Clinical and epidemiological features of tuberculosis isolated from critically ill patients

array:24 ["pii" => "S0325754121000468" "issn" => "03257541" "doi" => "10.1016/j.ram.2021.02.011" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "456" "copyright" => "Asociación Argentina de Microbiología" "copyrightAnyo" => "2021" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Argent Microbiol. 2022;54:43-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S0325754121000432" "issn" => "03257541" "doi" => "10.1016/j.ram.2021.03.001" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "453" "copyright" => "Asociación Argentina de Microbiología" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Argent Microbiol. 2022;54:48-52" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "Brief report" "titulo" => "Symbiotic pectin microparticles with native Jerusalem artichoke (Helianthus tuberosus L.) enhance Lactobacillus paracasei subsp. tolerans survival" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "48" "paginaFinal" => "52" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La encapsulación de Lactobacillus paracasei subsp. tolerans en microgeles de pectina con inulina extraída de topinambur (Helianthus tuberosus L.) incrementa su supervivencia" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2036 "Ancho" => 3177 "Tamanyo" => 139631 ] ] "descripcion" => array:1 [ "en" => "Growth curves of Lactobacillus paracasei subsp. tolerans F2 in MRS supplemented with 1% (w/v) glucose (MRS-G), 1% commercial inulin (MRS-CI), 1% (w/v) Jerusalem artichoke inulin (MRS-JAI) and without carbohydrates as negative control (MRS-B). Growth curves were determined by viable counts expressed as log CFU/ml. Samples were incubated at 25±1°C for 24h." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María C. Tarifa, Cristian M. Piqueras, Diego B. Genovese, Irene A. Rubel, María G. Sica, Lorena I. Brugnoni" "autores" => array:6 [ 0 => array:2 [ "nombre" => "María C." "apellidos" => "Tarifa" ] 1 => array:2 [ "nombre" => "Cristian M." "apellidos" => "Piqueras" ] 2 => array:2 [ "nombre" => "Diego B." "apellidos" => "Genovese" ] 3 => array:2 [ "nombre" => "Irene A." "apellidos" => "Rubel" ] 4 => array:2 [ "nombre" => "María G." "apellidos" => "Sica" ] 5 => array:2 [ "nombre" => "Lorena I." "apellidos" => "Brugnoni" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•L. paracasei F2 was able to ferment inulin in vitro.</li><li class="elsevierStyleListItem" id="lsti0010">•The entrapment yield of L. paracasei F2 in pectin microparticles was ∼92%.</li><li class="elsevierStyleListItem" id="lsti0015">•Inulin from Helianthus tuberosus L. significantly enhanced L. paracasei F2 viability.</li><li class="elsevierStyleListItem" id="lsti0020">•Encapsulated synbiotic presented major survival along storage time and GI passage.</li></ul>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0325754121000432?idApp=UINPBA00004N" "url" => "/03257541/0000005400000001/v1_202204020607/S0325754121000432/v1_202204020607/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0325754121000523" "issn" => "03257541" "doi" => "10.1016/j.ram.2021.04.001" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "462" "copyright" => "Asociación Argentina de Microbiología" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Argent Microbiol. 2022;54:39-42" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Brief report" "titulo" => "Mycoplasma maculosum and Mycoplasma spumans associated with fertility disorders in dogs from a Bernese Mountain dog kennel" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "39" "paginaFinal" => "42" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Mycoplasma maculosum y Mycoplasma spumans asociados con desórdenes de fertilidad en perros de un criadero de boyero de Berna" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Pablo Jesús Tamiozzo" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Pablo Jesús" "apellidos" => "Tamiozzo" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Mycoplasma maculosum and Mycoplasma spumans were detected by PCR in dogs.</li><li class="elsevierStyleListItem" id="lsti0010">•After antibiotic treatment reproductive disorders disappeared.</li><li class="elsevierStyleListItem" id="lsti0015">•Veterinarians not often consider Mycoplasma in the differential diagnosis of reproductive diseases.</li></ul>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0325754121000523?idApp=UINPBA00004N" "url" => "/03257541/0000005400000001/v1_202204020607/S0325754121000523/v1_202204020607/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "Brief report" "titulo" => "Clinical and epidemiological features of tuberculosis isolated from critically ill patients" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "43" "paginaFinal" => "47" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Joaquín Hurtado, Cecilia Coitinho, Nicolás Nin, María Buroni, Francisco Javier Hurtado, Carlos Robello, Gonzalo Greif" "autores" => array:7 [ 0 => array:3 [ "nombre" => "Joaquín" "apellidos" => "Hurtado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Cecilia" "apellidos" => "Coitinho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Nicolás" "apellidos" => "Nin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "María" "apellidos" => "Buroni" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Francisco Javier" "apellidos" => "Hurtado" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "Carlos" "apellidos" => "Robello" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 6 => array:4 [ "nombre" => "Gonzalo" "apellidos" => "Greif" "email" => array:1 [ 0 => "gonzalo.greif@pasteur.edu.uy" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Laboratorio de Interacciones Hospedero-Patógeno/Unidad de Biología Molecular, Institut Pasteur Montevideo (IPM), Montevideo, Uruguay" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Laboratory of Microbiology, Anti-tuberculosis and Prevalent Diseases Honorary Commission (CHLA-EP), Montevideo, Uruguay" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Español Dr. “Juan J. Crottoggini”, ASSE, Montevideo, Uruguay" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Fisiopatología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tuberculosis en la unidad de cuidados intensivos: características clínicas y epidemiológicas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1804 "Ancho" => 3175 "Tamanyo" => 299112 ] ] "descripcion" => array:1 [ "en" => "Minimum spanning tree cluster analysis. (A) Samples in red correspond to ICU samples; samples in blue correspond to community samples. Samples of both groups were present in all clusters. (B) Same analysis colored by lineage. LAM and Haarlem lineages correspond to the most frequent isolates." ] ] ] "textoCompleto" => "Although tuberculosis (TB) incidence is decreasing worldwide<a class="elsevierStyleCrossRef" href="#bib0150">15</a>, Uruguay has been reporting an increase in the number of cases since 2006. Despite the efforts made by the National Program Against Tuberculosis, the incidence rate in 2019 was 30 cases per 100000 inhabitants, placing Uruguay above the average of the region<a class="elsevierStyleCrossRef" href="#bib0150">15</a>. Based on this scenario, more cases with severe TB were diagnosed and admitted to Intensive Care Unit (ICU) during the last years.TB in critical care is associated with respiratory and other organ failures and requires ICU admission for advanced vital support. Despite the availability of effective therapies, mortality rates remain between 15.5 and 65.9% in critical care patients<a class="elsevierStyleCrossRefs" href="#bib0125">10,11</a>. In Uruguay, a high mortality rate (>50%) was observed in TB cases that required ICU admission.Information from classical and molecular epidemiology, along with patient clinical data represent key elements to achieve better control of the disease<a class="elsevierStyleCrossRef" href="#bib0090">3</a>.The genotypic variations, especially bacterial lineages, are associated with changes in transmission capacity and also in the ability to acquire drug resistance<a class="elsevierStyleCrossRefs" href="#bib0085">2,7–9</a>. Thus, changes in the prevalence of specific lineages or sub-lineages could have important consequences for the observed epidemiology and outcome of TB disease<a class="elsevierStyleCrossRefs" href="#bib0135">12,14</a>.We hypothesized that critically ill TB patients could be associated with strain virulence. This study aimed to describe the genetic diversity of Mycobacteriumtuberculosis using classical genotyping methods of clinical isolates obtained from TB patients in the critical care setting, and to analyze them with the genetic background structure observed in community TB. In addition, we aimed to determine the possible association of comorbidities and organ dysfunctions observed in these patients according to the TB genotype causing the disease.The research protocol used in this work was presented and approved by the Clinical Research Ethics Committee of Hospital Español, and has been performed following the ethical standards of the 1964 Declaration of Helsinki.Sixty M. tuberculosis isolates obtained from critically ill patients from a general public hospital (Hospital Español – ASSE, Montevideo, Uruguay) were genotyped and compared to ninety-five randomly selected community isolates within the same period (Suppl. Table 1 and Suppl. Fig. 1).All the community sample isolates correspond to patients treated with the standard drug protocol (daily HREZ for the first two months, four months HR 3 days a week). The cultures became negative after 3 months of treatment (Suppl. Table 1 and Suppl. Fig. 1). All the community samples were obtained from TB patients that did not require ICU admission at any time during treatment.Patients with TB admitted to the ICU were classified according to a TB clinical severity score as having low, moderate, and high risk TB disease<a class="elsevierStyleCrossRef" href="#bib0080">1</a>. Comorbidities and organ dysfunctions were documented upon admission, along with common clinical and laboratory studies.Isolate characteristics were summarized for each group (Community and Critically ill patient isolates) in Supplementary Table 1. In addition, the analysis pipeline was shown in Supplementary Figure 1. Microbiological cultures and DNA extractions were performed and stored, as previously described<a class="elsevierStyleCrossRef" href="#bib0095">4</a>. Molecular typing using spoligotyping and MIRU-VNTR were performed as described in Supplementary Figure 1.Lineage assignment was carried out based on similarity search and UPGMA tree when comparing reference strains located in the server with our isolates with a distance less than 0.3 using <a href="http://www.miru-vntr.org/">www.miru-vntr.org</a> tool. Comparative analysis between strain distribution of critical and non-critically ill patients was performed with the Chi-squared contingency tables for categorical data (p-value≤0.05 was considered a statistically significant difference). Minimum spanning trees were constructed for all isolates using the MST tool (miru-vntr.org).Based on the documented risk factors, forty-five of our initial set of sixty-five patients (69%) could be classified according to TB severity at the moment of ICU admission into three groups (low, moderate and high severity). Most ICU admissions correspond to moderate to high severity TB (86.6%): low (13.4%), moderate (40.0%), and high risk (46.6%) (Suppl. Fig. 1)<a class="elsevierStyleCrossRef" href="#bib0080">1</a>.Supplementary Figure 1 shows the main characteristics of TB patients admitted to an ICU including demographic data, bilateral pulmonary compromise, comorbidities, organ dysfunctions, relevant laboratory findings, classification according to a tuberculosis severity score<a class="elsevierStyleCrossRef" href="#bib0080">1</a>, and ICU mortality. In brief, patients were relatively young with male predominance. Bilateral pulmonary involvement was present in 44%, and HIV coinfection in 22% of the cases. Poor nutritional status was present in 76%. Respiratory and cardiovascular failure were the most frequent organ failures, and mechanical ventilation was implemented in 74% of the patients. Only 13.3% had a low tuberculosis risk severity score, while a moderate to high score was observed in 86.6% of these patients. Global mortality in ICU was 62% considering all patients (n=60) and reached 71.8% considering only high-to-moderate severity TB patients (n=39).Among the ICU M. tuberculosis isolates, strains clustered into five main sub-lineages (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1A</a>). Except for one particular case, all sub-lineages belong to Lineage 4 of M. tuberculosis. Typing of critical care patients reveals the Haarlem family as the most prominent in these samples (53.3%), followed by the LAM family (45.0%). On the contrary, LAM strains are more represented among community TB isolates (60.0%), followed by the Haarlem strains (34.7%), a significant statistical difference being observed when comparing these two populations (p<0.05).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>It is interesting to observe that the Haarlem family was more frequent in patients with bilateral TB (51.3%) versus unilateral TB (32.6%) in community patients (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1B</a>). Although the observed difference was not statistically significant, it could indicate a more aggressive form of the disease caused by the Haarlem lineage. This hypothesis needs to be corroborated and could explain the high representation of the Haarlem genotype among critically ill patients.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>More detailed analyses of typing results were performed analyzing the minimum spanning tree generated with the online tool MST (miru-vntrplus.org). Fourteen clonal complexes were obtained, community and critical isolates could be detected in each cluster (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and Supplementary Table 2). The biggest cluster comprises 44 isolates (22 of them – 9 ICU and 13 community samples – with the same MIRU pattern belonging to the Haarlem genotype (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B)). Finally, 24 community samples and 10 ICU samples remain unclustered.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>When analyzing the clonal complexes with more than six isolates (n=8), we could observe strains isolated during the whole studied period (Suppl. Table 2). This phenomenon also occurs when analyzing at group level. No clonal complexes were associated with a particular isolation year that could be due to a particular outbreak.We investigated the possible association of observed TB genotypes with ICU patient's comorbidities.A closer look into critically ill patients is shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>, comparing demographic data and some comorbidities such as drug abuse, HIV, COPD, and malnutrition, between the main represented strains (Haarlem and LAM families). We did not find any significant differences among comorbidities between the genotype groups.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Comparing organ dysfunctions observed among ICU patients (with a low to high severity score) between the different genotypes, we found that patients with the Haarlem genotypes showed hepatic dysfunction more frequently than patients with LAM (p=0.04) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>). The mortality observed in these patients was not statistically related to the M. tuberculosis genotype (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>), and no significant association between the outcome of patients with different lineages was found. As far as we know, this is the first communication relating clinical and molecular epidemiology in critically ill patients with severe TB. Furthermore, we were able to compare the main TB lineages that circulate both in the community and critical care setting, studying the association between these genotypes with clinical outcomes.The principal finding showed that lineages belong to the Haarlem and LAM families in both studied populations, but observing a statistically significant difference between the proportions of each family among these two populations. In addition, we were able to perform a lineage comparison considering the clinical outcome in community patients.Although, the genotype information obtained with MIRU and spoligotyping is partial (and WGS analysis could shed light about genome implications in clinical outcome), the data presented in this work suggest a more significant contribution of host factors related to the severity of the disease.In terms of ICU mortality, neither the LAM nor the Haarlem families showed higher virulence. Factors contributing to death in the present study were more likely related to host comorbidities (in particular, drug abuse, poor nutritional status, and lack of access to health care facilities).Although the presented series in our study is one of the largest reported<a class="elsevierStyleCrossRefs" href="#bib0100">5,6,13</a>, the limited number of patients enrolled warrants a more robust statistical analysis. The study of cases should continue to add more information leading to improve the understanding of the correlation between TB lineages and virulence.The results presented in this work represent a starting point, an in-depth study based on genomes could contribute to better understand the virulence observed in these strains and could help to improve the prognosis of these critically ill patients.Financial supportThis work was supported by grant FSS_2_2011_1_6850 (Fondo Sectorial de Salud, Agencia Nacional de Investigación e Innovación [ANII)]. FOCEM - Fondo para la Convergencia Estructural del Mercosur (COF 03/11).G.G., N.N., J.H. and C.R. are researchers from the Sistema Nacional de Investigadores (ANII), Montevideo, Uruguay.Conflict of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1688167" "titulo" => "Highlights" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1688165" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1497092" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1688166" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0015" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1497093" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 6 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-07-20" "fechaAceptado" => "2021-02-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1497092" "palabras" => array:3 [ 0 => "Mycobacterium tuberculosis" 1 => "Pulmonary infections" 2 => "Critically ill patients" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1497093" "palabras" => array:3 [ 0 => "Mycobacterium tuberculosis" 1 => "Infecciones pulmonares" 2 => "Medicina intensiva" ] ] ] ] "tieneResumen" => true "highlights" => array:2 [ "titulo" => "Highlights" "resumen" => "<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Genetic structure analysis of 60 TB strains isolated from patients from an ICU.</li><li class="elsevierStyleListItem" id="lsti0010">•We present a comparison with population circulating strains.</li><li class="elsevierStyleListItem" id="lsti0015">•We evaluate the correlation between the clinical outcome and genotypic data.</li><li class="elsevierStyleListItem" id="lsti0020">•We present an extensive cohort study done in critically ill patients with tuberculosis.</li></ul>" ] "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p<0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p<0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La tuberculosis (TB) aún representa un problema mayor de salud pública. En Uruguay, contrariamente a la tendencia mundial, se ha observado un incremento en el número de casos desde 2006. Aunque la incidencia de casos de multidrogorresistencia (MDR) es baja y no se han reportados casos de resistencia a fármacos de primera y segunda línea de tratamiento (XDR), se ha observado un incremento en el número de casos con TB grave, que requieren internación en unidad de terapia intensiva (CTI). Como primer objetivo del presente trabajo, se analizó la estructura genética de cepas de Mycobacteriumtuberculosis aisladas de pacientes internados en CTI. Comparamos estos resultados con los obtenidos con cepas circulantes en la comunidad. Observamos un incremento estadísticamente significativo del genotipo Haarlem en los pacientes internados en CTI (53,3 vs. 34,7%; p<0,05). Además, investigamos la asociación del desenlace clínico con el genotipo, y encontramos una mayor incidencia de disfunción hepática en los pacientes infectados con la cepa Haarlem (p<0,05). La cohorte presentada en este trabajo corresponde a una de las series con mayor número de pacientes con tuberculosis que requirieron internación en CTI." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia><elsevierMultimedia ident="upi0015"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0020" ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1804 "Ancho" => 3175 "Tamanyo" => 299112 ] ] "descripcion" => array:1 [ "en" => "Minimum spanning tree cluster analysis. (A) Samples in red correspond to ICU samples; samples in blue correspond to community samples. Samples of both groups were present in all clusters. (B) Same analysis colored by lineage. LAM and Haarlem lineages correspond to the most frequent isolates." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1A" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table 1" "rol" => "short" ] ] "tabla" => array:2 [ "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" style="border-bottom: 2px solid black">Lineages \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Critically ill patients, n (%)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Community patients, n (%)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">EAI \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 " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0.0)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.0)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.03 \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">Haarlem \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 " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (53.3)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (34.7)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">LAM10 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (8.3) \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 " rowspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (45.0)LAM<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (18.9) \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 " rowspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 (60.0)LAM<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">LAM3 and 9 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (36.7) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 (41.1) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">S \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.7) \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="" 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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.0) \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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">Others \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \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="" 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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3.3) \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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="6" align="left" valign="\n \t\t\t\t\ttop\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">Total \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 (100) \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="" 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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95 (100) \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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2871844.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Corresponds to the sum of genotypes LAM10, LAM9 and LAM3 in critically ill and community patients respectively." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Chi square comparing ICU vs community TB patients." ] ] ] "descripcion" => array:1 [ "en" => "Mycobacterium tuberculosis lineages in critically ill and community patients." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 1B" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table 1" "rol" => "short" ] ] "tabla" => array:2 [ "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" style="border-bottom: 2px solid black">Lineages \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Community unilateral, n (%)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Community bilateral, n (%)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value<a class="elsevierStyleCrossRef" href="#tblfn0020">b</a> \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">Haarlem \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 " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (32.6)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (51.3)</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">ns \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">LAM10 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (46.5) \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 " rowspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (62.8)LAM<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (25.6) \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 " rowspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (43.5)LAM<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">LAM3 and 9 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (16.3) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (17.9) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">Others \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4.6) \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="" 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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.1) \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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="6" align="left" valign="\n \t\t\t\t\ttop\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">Total \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 (100.0) \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="" 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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 (100.0) \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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2871843.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "Corresponds to the sum of genotypes LAM10, LAM9 and LAM3 in critically ill and community patients respectively." ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "b" "nota" => "Chi-square comparing Unilateral vs Bilateral pulmonary compromise. ns=non-significant." ] ] ] "descripcion" => array:1 [ "en" => "Mycobacterium tuberculosis lineage comparison in pulmonary community patients with unilateral or bilateral TB compromise." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "The values represent the percentage or mean±SD.COPD=chronic obstructive pulmonary disease, ARDS=acute respiratory distress syndrome. ns: non significant.a Considering only patients who survived." "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="" 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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Haarlem n=32 (%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LAM n=27 (%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value (chi-square test) \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">Age \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41±15 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38±14 \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">ns \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">APACHE II \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18±11 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16±9 \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">ns \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">Male sex% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (84.3) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (62.2) \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">0.05 \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">Mechanical ventilation \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (71.8) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (85.1) \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">ns \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 " colspan="4" align="left" valign="\n \t\t\t\t\ttop\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 " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Comorbidities</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">Drug abuse \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (37.5) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (37.0) \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">ns \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">HIV coinfection \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (25.0) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (22.2) \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">ns \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">COPD \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (12.5) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (18.5) \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">ns \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">Malnutrition \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (12.5) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (18.5) \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">ns \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 " colspan="4" align="left" valign="\n \t\t\t\t\ttop\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 " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Organ dysfunctions</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">Cardiovascular \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (56.3) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (59.3) \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">ns \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">Renal \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (25.0) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (22.2) \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">ns \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">Hepatic \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (28.2) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (7.4) \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">0.04 \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">ARDS \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (78.2) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (92.5) \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">ns \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">ICU stay (days)a \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9±9 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15±15 \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">ns \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">ICU-mortality \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (62.5) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (59.2) \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">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2871845.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic data, comorbidities, and overall outcomes comparing the Haarlem and LAM families in ICU patients with moderate to high severity score." ] ] 4 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pptx" "ficheroTamanyo" => 51553 ] ] 5 => array:5 [ "identificador" => "upi0010" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.xlsx" "ficheroTamanyo" => 21291 ] ] 6 => array:5 [ "identificador" => "upi0015" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc3.xlsx" "ficheroTamanyo" => 22304 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A prediction rule to stratify mortality risk of patients with pulmonary tuberculosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:20 [ 0 => "H.N. 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Tuberculosis en la unidad de cuidados intensivos: características clínicas y epidemiológicas

Joaquín Hurtadoa, Cecilia Coitinhob, Nicolás Ninc, María Buronic, Francisco Javier Hurtadoc,d, Carlos Robelloa,e, Gonzalo Greifa,

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gonzalo.greif@pasteur.edu.uy

Corresponding author.

a Laboratorio de Interacciones Hospedero-Patógeno/Unidad de Biología Molecular, Institut Pasteur Montevideo (IPM), Montevideo, Uruguay

b Laboratory of Microbiology, Anti-tuberculosis and Prevalent Diseases Honorary Commission (CHLA-EP), Montevideo, Uruguay

c Intensive Care Unit, Hospital Español Dr. “Juan J. Crottoggini”, ASSE, Montevideo, Uruguay

d Departamento de Fisiopatología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay

e Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay

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Despite the availability of effective therapies&#44; mortality rates remain between 15&#46;5 and 65&#46;9&#37; in critical care patients<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10&#44;11</span></a>&#46; In Uruguay&#44; a high mortality rate &#40;&#62;50&#37;&#41; was observed in TB cases that required ICU admission&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Information from classical and molecular epidemiology&#44; along with patient clinical data represent key elements to achieve better control of the disease<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The genotypic variations&#44; especially bacterial lineages&#44; are associated with changes in transmission capacity and also in the ability to acquire drug resistance<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#44;7&#8211;9</span></a>&#46; 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and has been performed following the ethical standards of the 1964 Declaration of Helsinki&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Sixty <span class="elsevierStyleItalic">M&#46; tuberculosis</span> isolates obtained from critically ill patients from a general public hospital &#40;Hospital Espa&#241;ol &#8211; ASSE&#44; Montevideo&#44; Uruguay&#41; were genotyped and compared to ninety-five randomly selected community isolates within the same period &#40;Suppl&#46; Table 1 and Suppl&#46; Fig&#46; 1&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All the community sample isolates correspond to patients treated with the standard drug protocol &#40;daily HREZ for the first two months&#44; four months HR 3 days a week&#41;&#46; The cultures became negative after 3 months of treatment &#40;Suppl&#46; Table 1 and Suppl&#46; Fig&#46; 1&#41;&#46; All the community samples were obtained from TB patients that did not require ICU admission at any time during treatment&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Patients with TB admitted to the ICU were classified according to a TB clinical severity score as having low&#44; moderate&#44; and high risk TB disease<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a>&#46; Comorbidities and organ dysfunctions were documented upon admission&#44; along with common clinical and laboratory studies&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Isolate characteristics were summarized for each group &#40;Community and Critically ill patient isolates&#41; in Supplementary Table 1&#46; In addition&#44; the analysis pipeline was shown in Supplementary Figure 1&#46; Microbiological cultures and DNA extractions were performed and stored&#44; as previously described<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a>&#46; Molecular typing using spoligotyping and MIRU-VNTR were performed as described in Supplementary Figure 1&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Lineage assignment was carried out based on similarity search and UPGMA tree when comparing reference strains located in the server with our isolates with a distance less than 0&#46;3 using <a href="http://www.miru-vntr.org/">www&#46;miru-vntr&#46;org</a> tool&#46; Comparative analysis between strain distribution of critical and non-critically ill patients was performed with the Chi-squared contingency tables for categorical data &#40;<span class="elsevierStyleItalic">p</span>-value<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered a statistically significant difference&#41;&#46; Minimum spanning trees were constructed for all isolates using the MST tool &#40;miru-vntr&#46;org&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Based on the documented risk factors&#44; forty-five of our initial set of sixty-five patients &#40;69&#37;&#41; could be classified according to TB severity at the moment of ICU admission into three groups &#40;low&#44; moderate and high severity&#41;&#46; Most ICU admissions correspond to moderate to high severity TB &#40;86&#46;6&#37;&#41;&#58; low &#40;13&#46;4&#37;&#41;&#44; moderate &#40;40&#46;0&#37;&#41;&#44; and high risk &#40;46&#46;6&#37;&#41; &#40;Suppl&#46; Fig&#46; 1&#41;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Supplementary Figure 1 shows the main characteristics of TB patients admitted to an ICU including demographic data&#44; bilateral pulmonary compromise&#44; comorbidities&#44; organ dysfunctions&#44; relevant laboratory findings&#44; classification according to a tuberculosis severity score<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a>&#44; and ICU mortality&#46; In brief&#44; patients were relatively young with male predominance&#46; Bilateral pulmonary involvement was present in 44&#37;&#44; and HIV coinfection in 22&#37; of the cases&#46; Poor nutritional status was present in 76&#37;&#46; Respiratory and cardiovascular failure were the most frequent organ failures&#44; and mechanical ventilation was implemented in 74&#37; of the patients&#46; Only 13&#46;3&#37; had a low tuberculosis risk severity score&#44; while a moderate to high score was observed in 86&#46;6&#37; of these patients&#46; Global mortality in ICU was 62&#37; considering all patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#41; and reached 71&#46;8&#37; considering only high-to-moderate severity TB patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Among the ICU <span class="elsevierStyleItalic">M&#46; tuberculosis</span> isolates&#44; strains clustered into five main sub-lineages &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1A</a>&#41;&#46; Except for one particular case&#44; all sub-lineages belong to Lineage 4 of <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46; Typing of critical care patients reveals the Haarlem family as the most prominent in these samples &#40;53&#46;3&#37;&#41;&#44; followed by the LAM family &#40;45&#46;0&#37;&#41;&#46; On the contrary&#44; LAM strains are more represented among community TB isolates &#40;60&#46;0&#37;&#41;&#44; followed by the Haarlem strains &#40;34&#46;7&#37;&#41;&#44; a significant statistical difference being observed when comparing these two populations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">It is interesting to observe that the Haarlem family was more frequent in patients with bilateral TB &#40;51&#46;3&#37;&#41; versus unilateral TB &#40;32&#46;6&#37;&#41; in community patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1B</a>&#41;&#46; Although the observed difference was not statistically significant&#44; it could indicate a more aggressive form of the disease caused by the Haarlem lineage&#46; This hypothesis needs to be corroborated and could explain the high representation of the Haarlem genotype among critically ill patients&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">More detailed analyses of typing results were performed analyzing the minimum spanning tree generated with the online tool MST &#40;miru-vntrplus&#46;org&#41;&#46; Fourteen clonal complexes were obtained&#44; community and critical isolates could be detected in each cluster &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and Supplementary Table 2&#41;&#46; The biggest cluster comprises 44 isolates &#40;22 of them &#8211; 9 ICU and 13 community samples &#8211; with the same MIRU pattern belonging to the Haarlem genotype &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#41;&#46; Finally&#44; 24 community samples and 10 ICU samples remain unclustered&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">When analyzing the clonal complexes with more than six isolates &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#44; we could observe strains isolated during the whole studied period &#40;Suppl&#46; Table 2&#41;&#46; This phenomenon also occurs when analyzing at group level&#46; No clonal complexes were associated with a particular isolation year that could be due to a particular outbreak&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">We investigated the possible association of observed TB genotypes with ICU patient&#39;s comorbidities&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">A closer look into critically ill patients is shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#44; comparing demographic data and some comorbidities such as drug abuse&#44; HIV&#44; COPD&#44; and malnutrition&#44; between the main represented strains &#40;Haarlem and LAM families&#41;&#46; We did not find any significant differences among comorbidities between the genotype groups&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Comparing organ dysfunctions observed among ICU patients &#40;with a low to high severity score&#41; between the different genotypes&#44; we found that patients with the Haarlem genotypes showed hepatic dysfunction more frequently than patients with LAM &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#41;&#46; The mortality observed in these patients was not statistically related to the <span class="elsevierStyleItalic">M&#46; tuberculosis</span> genotype &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#41;&#44; and no significant association between the outcome of patients with different lineages was found&#46; As far as we know&#44; this is the first communication relating clinical and molecular epidemiology in critically ill patients with severe TB&#46; Furthermore&#44; we were able to compare the main TB lineages that circulate both in the community and critical care setting&#44; studying the association between these genotypes with clinical outcomes&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The principal finding showed that lineages belong to the Haarlem and LAM families in both studied populations&#44; but observing a statistically significant difference between the proportions of each family among these two populations&#46; In addition&#44; we were able to perform a lineage comparison considering the clinical outcome in community patients&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Although&#44; the genotype information obtained with MIRU and spoligotyping is partial &#40;and WGS analysis could shed light about genome implications in clinical outcome&#41;&#44; the data presented in this work suggest a more significant contribution of host factors related to the severity of the disease&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In terms of ICU mortality&#44; neither the LAM nor the Haarlem families showed higher virulence&#46; Factors contributing to death in the present study were more likely related to host comorbidities &#40;in particular&#44; drug abuse&#44; poor nutritional status&#44; and lack of access to health care facilities&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Although the presented series in our study is one of the largest reported<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5&#44;6&#44;13</span></a>&#44; the limited number of patients enrolled warrants a more robust statistical analysis&#46; The study of cases should continue to add more information leading to improve the understanding of the correlation between TB lineages and virulence&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The results presented in this work represent a starting point&#44; an in-depth study based on genomes could contribute to better understand the virulence observed in these strains and could help to improve the prognosis of these critically ill patients&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0150" class="elsevierStylePara elsevierViewall">This work was supported by grant FSS&#95;2&#95;2011&#95;1&#95;6850 &#40;<span class="elsevierStyleGrantSponsor" id="gs1">Fondo Sectorial de Salud&#44; Agencia Nacional de Investigaci&#243;n e Innovaci&#243;n</span> &#91;ANII&#41;&#93;&#46; FOCEM - Fondo para la Convergencia Estructural del Mercosur &#40;COF 03&#47;11&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">G&#46;G&#46;&#44; N&#46;N&#46;&#44; J&#46;H&#46; and C&#46;R&#46; are researchers from the Sistema Nacional de Investigadores &#40;ANII&#41;&#44; Montevideo&#44; Uruguay&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflict <span class="elsevierStyleBold">of interest</span></span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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    "highlights" => array:2 [
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      "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0005" class="elsevierStylePara elsevierViewall">Genetic structure analysis of 60 TB strains isolated from patients from an ICU&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0010" class="elsevierStylePara elsevierViewall">We present a comparison with population circulating strains&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall">We evaluate the correlation between the clinical outcome and genotypic data&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">We present an extensive cohort study done in critically ill patients with tuberculosis&#46;</p></li></ul></p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Human tuberculosis is still a major world health concern&#46; In Uruguay&#44; contrary to the world trend&#44; an increase in cases has been observed since 2006&#46; Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered&#44; an increase in the number of patients with severe tuberculosis requiring critical care admission was observed&#46; As a first aim&#44; we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit&#46; We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients &#40;53&#46;3&#37; vs 34&#46;7&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; In addition&#44; we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; The cohort presented is one of the largest studied series of critically ill patients with tuberculosis&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La tuberculosis &#40;TB&#41; a&#250;n representa un problema mayor de salud p&#250;blica&#46; En Uruguay&#44; contrariamente a la tendencia mundial&#44; se ha observado un incremento en el n&#250;mero de casos desde 2006&#46; Aunque la incidencia de casos de multidrogorresistencia &#40;MDR&#41; es baja y no se han reportados casos de resistencia a f&#225;rmacos de primera y segunda l&#237;nea de tratamiento &#40;XDR&#41;&#44; se ha observado un incremento en el n&#250;mero de casos con TB grave&#44; que requieren internaci&#243;n en unidad de terapia intensiva &#40;CTI&#41;&#46; Como primer objetivo del presente trabajo&#44; se analiz&#243; la estructura gen&#233;tica de cepas de <span class="elsevierStyleItalic">Mycobacterium</span><span class="elsevierStyleItalic">tuberculosis</span> aisladas de pacientes internados en CTI&#46; Comparamos estos resultados con los obtenidos con cepas circulantes en la comunidad&#46; Observamos un incremento estad&#237;sticamente significativo del genotipo Haarlem en los pacientes internados en CTI &#40;53&#44;3 vs&#46; 34&#44;7&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Adem&#225;s&#44; investigamos la asociaci&#243;n del desenlace cl&#237;nico con el genotipo&#44; y encontramos una mayor incidencia de disfunci&#243;n hep&#225;tica en los pacientes infectados con la cepa Haarlem &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; La cohorte presentada en este trabajo corresponde a una de las series con mayor n&#250;mero de pacientes con tuberculosis que requirieron internaci&#243;n en CTI&#46;</p></span>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Minimum spanning tree cluster analysis&#46; &#40;A&#41; Samples in red correspond to ICU samples&#59; samples in blue correspond to community samples&#46; Samples of both groups were present in all clusters&#46; &#40;B&#41; Same analysis colored by lineage&#46; LAM and Haarlem lineages correspond to the most frequent isolates&#46;</p>"
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                  \t\t\t\t">Haarlem&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;34&#46;7&#41;</td><td class="td" title="\n
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                  \t\t\t\t">LAM10&nbsp;\t\t\t\t\t\t\n
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                  \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">LAM3 and 9&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;36&#46;7&#41;&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39 &#40;41&#46;1&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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">S&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;7&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;0&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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">Others&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;3&#46;3&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></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">Total&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;100&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95 &#40;100&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2871844.png"
              ]
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Corresponds to the sum of genotypes LAM10&#44; LAM9 and LAM3 in critically ill and community patients respectively&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Chi square comparing ICU vs community TB patients&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> lineages in critically ill and community patients&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 1B"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table 1"
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "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" style="border-bottom: 2px solid black">Lineages&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Community unilateral&#44; n &#40;&#37;&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Community bilateral&#44; n &#40;&#37;&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\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">Haarlem&nbsp;\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  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;32&#46;6&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;51&#46;3&#41;</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">ns&nbsp;\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">LAM10&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;46&#46;5&#41;&nbsp;\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  " rowspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;62&#46;8&#41;LAM<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;25&#46;6&#41;&nbsp;\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  " rowspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;43&#46;5&#41;LAM<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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">LAM3 and 9&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;16&#46;3&#41;&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;17&#46;9&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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">Others&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#46;6&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#46;1&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></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">Total&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 &#40;100&#46;0&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39 &#40;100&#46;0&#41;&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2871843.png"
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            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Corresponds to the sum of genotypes LAM10&#44; LAM9 and LAM3 in critically ill and community patients respectively&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Chi-square comparing Unilateral vs Bilateral pulmonary compromise&#46; ns<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>non-significant&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> lineage comparison in pulmonary community patients with unilateral or bilateral TB compromise&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The values represent the percentage or mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">COPD<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>chronic obstructive pulmonary disease&#44; ARDS<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acute respiratory distress syndrome&#46; ns&#58; non significant&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Considering only patients who survived&#46;</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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Haarlem n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32 &#40;&#37;&#41;&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LAM n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27 &#40;&#37;&#41;&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value &#40;chi-square test&#41;&nbsp;\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
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">23 &#40;85&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Drug abuse&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">10 &#40;37&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;22&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>COPD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;18&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">4 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">5 &#40;18&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">16 &#40;59&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">6 &#40;22&#46;2&#41;&nbsp;\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
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hepatic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">9 &#40;28&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">2 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;04&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ARDS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">25 &#40;78&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">25 &#40;92&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ICU stay &#40;days&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \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>ICU-mortality&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;62&#46;5&#41;&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;59&#46;2&#41;&nbsp;\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">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Demographic data&#44; comorbidities&#44; and overall outcomes comparing the Haarlem and LAM families in ICU patients with moderate to high severity score&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:15 [
            0 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "1"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "A prediction rule to stratify mortality risk of patients with pulmonary tuberculosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:20 [
                            0 => "H&#46;N&#46; Bastos"
                            1 => "N&#46;S&#46; Os&#243;rio"
                            2 => "A&#46;G&#46; Castro"
                            3 => "A&#46; Ramos"
                            4 => "T&#46; Carvalho"
                            5 => "L&#46; Meira"
                            6 => "D&#46; Ara&#250;jo"
                            7 => "L&#46; Almeida"
                            8 => "R&#46; Boaventura"
                            9 => "P&#46; Fragata"
                            10 => "C&#46; Chaves"
                            11 => "P&#46; Costa"
                            12 => "M&#46; Portela"
                            13 => "I&#46; Ferreira"
                            14 => "S&#46;P&#46; Magalh&#227;es"
                            15 => "F&#46; Rodrigues"
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Article information

ISSN: 03257541
Original language: English

DOI:10.1016/j.ram.2021.02.011

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2024 June	21	7	28
2024 May	15	6	21
2024 April	42	5	47
2024 March	22	8	30
2024 February	14	5	19
2024 January	39	7	46
2023 December	21	9	30
2023 November	19	10	29
2023 October	18	10	28
2023 September	24	5	29
2023 August	17	3	20
2023 July	17	6	23
2023 June	19	1	20
2023 May	30	7	37
2023 April	15	6	21
2023 March	19	2	21
2023 February	11	6	17
2023 January	15	3	18
2022 December	18	10	28
2022 November	21	10	31
2022 October	23	5	28
2022 September	18	15	33
2022 August	16	10	26
2022 July	19	6	25
2022 June	26	15	41
2022 May	42	12	54
2022 April	22	16	38
2022 March	3	11	14
2022 February	1	8	9
2022 January	4	6	10
2021 December	4	10	14
2021 November	4	8	12
2021 October	13	16	29
2021 September	3	4	7
2021 August	0	2	2
2021 July	7	14	21
2021 June	8	17	25
2021 May	1	5	6

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