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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bleomycinis is an antineoplastic agent that is effectively used for the treatment of cancers such as germ cell tumors&#44; lymphomas&#44; and cervical carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a> One of the most common adverse effects is pulmonary toxicity&#44; which leads to diffuse alveolar damage in the lungs&#46; The toxic effect occurs in two phases&#46; During the initial phase&#44; there is an accumulation of neutrophils&#44; lymphocytes&#44; and macrophages in the interstitial and alveolar areas&#46; In the second phase&#44; damage occurs in the pulmonary interstitial tissue mediated by reactive oxygen molecules and proteases&#44; as well as fibrosis&#44; along with the initiation of a repair process for this damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">2&#44;3</span></a> Experimental studies provided evidence for infiltration of inflammatory cells such as neutrophils&#44; macrophages&#44; and lymphocytes&#44; accumulation of collagen into the lungs&#44; and myofibroblast activation&#44; with increased release of cytokines&#44; chemokines&#44; and profibrotic mediators in bronchoalveolar lavage fluid&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Bleomycin-induced toxicity &#40;BT&#41; is a rare condition&#44; but has a high morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a> Thus&#44; early diagnosis and treatment is important&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> It is clinically&#47;radiologically diagnosed through clinical symptoms such as shortness of breath and dry cough&#44; which occur during the course of treatment&#59; crepitant rales during the physical examination&#59; changes in high-resolution computed tomography &#40;HRCT&#41; of the lung not seen in prior radiologic imaging that cannot be attributed to any other cause&#44; and which are consistent with interstitial lung diseases&#59; and decreased diffusing capacity of the lung for carbon monoxide &#40;DLCO&#41;&#44; which cannot be explained by another cause in patients who received bleomycin&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Thoracic ultrasonography &#40;USG&#41; is widely used for the diagnostic procedures in the field of chest diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a> Another little known area of use is for diagnosis of diseases involving the interstitium&#44; mainly interstitial lung disease &#40;ILD&#41; and pulmonary edema&#46; Interstitial inflammation&#44; fibrosis&#44; thickened interstitial surface&#44; and thickened interlobular septa are common in diseases involving the interstitium of the lung&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> High-frequency sound waves are transmitted to tissues using USG&#46; An image is generated on the monitor when these sound waves are reflected or refracted back to the USG probe&#46; Multiple sound waves traveling back and forth between the tissue and probe or between two tissues is called reverberation artifact&#46; In the absence of any pathology&#44; a normal lung cannot be imaged well sonographically because it contains air&#46; However&#44; ILD involves the interstitium of the lung&#46; The changes associated with this involvement and thickening interlobular septa lead to comet tail artifact &#40;CTA&#41;&#44; a type of reverberation artifact that can be detected using USG&#46; CTA occurs when a sound beam meets a reflective surface&#46; A dense tail image is generated behind the bouncing echoes that return to the transducer&#44; with a tapering echogenic line<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#44;11</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">This study was designed to evaluate the diagnostic value of thoracic USG&#44; an easy and readily available and reproducible imaging procedure without radiation exposure in the assessment of BT&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patient Population</span><p id="par0025" class="elsevierStylePara elsevierViewall">This prospective cross-sectional study was designed according to the International Helsinki Declaration&#46; Upon receipt of approval of the local ethics committee&#44; patients referred to the thoracic diseases inpatient&#47;outpatient service of our hospital due to suspected BT during treatment with bleomycin for several oncologic diseases between June 2015 and May 2017 were enrolled in the study&#46; Patients with a prior diagnosis of ILD and congestive heart failure were excluded&#46; Patients were initially evaluated through a comprehensive clinical examination for BT&#44; physical examination &#40;PE&#41;&#44; HCRT&#44; pulmonary function test &#40;PFT&#41;&#44; and DLCO by a pulmonologist&#46; A clinical and radiologic diagnosis of BT was made based on clinical symptoms such as shortness of breath and dry cough&#44; which were previously not seen&#44; but occurred during the course of treatment&#44; crepitant rales during PE&#44; changes in HRCT not seen in prior radiologic imaging that could not be attributed to any other cause&#44; and which were consistent with ILD&#44; and decreased diffusing capacity &#40;DLCO&#41;&#44; which could not be explained by another cause&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> Then&#44; a different pulmonologist&#44; who only knew the clinical examination results before HCRT and PFT&#8211;DLCO findings&#44; detected and registered the number of CTAs in thoracic USG&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">High-Resolution Computerized Tomography</span><p id="par0030" class="elsevierStylePara elsevierViewall">HRCTs were obtained after deep inspiration using a high-resolution technique from the axial plane&#44; starting with the apex toward the end of the diaphragm&#44; with 15-mm table movement&#44; at 120<span class="elsevierStyleHsp" style=""></span>kV&#44; 200<span class="elsevierStyleHsp" style=""></span>mA&#44; with a section thickness of 2<span class="elsevierStyleHsp" style=""></span>mm&#44; at a 512<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>512 matrix and bone algorithm using a Siemens Medical Solutions-2010 &#40;Forchheim&#44; Germany&#41; device without the use of contrasting agent&#46; Images were obtained with a window width of 1200 Hounsfield units &#40;HU&#41;&#44; at a window level of 700 HU&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Pulmonary Function Test and Carbon Monoxide Diffusion Test</span><p id="par0035" class="elsevierStylePara elsevierViewall">The PFT&#8211;DLCO tests of the participants were conducted according to the Guidelines of the American Thoracic Society &#40;ATS&#41; and European Respiration Society &#40;ERS&#41; for the standardization of pulmonary function tests&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">13&#44;14</span></a> The SFT and DLCO measurement tests were performed on a Sensor Medics Vi-Max 22&#44; Care Fusion &#40;San Diego&#44; California&#41; device using the single breath technique&#46; With normal test values falling between 80 and 120&#37; of the predicted value for each lung volume&#44; forced vital capacity &#40;FVC&#41;&#44; forced expiratory volume in one second &#40;FEV1&#41;&#44; and FEV1&#47;FVC values were recorded in liters and percentages&#46; The ratio of DLCO &#40;mL&#47;min&#47;mmHg&#47;Lt&#41; and DLCO&#47;alveolar ventilation &#40;VA&#41; &#40;DLCO&#47;VA&#44; &#37;&#41; was recorded in liters and percentages with normal test values falling between 80 and 120&#37; of the predicted value for each lung volume&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Thoracic USG</span><p id="par0040" class="elsevierStylePara elsevierViewall">Thoracic USG was performed by an experienced pulmonologist using a General Electric &#40;GE&#41; Logic 7 system with a 3&#46;5<span class="elsevierStyleHsp" style=""></span>MHz convex probe in the abdominal mode&#46; Sonographic screening of the thorax was conducted on predefined anatomic lines&#46; One of these anatomic lines was the linea mid-clavicularis&#44; a vertical line passing through the midpoint of the claviclein anterior thorax&#46; Another one was the linea axillaris anterior&#44; passing through the plica axillaris anterior in the lateral side of the thorax&#59; the linea axillaris media&#44; a vertical line originating from the apex of the axilla and the linea axillaris posterior&#46; Finally&#44; in the posterior part of the thorax&#44; the lines were the linea scapularis&#44; a vertical line passing through the angulus inferior scapula&#44; and the linea paravertebralis&#44; which runs parallel to the vertebral column &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Definition of CTA and Clinical-ultrasonographic Diagnosis of BT</span><p id="par0045" class="elsevierStylePara elsevierViewall">CTA was defined as an hyperechogenic coherent bundle&#44; starting at a narrow basis from the visceral pleural space&#44; and enlarging and extending to the periphery along the screen provided that USG probe&#44; which was located at the intercostal interval<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> &#40;Diagram 1&#41;&#46; The probe was moved longitudinally along the intercostal spaces in line with each predefined anatomic line&#44; with patients in the sitting position in order to determine the area with the highest number of CTAs&#46; The number of CTAs in this area was recorded&#46; Those with a CTA number of &#60;3 were considered normal&#46; The clinical-ultrasonographic diagnosis of bleomycin-induced toxicity was made in patients with three or more CTAs&#44; and clinically in the presence of findings consistent with BT&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">With a BT diagnosis based on clinical&#44; radiologic&#44; and spirometric characteristics considered as the gold standard&#44; the sensitivity&#44; specificity&#44; and positive and negative predictive values of the clinical-ultrasonographic modality in diagnosing BT were evaluated&#46; We compared the clinical&#44; radiologic&#44; spirometric&#44; and ultrasonographic &#40;number of CTAs&#41; findings of the patients with a final diagnosis of BT with those of patients without BT&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical Analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using the SPSS 17&#46;0 &#40;IBM Inc&#46;&#44; Released 2008&#44; SPSS Statistics for Windows&#59; Chicago&#44; USA&#41; software program&#46; In descriptive statistics&#44; continuous variables are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#44; and categorical variables as percentages&#46; For normal distribution tests&#44; we used the Kolmogorov&#8211;Smirnov test&#46; Group data were evaluated using the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span>-test&#46; A correlation analysis was performed to evaluate the relationship between PFT&#8211;DLCO parameters and the number of CTAs in patients&#46; The correlation coefficient is expressed as <span class="elsevierStyleItalic">r</span>&#46; A <span class="elsevierStyleItalic">P</span>-value of &#60;&#46;05 was considered statistically significant in all tests&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">The study included 30 of 32 patients who presented to the Outpatient Clinic of Chest Diseases with suspected BT&#59; two patients were excluded due to prior diagnosis of congestive heart failure&#46; The mean age of the patients was 40&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;2 years &#40;range&#44; 22&#8211;69 years&#41;&#46; Nine &#40;30&#37;&#41; were female&#44; and 21 &#40;70&#37;&#41; were male&#46; Thirteen &#40;43&#46;3&#37;&#41; patients were ex-smokers and 17 &#40;56&#46;7&#37;&#41; were non-smokers&#46; The mean history of smoking was 18&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;1 pack-years &#40;range&#44; 2&#8211;45 pack-years&#41;&#46; A review of the distribution of primary diseases showed that 17 &#40;56&#46;7&#37;&#41; patients had Hodgkin&#39;s lymphoma&#44; 9 &#40;30&#37;&#41; had testis tumors&#44; and 4 &#40;13&#46;3&#37;&#41; had non-Hodgkin&#39;s lymphoma&#46; Twenty &#40;66&#46;7&#37;&#41; patients had no symptoms of chest diseases&#44; but 6 &#40;20&#37;&#41; had new-onset shortness of breath&#44; 3 &#40;10&#37;&#41; had new-onset cough&#44; and 1 &#40;3&#46;3&#37;&#41; patient had chest pain&#46; Physical examination showed that 24 &#40;80&#37;&#41; patients had normal PE&#46; Five patients &#40;16&#46;7&#37;&#41; had bilateral basilar rales&#44; and one &#40;3&#46;3&#37;&#41; patient had decreased breathing sounds&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Nine patients were diagnosed as having BT based on the clinical and radiologic findings and PFT&#8211;DLCO values&#46; BT was not considered in 21 patients&#46; The mean number of CTAs as determined using thoracic USG was 68&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22 in patients diagnosed with BT vs 28&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;3 in those without BT &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">HRCT findings showed that in those with BT&#44; nine &#40;100&#37;&#41; patients had bilateral ground glass densities&#44; six &#40;66&#46;7&#37;&#41; had interlobular septal thickening&#44; and two &#40;22&#46;2&#37;&#41; patients each had honeycomb pattern and traction bronchiectasis&#46; None of the patients in the group without BT showed evidence suggesting interstitial involvement in HRCT &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In HRCT&#44; the difference in the number of CTAs between patients without interlobular septal thickening and those with interlobular septal thickening was statistically significant &#40;32&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;3 and 73&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;2&#44; respectively&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; The difference in the number of CTAs between patients without ground glass densities and those with ground glass densities in HRCT was statistically significant &#40;28&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;5 and 64&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;5&#44; respectively&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A comparison of PFT and DLCO findings between the two groups showed that FVC&#37; and DLCO&#37; values were significantly lower in the group with BT compared with the non-BT group &#40;76 and 98&#37;&#44; respectively&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#59; 51 and 86&#37;&#44; respectively&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; The PFT&#8211;DLCO values of the patients are given in detail in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; A negative correlation was found between the number of CTAs and DLCO percentages &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;004&#59; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;51&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The difference in the number of CTAs was statistically significant between patients with a DLCO&#37; of &#60;70 and those &#62;70 &#40;62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;3 and 29&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8&#44; respectively&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41;&#46; A negative correlation was found between the number of CTAs and FVC percentages &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;016&#59; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;43&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; In PFT&#44; the difference in the number of CTAs was statistically significant between patients with an FVC percentage of &#60;80 and those &#62;80 &#40;59&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;6 and 32&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;3 respectively&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;006&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Ten patients received a clinical-ultrasonographic diagnosis of BT and 20 patients had no BT&#46; In patients with BT whose diagnoses were based on clinical-radiologic and DLCO findings&#44; the sensitivity&#44; specificity&#44; and positive and negative predictive values of thoracic USG were found as 100&#44; 95&#44; 90&#44; and 100&#37;&#44; respectively&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">We found that the patients whose BT was diagnosed based on their clinical&#44; radiologic&#44; PFT&#44; and DLCO characteristics had a significantly greater number of CTAs as determined using thoracic USG&#46; There was a negative correlation between DLCO&#37; and FVC&#37; values and CTAs in patients with BT&#46; HRCT showed that in patients with ground glass densities and interlobular septal thickening&#44; the number of CTAs was statistically significantly higher&#46; Thoracic USG had a 100&#37; sensitivity and 95&#37; specificity in diagnosing BT&#46; Our study is important because it draws attention to the role of thoracic USG&#44; a reliable&#44; non-invasive&#44; easily available imaging modality performed by a pulmonologist and with no radiation exposure to the physician and the patient&#44; as a potential modality in the diagnosis of BT&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Thickening of interlobular septa is seen in diseases involving the interstitium of the lung such as ILDs and pulmonary edema&#46; CTAs are detected sonographically through the bouncing of sound waves from thickened interlobular septa&#46; Three or more CTAs as sonographically detected from the area between two costas suggest interstitial involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">16&#8211;20</span></a> In our study&#44; the mean number of CTAs was 2&#46;3 in the non-BT group vs 5&#46;6 in the BT group &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; As a result of the acute exudative phase&#44; which begins with cell accumulation in the interstitial area in BT and the organization period in which a repair process is observed&#44; HRCT shows patchy or diffuse ground glass opacities&#44; interlobular septal thickening&#44; and fibrosis&#46; Progression of fibrosis results in the development of a honeycomb appearance&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> In thoracic USG&#44; the number of CTAs is increased with parenchymal changes such as fibrosis and interlobular septal thickening&#44; and these penetrate ultrasonic sound waves in lungs&#44; which typically contain air&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> Lichtenstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> in 1997 were the first to show that the number of CTAs increased in patients developing diffuse interstitial fibrosis using USG&#46; In comparative studies with HRCT&#44; HRCT being the gold standard&#44; in diseases leading to pulmonary fibrosis&#44; mainly connective tissue diseases revealed increased numbers of CTAs with thoracic USG&#44; thereby demonstrating its value as an imaging modality&#44; and many studies demonstrated that the number of CTAs increased significantly in the presence of findings consistent with ILD in HRCT&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">24&#8211;26</span></a> Gargani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> reported that the number of CTAs was positively correlated with the degree of pulmonary fibrosis in HRCT&#46; In our study&#44; the main HRCT findings in patients with BT included bilateral ground glass densities &#40;100&#37;&#41; and interlobular septal thickening &#40;66&#46;7&#37;&#41;&#46; In a study evaluating the role of thoracic USG in the diagnosis of ILD in patients with systemic sclerosis&#44; Barskova et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a> found that the presence of CTAs was correlated with ILD in HRCT&#46; In their study&#44; there was a statistically significant difference in the number of CTAs between patients with and without ILD on HCRT &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; Similarly&#44; the number of CTAs was significantly higher in patients with ground glass densities compared with those with none on HCRT &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; Our findings are consistent with those of Barskova et al&#46; In our study&#44; the number of CTAs was 64 in patients with BT who had ground glass densities vs 28 in patients with no ground glass densities on HRCT &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Although they are no established criteria for monitoring BT along with respiratory function tests and DLCO tests&#44; reductions of more than 15&#37;&#8211;25&#37; in vital capacity and DLCO values&#44; which were previously normal in PFT&#8211;DLCO as well as cough&#44; shortness of breath&#44; which cannot be explained by any other cause&#44; bilateral crepitant rales&#44; and other unexplained changes in HRCT suggest BT&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">14&#44;28</span></a> Bleomycin is associated with necrosis of type 2 pneumocytes and alveolar epithelial cells&#44; resulting in diffuse alveolar damage in the lungs&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> With a pathophysiologic mechanism similar to other ILDs&#44; there is an accumulation of inflammatory and immune effector cells within the alveolar-capillary unit in BT&#46; Progression of resulting alveolitis and initiation of repair mechanisms naturally lead to fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">4</span></a> These changes in the alveolar-capillary unit disrupt gas exchange in the alveolar-capillary membrane and manifest with changes such as decreased lung volumes &#40;vital capacity&#41; and reduction in DLCO&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> This damage to the interstitium of the lung results in increased capillary permeability&#44; interstitial edema&#44; hyaline membranes during the acute period&#44; and proliferation of type 2 pneumocytes&#44; changes in interstitial connective tissue&#44; interlobular septal thickening&#44; and interstitial fibrosis during the late period&#46; A normal lung exhibits permeability to ultrasonic sound waves because it contains air in its tissue&#44; thus USG has poor imaging performance&#46; With the interstitial changes due to diffuse alveolar damage by bleomycin as described above&#44; there are increased CTAs in BT&#46; Many studies showed that there was a reverse correlation between the number of CTAs determined using USG in ILD and FVC and DLCO values&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a> In a study evaluating the efficacy of thoracic USG in patients with systemic sclerosis&#44; Edis <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> examined a total of 48 patients using thoracic USG and showed a negative correlation between DLCO values and the number of CTAs &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;56&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; In a prospective study&#44; Hasan and Makhlouf<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> compared CTAs determined using thoracic USG in ILD with HRCT and PFT findings and showed a negative correlation between DLCO values and frequency of CTAs &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;817&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; The authors concluded that thoracic USG might be of benefit in evaluating ILDs&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Our study was designed to demonstrate that thoracic USG might be a new imaging modality in diagnosing BT&#46; HRCT and PFT&#8211;DLCO are certainly very valuable methods in the diagnosis of BT&#44; which is a disease with high morbidity and mortality&#46; However&#44; HRCT cannot be repeated frequently due to a radiation exposure equivalent to 250&#8211;300 chest radiographs with 5&#8211;7<span class="elsevierStyleHsp" style=""></span>mSv&#44; and being relatively expensive&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> PFT&#8211;DLCO tests may not always be used because it requires a patient&#39;s cooperation&#44; it is always difficult to perform in older patients&#44; and it may not be available in the early period in patients with rapidly worsening manifestations&#44; particularly with BT&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> Thoracic USG&#44; which can be repeated frequently and does not expose the patient and physician to radiation&#44; is relatively inexpensive&#44; easy to perform at the patient&#39;s bedside&#44; and easy to use by well-trained pulmonologists&#44; can have advantages over HRCT and PFT&#8211;DLCO because of all these reasons&#46; On the other hand&#44; the disadvantages of thoracic USG are that it is operator-dependent&#44; it is difficult to obtain images in obese patients&#44; and CTAs are not specific to BT &#40;they can be seen in pulmonary edema or a different ILD&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Almost all USG studies conducted in patients with ILD have investigated diagnostic usability of USG imaging&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a> A literature search revealed two case presentations investigating the usability of chest USG in the follow up of ILD and in the assessment of the response to treatment&#46; One of these case presentations is about a patient with scleroderma&#46; Buda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a> demonstrated a reduction in the number of CTAs in this patient following cyclophosphamide treatment for 6 months&#46; The other patient was diagnosed with rheumatoid arthritis-associated ILD&#44; and Laria et al&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a> reported that CTAs were no more detectable by USG&#44; following treatment with methotrexate and prednisone&#46; These cases suggest that USG may be used in combination with HRCT&#44; in patient follow and in the assessment of responses to treatment&#44; considering that patients mostly recover from bleomycin toxicity&#44; particularly if detected and treated earlier&#46; Randomized controlled studies demonstrating reductions in the number of CTAs detectable by USG may provide further clarification&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">This study has some limitations&#46; It was conducted with a small number of patients&#44; reflecting experience only in a single center&#59; therefore&#44; the results cannot be generalized&#46; Another limitation is that the inter-observer variability is unknown because thoracic USG was performed by a single pulmonologist&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; thoracic USG performed by a chest physician has a high sensitivity and specificity in diagnosing BT&#46; Use of thoracic USG in follow up of BT can be demonstrated if studies are conducted showing decreased numbers of CTAs in patients monitored using thoracic USG&#44; which are further supported by clinical-radiologic examinations and PFT&#8211;DLCO values&#46; Although healthy lung parenchyma cannot be visualized using USG&#44; we believe that diffuse lung parenchyma involvement such as ILD can be well evaluated using USG&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of Interests</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interests&#46;</p></span></span>"
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          "titulo" => "Abstract"
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              "titulo" => "Objective"
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          "identificador" => "xpalclavsec1057097"
          "titulo" => "Keywords"
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        2 => array:3 [
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          "titulo" => "Resumen"
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          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Material and Methods"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patient Population"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "High-Resolution Computerized Tomography"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Pulmonary Function Test and Carbon Monoxide Diffusion Test"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Thoracic USG"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Definition of CTA and Clinical-ultrasonographic Diagnosis of BT"
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            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Statistical Analysis"
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          "identificador" => "sec0045"
          "titulo" => "Results"
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          "titulo" => "Discussion"
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          "identificador" => "sec0055"
          "titulo" => "Conflict of Interests"
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          "identificador" => "xack381933"
          "titulo" => "Acknowledgement"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-04-05"
    "fechaAceptado" => "2018-06-06"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1057097"
          "palabras" => array:3 [
            0 => "Bleomycin toxicity"
            1 => "High-resolution computed tomography"
            2 => "Ultrasonography"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1057098"
          "palabras" => array:3 [
            0 => "Toxicidad a bleomicina"
            1 => "Tomograf&#237;a computarizada de alta resoluci&#243;n"
            2 => "Ecograf&#237;a"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To evaluate the role of ultrasonography &#40;USG&#41; in the diagnosis of bleomycin-induced pulmonary toxicity &#40;BT&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The study included patients with suspected BT during treatment with bleomycin due to various oncologic diseases between June 2015 and May 2017&#46; The patients initially underwent clinical and high-resolution computed tomography &#40;HRCT&#41; examinations and pulmonary function tests &#40;PFT&#41;-diffusing capacity of the lung for carbon monoxide &#40;DLCO&#41;&#44; followed by registration of USG findings&#8212;number of comet tail artifact &#40;CTA&#41; images by a different pulmonologist&#46; We compared the findings from USG&#44; HRCT&#44; and PFT&#8211;DLCO tests between BT and non-BT groups&#46; With the diagnosis based on clinical-radiologic and PFT&#8211;DLCO assessments taken as the gold standard&#44; we determined the sensitivity and specificity of the USG outcomes for diagnosis of BT&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The study included a total of 30 patients&#46; Nine patients were diagnosed as having BT according to their clinical and radiologic findings and PFT&#8211;DLCO measurements&#46; The mean number of CTA images was 68&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22 in patients with BT vs 28&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;3 in those without BT &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; The difference in CTA images between the patients with and without ground glass density was statistically significant &#40;28&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;5 and 64&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;5&#44; respectively&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; In patients with BT&#44; there was a negative correlation between the number of CTAs and DLCO&#37; and FVC&#37; values &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;004&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;016&#41;&#46; USG had a sensitivity of 100&#37;&#44; and a specificity of 95&#37; diagnosing BT in selected patients&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In bleomycin-induced toxicity&#44; USG findings are correlated with HRCT and PFT&#8211;DLCO findings&#44; with a remarkably increased number of CTAs in BT&#46; Thoracic USG examination is a diagnostic tool with a high sensitivity and specificity for diagnosing BT&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">evaluar el papel de la ecograf&#237;a en el diagn&#243;stico de la toxicidad pulmonar inducida por bleomicina &#40;BT&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y m&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">se incluyeron pacientes con sospecha de BT durante el tratamiento con bleomicina por enfermedad oncol&#243;gica entre junio de 2015 y mayo de 2017&#46; Se les someti&#243; a evaluaci&#243;n cl&#237;nica inicial y tomograf&#237;a computarizada de alta resoluci&#243;n &#40;TACAR&#41;&#44; as&#237; como a pruebas de funci&#243;n pulmonar &#40;PFP&#44; prueba de difusi&#243;n de mon&#243;xido de carbono &#91;DLCO&#93;&#41;&#46; Se recopilaron los hallazgos ecogr&#225;ficos obtenidos por otro neum&#243;logo &#40;n&#250;mero de im&#225;genes de artefacto en cola de cometa &#91;CTA&#93;&#41;&#46; Se compararon los resultados de las ecograf&#237;as&#44; TACAR y PFP&#8211;DLCO entre los grupos con y sin BT&#46; Con el diagn&#243;stico basado en las valoraciones cl&#237;nico-radiol&#243;gicas y de PFP&#8211;DLCO como <span class="elsevierStyleItalic">gold standard</span>&#44; se determin&#243; la sensibilidad y especificidad de la ecograf&#237;a para diagnosticar BT&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 30 pacientes&#46; Se diagnostic&#243; BT en nueve por los hallazgos cl&#237;nicos y radiol&#243;gicos y de PFP&#8211;DLCO&#46; El n&#250;mero medio de im&#225;genes CTA fue 68&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22 en pacientes con BT vs&#46; 28&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;3 en aquellos sin BT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; La diferencia en im&#225;genes CTA entre los pacientes con y sin densidades en vidrio esmerilado fue estad&#237;sticamente significativa &#40;28&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;5 and 64&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;5&#44; respectivamente&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; En pacientes con BT&#44; se observ&#243; una correlaci&#243;n negativa entre el n&#250;mero de CTA y los valores porcentuales de DLCO y de CVF &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#41;&#46; La USG tuvo una sensibilidad del 100&#37; y una especificidad del 95&#37; para el diagn&#243;stico de la BT en pacientes seleccionados&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">En la toxicidad inducida por bleomicina&#44; los hallazgos de US se correlacionan con los de TACAR y PFT&#8211;DLCO&#44; con un incremento remarcable en el n&#250;mero de CTA en BT&#46; La exploraci&#243;n tor&#225;cica mediante USG es una herramienta de diagn&#243;stico con elevada sensibilidad y especificidad para el diagn&#243;stico de la BT&#46;</p></span>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Predefined anatomic lines &#40;1&#8212;linea mid-clavicularis&#44; 2&#8212;linea axillaris anterior&#44; 3&#8212;linea axillaris media&#44; 4&#8212;linea axillaris posterior&#44; 5&#8212;linea scapularis&#44; 6&#8212;linea para vertebralis&#41;&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The curve shows the negative correlation between the DLCO&#37; value and the total number of CTAs in patients with bleomycin-induced toxicity&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The curve shows the negative correlation between the FVC&#37; value and the total number of CTAs in patients with bleomycin-induced toxicity&#46;</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">CTA&#58; comet tail artifact&#46; ICI&#58; intercostal interval&#46;</p>"
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                  <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">With BT &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#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">Without BT &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#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"><span class="elsevierStyleItalic">P</span> value&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">Linea para vertebralis&#44; right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&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">Linea scapularis&#44; right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&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">Linea axillaris posterior&#44; right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;004&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">Linea axillaris media&#44; right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;001&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">Linea axillaris anterior&#44; right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;003&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">Linea midclavicularis&#44; right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;002&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">Linea para vertebralis&#44; left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&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">Linea scapularis&#44; left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&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">Linea axillaris posterior&#44; left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;012&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">Linea axillaris media&#44; left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;001&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">Linea axillaris anterior&#44; left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;004&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">Linea midclavicularis&#44; left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;104&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">Mean CTA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&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">No&#46; of CTA images per ICI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Distribution of CTA Images by Anatomy&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">LAP&#58; lymphadenopathy&#46;</p>"
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            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">&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">With BT &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#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">Without BT &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#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"><span class="elsevierStyleItalic">P</span> value&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">Bilateral ground glass density&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#47;100&#37;&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">&#60;&#46;001&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">Interlobular septal thickening&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;66&#46;7&#37;&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">&#60;&#46;001&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">Traction bronchiectasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;22&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;4&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;207&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">Honeycomb pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;22&#46;2&#37;&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">&#46;083&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">Reticular pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;11&#46;1&#37;&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">&#46;300&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">Mediastinal-hilar LAP &#40;<span class="elsevierStyleItalic">n</span>&#47;&#37;&#41;&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">3&#47;14&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;534&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">Parenchymal nodules greater than 1<span class="elsevierStyleHsp" style=""></span>cm&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">4&#47;19&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;287&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">Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;11&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;14&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;519&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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      6 => array:8 [
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        "etiqueta" => "Table 3"
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            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">&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">With BT &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#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">Without BT &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#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"><span class="elsevierStyleItalic">P</span> value&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">FEV1&#47;FVC &#40;mean&#47;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">79&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;1&nbsp;\t\t\t\t\t\t\n
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