Brief report
Effectiveness of corticoid pulses in patients with cytokine storm syndrome induced by SARS-CoV-2 infection
Eficacia de los pulsos de corticoides en pacientes con síndrome de liberación de citocinas inducido por infección por SARS-CoV-2
José Luis Callejas Rubioa,
, Juan de Dios Luna del Castillob, Javier de la Hera Fernándezc, Emilio Guirao Arrabald, Manuel Colmenero Ruize, Norberto Ortego Centenoa
Corresponding author
a Unidad de Enfermedades Sistémicas, Servicio de Medicina Interna, Hospital Universitario Clínico San Cecilio, Granada, Spain
b Departamento de Bioestadística, Facultad de Medicina, Universidad de Granada, Granada, Spain
c Servicio de Medicina Interna, Hospital Universitario Clínico San Cecilio, Granada, Spain
d Unidad de Enfermedades Infecciosas, Hospital Universitario Clínico San Cecilio, Granada, Spain
e Servicio de Cuidados Intensivos, Hospital Universitario Clínico San Cecilio, Granada, Spain
Read
2023
Timeswas read the article
578
Total PDF
1445
Total HTML
Share statistics
array:24 [ "pii" => "S2387020620302941" "issn" => "23870206" "doi" => "10.1016/j.medcle.2020.07.002" "estado" => "S300" "fechaPublicacion" => "2020-08-28" "aid" => "5197" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2020;155:159-61" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775320302839" "issn" => "00257753" "doi" => "10.1016/j.medcli.2020.04.018" "estado" => "S300" "fechaPublicacion" => "2020-08-28" "aid" => "5197" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2020;155:159-61" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original breve</span>" "titulo" => "Eficacia de los pulsos de corticoides en pacientes con síndrome de liberación de citocinas inducido por infección por SARS-CoV-2" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "159" "paginaFinal" => "161" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Effectiveness of corticoid pulses in patients with cytokine storm syndrome induced by SARS-CoV-2 infection" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Luis Callejas Rubio, Juan de Dios Luna del Castillo, Javier de la Hera Fernández, Emilio Guirao Arrabal, Manuel Colmenero Ruiz, Norberto Ortego Centeno" "autores" => array:6 [ 0 => array:2 [ "nombre" => "José Luis" "apellidos" => "Callejas Rubio" ] 1 => array:2 [ "nombre" => "Juan de Dios" "apellidos" => "Luna del Castillo" ] 2 => array:2 [ "nombre" => "Javier" "apellidos" => "de la Hera Fernández" ] 3 => array:2 [ "nombre" => "Emilio" "apellidos" => "Guirao Arrabal" ] 4 => array:2 [ "nombre" => "Manuel" "apellidos" => "Colmenero Ruiz" ] 5 => array:2 [ "nombre" => "Norberto" "apellidos" => "Ortego Centeno" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020620302941" "doi" => "10.1016/j.medcle.2020.07.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620302941?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320302839?idApp=UINPBA00004N" "url" => "/00257753/0000015500000004/v1_202008110620/S0025775320302839/v1_202008110620/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020620302916" "issn" => "23870206" "doi" => "10.1016/j.medcle.2020.04.012" "estado" => "S300" "fechaPublicacion" => "2020-08-28" "aid" => "5188" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2020;155:162-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "Clinical challenges in chronic obstructive pulmonary disease in patients who suffered SARS-CoV-2 infection" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "162" "paginaFinal" => "164" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Retos clínicos en pacientes con enfermedad pulmonar obstructiva crónica que han sufrido una infección por SARS-CoV-2" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan Marco Figueira Gonçalves, Rafael Golpe" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Juan Marco" "apellidos" => "Figueira Gonçalves" ] 1 => array:2 [ "nombre" => "Rafael" "apellidos" => "Golpe" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775320302669" "doi" => "10.1016/j.medcli.2020.04.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320302669?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620302916?idApp=UINPBA00004N" "url" => "/23870206/0000015500000004/v2_202008242222/S2387020620302916/v2_202008242222/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020620302904" "issn" => "23870206" "doi" => "10.1016/j.medcle.2019.11.010" "estado" => "S300" "fechaPublicacion" => "2020-08-28" "aid" => "5044" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2020;155:152-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Clinico-biological characteristics of patients with myelofibrosis: an analysis of 1,000 cases from the Spanish Registry of Myelofibrosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "152" "paginaFinal" => "158" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Características clínico-biológicas de los pacientes con mielofibrosis: un análisis de 1.000 casos del Registro Español de Mielofibrosis" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1559 "Ancho" => 1528 "Tamanyo" => 70674 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Overall survival of the series of 1000 patients with myelofibrosis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Irene Pastor-Galán, Juan Carlos Hernández-Boluda, Juan-Gonzalo Correa, Alberto Alvarez-Larrán, Francisca Ferrer-Marín, José María Raya, Rosa Ayala, Patricia Velez, Manuel Pérez-Encinas, Natalia Estrada, Valentín García-Gutiérrez, María Laura Fox, Angel Payer, Ana Kerguelen, Beatriz Cuevas, María Antonia Durán, María José Ramírez, María Teresa Gómez-Casares, María Isabel Mata-Vázquez, Elvira Mora, Clara Martínez-Valverde, Elisa Arbelo, Anna Angona, Elena Magro, María Luisa Antelo, Nieves Somolinos, Francisco Cervantes" "autores" => array:28 [ 0 => array:2 [ "nombre" => "Irene" "apellidos" => "Pastor-Galán" ] 1 => array:2 [ "nombre" => "Juan Carlos" "apellidos" => "Hernández-Boluda" ] 2 => array:2 [ "nombre" => "Juan-Gonzalo" "apellidos" => "Correa" ] 3 => array:2 [ "nombre" => "Alberto" "apellidos" => "Alvarez-Larrán" ] 4 => array:2 [ "nombre" => "Francisca" "apellidos" => "Ferrer-Marín" ] 5 => array:2 [ "nombre" => "José María" "apellidos" => "Raya" ] 6 => array:2 [ "nombre" => "Rosa" "apellidos" => "Ayala" ] 7 => array:2 [ "nombre" => "Patricia" "apellidos" => "Velez" ] 8 => array:2 [ "nombre" => "Manuel" "apellidos" => "Pérez-Encinas" ] 9 => array:2 [ "nombre" => "Natalia" "apellidos" => "Estrada" ] 10 => array:2 [ "nombre" => "Valentín" "apellidos" => "García-Gutiérrez" ] 11 => array:2 [ "nombre" => "María Laura" "apellidos" => "Fox" ] 12 => array:2 [ "nombre" => "Angel" "apellidos" => "Payer" ] 13 => array:2 [ "nombre" => "Ana" "apellidos" => "Kerguelen" ] 14 => array:2 [ "nombre" => "Beatriz" "apellidos" => "Cuevas" ] 15 => array:2 [ "nombre" => "María Antonia" "apellidos" => "Durán" ] 16 => array:2 [ "nombre" => "María José" "apellidos" => "Ramírez" ] 17 => array:2 [ "nombre" => "María Teresa" "apellidos" => "Gómez-Casares" ] 18 => array:2 [ "nombre" => "María Isabel" "apellidos" => "Mata-Vázquez" ] 19 => array:2 [ "nombre" => "Elvira" "apellidos" => "Mora" ] 20 => array:2 [ "nombre" => "Clara" "apellidos" => "Martínez-Valverde" ] 21 => array:2 [ "nombre" => "Elisa" "apellidos" => "Arbelo" ] 22 => array:2 [ "nombre" => "Anna" "apellidos" => "Angona" ] 23 => array:2 [ "nombre" => "Elena" "apellidos" => "Magro" ] 24 => array:2 [ "nombre" => "María Luisa" "apellidos" => "Antelo" ] 25 => array:2 [ "nombre" => "Nieves" "apellidos" => "Somolinos" ] 26 => array:2 [ "nombre" => "Francisco" "apellidos" => "Cervantes" ] 27 => array:1 [ "colaborador" => "on behalf of the Spanish Group of Philadelphia-Negative Myeloproliferative Diseases (GEMFIN)" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S002577531930716X" "doi" => "10.1016/j.medcli.2019.11.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577531930716X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620302904?idApp=UINPBA00004N" "url" => "/23870206/0000015500000004/v2_202008242222/S2387020620302904/v2_202008242222/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Brief report</span>" "titulo" => "Effectiveness of corticoid pulses in patients with cytokine storm syndrome induced by SARS-CoV-2 infection" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "159" "paginaFinal" => "161" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "José Luis Callejas Rubio, Juan de Dios Luna del Castillo, Javier de la Hera Fernández, Emilio Guirao Arrabal, Manuel Colmenero Ruiz, Norberto Ortego Centeno" "autores" => array:6 [ 0 => array:4 [ "nombre" => "José Luis" "apellidos" => "Callejas Rubio" "email" => array:1 [ 0 => "jlcalleja@telefonica.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Juan de Dios" "apellidos" => "Luna del Castillo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Javier" "apellidos" => "de la Hera Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Emilio" "apellidos" => "Guirao Arrabal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Manuel" "apellidos" => "Colmenero Ruiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Norberto" "apellidos" => "Ortego Centeno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Unidad de Enfermedades Sistémicas, Servicio de Medicina Interna, Hospital Universitario Clínico San Cecilio, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Bioestadística, Facultad de Medicina, Universidad de Granada, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario Clínico San Cecilio, Granada, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad de Enfermedades Infecciosas, Hospital Universitario Clínico San Cecilio, Granada, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Cuidados Intensivos, Hospital Universitario Clínico San Cecilio, Granada, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eficacia de los pulsos de corticoides en pacientes con síndrome de liberación de citocinas inducido por infección por SARS-CoV-2" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cytokine release syndrome (CRS) is a serious complication of SARS-CoV-2 disease (COVID-19).<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> The basis of its treatment is essentially tocilizumab, an anti-IL-6 agent.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The use of glucocorticoids (GC) is controversial.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> However, in the hyperinflammation phase, they could be very beneficial, as in other diseases in which there is a cytokine storm similar to the one that occurs in COVID-19, like macrophage activation syndrome (MAS) or hemophagocytic syndrome (HPS).<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The objective of this study is to evaluate the efficacy of the administration of GC pulses in patients who have an CRS due to COVID-19.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">Retrospective observational study in the internal and intensive medicine departments. Patients admitted for SARS-CoV-2 infection confirmed by PCR and who met CRS criteria defined by elevation of IL-6 > 40 pg/ml and/or 2 of the following: ferritin > 300 µg/l, <span class="elsevierStyleSmallCaps">d</span>-dimers > 1 mg/l and/or triglycerides > 300 mg/dl were included. We classified patients into 3 groups: (1) those who received only GC pulses; (2) GC pulses and tocilizumab simultaneously, and (3) exclusively tocilizumab. Pulses were classified into 2 mg/kg/day for 3 days, 250 mg/day for 3 days and 500 mg/day for 3 days. Serum levels of ferritin, CRP and <span class="elsevierStyleSmallCaps">d</span>-dimers before administration and during follow-up, with intervals of 24–72 h following routine practice. Survival, the need for intubation and a combined variable of the latter 2 were established as endpoints. All patients gave their consent for treatment.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The main variables of the study were described according to the frequency distribution and the basic measurements of numerical summary, mean, standard deviation and range. The analysis of the time until each of the response variables occurred was made by calculating the survival curves using the Kaplan–Meier method and the estimates of the risk ratios were made using the Cox proportional hazards model. Comparisons between treatments and within treatments between intervals were analysed using a mixed linear model with pairwise comparisons when it was significant. Stata v.14.1 software was used.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0025" class="elsevierStylePara elsevierViewall">A total of 92 patients were included. The baseline characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Of the 92 patients, 60 (65.2%) received GC pulses alone, 23 (25%) pulses combined with tocilizumab and 9 (9.8%) tocilizumab alone. There were 7 (7.6%) deaths and 5 (5.6%) intubations; one of the patients requiring intubation died. The combined intubation/death variable occurred in 11 (12.4%) cases. The median follow-up of the patients was 11 days.</p><p id="par0035" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the percentages, per treatment, of presentation of each of the endpoints considered, as well as the risk ratio of the treatments compared to the treatment in which CG is not included. In all cases, the percentages of events were lower in the group of patients in whom GC was administered, with the combined treatment group being the one with the lowest percentage of events.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Regarding the risk ratios of the different outcome variables of the groups with GC versus the group in which only tocilizumab was administered, it was observed that the risk of each of the events was lower as treatment with GC was considered, reaching statistical significance in the case of survival and a trend, although without reaching significance, both for intubation and for the combined variable.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In the Kaplan–Meier survival curves, there was a trend towards less need for intubation, death, and the combined variable. It was clear that there was no increase in deaths in the group of patients receiving GC.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The evolution of biochemical markers was highly variable. The initial mean ferritin levels were 1238 µg/l in the GC and tocilizumab group, 832 µg/l in GC and 1024 µg/l in that of tocilizumab, without observing a significant decrease in any of the groups at the end of the follow-up. A significant decrease in CRP was observed already in the first determination after treatment, which was maintained until the end of the follow-up in the 3 groups. <span class="elsevierStyleSmallCaps">d</span>-dimers remained high without significant decreases.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">The results of this study show that, in patients with COVID-19-induced CRS, the combination of GC pulses seems to be associated with a better prognosis of the disease, with a clear tendency towards lower mortality and lower need for intubation.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The role of GCs in COVID-19 patients is not well established. In the review carried out by Russell et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> on lung injury induced by different viruses including SARS and MERS and in the study by Wang et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> no beneficial effect was observed; they were even associated to a probable increase in mortality. Therefore, the use of GC has not been recommended. Recently, Wu et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> demonstrated a decreased risk of mortality in patients with respiratory distress who received methylprednisolone.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The objective of our work has been to evaluate the efficacy of GC in another serious complication of SARS-CoV-2 such as CRS. Increased levels of CRP and ferritin are 2 characteristic and key data for its diagnosis. Unlike HPS, which has a diagnostic criteria<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and a scoring system that helps to estimate the probability of suffering from it, called HScore,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> there are no well-established criteria for the definition of CRS. The presence of elevated IL-6 and/or the combination of 2 or more laboratory anomalies, mainly increased levels of ferritin suggests the presence of CRS. All the included patients met the criteria, with remarkably high ferritin levels. Treatment of HPS, often associated with infectious processes,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and others with different systemic autoimmune diseases, in this case called MAS,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> is based on 2 pillars: on the one hand, the etiological treatment, if any, and on the other, the treatment of the cytokine storm.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In all cases, high-dose and mainly pulsed GCs are the basis of treatment. In the case of SARS-CoV-2-induced CRS, the recommended treatment has been tocilizumab,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> an expensive drug and difficult to access for all patients. The fact that GCs have been effective in a large number of patients may allow it to be administered as a second option for non-respondents.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In our study we decided to assess the response to treatment by means of 2 high impact clinical variables such as the need for intubation and mortality; therefore, we only included deceased patients who had received some of the treatment arms, and excluded those who were admitted due to requiring intubation. We observed that in the patients who received GC pulses, either alone or in combination with tocilizumab, there was a tendency to decrease in the events of death, intubation, and the combination of both, being higher in cases of combination of both drugs. We did not find differences between the different doses used, therefore, probably the lowest dose of 2 mg/kg/day for 3 days is the most recommended dose.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The interest of our study is based on the administration of GC pulses, an effective treatment for other diseases similar to SARS-CoV-2-induced CRS, more economical and accessible to other experimental treatments used in this disease such as tocilizumab, and which for different reasons it has been discouraged, demonstrating its objective clinical benefit. The limitations of the study are its retrospective nature, the sample size, the reduced number of clinical events and the short follow-up period, so the results must be confirmed with a clinical trial with a larger sample size and a longer follow-up.</p><p id="par0080" class="elsevierStylePara elsevierViewall">We conclude that early identification of CRS is essential in patients with COVID-19 and that, in case of onset, the early use of GC pulses can control it, probably with a lower requirement to use tocilizumab and with a decrease in events such as intubation and death.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1376978" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1264652" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1376979" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1264653" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-04-10" "fechaAceptado" => "2020-04-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1264652" "palabras" => array:3 [ 0 => "Coronavirus COVID-19" 1 => "Cytokine release syndrome" 2 => "Hemophagocytic" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1264653" "palabras" => array:3 [ 0 => "Coronavirus COVID-19" 1 => "Síndrome de liberación de citocinas" 2 => "Hemofagocítico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Cytokine storm syndrome (CSS) is a serious complication of COVID-19 patients. Treatment is tocilizumab. The use of glucocorticoids (GC) is controversial. In other very similar CSS, such as macrophage activation syndrome (MAS) and hemophagocytic syndrome (HFS), the main treatment are corticosteroids. Our objective is to evaluate the efficacy of GC in the CSS by COVID-19.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We included 92 patients with CSS associated to COVID-19 who received GC, GC, and tocilizumab and only tocilizumab. We determine CSS markers. We evaluated mortality, intubation, and a combined variable.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In all cases the percentages of events were lower in the group of patients with GC was administered. The hazard ratio of the final variables with GC versus the group in which only tocilizumab was administered was lower as CGs were considered, with statistical significance for survival.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The early use of GC pulses could control SLC, with a lower requirement to use tocilizumab and a decrease in events such as intubation and death.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El síndrome de liberación de citocinas (SLC) es una complicación grave de los pacientes COVID-19. La base del tratamiento es tocilizumab. El uso de glucocorticoides (GC) es controvertido. En otros SLC muy parecidos, como son el síndrome de activación macrofágica (SAM) y el síndrome hemofagocítico (SHF) el tratamiento con los corticoides es fundamental. Nuestro objetivo es evaluar la eficacia de los GC en el SLC por COVID-19.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Incluimos 92 pacientes con SLC por COVID-19 que recibieron GC, GC y tocilizumab y sólo tocilizumab. Determinamos marcadores de SLC. Evaluamos mortalidad, intubación y una variable combinada.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">En todos los casos los porcentajes de eventos fueron menores en el grupo de pacientes en los que se administraron GC. Las razones de riesgo de las variables finales de los grupos con GC frente al grupo en el que se administró sólo tocilizumab fue menor conforme se consideraron los GC, con significación estadística para la supervivencia.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discusión</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">El uso precoz de pulsos de GC puede controlar el SLC, con un menor requerimiento de uso de tocilizumab y una disminución de eventos como la intubación y muerte.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Callejas Rubio JL, Luna del Castillo JD, de la Hera Fernández J, Guirao Arrabal E, Colmenero Ruiz M, Ortego Centeno N. Eficacia de los pulsos de corticoides en pacientes con síndrome de liberación de citocinas inducido por infección por SARS-CoV-2. Med Clin (Barc). 2020;155:159–161.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">GC: glucocorticoids; mg/d: milligrams per day; mg/kg/d: milligrams per kilogram of weight per day.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age (years)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.9 ± 12.9 (32–88) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Male/female</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (63%)/34 (37%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GC pulses for 3 days</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 mg/kg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30/82 (36.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>250 mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27/82 (32.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>500 mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26/82 (31.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2364204.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient characteristics.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Fr/n: frequencies by outcome; GC: glucocorticoids; HR: <span class="elsevierStyleItalic">hazard ratio</span> (risk ratio) estimated using the Cox proportional hazards model; CI: confidence interval.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Survival</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intubation</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Combined</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fr/n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR (95% CI) significance \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fr/n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR (95% CI) significance \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fr/n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR (95% CI) significance \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tocilizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/9 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/6 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/6 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GC pulses</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5/60 (8.3)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.064 (0.03–1.181) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3/60 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 (0.019–4.19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8/60 (13.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.339 (0.032–3.64) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p = 0.065 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p = 0.356 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p = 0.372 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GC pulses and tocilizumab</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/23 (4.4)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.0004–0.835) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.24 (0.009–6.261) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2/23 (8.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.175 (0.011–2.827) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p = 0.040 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p = 0.391 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p = 0.219 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2364205.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Frequencies of the 3 outcome measures according to treatments and HR for the Cox regression models of time up to the event.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P. Mehta" 1 => "D.F. McAuley" 2 => "M. Brown" 3 => "E. Sanchez" 4 => "R.S. Tattersall" 5 => "J.J. Manson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(20)30628-0" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2020" "volumen" => "395" "paginaInicial" => "1033" "paginaFinal" => "1034" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32192578" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-6 use in COVID-19 pneumonia related macrophage activation syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. McGonagle" 1 => "K. Sharif" 2 => "A. O’Regan" 3 => "C. Bridgewood" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2020.102537" "Revista" => array:3 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2020" "itemHostRev" => array:3 [ "pii" => "S1058274611002035" "estado" => "S300" "issn" => "10582746" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Zhang" 1 => "Y. Zhao" 2 => "F. Zhang" 3 => "Q. Wang" 4 => "T. Li" 5 => "Z. Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clim.2020.108393" "Revista" => array:5 [ "tituloSerie" => "Clin Immunol" "fecha" => "2020" "volumen" => "214" "paginaInicial" => "108393" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32222466" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.D. Russell" 1 => "J.E. Millar" 2 => "J.K. Baillie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(20)30317-2" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2020" "volumen" => "395" "paginaInicial" => "473" "paginaFinal" => "475" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32043983" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Wang" 1 => "B. Hu" 2 => "C. Hu" 3 => "F. Zhu" 4 => "X. Liu" 5 => "J. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2020.1585" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2020" "volumen" => "323" "paginaInicial" => "1061" "paginaFinal" => "1069" "itemHostRev" => array:3 [ "pii" => "S0749806318308260" "estado" => "S300" "issn" => "07498063" ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors associated with acute respiratory distress ayndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Wu" 1 => "X. Chen" 2 => "Y. Cai" 3 => "J. Xia" 4 => "X. Zhou" 5 => "S. Xu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamainternmed.2020.0994" "Revista" => array:2 [ "tituloSerie" => "Intern Med" "fecha" => "2020" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemophagocytic lymphohistiocytosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Skinner" 1 => "B. Yankey" 2 => "B.K. Shelton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4037/aacnacc2019463" "Revista" => array:6 [ "tituloSerie" => "AACN Adv Crit Care" "fecha" => "2019" "volumen" => "30" "paginaInicial" => "151" "paginaFinal" => "164" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31151946" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Macrophage activation syndrome: early diagnosis is key" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Lerkvaleekul" 1 => "S. Vilaiyuk" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/OARRR.S151013" "Revista" => array:7 [ "tituloSerie" => "Open Access Rheumatol" "fecha" => "2018" "volumen" => "10" "paginaInicial" => "117" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30214327" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0749806318300331" "estado" => "S300" "issn" => "07498063" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Fardet" 1 => "L. Galicier" 2 => "O. Lambotte" 3 => "C. Marzac" 4 => "C. Aumont" 5 => "D. Chahwan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.38690" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheumatol" "fecha" => "2014" "volumen" => "66" "paginaInicial" => "2613" "paginaFinal" => "2620" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24782338" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult haemophagocytic lymphohistiocytosis: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. Yildiz" 1 => "E. Van Den Neste" 2 => "J.P. Defour" 3 => "E. Danse" 4 => "J.C. Yombi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/qjmed/hcaa011" "Revista" => array:2 [ "tituloSerie" => "QJM" "fecha" => "2020" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015500000004/v2_202008242222/S2387020620302941/v2_202008242222/en/main.assets" "Apartado" => array:4 [ "identificador" => "44146" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Brief report" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015500000004/v2_202008242222/S2387020620302941/v2_202008242222/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620302941?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 1 | 5 |
| 2024 October | 31 | 6 | 37 |
| 2024 September | 27 | 5 | 32 |
| 2024 August | 26 | 2 | 28 |
| 2024 July | 20 | 6 | 26 |
| 2024 June | 27 | 5 | 32 |
| 2024 May | 35 | 2 | 37 |
| 2024 April | 36 | 7 | 43 |
| 2024 March | 36 | 7 | 43 |
| 2024 February | 30 | 6 | 36 |
| 2024 January | 31 | 6 | 37 |
| 2023 December | 35 | 14 | 49 |
| 2023 November | 23 | 11 | 34 |
| 2023 October | 30 | 6 | 36 |
| 2023 September | 18 | 2 | 20 |
| 2023 August | 18 | 5 | 23 |
| 2023 July | 9 | 5 | 14 |
| 2023 June | 20 | 4 | 24 |
| 2023 May | 37 | 6 | 43 |
| 2023 April | 40 | 1 | 41 |
| 2023 March | 18 | 9 | 27 |
| 2023 February | 18 | 1 | 19 |
| 2023 January | 21 | 7 | 28 |
| 2022 December | 20 | 13 | 33 |
| 2022 November | 19 | 11 | 30 |
| 2022 October | 16 | 17 | 33 |
| 2022 September | 14 | 15 | 29 |
| 2022 August | 24 | 15 | 39 |
| 2022 July | 20 | 13 | 33 |
| 2022 June | 17 | 13 | 30 |
| 2022 May | 20 | 5 | 25 |
| 2022 April | 21 | 17 | 38 |
| 2022 March | 34 | 13 | 47 |
| 2022 February | 64 | 13 | 77 |
| 2022 January | 40 | 16 | 56 |
| 2021 December | 34 | 20 | 54 |
| 2021 November | 37 | 14 | 51 |
| 2021 October | 30 | 23 | 53 |
| 2021 September | 23 | 16 | 39 |
| 2021 August | 42 | 12 | 54 |
| 2021 July | 25 | 12 | 37 |
| 2021 June | 23 | 14 | 37 |
| 2021 May | 34 | 16 | 50 |
| 2021 April | 90 | 52 | 142 |
| 2021 March | 21 | 12 | 33 |
| 2021 February | 22 | 17 | 39 |
| 2021 January | 22 | 15 | 37 |
| 2020 December | 22 | 5 | 27 |
| 2020 November | 25 | 8 | 33 |
| 2020 October | 31 | 9 | 40 |
| 2020 September | 41 | 14 | 55 |
| 2020 August | 20 | 23 | 43 |
| 2020 July | 4 | 11 | 15 |
Show all
