Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease

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Lanes 1 and 19: Molecular Weight Marker 100bp; lanes 2–18: strains with molecular pattern VNI." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cristian Anacona, Fabiola E. González C., Luis Reinel Vásquez-A, Patricia Escandón" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Cristian" "apellidos" => "Anacona" ] 1 => array:2 [ "nombre" => "Fabiola E." "apellidos" => "González C." ] 2 => array:2 [ "nombre" => "Luis Reinel" "apellidos" => "Vásquez-A" ] 3 => array:2 [ "nombre" => "Patricia" "apellidos" => "Escandón" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140618300354?idApp=UINPBA00004N" "url" => "/11301406/0000003500000003/v1_201810180606/S1130140618300354/v1_201810180606/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "117" "paginaFinal" => "122" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rosa Belén Mohedano del Pozo, Margarita Rubio Alonso, Mª Soledad Cuétara García" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Rosa Belén" "apellidos" => "Mohedano del Pozo" "email" => array:1 [ 0 => "rosabelen.mohedano@universidadeuropea.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Margarita" "apellidos" => "Rubio Alonso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Mª Soledad" "apellidos" => "Cuétara García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Especialidades Médicas, Universidad Europea de Madrid, C/ Tajo s/n, 28670 Villaviciosa de Odón, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Microbiología y Parasitología Clínica, Hospital Universitario Severo Ochoa de Madrid, Avda/ de Orellana s/n, 28911 Leganés, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diagnóstico de micosis invasora en pacientes hospitalizados con enfermedad pulmonar obstructiva crónica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1570 "Ancho" => 1499 "Tamanyo" => 70332 ] ] "descripcion" => array:1 [ "en" => "ROC curves: (1-3)-β-d-glucan in the diagnosis of proven or probable IA. Area=0.603 (95% CI: 0.435–0.770); standard error=0.085; p=0.225." ] ] ] "textoCompleto" => "Invasive fungal diseases (IFDs) are common infections in immunocompromised patients, not only in traditional risk populations (e.g. oncohematologic patients), but also in other at-risk populations such as critically ill patients or those with chronic obstructive pulmonary disease (COPD). In COPD patients, mucociliary activity impairment, immunosuppression due to the inhibition of alveolar macrophages and neutrophils by steroids, and treatment with broad-spectrum antibiotics play a role in the development of IFD.<a class="elsevierStyleCrossRef" href="#bib0230">7</a>Candida is the most frequent fungal pathogen in IFD. Among the emerging invasive mycoses are those caused by filamentous fungi, such as Aspergillus, Fusarium, mucorales, and Scedosporium.<a class="elsevierStyleCrossRef" href="#bib0330">22</a>IFD in patients under intensive care is among the most difficult infectious diseases to recognize clinically and its diagnosis is frequently missed.<a class="elsevierStyleCrossRefs" href="#bib0200">1,17,22</a> Nevertheless, the importance of early diagnosis and antifungal therapy for the prognosis of patients with IFD is clear. Because of this, diagnostic methods with appropriate sensitivity and specificity are needed.Microbiological diagnostic techniques for IFD can be classified into:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Conventional techniques: direct examination and culture.</li><li class="elsevierStyleListItem" id="lsti0010">•Unconventional techniques (culture-independent methods): detection of galactomannan (GM), (1-3)-β-d-glucan and antibodies, and molecular amplification techniques.</li></ul>The origin of the samples for performing diagnostic techniques is very important. Sample availability, especially in selected patients whose clinical situation is very critical, is also a decisive factor when choosing the most appropriate diagnostic methods. For example, skin lesions, if present, are relatively easy to biopsy; corneal samples are useful in the diagnosis of keratitis produced by Aspergillus or Fusarium. Lung biopsy may be required if IFD with a pulmonary focus is suspected and the clinical situation of the patient is appropriate in order to tolerate the biopsy.Culture allows us not only to identify the etiologic agent at the species level, but also to evaluate its antifungal susceptibility. However, specimen retrieval for culture may require invasive techniques, is laborious, and culture sensitivity is generally low (around 50% depending upon the patient, infectious focus and sample). Furthermore, the isolation of a certain etiological agent in a non-sterile sample does not exclude contamination or colonization.Accordingly, the diagnosis of IFD often depends on a combination of clinical criteria and the presence of fungal etiologic agents in the most appropriate samples from the sites of infection. It is worth noting the high rate of confirmation of suspected IFDs in critically ill patients, especially if they have risk factors.<a class="elsevierStyleCrossRef" href="#bib0255">11</a> Early diagnosis and treatment have been shown to improve patient outcomes, but an early diagnosis is still a challenge, and a wider variety of validated diagnostic techniques is needed. Recently, testing both galactomannan and (1-3)-β-d-glucan in serum and galactomannan in bronchoalveolar lavage has been accepted by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) as complementary diagnostic techniques in the diagnosis of IFD.<a class="elsevierStyleCrossRef" href="#bib0235">8</a> Monitoring of at-risk patients with galactomannan is recommended to establish an early diagnosis and check fungal disease progression.<a class="elsevierStyleCrossRef" href="#bib0250">10</a> In contrast, PCR is still under investigation for the diagnosis of IFD. Lack of standardization of the various molecular assays has hindered their widespread acceptance in the diagnosis of IFD. Nevertheless, the close future is promising.<a class="elsevierStyleCrossRefs" href="#bib0285">14,15,26,27</a> The use of culture-independent techniques appears to be helpful for an early diagnosis of IFD. There is abundant literature offering useful conclusions for clinical practice concerning the role these techniques have in hematological patients. However, there are no clear conclusions in the case of other groups such as patients suffering from COPD.<a class="elsevierStyleCrossRefs" href="#bib0245">9,16,23</a>The overall objective of this work is to study the usefulness of nonculture-based diagnostic techniques for IFD diagnosis in non-neutropenic, hospitalized patients with COPD who are at risk for IFD.Patients and methodsThe study was conducted at the Department of Clinical Microbiology and the Intensive Care Unit (ICU) of the University Hospital Severo Ochoa located in Madrid (Spain).It was a prospective observational study carried out over a period of three years (January 2008 to December 2010) as part of a project (FIS 070134), and was approved by the Ethics Committee.Selection of patientsInclusion criteria: COPD patients admitted to hospital with risk factors for developing IFD.<a class="elsevierStyleCrossRef" href="#bib0320">20</a>Exclusion criteria:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">•Community-acquired infection</li><li class="elsevierStyleListItem" id="lsti0020">•Estimated life expectancy of less than a week</li><li class="elsevierStyleListItem" id="lsti0025">•Patients under 18 years</li><li class="elsevierStyleListItem" id="lsti0030">•Neutropenia (neutrophil count<500neutrophils/mm3)</li><li class="elsevierStyleListItem" id="lsti0035">•Pregnant or lactating women</li><li class="elsevierStyleListItem" id="lsti0040">•Patients who refused to give informed consent</li></ul>Data collectionData was collected sequentially over the entire project, with a follow up of the patients along the different episodes that they might suffer in the three years of observation.Patients underwent clinical, microbiological and radiological monitoring. The data collection protocol consisted of the following variables:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045">•Personal variables (age and gender)</li><li class="elsevierStyleListItem" id="lsti0050">•Hospitalization time</li><li class="elsevierStyleListItem" id="lsti0055">•Diagnosis in admission</li><li class="elsevierStyleListItem" id="lsti0060">•Risk factors for IFD up to a month before and during admission according to Meersseman, 2007:<a class="elsevierStyleCrossRef" href="#bib0310">18</a></li><li class="elsevierStyleListItem" id="lsti0065">∘Simultaneous administration of two or more antibiotics, prescription of broad-spectrum antibiotics over a minimum of 5 days.</li><li class="elsevierStyleListItem" id="lsti0070">∘High doses of corticosteroids or other immunosuppressive drugs.</li><li class="elsevierStyleListItem" id="lsti0075">∘Chemotherapy and/or radiation therapy during the hospitalization.</li><li class="elsevierStyleListItem" id="lsti0080">∘Parenteral nutrition and/or mechanical ventilation for 48h or more.</li><li class="elsevierStyleListItem" id="lsti0085">∘Central venous catheter.</li><li class="elsevierStyleListItem" id="lsti0090">∘Hospitalization in ICU for at least 7 days with a diagnosis of liver cirrhosis.</li><li class="elsevierStyleListItem" id="lsti0095">∘Acute pancreatitis and abdominal surgery or other surgeries during the episode.</li><li class="elsevierStyleListItem" id="lsti0100">•Category of IFD (proven, probable, possible) according to De Pauw.<a class="elsevierStyleCrossRef" href="#bib0235">8</a></li><li class="elsevierStyleListItem" id="lsti0105">•Clinical variables:</li><li class="elsevierStyleListItem" id="lsti0110">∘Clinical severity according to the SOFA – Sequential Organ Failure Assessment – score.<a class="elsevierStyleCrossRef" href="#bib0380">29</a></li><li class="elsevierStyleListItem" id="lsti0115">∘Mucositis during the episode</li><li class="elsevierStyleListItem" id="lsti0120">∘Fever during the episodeMicrobiological variables:</li><li class="elsevierStyleListItem" id="lsti0125">∘Sample type</li><li class="elsevierStyleListItem" id="lsti0130">∘Date of sampling</li><li class="elsevierStyleListItem" id="lsti0135">∘Results of microbiological tests, including those for nonculture-based diagnostic techniques –galactomannan, (1-3)-β-d-glucan and CAGTA.</li><li class="elsevierStyleListItem" id="lsti0140">∘Known circumstances relating to false positive galactomannan (bacteremia, dialysis and fiber-rich diet).<a class="elsevierStyleCrossRef" href="#bib0225">6</a></li><li class="elsevierStyleListItem" id="lsti0145">∘Factors related to false positive (1-3)-β-d-glucan (hemodialysis equipment having cellulose membranes, treatment with albumin, immunoglobulins and some anticancer agents as lentinan or polysaccharide K, and sulfonamides).<a class="elsevierStyleCrossRefs" href="#bib0260">12,14</a></li><li class="elsevierStyleListItem" id="lsti0150">•Antifungal prophylaxis in the month prior to hospitalization (drug, dose and duration of treatment)</li><li class="elsevierStyleListItem" id="lsti0155">•Empirical antifungal treatment (drug, dose, and duration of treatment)</li><li class="elsevierStyleListItem" id="lsti0160">•High-resolution CT scan</li><li class="elsevierStyleListItem" id="lsti0165">•Histopathologic analysis</li></ul>Microbiological assayGalactomannan (Platelia Aspergillus, Bio-Rad Laboratories, Marnes La Coquette, France), (1-3)-β-d-glucan (Fungitell, Associates of Cape Cod, Falmouth, MA, USA) and CAGTA (Candida albicans IFA IgG, Vircell, Spain) were performed according to the manufacturer's recommendations for testing serum samples. They were performed twice a week. The optical density value of the serum galactomannan cut-off was 0.5. A galactomannan result was considered positive when two sequential determinations had a value of 0.5 or greater. Serum concentrations of (1-3)-β-d-glucan are interpreted as negative (<60pg/ml), indeterminate (60–79pg/ml) or positive (>80pg/ml). A CAGTA result was considered positive with a serum titer ≥1:160 in at least one sample.Blood and sterile sites cultures were processed with automated systems (Bactec 9240, Becton Dickinson Diagnostic Instruments System, Sparks, MD, USA). Yeast species were identified with the API ID32C (bioMérieux, Madrid, Spain). Additional studies of fungal colonization were performed on rectum, oropharynx, pericatheter area and urine.Data analysisAll quantitative data are presented as mean±SD. Sensitivity (Se), specificity (Sp) and predictive values (PPV and NPV) of IFD culture-independent diagnostic markers were calculated according to Altman and Bland.<a class="elsevierStyleCrossRefs" href="#bib0215">4,5</a> The criteria that define proven or probable IFD according to De Pauw<a class="elsevierStyleCrossRef" href="#bib0235">8</a> were considered the gold standard. The corresponding ROC curves were also calculated. The highest measurements obtained from each patient's values were considered to calculate receiver operating characteristic (ROC) curves. Data analysis was performed using IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.ResultsThe characteristics of the 43 patients with COPD and risk factors for developing IFD are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The underlying diseases of these patients were the following: type 2 diabetes mellitus (18.6%), surgical history in the year before (14%), cancer history in the last 9 months (16.3%), non-invasive fungal infection history (4.7%), and transplant (2.3%). No COPD patient was found with positive serology for HIV. In terms of frequency, respiratory infection as a cause of hospitalization (83.7%) was followed by bacteremia/sepsis (9.3%). Other causes of hospitalization were abdominal infection (7%), abdominal surgery (4.7%), suspected IFD (2.3%), study of pulmonary nodules (2.3%), and palliative care (2.3%). Eighteen patients (41.9%) were hospitalized in ICU.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Risk factors for IFD in COPD patients are specified in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The most frequent was the use of broad-spectrum antibiotics (90.7%). The results of colonization studies are detailed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. Multifocal colonization was present in 15% of patients. The average corrected colonization index (CCI) in these patients was 0.15±0.2 (0–1), and 16.1% showed a CCI above 0.4. Sixteen IFD cases (37.2%) were diagnosed among 43 patients (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). The results of the microbiological cultures associated with the diagnosis of IFD are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Regarding the nonculture-based diagnostic techniques, the results of sensitivity, specificity, predictive values and ROC curves are shown in <a class="elsevierStyleCrossRefs" href="#tbl0025">Tables 5 and 6</a>, and in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1–4</a>. Positive (1-3)-β-d-glucan preceded in 1.7 days on average the growth of Candida in blood culture. The tables only refer to invasive candidemia and invasive aspergillosis. With respect to other types of fungal disease, only one rhinocerebral zygomycosis was diagnosed (probable invasive aspergillosis was also diagnosed in the same patient). In this patient, both the (1-3)-β-d-glucan and galactomannan were positive. The false positive rates obtained with galactomannan, (1-3)-β-d-glucan and CAGTA were 2.4%, 4.5% and 3.1% respectively.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>DiscussionAccording to the literature, the incidence of IFD in COPD patients can exceed that of “classic” at-risk IFD patients, and its evolution is nearly always unfavorable.<a class="elsevierStyleCrossRef" href="#bib0250">10</a> The incidence of IA in hematological patients is between 4% and 22%, depending on the publication.<a class="elsevierStyleCrossRef" href="#bib0375">28</a> In this study we actually observed a high incidence among the COPD patients analyzed (specifically, 34.9% of IFD and 20% of IA). On the other hand, the mortality rate in our COPD patients stood at 32.6%. Compared to the mortality data relating to hematological patients (20–50%),<a class="elsevierStyleCrossRef" href="#bib0300">16</a> this study shows a higher mortality rate. Mortality associated with candidemia ranges from 35% to 49%, depending on the study.<a class="elsevierStyleCrossRefs" href="#bib0210">3,27</a> Mortality among our patients with candidemia was 72%; in ICU, mortality in patients with candidemia was 76.9%. This high mortality rate compared to that described in the literature may be explained by the fact that data collection in the present study did not guarantee that the patient's death was caused by IFD. Given the critical condition of the patients, mortality may have been influenced by comorbidities and the highly variable risk factors presented by these patients (SOFA score>12 in 23% of our patients in ICU). However, according to other publications, mortality associated with IC exceeds 40%, with the highest rates in critically ill patients.<a class="elsevierStyleCrossRefs" href="#bib0380">29,30</a>In several studies where (1-3)-β-d-glucan was evaluated in the diagnosis of IFD,<a class="elsevierStyleCrossRefs" href="#bib0320">20,21</a> the NPV exceeded 90%. The data presented here are similar. This supports the work conducted by Karageorgopoulos et al.,<a class="elsevierStyleCrossRef" href="#bib0270">13</a> in which the (1-3)-β-d-glucan determination was helpful in ruling out IFD in critically ill patients. The sensitivity figures of Moragues et al.<a class="elsevierStyleCrossRef" href="#bib0315">19</a> concerning CAGTA marker in critically ill patients with IC were similar to those obtained in the present study (Se=70–89% vs. Se=85.7% in this study). In terms of specificity, our data shows lower values (Sp=91–100% vs. Sp=72.2% in this study). It is well known that patients with invasive infections caused by species other than C. albicans usually have lower CAGTA titers.<a class="elsevierStyleCrossRef" href="#bib0360">25</a> The high percentage of non-C. albicans Candida species in these patients (66.6%) could explain why the specificity results were lower.In the meta-analysis conducted by Pfeiffer et al.<a class="elsevierStyleCrossRef" href="#bib0345">24</a> – with a predominance of oncohematologic patients – both sensitivity and specificity in galactomannan detection in serum to diagnose IA were similar to those calculated in this study (Se=61% and Sp=93% vs. Se=62.5% and Sp=88.5% in this study). NPV results were particularly good for both studies (>91%). Therefore, it is suggested that a negative galactomannan could be sufficient to exclude the diagnosis of IA. When considering an index ≥0.5 for galactomannan, several prospective studies in adult oncohematologic patients have confirmed low levels of false positives (3–10%).<a class="elsevierStyleCrossRefs" href="#bib0205">2,18,19</a> A galactomannan false positive rate of 2.4% was observed among our patients, which is lower than that described in the literature for oncohematologic patients. The extreme care of the clinicians to avoid cross-contamination could explain the low false positive rate found. Furthermore, the false positives for (1–3)-β-d-glucan and CAGTA were 4.5% and 3.1%, respectively. These are very acceptable rates and well below the usual published values (up to 25% (1-3)-β-d-glucan false positive in the first three days after the surgery in critically ill patients according to Pemán et al.<a class="elsevierStyleCrossRef" href="#bib0335">23</a>).The IFD spectrum is currently undergoing changes that raise questions about how to treat and prevent IFD. At present, it is essential to pay attention to new populations at risk for IFD. The definitive diagnosis is made using histopathology and identifying the causative agent. However, in recent years, culture-independent techniques have permitted earlier diagnosis. On the other hand, while autopsy is considered a gold-standard arbiter of the presence of IFD, one must consider whether, in the last days of life of a critically ill patient, the collapse of normal physiology and normal anatomical integrity (the loss of gut mucosal permeability barrier integrity due to anoxia, uremia, dysbiosis or inflammation) may lead to the inappropriate presence of microorganisms as a mortality-associated process. The results of this study suggest that culture-independent techniques are particularly useful in COPD patients, especially for ruling out IFD. Besides, it is necessary to conduct a thorough selection of COPD-patients at risk for IFD. In these patients at risk, the finding of sequentially positive galactomannan and / or (1-3)-β-d-glucan tests are indicative of IFD when associated with a strong clinical suspicion. Anyway, the limitations of this study were the following: (i) Lack of a reliable gold standard that may lead to misdiagnose or underdiagnose IFD; (ii) the inclusion of cases of probable IFD along with proven IFD when calculating sensitivity, specificity and predictive values of biomarkers that are used to define precisely the concept of probable IFD; (iii) the difficulty in discriminating between colonization and fungal disease; (iv) insufficient galactomannan and (1-3)-β-d-glucan positive cases to draw conclusions about the usefulness of these techniques in such samples.Conflict of interestsThe authors declare no conflict of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1096126" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aims" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1037934" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1096125" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1037933" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Patients and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Selection of patients" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Data collection" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Microbiological assay" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Data analysis" ] ] ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interests" ] 8 => array:2 [ "identificador" => "xack372376" "titulo" => "Acknowledgments" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-01-28" "fechaAceptado" => "2017-07-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1037934" "palabras" => array:7 [ 0 => "Fungemia" 1 => "COPD" 2 => "Galactomannan" 3 => "(1-3)-β-d-glucan" 4 => "CAGTA" 5 => "Sensitivity" 6 => "Specificity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1037933" "palabras" => array:7 [ 0 => "Fungemia" 1 => "EPOC" 2 => "Galactomanano" 3 => "(1-3)-β-d-glucano" 4 => "CAGTA" 5 => "Sensibilidad" 6 => "Especificidad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundThe role of culture-independent techniques (galactomannan, (1-3)-β-d-glucan) in the early diagnosis of invasive fungal diseases (IFD) is well assessed in hematological patients, but there are no clear conclusions in patients with chronic obstructive pulmonary disease (COPD). AimsTo study the usefulness of nonculture-based techniques in the diagnosis of IFD in COPD-patients at risk for IFD. MethodsA prospective observational study based on monitoring COPD patients at risk for IFD during 2007–2010 was carried out. The presence of galactomannan, (1-3)-β-d-glucan and an indirect immunofluorescence of Candida albicans germ tube specific antibodies (CAGTA) were performed. ResultsAmong 43 COPD patients, 16 (37.2%) were diagnosed with IFD: seven cases were proven IFD (five invasive candidemia – IC, one invasive aspergillosis – IA and a rhinocerebral zygomycosis) and nine probable IFD (seven IA and two IC). In the diagnosis of IC and IA, the negative predictive value (NPV) of (1-3)-β-d-glucan was 100%. Regarding CAGTA in IC, NPV was 96.2%. Finally, NPV of galactomannan in IA was 91.2%. The area under the ROC curve for (1-3)-β-d-glucan in IC and for the rest of the IFD cases was 0.86 (95% CI, 0.79–0.93) and 0.60 (95% CI, 0.43–0.77), for CAGTA in IC was 0.83 (95% CI, 0.74–0.91) and for galactomannan in IA was 0.71 (95% CI, 0.56–0.85). Positive (1-3)-β-d-glucan preceded the growth of Candida (average of 1.7 days) in blood culture. ConclusionsIn COPD patients at risk for IFD the assayed techniques are especially useful to rule out the presence of IFD." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aims" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesEl papel de las técnicas independientes de cultivo [galactomanano, (1-3)-β-D-glucano] en el diagnóstico precoz de micosis invasoras (MI) está bien establecido en pacientes hematológicos, pero no existen conclusiones claras en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). ObjetivosEstudiar la utilidad de las técnicas independientes de cultivo en el diagnóstico de MI en pacientes con EPOC que corren el riesgo de contraer una MI. MétodosSe llevó a cabo un estudio prospectivo y observacional en que se supervisaron pacientes con EPOC que corrían el riesgo de contraer una MI de 2007 a 2010. Para ello se estableció la existencia de galactomanano, (1-3)-β-D-glucano y se realizó el ensayo CAGTA (inmunofluorescencia indirecta para determinar la existencia de anticuerpos IgG frente a antígenos de la superficie de la fase micelial de Candida albicans). ResultadosSe diagnosticaron 16MI en 43pacientes con EPOC (37,2%): siete fueron MI probadas (cinco candidemias invasoras [CI], una aspergilosis invasora [AI] y una cigomicosis rinocerebral) y nueve fueron MI probables (siete AI y dos CI). En el diagnóstico de CI y AI, el valor predictivo negativo (VPN) del (1-3)-β-D-glucano fue del 100%. En cuanto al CAGTA en CI, el VPN fue del 96,2%. Finalmente, el VPN del galactomanano en AI fue del 91,2%. El área bajo la curva ROC (receiver operating characteristic) del (1-3)-β-D-glucano en CI y en el resto de los casos de MI fue 0,86 (IC95%=0,79-0,93) y 0,60 (IC95%=0,43-0,77), para CAGTA en CI fue 0,83 (IC95%=0,74-0,91) y para galactomanano en AI fue 0,71 (IC95%=0,56-0,85). La positividad del (1-3)-β-D-glucano se anticipó como media 1,7días al crecimiento de Candida en el hemocultivo. ConclusionesEn pacientes con EPOC que corren el riesgo de contraer MI, estas técnicas son muy útiles para descartar la existencia de MI." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:10 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1647 "Ancho" => 1504 "Tamanyo" => 68230 ] ] "descripcion" => array:1 [ "en" => "ROC curves: (1-3)-β-d-glucan in the diagnosis of proven IC – including candidemias- or probable IC. Area=0.865 (95% CI: 0.798–0.932); standard error=0.034; p<0.0001." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1395 "Ancho" => 1494 "Tamanyo" => 66584 ] ] "descripcion" => array:1 [ "en" => "ROC curves: CAGTA in the diagnosis of proven or probable IC. Area=0.830 (95% CI: 0.744–0.917); standard error=0.044; p<0.0001." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1570 "Ancho" => 1499 "Tamanyo" => 70332 ] ] "descripcion" => array:1 [ "en" => "ROC curves: (1-3)-β-d-glucan in the diagnosis of proven or probable IA. Area=0.603 (95% CI: 0.435–0.770); standard error=0.085; p=0.225." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1545 "Ancho" => 1484 "Tamanyo" => 69945 ] ] "descripcion" => array:1 [ "en" => "ROC curves: galactomannan in the diagnosis of proven or probable IA. Area=0.707 (95% CI: 0.561–0.853); standard error=0.074; p=0.015." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">COPD (n=43) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72.4±8.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Men 88.4% Women 11.6% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients at ICU \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41.9% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hospital stay (days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37.6±19.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stay in ICU (days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.3±19.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with parenteral nutrition ≥48h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.9% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Corrected colonization index (CCI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with SOFA score>12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15.1% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with antifungal prophylaxis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.6% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1873683.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the study population." ] ] 5 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">COPD (n=43) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Broad-spectrum antibiotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 (90.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">More than 2 antibiotics simultaneously \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 (65.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Corticosteroids at high doses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (60.5%) One of them received methotrexate to treat rheumatoid arthritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Central venous catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (44.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mechanical ventilation for ≥48h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (32.6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (14%) 4 patients underwent major abdominal surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute pancreatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (4.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chemotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (2.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1873681.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk factors for IFD." ] ] 6 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oropharynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Neg: 6/17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A. fumigatus: 5/17<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C. tropicalis: 3/17<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C. albicans: 2/17<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Neg: 8/12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C. tropicalis: 3/12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C. glabrata: 1/12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rectum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Neg: 8/10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C. glabrata: 1/10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C. albicans+ C. tropicalis: 1/10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pericatheter area \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Neg: 7/8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C. albicans+ C. tropicalis: 1/8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1873678.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Two patients were coinfected with Aspergillus niger and Aspergillus terreus, respectively." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "In one colonization study C. albicans and C. tropicalis appear as co-responsible for oropharyngeal colonization." ] ] ] "descripcion" => array:1 [ "en" => "Results of fungal colonization studies." ] ] 7 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cultures \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Performed (n) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BAL and bronchial aspirates \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 A. fumigatus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 C. albicans \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peritoneal fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 C. parapsilosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 C. albicans \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 C. parapsilosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surgical exudate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 C. parapsilosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 C. tropicalis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pleural fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 A. fumigatus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sinus puncture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 Rhizopus arrhizus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transbronchial biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 A. fumigatus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 C. tropicalis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 C. parapsilosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 C. albicans \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1873684.png" ] ] 1 => 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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IFD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proven IFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Candidemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Invasive aspergillosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinocerebral zygomycosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Probable IFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Invasive candidemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Invasive aspergillosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible IFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1873680.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Microbiological cultures and diagnosed IFD in the study population (43 patients)." ] ] 8 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Se % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sp % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PPV % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NPV % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62.5 (25.9–89.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88.5 (72.3–96.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.5 (22.6–84.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91.2 (75.2–97.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (59.8–98.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.8 (26.8–60.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.5 (13.9–48.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (74.6–99.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1873679.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Sensitivity (Se), specificity (Sp) and predictive values (positive – PPV – and negative – NPV –) of galactomannan and (1-3)-β-d-glucan in the diagnosis of proven or probable IA in COPD patients." ] ] 9 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Se % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sp % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PPV % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NPV % (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CAGTA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85.7 (42–99.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.2 (54.6–85.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.5 (6.3–64.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.2 (79.1–99.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (56.1–98.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.6 (25.9–59.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (11.4–45.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (74.6–99.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1873682.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Sensitivity (Se), specificity (Sp), PPV and NPV of CAGTA and (1-3)-β-d-glucan in the diagnosis of proven IC – including candidemias – or probable IC in COPD patients." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0200" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective study in critically ill non-neutropenic patients: diagnostic potential of (1-3)-β-d-glucan assay and circulating galactomannan for the diagnosis of invasive fungal disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. 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Mutschlechner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cmi.2015.09.009" "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Infect" "fecha" => "2016" "volumen" => "22" "paginaInicial" => "80" "paginaFinal" => "86" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26400571" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0375" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infección fúngica invasora en los pacientes hematológicos" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.C. Vallejo" 1 => "I. 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Moreno" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc8204" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2010" "volumen" => "14" "paginaInicial" => "207" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20392287" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0385" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Wisplinghoff" 1 => "T. Bischoff" 2 => "S.M. Tallent" 3 => "H. Seifert" 4 => "R.P. Wenzel" 5 => "M.B. Edmond" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/421946" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2004" "volumen" => "39" "paginaInicial" => "309" "paginaFinal" => "317" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15306996" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack372376" "titulo" => "Acknowledgments" "texto" => "The authors would like to thank Malcolm Finkelman, Ph.D. for the revision of the manuscript." 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Original article

Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease

Diagnóstico de micosis invasora en pacientes hospitalizados con enfermedad pulmonar obstructiva crónica

Rosa Belén Mohedano del Pozoa,

Corresponding author

rosabelen.mohedano@universidadeuropea.es

Corresponding author.

, Margarita Rubio Alonsoa, Mª Soledad Cuétara Garcíab

a Departamento de Especialidades Médicas, Universidad Europea de Madrid, C/ Tajo s/n, 28670 Villaviciosa de Odón, Madrid, Spain

b Servicio de Microbiología y Parasitología Clínica, Hospital Universitario Severo Ochoa de Madrid, Avda/ de Orellana s/n, 28911 Leganés, Spain

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direct examination and culture&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Unconventional techniques &#40;culture-independent methods&#41;&#58; detection of galactomannan &#40;GM&#41;&#44; &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan and antibodies&#44; and molecular amplification techniques&#46;</p></li></ul></p><p id="par0035" class="elsevierStylePara elsevierViewall">The origin of the samples for performing diagnostic techniques is very important&#46; Sample availability&#44; especially in selected patients whose clinical situation is very critical&#44; is also a decisive factor when choosing the most appropriate diagnostic methods&#46; For example&#44; skin lesions&#44; if present&#44; are relatively easy to biopsy&#59; corneal samples are useful in the diagnosis of keratitis produced by <span class="elsevierStyleItalic">Aspergillus</span> or <span class="elsevierStyleItalic">Fusarium</span>&#46; Lung biopsy may be required if IFD with a pulmonary focus is suspected and the clinical situation of the patient is appropriate in order to tolerate the biopsy&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Culture allows us not only to identify the etiologic agent at the species level&#44; but also to evaluate its antifungal susceptibility&#46; However&#44; specimen retrieval for culture may require invasive techniques&#44; is laborious&#44; and culture sensitivity is generally low &#40;around 50&#37; depending upon the patient&#44; infectious focus and sample&#41;&#46; Furthermore&#44; the isolation of a certain etiological agent in a non-sterile sample does not exclude contamination or colonization&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Accordingly&#44; the diagnosis of IFD often depends on a combination of clinical criteria and the presence of fungal etiologic agents in the most appropriate samples from the sites of infection&#46; It is worth noting the high rate of confirmation of suspected IFDs in critically ill patients&#44; especially if they have risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> Early diagnosis and treatment have been shown to improve patient outcomes&#44; but an early diagnosis is still a challenge&#44; and a wider variety of validated diagnostic techniques is needed&#46; Recently&#44; testing both galactomannan and &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan in serum and galactomannan in bronchoalveolar lavage has been accepted by the European Organization for the Research and Treatment of Cancer&#47;Mycoses Study Group &#40;EORTC&#47;MSG&#41; as complementary diagnostic techniques in the diagnosis of IFD&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> Monitoring of at-risk patients with galactomannan is recommended to establish an early diagnosis and check fungal disease progression&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> In contrast&#44; PCR is still under investigation for the diagnosis of IFD&#46; Lack of standardization of the various molecular assays has hindered their widespread acceptance in the diagnosis of IFD&#46; Nevertheless&#44; the close future is promising&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">14&#44;15&#44;26&#44;27</span></a> The use of culture-independent techniques appears to be helpful for an early diagnosis of IFD&#46; There is abundant literature offering useful conclusions for clinical practice concerning the role these techniques have in hematological patients&#46; However&#44; there are no clear conclusions in the case of other groups such as patients suffering from COPD&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">9&#44;16&#44;23</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The overall objective of this work is to study the usefulness of nonculture-based diagnostic techniques for IFD diagnosis in non-neutropenic&#44; hospitalized patients with COPD who are at risk for IFD&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and methods</span><p id="par0055" class="elsevierStylePara elsevierViewall">The study was conducted at the Department of Clinical Microbiology and the Intensive Care Unit &#40;ICU&#41; of the University Hospital Severo Ochoa located in Madrid &#40;Spain&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">It was a prospective observational study carried out over a period of three years &#40;January 2008 to December 2010&#41; as part of a project &#40;FIS 070134&#41;&#44; and was approved by the Ethics Committee&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Selection of patients</span><p id="par0065" class="elsevierStylePara elsevierViewall">Inclusion criteria&#58; COPD patients admitted to hospital with risk factors for developing IFD&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">20</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Exclusion criteria&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Community-acquired infection</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Estimated life expectancy of less than a week</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Patients under 18 years</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Neutropenia &#40;neutrophil count<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>neutrophils&#47;mm<span class="elsevierStyleSup">3</span>&#41;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Pregnant or lactating women</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Patients who refused to give informed consent</p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data collection</span><p id="par0105" class="elsevierStylePara elsevierViewall">Data was collected sequentially over the entire project&#44; with a follow up of the patients along the different episodes that they might suffer in the three years of observation&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Patients underwent clinical&#44; microbiological and radiological monitoring&#46; The data collection protocol consisted of the following variables&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Personal variables &#40;age and gender&#41;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Hospitalization time</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Diagnosis in admission</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Risk factors for IFD up to a month before and during admission according to <span class="elsevierStyleItalic">Meersseman&#44; 2007</span>&#58;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">18</span></a></p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8728;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Simultaneous administration of two or more antibiotics&#44; prescription of broad-spectrum antibiotics over a minimum of 5 days&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8728;</span><p id="par0140" class="elsevierStylePara elsevierViewall">High doses of corticosteroids or other immunosuppressive drugs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8728;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Chemotherapy and&#47;or radiation therapy during the hospitalization&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8728;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Parenteral nutrition and&#47;or mechanical ventilation for 48<span class="elsevierStyleHsp" style=""></span>h or more&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8728;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Central venous catheter&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8728;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Hospitalization in ICU for at least 7 days with a diagnosis of liver cirrhosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8728;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Acute pancreatitis and abdominal surgery or other surgeries during the episode&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Category of IFD &#40;proven&#44; probable&#44; possible&#41; according to De Pauw&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a></p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Clinical variables&#58;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8728;</span><p id="par0180" class="elsevierStylePara elsevierViewall">Clinical severity according to the SOFA &#8211; Sequential Organ Failure Assessment &#8211; score&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">29</span></a></p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8728;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Mucositis during the episode</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8728;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Fever during the episode</p><p id="par0195" class="elsevierStylePara elsevierViewall">Microbiological variables&#58;</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8728;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Sample type</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8728;</span><p id="par0205" class="elsevierStylePara elsevierViewall">Date of sampling</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8728;</span><p id="par0210" class="elsevierStylePara elsevierViewall">Results of microbiological tests&#44; including those for nonculture-based diagnostic techniques &#8211;galactomannan&#44; &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan and CAGTA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8728;</span><p id="par0215" class="elsevierStylePara elsevierViewall">Known circumstances relating to false positive galactomannan &#40;bacteremia&#44; dialysis and fiber-rich diet&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">6</span></a></p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8728;</span><p id="par0220" class="elsevierStylePara elsevierViewall">Factors related to false positive &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan &#40;hemodialysis equipment having cellulose membranes&#44; treatment with albumin&#44; immunoglobulins and some anticancer agents as lentinan or polysaccharide K&#44; and sulfonamides&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">12&#44;14</span></a></p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall">Antifungal prophylaxis in the month prior to hospitalization &#40;drug&#44; dose and duration of treatment&#41;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">&#8226;</span><p id="par0230" class="elsevierStylePara elsevierViewall">Empirical antifungal treatment &#40;drug&#44; dose&#44; and duration of treatment&#41;</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">&#8226;</span><p id="par0235" class="elsevierStylePara elsevierViewall">High-resolution CT scan</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">&#8226;</span><p id="par0240" class="elsevierStylePara elsevierViewall">Histopathologic analysis</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Microbiological assay</span><p id="par0245" class="elsevierStylePara elsevierViewall">Galactomannan &#40;Platelia Aspergillus&#44; Bio-Rad Laboratories&#44; Marnes La Coquette&#44; France&#41;&#44; &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan &#40;Fungitell&#44; Associates of Cape Cod&#44; Falmouth&#44; MA&#44; USA&#41; and CAGTA &#40;<span class="elsevierStyleItalic">Candida albicans</span> IFA IgG&#44; Vircell&#44; Spain&#41; were performed according to the manufacturer&#39;s recommendations for testing serum samples&#46; They were performed twice a week&#46; The optical density value of the serum galactomannan cut-off was 0&#46;5&#46; A galactomannan result was considered positive when two sequential determinations had a value of 0&#46;5 or greater&#46; Serum concentrations of &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan are interpreted as negative &#40;&#60;60<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41;&#44; indeterminate &#40;60&#8211;79<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; or positive &#40;&#62;80<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41;&#46; A CAGTA result was considered positive with a serum titer &#8805;1&#58;160 in at least one sample&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Blood and sterile sites cultures were processed with automated systems &#40;Bactec 9240&#44; Becton Dickinson Diagnostic Instruments System&#44; Sparks&#44; MD&#44; USA&#41;&#46; Yeast species were identified with the API ID32C &#40;bioM&#233;rieux&#44; Madrid&#44; Spain&#41;&#46; Additional studies of fungal colonization were performed on rectum&#44; oropharynx&#44; pericatheter area and urine&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Data analysis</span><p id="par0255" class="elsevierStylePara elsevierViewall">All quantitative data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; Sensitivity &#40;Se&#41;&#44; specificity &#40;Sp&#41; and predictive values &#40;PPV and NPV&#41; of IFD culture-independent diagnostic markers were calculated according to <span class="elsevierStyleItalic">Altman and Bland</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">4&#44;5</span></a> The criteria that define proven or probable IFD according to De Pauw<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> were considered the gold standard&#46; The corresponding ROC curves were also calculated&#46; The highest measurements obtained from each patient&#39;s values were considered to calculate receiver operating characteristic &#40;ROC&#41; curves&#46; Data analysis was performed using IBM SPSS Statistics for Windows&#44; Version 20&#46;0&#46; Armonk&#44; NY&#58; IBM Corp&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0260" class="elsevierStylePara elsevierViewall">The characteristics of the 43 patients with COPD and risk factors for developing IFD are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The underlying diseases of these patients were the following&#58; type 2 diabetes mellitus &#40;18&#46;6&#37;&#41;&#44; surgical history in the year before &#40;14&#37;&#41;&#44; cancer history in the last 9 months &#40;16&#46;3&#37;&#41;&#44; non-invasive fungal infection history &#40;4&#46;7&#37;&#41;&#44; and transplant &#40;2&#46;3&#37;&#41;&#46; No COPD patient was found with positive serology for HIV&#46; In terms of frequency&#44; respiratory infection as a cause of hospitalization &#40;83&#46;7&#37;&#41; was followed by bacteremia&#47;sepsis &#40;9&#46;3&#37;&#41;&#46; Other causes of hospitalization were abdominal infection &#40;7&#37;&#41;&#44; abdominal surgery &#40;4&#46;7&#37;&#41;&#44; suspected IFD &#40;2&#46;3&#37;&#41;&#44; study of pulmonary nodules &#40;2&#46;3&#37;&#41;&#44; and palliative care &#40;2&#46;3&#37;&#41;&#46; Eighteen patients &#40;41&#46;9&#37;&#41; were hospitalized in ICU&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0265" class="elsevierStylePara elsevierViewall">Risk factors for IFD in COPD patients are specified in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The most frequent was the use of broad-spectrum antibiotics &#40;90&#46;7&#37;&#41;&#46; The results of colonization studies are detailed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Multifocal colonization was present in 15&#37; of patients&#46; The average corrected colonization index &#40;CCI&#41; in these patients was 0&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2 &#40;0&#8211;1&#41;&#44; and 16&#46;1&#37; showed a CCI above 0&#46;4&#46; Sixteen IFD cases &#40;37&#46;2&#37;&#41; were diagnosed among 43 patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The results of the microbiological cultures associated with the diagnosis of IFD are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0270" class="elsevierStylePara elsevierViewall">Regarding the nonculture-based diagnostic techniques&#44; the results of sensitivity&#44; specificity&#44; predictive values and ROC curves are shown in <a class="elsevierStyleCrossRefs" href="#tbl0025">Tables 5 and 6</a>&#44; and in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;4</a>&#46; Positive &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan preceded in 1&#46;7 days on average the growth of <span class="elsevierStyleItalic">Candida</span> in blood culture&#46; The tables only refer to invasive candidemia and invasive aspergillosis&#46; With respect to other types of fungal disease&#44; only one rhinocerebral zygomycosis was diagnosed &#40;probable invasive aspergillosis was also diagnosed in the same patient&#41;&#46; In this patient&#44; both the &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan and galactomannan were positive&#46; The false positive rates obtained with galactomannan&#44; &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan and CAGTA were 2&#46;4&#37;&#44; 4&#46;5&#37; and 3&#46;1&#37; respectively&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0275" class="elsevierStylePara elsevierViewall">According to the literature&#44; the incidence of IFD in COPD patients can exceed that of &#8220;classic&#8221; at-risk IFD patients&#44; and its evolution is nearly always unfavorable&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> The incidence of IA in hematological patients is between 4&#37; and 22&#37;&#44; depending on the publication&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">28</span></a> In this study we actually observed a high incidence among the COPD patients analyzed &#40;specifically&#44; 34&#46;9&#37; of IFD and 20&#37; of IA&#41;&#46; On the other hand&#44; the mortality rate in our COPD patients stood at 32&#46;6&#37;&#46; Compared to the mortality data relating to hematological patients &#40;20&#8211;50&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">16</span></a> this study shows a higher mortality rate&#46; Mortality associated with candidemia ranges from 35&#37; to 49&#37;&#44; depending on the study&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#44;27</span></a> Mortality among our patients with candidemia was 72&#37;&#59; in ICU&#44; mortality in patients with candidemia was 76&#46;9&#37;&#46; This high mortality rate compared to that described in the literature may be explained by the fact that data collection in the present study did not guarantee that the patient&#39;s death was caused by IFD&#46; Given the critical condition of the patients&#44; mortality may have been influenced by comorbidities and the highly variable risk factors presented by these patients &#40;SOFA score<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>12 in 23&#37; of our patients in ICU&#41;&#46; However&#44; according to other publications&#44; mortality associated with IC exceeds 40&#37;&#44; with the highest rates in critically ill patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">29&#44;30</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">In several studies where &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan was evaluated in the diagnosis of IFD&#44;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">20&#44;21</span></a> the NPV exceeded 90&#37;&#46; The data presented here are similar&#46; This supports the work conducted by Karageorgopoulos et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">13</span></a> in which the &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan determination was helpful in ruling out IFD in critically ill patients&#46; The sensitivity figures of Moragues et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">19</span></a> concerning CAGTA marker in critically ill patients with IC were similar to those obtained in the present study &#40;Se<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#8211;89&#37; vs&#46; Se<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>85&#46;7&#37; in this study&#41;&#46; In terms of specificity&#44; our data shows lower values &#40;Sp<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91&#8211;100&#37; vs&#46; Sp<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>72&#46;2&#37; in this study&#41;&#46; It is well known that patients with invasive infections caused by species other than <span class="elsevierStyleItalic">C&#46; albicans</span> usually have lower CAGTA titers&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">25</span></a> The high percentage of non-<span class="elsevierStyleItalic">C&#46; albicans Candida</span> species in these patients &#40;66&#46;6&#37;&#41; could explain why the specificity results were lower&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">In the meta-analysis conducted by Pfeiffer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">24</span></a> &#8211; with a predominance of oncohematologic patients &#8211; both sensitivity and specificity in galactomannan detection in serum to diagnose IA were similar to those calculated in this study &#40;Se<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>61&#37; and Sp<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>93&#37; vs&#46; Se<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>62&#46;5&#37; and Sp<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>88&#46;5&#37; in this study&#41;&#46; NPV results were particularly good for both studies &#40;&#62;91&#37;&#41;&#46; Therefore&#44; it is suggested that a negative galactomannan could be sufficient to exclude the diagnosis of IA&#46; When considering an index &#8805;0&#46;5 for galactomannan&#44; several prospective studies in adult oncohematologic patients have confirmed low levels of false positives &#40;3&#8211;10&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">2&#44;18&#44;19</span></a> A galactomannan false positive rate of 2&#46;4&#37; was observed among our patients&#44; which is lower than that described in the literature for oncohematologic patients&#46; The extreme care of the clinicians to avoid cross-contamination could explain the low false positive rate found&#46; Furthermore&#44; the false positives for &#40;1&#8211;3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan and CAGTA were 4&#46;5&#37; and 3&#46;1&#37;&#44; respectively&#46; These are very acceptable rates and well below the usual published values &#40;up to 25&#37; &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan false positive in the first three days after the surgery in critically ill patients according to Pem&#225;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">23</span></a>&#41;&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">The IFD spectrum is currently undergoing changes that raise questions about how to treat and prevent IFD&#46; At present&#44; it is essential to pay attention to new populations at risk for IFD&#46; The definitive diagnosis is made using histopathology and identifying the causative agent&#46; However&#44; in recent years&#44; culture-independent techniques have permitted earlier diagnosis&#46; On the other hand&#44; while autopsy is considered a gold-standard arbiter of the presence of IFD&#44; one must consider whether&#44; in the last days of life of a critically ill patient&#44; the collapse of normal physiology and normal anatomical integrity &#40;the loss of gut mucosal permeability barrier integrity due to anoxia&#44; uremia&#44; dysbiosis or inflammation&#41; may lead to the inappropriate presence of microorganisms as a mortality-associated process&#46; The results of this study suggest that culture-independent techniques are particularly useful in COPD patients&#44; especially for ruling out IFD&#46; Besides&#44; it is necessary to conduct a thorough selection of COPD-patients at risk for IFD&#46; In these patients at risk&#44; the finding of sequentially positive galactomannan and &#47; or &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan tests are indicative of IFD when associated with a strong clinical suspicion&#46; Anyway&#44; the limitations of this study were the following&#58; &#40;i&#41; Lack of a reliable gold standard that may lead to misdiagnose or underdiagnose IFD&#59; &#40;ii&#41; the inclusion of cases of probable IFD along with proven IFD when calculating sensitivity&#44; specificity and predictive values of biomarkers that are used to define precisely the concept of probable IFD&#59; &#40;iii&#41; the difficulty in discriminating between colonization and fungal disease&#59; &#40;iv&#41; insufficient galactomannan and &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan positive cases to draw conclusions about the usefulness of these techniques in such samples&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0295" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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    "fechaRecibido" => "2016-01-28"
    "fechaAceptado" => "2017-07-19"
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            0 => "Fungemia"
            1 => "COPD"
            2 => "Galactomannan"
            3 => "&#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan"
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            1 => "EPOC"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The role of culture-independent techniques &#40;galactomannan&#44; &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan&#41; in the early diagnosis of invasive fungal diseases &#40;IFD&#41; is well assessed in hematological patients&#44; but there are no clear conclusions in patients with chronic obstructive pulmonary disease &#40;COPD&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To study the usefulness of nonculture-based techniques in the diagnosis of IFD in COPD-patients at risk for IFD&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A prospective observational study based on monitoring COPD patients at risk for IFD during 2007&#8211;2010 was carried out&#46; The presence of galactomannan&#44; &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan and an indirect immunofluorescence of <span class="elsevierStyleItalic">Candida albicans</span> germ tube specific antibodies &#40;CAGTA&#41; were performed&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Among 43 COPD patients&#44; 16 &#40;37&#46;2&#37;&#41; were diagnosed with IFD&#58; seven cases were proven IFD &#40;five invasive candidemia &#8211; IC&#44; one invasive aspergillosis &#8211; IA and a rhinocerebral zygomycosis&#41; and nine probable IFD &#40;seven IA and two IC&#41;&#46; In the diagnosis of IC and IA&#44; the negative predictive value &#40;NPV&#41; of &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan was 100&#37;&#46; Regarding CAGTA in IC&#44; NPV was 96&#46;2&#37;&#46; Finally&#44; NPV of galactomannan in IA was 91&#46;2&#37;&#46; The area under the ROC curve for &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan in IC and for the rest of the IFD cases was 0&#46;86 &#40;95&#37; CI&#44; 0&#46;79&#8211;0&#46;93&#41; and 0&#46;60 &#40;95&#37; CI&#44; 0&#46;43&#8211;0&#46;77&#41;&#44; for CAGTA in IC was 0&#46;83 &#40;95&#37; CI&#44; 0&#46;74&#8211;0&#46;91&#41; and for galactomannan in IA was 0&#46;71 &#40;95&#37; CI&#44; 0&#46;56&#8211;0&#46;85&#41;&#46; Positive &#40;1-3&#41;-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucan preceded the growth of <span class="elsevierStyleItalic">Candida</span> &#40;average of 1&#46;7 days&#41; in blood culture&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In COPD patients at risk for IFD the assayed techniques are especially useful to rule out the presence of IFD&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El papel de las t&#233;cnicas independientes de cultivo &#91;galactomanano&#44; &#40;1-3&#41;-&#946;-D-glucano&#93; en el diagn&#243;stico precoz de micosis invasoras &#40;MI&#41; est&#225; bien establecido en pacientes hematol&#243;gicos&#44; pero no existen conclusiones claras en pacientes con enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Estudiar la utilidad de las t&#233;cnicas independientes de cultivo en el diagn&#243;stico de MI en pacientes con EPOC que corren el riesgo de contraer una MI&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se llev&#243; a cabo un estudio prospectivo y observacional en que se supervisaron pacientes con EPOC que corr&#237;an el riesgo de contraer una MI de 2007 a 2010&#46; Para ello se estableci&#243; la existencia de galactomanano&#44; &#40;1-3&#41;-&#946;-D-glucano y se realiz&#243; el ensayo CAGTA &#40;inmunofluorescencia indirecta para determinar la existencia de anticuerpos IgG frente a ant&#237;genos de la superficie de la fase micelial de <span class="elsevierStyleItalic">Candida albicans</span>&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se diagnosticaron 16<span class="elsevierStyleHsp" style=""></span>MI en 43<span class="elsevierStyleHsp" style=""></span>pacientes con EPOC &#40;37&#44;2&#37;&#41;&#58; siete fueron MI probadas &#40;cinco candidemias invasoras &#91;CI&#93;&#44; una aspergilosis invasora &#91;AI&#93; y una cigomicosis rinocerebral&#41; y nueve fueron MI probables &#40;siete AI y dos CI&#41;&#46; En el diagn&#243;stico de CI y AI&#44; el valor predictivo negativo &#40;VPN&#41; del &#40;1-3&#41;-&#946;-D-glucano fue del 100&#37;&#46; En cuanto al CAGTA en CI&#44; el VPN fue del 96&#44;2&#37;&#46; Finalmente&#44; el VPN del galactomanano en AI fue del 91&#44;2&#37;&#46; El &#225;rea bajo la curva ROC <span class="elsevierStyleItalic">&#40;receiver operating characteristic&#41;</span> del &#40;1-3&#41;-&#946;-D-glucano en CI y en el resto de los casos de MI fue 0&#44;86 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;79-0&#44;93&#41; y 0&#44;60 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;43-0&#44;77&#41;&#44; para CAGTA en CI fue 0&#44;83 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;74-0&#44;91&#41; y para galactomanano en AI fue 0&#44;71 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;56-0&#44;85&#41;&#46; La positividad del &#40;1-3&#41;-&#946;-D-glucano se anticip&#243; como media 1&#44;7<span class="elsevierStyleHsp" style=""></span>d&#237;as al crecimiento de <span class="elsevierStyleItalic">Candida</span> en el hemocultivo&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">En pacientes con EPOC que corren el riesgo de contraer MI&#44; estas t&#233;cnicas son muy &#250;tiles para descartar la existencia de MI&#46;</p></span>"
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">COPD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Broad-spectrum antibiotics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39 &#40;90&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">More than 2 antibiotics simultaneously&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28 &#40;65&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Corticosteroids at high doses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;60&#46;5&#37;&#41;<br>One of them received methotrexate to treat rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Central venous catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 &#40;44&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mechanical ventilation for &#8805;48<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;32&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;14&#37;&#41;<br>4 patients underwent major abdominal surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute pancreatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;4&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;2&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1873681.png"
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Risk factors for IFD&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0015"
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          0 => array:3 [
            "identificador" => "at3"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oropharynx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Neg&#58; 6&#47;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">A&#46; fumigatus</span>&#58; 5&#47;17<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">C&#46; tropicalis</span>&#58; 3&#47;17<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">C&#46; albicans</span>&#58;<br>2&#47;17<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Neg&#58; 8&#47;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">C&#46; tropicalis</span>&#58; 3&#47;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">C&#46; glabrata</span>&#58; 1&#47;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rectum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Neg&#58; 8&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">C&#46; glabrata</span>&#58; 1&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">C&#46; albicans</span>&#43;<br><span class="elsevierStyleItalic">C&#46; tropicalis&#58;</span> 1&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pericatheter area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Neg&#58; 7&#47;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">C&#46; albicans</span>&#43;<br><span class="elsevierStyleItalic">C&#46; tropicalis&#58;</span><br>1&#47;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1873678.png"
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Two patients were coinfected with <span class="elsevierStyleItalic">Aspergillus niger</span> and <span class="elsevierStyleItalic">Aspergillus terreus</span>&#44; respectively&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">In one colonization study <span class="elsevierStyleItalic">C&#46; albicans</span> and <span class="elsevierStyleItalic">C&#46; tropicalis</span> appear as co-responsible for oropharyngeal colonization&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Results of fungal colonization studies&#46;</p>"
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      7 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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                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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Performed &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BAL and bronchial aspirates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16 <span class="elsevierStyleItalic">A&#46; fumigatus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16 <span class="elsevierStyleItalic">C&#46; albicans</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peritoneal fluid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 <span class="elsevierStyleItalic">C&#46; albicans</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surgical exudate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">C&#46; tropicalis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pleural fluid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">A&#46; fumigatus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sinus puncture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">Rhizopus arrhizus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transbronchial biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">A&#46; fumigatus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 <span class="elsevierStyleItalic">C&#46; tropicalis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 <span class="elsevierStyleItalic">C&#46; albicans</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            1 => 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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IFD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proven IFD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Candidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Invasive aspergillosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinocerebral zygomycosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Probable IFD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Invasive candidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Invasive aspergillosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible IFD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Microbiological cultures and diagnosed IFD in the study population &#40;43 patients&#41;&#46;</p>"
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    "idiomaDefecto" => "es"
  ]
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  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140618300329?idApp=UINPBA00004N"
]

Article information

ISSN: 11301406
Original language: English

DOI:10.1016/j.riam.2017.07.004

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 October	9	2	11
2024 September	24	2	26
2024 August	21	4	25
2024 July	21	6	27
2024 June	6	1	7
2024 May	14	4	18
2024 April	26	6	32
2024 March	34	4	38
2024 February	23	3	26
2024 January	16	2	18
2023 December	17	2	19
2023 November	20	7	27
2023 October	19	3	22
2023 September	19	0	19
2023 August	16	0	16
2023 July	16	2	18
2023 June	16	0	16
2023 May	39	6	45
2023 April	14	1	15
2023 March	20	2	22
2023 February	18	5	23
2023 January	22	5	27
2022 December	23	6	29
2022 November	31	6	37
2022 October	25	20	45
2022 September	21	10	31
2022 August	26	15	41
2022 July	37	12	49
2022 June	43	11	54
2022 May	24	6	30
2022 April	31	22	53
2022 March	32	10	42
2022 February	15	9	24
2022 January	25	9	34
2021 December	41	14	55
2021 November	30	7	37
2021 October	37	16	53
2021 September	17	15	32
2021 August	27	6	33
2021 July	36	6	42
2021 June	28	8	36
2021 May	14	18	32
2021 April	76	27	103
2021 March	20	20	40
2021 February	24	10	34
2021 January	23	23	46
2020 December	17	12	29
2020 November	15	9	24
2020 October	22	11	33
2020 September	17	15	32
2020 August	18	14	32
2020 July	22	10	32
2020 June	23	14	37
2020 May	23	25	48
2020 April	20	27	47
2020 March	31	14	45
2020 February	17	5	22
2020 January	19	6	25
2019 December	20	14	34
2019 November	17	23	40
2019 October	14	19	33
2019 September	26	23	49
2019 August	6	26	32
2019 July	21	20	41
2019 June	37	20	57
2019 May	73	14	87
2019 April	13	21	34
2019 March	12	13	25
2019 February	8	5	13
2019 January	15	9	24
2018 December	14	18	32
2018 November	37	31	68
2018 October	34	52	86
2018 August	0	2	2

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