pérez-Galera, Luisa González-Iglesias, Gabriela Abelenda-Alonso, Claudia Álvarez-Pouso, Francesc Escrihuela, Carlota Gudiol, Laia Lorenzo-Esteller, Jordi Niubó, Daniel Podzamczer, Miquel Pujol, Alexander Rombauts, Miguel Salvert Lletí, Ricardo Gil Sánchez, Marta Jiménez Escrig, Laura Parra Gómez, Mariona Tasias Pitarch, Marta Navarro Vilasaró, María Luisa Machado Sicilia, Aina Gomila Grange, Sonia Calzado Isbert, Nerea Carrasco Antón, Elizabet Petkova-Saiz, Alfonso Cabello Úbeda, Miguel Górgolas Hernández-Mora, Olga Sánchez-Pernaute, Carlos Dueñas Gutiérrez, Javier Martin Guerra, José Javier Castrodeza Sanz, Virginia Fernández Espinilla, Laura Rodríguez Fernández, Juan González-Moreno, Aroa Villoslada Gelabert, María Antonia Ribot Sanso, María Victoria Fernández-Baca, Almudena Hernández Milian, Miguel Ángel Morán Rodríguez, Zuriñe Ortiz de Zárate Ibarra, José Joaquin Portu Zapirain, Ester Saez de Adana Arroniz, Juan Carlos Gainzarain Arana, Olga Meca Birlanga, Ma Jesús del Amor Espín, Montserrat Viqueira González, Josefina García García, Onofre Martínez Madrid, Enrique Bernal Morell, Antonia Alcaraz, Ángeles Muñoz, Ignacio Pina, Vicente de la Rosa, Tamara Caínzos Romero, Sabela Sánchez Trigo, Ana Isabel Mariño Callejo, Hortensia Álvarez Díaz, Nieves Valcarce Pardeiro, Adriana Sánchez Serrano, Diana Piñar Cabezos, Eva Pilar García Villalba, Carmen Aguayo Jiménez, María Ruíz Campuzano, Virginia Naranjo Velasco, Marta Santos Peña, Juan Mora Delgado, Israel Sevilla Moreno, Cristina Lojo Cruz, Xabier Kortajarena Urkola, José Antonio Iribarren Loyarte, María Jesús Bustinduy Odriozola, Maialen Ibarguren Pinilla, Ignacio Álvarez Rodríguez, Francisco Javier Martínez Marcos, Francisco Javier Rodríguez Gómez, Isabel Asschert Agüero, Francisco Muñoz Beamud, Antonio José Ruiz Reina, Jara Llenas-García, Inmaculada González-Cuello, Elena Hellín-Valiente, Esther Martínez Birlanga, José Manuel Tafalla Torres, Jorge Calderón Parra, Gabriela Escudero López, Isabel Gutiérrez Martín, Ane Andrés Eisenhofer, Sonia García Prieto, Raquel Álvarez Franco, Daniel Roger Zapata, Blanca Martínez Cifre, Elena Aranda Rife, Irene Martín Rubio, André Barbosa Ventura, Javier Garrido, Concepción Gonzalo, Iván Piñero, Nieves de la Cruz Felipe, Eva Talavera García, Marta Lamata Subero, Paula Mendoza Roy, María Soledad García de Carlos, Justo Lajusticia Aisa, Lorea Arteche Eguizabal, Ainhoa Urrutia Losada, Saioa Domingo Echaburu, Pedro Ángel Cuadros Tito, Gurutz Orbe Narváez, Ma del Carmen Liébana Martos, Carolina Roldán Fontana, Carmen Herrero Rodríguez, Gaspar Duro Ruiz, Santiago Pérez Parra, Arantzazu Mera Fidalgo, Miquel Hortos Alsina, Ana Alberich Conesa, Lourdes Bladé Vidal, Nicolás Merchante Gutiérrez, Eva León Jiménez, Reinaldo Espíndola Gómez, María Erostarbe Gallardo, Pedro Martínez Pérez-Crespo, José Miguel Cisneros, Manuela Aguilar-Guisado, Teresa Aldabó, Claudio Bueno, Elisa Cordero-Matía, Ana Escoresca, Carmen Infante, Martín Guillermo, Sonsoles Salto, Francesca Gioia, Pilar Vizcarra, Jesús Fortún Abete, Pilar Martín Dávila, Santiago Moreno Guillén, José A. Oteo Revuelta, Concepción García-García, Paula Santibañez Sáenz, Cristina Cervera Acedo, José M. Azcona Gutiérrez, José María Reguera Iglesias, Antonio Plata Ciezar, Lucia Valiente de Santis, Beatriz Sobrino Diaz, Juan Diego Ruiz Mesa, Ministerio de Ciencia e Innovación, Fundación SEIMC/GeSIDA, Instituto de Salud Carlos III - ISCIII, European Regional Development Fund (ERDF/FEDER), Red Española de Investigación en SIDA, Red Española de Investigación en Patología Infecciosa, UAM. Departamento de Medicina, UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, Universidad de Cantabria, SAM-COVID Study Group, [Rodríguez-Baño,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Rodríguez-Baño,J, Pachón,J] Departamento de Medicina, Universidad de Sevilla, Spain. [Rodríguez-Baño,J, Pachón,J] Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. [Pachón,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Carratalà,J] Servei de Malalties Infeccioses, Hospital Universitari de Bellvitge, Barcelona, Spain. [Carratalà,J] Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain. [Carratalà,J] Universitat de Barcelona, Barcelona, Spain. [Ryan,P] Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain. [Jarrín,I] Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain. [Yllescas,M] Fundación SEIMC/GeSIDA, Madrid, Spain. [Arribas,JR] Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. [Arribas,JR] Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain. [Berenguer,J] Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Berenguer,J] Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain., Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Red de Investigación Cooperativa en Investigación en Sida (España), Red de Investigación Cooperativa en Investigación en Patología Infecciosa (España), Gilead Sciences, ViiV Healthcare, AbbVie Pharmaceuticals, Merck & Co, Janssen Biotech, Teva Pharmaceutical Industries, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Universidad de Sevilla. Departamento de Medicina, Instituto Carlos III (España), and Unión Europea

Subjects
0301 basic medicine, Male, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Organisms::Viruses::RNA Viruses::Nidovirales::Coronaviridae [Medical Subject Headings], Randomized controlled trial, law, Adrenal Cortex Hormones, Clinical endpoint, Medicine, 030212 general & internal medicine, Hospital Mortality, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Vital Statistics::Mortality [Medical Subject Headings], Adrenocortical hormones, Hazard ratio, General Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Intubation::Intubation, Intratracheal [Medical Subject Headings], Middle Aged, Tocilizumab, Hospitalization, Infectious Diseases, Treatment Outcome, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections [Medical Subject Headings], Drug Therapy, Combination, Female, Cohort study, Microbiology (medical), medicine.medical_specialty, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections::Severe Acute Respiratory Syndrome [Medical Subject Headings], Combination therapy, Medicina, Hyperinflammatory state, 030106 microbiology, Estudios de cohortes, Antibodies, Monoclonal, Humanized, Article, 03 medical and health sciences, Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], Intubation, Intratracheal, Mortalitat, Humans, Corticosteroids, Mortality, Corticoesteroides, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Aged, Proportional Hazards Models, Retrospective Studies, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Inflammation, business.industry, SARS-CoV-2, COVID-19, Odds ratio, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Adrenal Cortex Hormones [Medical Subject Headings], Corticosteroides, COVID-19 Drug Treatment, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Propensity Score [Medical Subject Headings], chemistry, Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Propensity score matching, Mortalidad, Monoclonal antibodies, business, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Anticossos monoclonals
Abstract

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

Published
2021

49. 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

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