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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Infection is one of the main causes of morbidity and mortality throughout the life of lung transplant recipients&#46; The frequency of infection in lung transplantation is much higher than in other types of solid organ transplant &#40;SOT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> However&#44; there are no tests that enable us to evaluate the specific risk of infection in a given patient&#46; The immune cell functional assay &#40;ImmuKnow&#174;&#41; is a noninvasive technique used to evaluate the global immune response&#46; It has been approved by the United States Food and Drug Administration for monitoring immunosuppression in solid organ recipients&#46; The assay quantifies production of adenosine triphosphate &#40;ATP&#41; in CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T lymphocytes when these are stimulated <span class="elsevierStyleItalic">in vitro</span> with phytohemagglutinin &#40;PHA&#41; and is both reproducible and affordable&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">2&#44;3</span></a> In published studies&#44; its usefulness for predicting infections varies with the type of transplant&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">4&#44;5</span></a> and it could prove useful in lung transplantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6&#8211;10</span></a> The objectives of this study were to evaluate the prognostic value of this assay for predicting infection other than cytomegalovirus &#40;CMV&#41; in lung transplant recipients&#46; The predictive value was determined in the short term &#40;the 2 months following testing&#41; and in the medium term &#40;the 6 months following testing&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Design and study population</span><p id="par0010" class="elsevierStylePara elsevierViewall">This was a multicenter&#44; prospective&#44; observational study performed at 7 centers with a lung transplant program&#46; The study population comprised 92 transplant recipients who were followed up during the period 6&#8211;12 months post-transplant&#46; Follow-up began at 6 months to minimize other factors influencing infection development &#40;e&#46;g&#46; surgery&#44; postoperative complications or prophylaxis used&#41;&#46; To be included&#44; patients had to be adults&#44; have positive pre-transplant CMV serology&#44; and no active infection&#46; Active infection was defined as an infection that produced symptoms and&#47;or in which the microorganism actively replicated infecting new cells and tissues&#46; Patients were recruited between January 2014 and April 2015&#46; The assay was carried out during scheduled patient visits at 6&#44; 8&#44; 10&#44; and 12 months after transplant&#44; and results were blind to clinicians&#46; Any type of infection since the previous visit was recorded&#46; Additional variables recorded included blood or laboratory test results&#44; immunosuppression&#44; respiratory function&#44; acute rejection&#44; and other complications&#46; Acute rejection was classified according to the criteria of the International Society for Heart and Lung Transplantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">11&#44;12</span></a> These data were recorded prospectively using a purpose-designed electronic case report form&#46; Data were sent electronically and stored in a central server using the &#8220;e-Clinical&#8221; methodology according to regulation FDA 21 CRF Part 11&#44; which guarantees data confidentiality&#44; safety&#44; and authenticity&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Written informed consent was obtained from all participants&#46; The study was approved by the Clinical Research Ethics Committee of Hospital Universitari Vall d&#8217;Hebron&#44; Barcelona&#44; Spain&#44; which was the lead center &#40;EPA&#40;AG&#41;47&#47;2013&#41;&#44; and a further two ethics committees&#46; It was also approved by the health authorities of the relevant autonomous communities&#46; The data that support the findings of this study are available from the corresponding author upon reasonable request&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Immune cell functional assay &#40;ImmuKnow&#174;&#41;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Patient immune function was assessed using the commercially available ImmuKnow&#174; assay &#40;Cylex Inc&#46;&#44; Columbia&#44; USA&#41;&#44; which determines intracellular ATP levels in CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T cells&#46; Whole blood samples were collected in a sodium heparin vacutainer tube&#44; and the intracellular ATP concentration was measured according to the manufacturer&#39;s protocol&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Briefly&#44; 250<span class="elsevierStyleHsp" style=""></span>&#956;L of anticoagulated whole blood was diluted with sample diluent&#44; added to the wells of a 96-well microtiter plate&#44; and incubated for 15&#8211;18<span class="elsevierStyleHsp" style=""></span>h with phytohemagglutinin &#40;PHA&#41; in a 37<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 5&#37; CO<span class="elsevierStyleInf">2</span> incubator&#46; Whole blood was incubated concurrently in the absence of stimulant to assess baseline ATP activity&#46; The following day&#44; CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T cells were positively selected within the microwells using magnetic particles coated with anti-human CD4 monoclonal antibodies and a strong magnet&#44; washed to remove residual cells&#44; and lysed to release intracellular ATP&#46; Released ATP was detected using luciferin&#47;luciferase mixture and measured in a luminometer at a maximum emission wavelength of 562<span class="elsevierStyleHsp" style=""></span>nm &#40;GloRunner Microplate Luminometer&#44; Turner biosystems&#44; Sunnyvale&#44; CA&#44; USA&#41;&#46; ATP concentration &#40;ng&#47;mL&#41; was calculated comparing with a calibration curve&#46; The cut-off values were those recommended by the manufacturer&#44; which were established by testing 155 healthy adults and 127 transplant recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a> A low immune response was defined as ATP levels<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#60;</span><span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; moderate as ATP levels 225&#8211;524<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; and strong as ATP levels<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>525<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; Other cut-off points that could improve the sensitivity and specificity for predicting infection based on receiver operating characteristic &#40;ROC&#41; curves were also investigated&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Antimicrobial prophylaxis</span><p id="par0030" class="elsevierStylePara elsevierViewall">In the immediate postoperative period&#44; patients without preoperative bronchial colonization received amoxicillin-clavulanate&#44; piperacillin tazobactam or imipem according to the protocols of the participating center&#46; In patients with bronchial colonization&#44; antibiotics were modified depending on the latest cultures and inhaled colistin or tobramycin were also given&#46; All patients received CMV prophylaxis&#44; which consisted of intravenous ganciclovir following surgery until oral intake was resumed&#44; then switched to valganciclovir at 900<span class="elsevierStyleHsp" style=""></span>mg&#47;d &#40;dose adjusted to renal function&#41; until 180 days after surgery&#46; Three centers gave isoniazid for 9 months or isoniazid plus rifampicin for 3 months in patients with tuberculosis infection &#40;positive PPD test&#41; before transplantation&#46; Universal prophylaxis for <span class="elsevierStyleItalic">Aspergillus</span> infection was with nebulized amphotericin B &#40;liposomal or lipid complex&#41;&#44; and two centers also gave fluconazole&#59; the length of this prophylaxis ranged from 1&#46;5 months to indefinitely&#44; depending on the center&#46; All patients received cotrimoxazole for <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> prophylaxis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Immunosuppressive regimens</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were treated according to local protocol with tacrolimus plus mycophenolate mofetil &#40;1&#8211;2<span class="elsevierStyleHsp" style=""></span>g&#47;d&#41; or mycophenolic acid &#40;720&#8211;1440<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41; and corticosteroids&#46; Cyclosporine and azathioprine were used in 1 case each&#46; The dose of tacrolimus was adjusted for target trough serum levels of 10&#8211;15<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; Methylprednisolone was started in the operating room &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; before graft reperfusion&#44; followed by 375<span class="elsevierStyleHsp" style=""></span>mg&#47;d on the first day and gradual tapering over the first year to reach a maintenance dose of 0&#46;1&#8211;0&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#46; mTOR inhibitors were used as rescue therapy in chronic and recurrent acute rejection or to replace other immunosuppressive agents due to adverse effects&#46; Induction therapy with basiliximab was used according to local protocols&#46; Depending on the severity of the episode&#44; acute rejections were treated with an IV pulse of methylprednisolone 5&#8211;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for 3 days or 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for 10 days&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Infection definitions</span><p id="par0040" class="elsevierStylePara elsevierViewall">Tracheobronchitis was defined as new onset of shortness of breath&#44; cough&#44; sputum&#44; rales&#44; or wheezing plus microbiological isolation from sputum or bronchoscopy sample&#46; When microbiological isolation was not possible&#44; it was considered possible tracheobronchitis if the patient had purulent sputum and responded to antibiotic treatment&#46; Ulcerative or pseudomembranous tracheobronchitis was defined on the basis of observation of necrotic ulcers or pseudomembrane in the anastomosis on by bronchoscopy plus microbiological isolation&#46; Pneumonia was distinguished from tracheobronchitis if it was associated with a new pulmonary infiltrate on chest X-ray or computed tomography&#46; Extrapulmonary infections were defined by microbiological isolation at the site of infection associated with symptoms and signs suggestive of disease&#46; The definitions were adapted from ISHLT consensus for standardization of definitions in cardiothoracic transplant recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Sample size was determined based on previous reports using the program Ene-3&#46;0&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6&#44;7</span></a> In order to estimate a proportion with a 2-sided 95&#37; confidence interval and 5&#37; accuracy&#44; and assuming that the expected proportion would be 95&#37;&#44; 73 patients were required&#46; Assuming a 20&#37; loss or invalid results&#44; we aimed to recruit 92 patients to achieve the study objectives&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Student <span class="elsevierStyleItalic">t</span>-test was used to analyze continuous variables with a normal distribution&#46; For those with a non-normal distribution&#44; the Mann-Whitney test &#40;unpaired data&#41; and Wilcoxon test &#40;paired data&#41; were used&#46; The chi-squared test &#40;or Fisher exact test when applicable&#41; was used to analyze contingency tables&#44; proportions&#44; and frequency distribution&#46; The McNemar test was used to measure attributes at 2 different time points&#46; The Pearson or Spearman correlation coefficient was used to determine the correlation between 2 continuous variables&#46; Receiver operating characteristic &#40;ROC&#41; curves were used to determine the sensitivity and specificity of the assay&#46; Positive predictive value &#40;PPV&#41; and negative predictive value &#40;NPV&#41; were calculated using contingency tables&#46; Survival rates were calculated using the Kaplan&#8211;Meier method&#46; Statistical comparisons were made using the log-rank test&#46; All hypothesis tests were 2-tailed&#46; Statistical significance was set at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; Data were analyzed using SPSS version 22&#46;0&#46; Confidence intervals were calculated at 95&#37;&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Between months 6 and 12 post-transplantation&#44; 23 of the 92 patients &#40;25&#46;0&#37;&#41; developed 29 non-CMV infections&#46; No significant differences were found between patients who developed infection and those who did not&#44; in terms of the demographic and clinical variables recorded &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Infections occurred in the form of bacterial or fungal tracheobronchitis in 11 cases &#40;3 cases of <span class="elsevierStyleItalic">Aspergillus</span> spp&#44; 2 cases of <span class="elsevierStyleItalic">Pseudomonas</span> spp and one case each of S<span class="elsevierStyleItalic">taphylococcus aureus</span>&#44; <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>&#44; <span class="elsevierStyleItalic">Morganella</span> spp&#44; <span class="elsevierStyleItalic">Enterococcus</span> spp&#44; <span class="elsevierStyleItalic">Rhizopus spp</span> and <span class="elsevierStyleItalic">Mycobacterium gordonae</span>&#41;&#44; 8 cases of possible bacterial tracheobronchitis&#44; and 2 cases of pneumonia &#40;1 <span class="elsevierStyleItalic">Pseudomonas</span> spp and 1 unidentified fungus&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Other diagnoses were 3 cutaneous infections &#40;2 <span class="elsevierStyleItalic">herpes zoster</span> and 1 olecranon bursitis due to <span class="elsevierStyleItalic">Staphylococcus aureus&#41;&#44;</span> 2 esophageal candidiasis&#44; 1 gastroenteritis due to S<span class="elsevierStyleItalic">almonella</span> spp&#44; 1 thoracotomy scar infection with <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> and 1 endocarditis due to <span class="elsevierStyleItalic">Pseudomonas</span> spp&#46; Three of the 92 patients &#40;3&#46;3&#37;&#41; died before completing the study &#40;1 septic shock secondary to pneumonia&#44; 1 kidney failure&#44; and 1 sudden death&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Mean ImmuKnow&#174; values significantly increased from month 6 &#40;142&#46;45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>88&#46;60<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; to month 12 &#40;204&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>121&#46;67<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; after surgery &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Mean ImmuKnow&#174; values were lower in patients who developed infection than in those who did not &#40;111<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>58&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;mL vs&#46; 155&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>96&#46;40<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; Trough serum tacrolimus levels were similar in both groups &#40;9&#46;70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;81<span class="elsevierStyleHsp" style=""></span>ng&#47;mL vs&#46; 10&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;99<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;22&#41;&#44; as were doses of mycophenolate or mycophenolic acid &#40;1447&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>497&#46;06<span class="elsevierStyleHsp" style=""></span>mg vs&#46; 1366&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>585&#46;53<span class="elsevierStyleHsp" style=""></span>mg&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;509&#41; and corticosteroids &#40;12&#46;62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;12<span class="elsevierStyleHsp" style=""></span>mg vs&#46; 11&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;41<span class="elsevierStyleHsp" style=""></span>mg&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;164&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We observed a weak correlation between the dose of mycophenolate &#40;mycophenolic acid&#41; and ImmuKnow&#174; values &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;149&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#41;&#46; No correlation was observed for trough blood levels of tacrolimus &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;069&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;28&#41; or dose of corticosteroids &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;037&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;560&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Mean ImmuKnow&#174; values between 6 and 12 months post-transplant were similar in patients who received induction immunosuppressive treatment to those who did not &#40;168&#46;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>60&#46;17<span class="elsevierStyleHsp" style=""></span>ng&#47;mL vs&#46; 155&#46;58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>58&#46;19<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;294&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">At 6 months post-transplant&#44; a moderate immune response was detected in 14 of the 92 patients studied &#40;15&#46;2&#37;&#41; and a low response in 78 patients &#40;84&#46;8&#37;&#41;&#46; No patients showed a strong immune response&#46; Only 1 of the 14 patients &#40;7&#46;1&#37;&#41; with moderate immune response developed an infection between 6 and 12 months after surgery compared with 22 of the 78 patients &#40;28&#46;2&#37;&#41; with low response&#46; In the ROC curve analysis&#44; the assay had a sensitivity of 95&#46;7&#37; and a specificity of 18&#46;8&#37; &#40;AUC&#44; 0&#46;641&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#41;&#46; With an ATP cut-off of 225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; the PPV and NPV were 28&#46;2&#37;&#44; and 92&#46;9&#37; respectively&#46; Specificity improved at an ATP cut-off of<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;86&#46;36&#37;&#41; but sensitivity decreased &#40;9&#46;23&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Of the 273 assays performed&#44; a moderate immune response was detected in 55 samples &#40;20&#46;2&#37;&#41; and a low response in 216 &#40;79&#46;1&#37;&#41;&#46; Two samples showed a strong immune response &#40;0&#46;7&#37;&#41;&#46; The rate of infection during the 2 months following testing was 0&#37; in patients with strong or moderate immune response and 12&#46;5&#37; in those with a low response&#46; ROC curve analysis revealed a sensitivity of 100&#37; and a specificity of 22&#46;5&#37;&#44; &#40;AUC&#44; 0&#46;632&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41; with a PPV of 12&#46;5&#37;&#44; and NPV of 100&#37;&#37; at an ATP cut-off of 225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; Specificity improved at an ATP cut-off of<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;88&#46;89&#37;&#41; and sensitivity decreased &#40;9&#46;02&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Between 6 and 12 months after surgery&#44; 14 of the 92 patients studied &#40;15&#46;2&#37;&#41; had mean ATP values<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and 78 &#40;84&#46;8&#37;&#41; had mean ATP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; Acute rejection was recorded in 1 of the 14 patients with mean ATP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;7&#46;1&#37;&#41; and in 7 of the 77 patients with mean ATP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;9&#46;1&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;81&#41;&#46; Similarly&#44; there were no differences in respiratory function progress between the groups&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Little is known about the diagnostic value of the ImmuKnow&#174; assay in lung transplantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6&#8211;10</span></a> To our knowledge&#44; this is the first multicenter prospective study to analyze the predictive value of ImmuKnow&#174; for infections other than CMV in this type of transplant&#46; We observed that patients with ImmuKnow&#174; ATP values &#8805;225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL had a very low risk of developing non-CMV infection both short term and medium term&#44; with no increase in the acute rejection rate or worsening in the evolution of respiratory function&#46; In the 2 months following performance of the assay&#44; the NPV was 100&#37;&#44; and in the following 6 months it was 93&#37;&#46; However&#44; the specificity and PPV were low&#46; Therefore ImmuKnow&#174; does not seem useful to predict episodes of non-CMV infection in lung transplant recipients&#44; but could identify patients with a very low risk &#40;ATP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; and help us define a target for an optimal immunosuppression&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The ImmuKnow&#174; assay has been evaluated in lung transplant in a few studies with different designs to that of the present study&#46; The novel aspects of our study are that it was designed to evaluate the sensitivity and specificity of the assay to predict which patients will go on to develop infections&#44; that it included non-respiratory infections&#44; and that it was a multicenter study&#46; Bhorade et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> studied 143 samples from 57 lung transplant recipients&#46; Like us&#44; the authors observed that patients who developed infection had lower ImmuKnow&#174; values&#44; but unlike our study the assays were performed at the time of infection&#44; not before&#46; Husain et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> found that patients with bacterial pneumonia&#44; viral infection&#44; CMV disease&#44; and fungal infection had lower ImmuKnow&#174; values &#40;also at time of infection&#41; than uninfected patients and that ImmuKnow&#174; values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>ng&#47;mL were an independent risk factor for infection&#44; with an odds ratio of 2&#46;81&#46; In a retrospective study&#44; Shino et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> correlated ImmuKnow&#174; values with findings from bronchoscopy&#46; Their findings differed&#44; in that ImmuKnow&#174; values were similar in patients who developed infection and in those who did not&#46; It should be noted that in this study&#44; ImmuKnow&#174; values were very high compared with those reported in other published studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6&#44;7&#44;9&#44;10</span></a> Even so&#44; Shino et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> found that 40&#37; of patients with ATP levels<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL developed an infection &#40;odds ratio&#44; 1&#46;9&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">This assay provides information on global T cell immunocompetence and risk of all types of opportunistic infection&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> However&#44; Husain et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> observed than patients with CMV disease showed the lowest ImmuKnow&#174; values&#44; followed by those with fungal and then bacterial infections&#58; this is probably because T cells are more involved in the control of CMV infection than in bacterial or fungal infections where innate immunity is the first line of defense&#46; We therefore decided to study the predictive value of ImmuKnow&#174; for infections other than CMV&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">ImmuKnow&#174; assay has been extensively studied in other types of SOT&#46; Its value for predicting infection is controversial and varies with the organ transplanted&#46; Discrepancies are probably due to differences in the incidence of infection between organs&#44; immunosuppression protocols and study design&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a> Overall&#44; the sensitivity for predicting the risk of infection is high for liver transplant but lower for kidney transplant&#46; In their meta-analysis&#44; Ling et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> found that in 3 studies on liver transplant&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">16&#8211;18</span></a> sensitivity ranged from 81&#37; to 100&#37;&#44; whereas in 3 studies on kidney transplant&#44;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">19&#8211;21</span></a> sensitivity was between 21&#37; and 68&#37;&#46; Specificity for both organs was similar&#44; between 60&#37; and 79&#37; in liver transplant and between 74&#37; and 100&#37; in kidney transplant&#46; In another meta-analysis&#44; Rodrigo et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5&#44;16&#44;18&#44;22&#44;23</span></a> found sensitivity to be 83&#37; and specificity 75&#37; for liver transplant&#46; Huskey et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">21</span></a> also in a retrospective study with 583 renal transplant recipients at a single center&#44; observed a lack of sensitivity and specificity as a predictive test for infection&#46; Kowalski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a> observed in a meta-analysis with 504 SOT recipients that ATP levels around 280<span class="elsevierStyleHsp" style=""></span>ng&#47;mL may protect against allograft rejection and infection&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In our study&#44; tacrolimus levels were no higher in patients who developed infection than in those who did not&#46; Similarly&#44; they did not correlate with ImmuKnow&#174; levels&#46; This finding is well documented<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6&#44;24&#44;25</span></a> and points to inappropriate monitoring of levels of immunosuppression based only on pharmacokinetic parameters&#46; In addition to ImmuKnow&#174;&#44; other assays have been proposed for monitoring the immune response &#40;eg&#44; cytokine genetic polymorphisms&#44; mixed lymphocyte reaction&#44; enzyme-linked immunosorbent spot assay&#44; Quantiferon assay or monitoring of nuclear factor of activated T cells-regulated gene expression&#41;&#44; although they have not been implemented in clinical practice&#44; since they involve complicated laboratory procedures or are subject to problems of reproducibility and cost&#46; However&#44; the main impediment to their use in clinical practice is the lack of prospective studies and randomized clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">2&#44;3&#44;26&#8211;28</span></a> Ravaioli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a> performed a randomized controlled trial in liver transplant recipients in which they modified the dose of tacrolimus according to the ImmuKnow&#174; result&#44; with a 25&#37; dose reduction if ATP levels were<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>130<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and a 25&#37; dose increase if they were<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>450<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; With this strategy&#44; patients developed fewer infections than in the control group &#40;42&#37; vs 54&#46;9&#37;&#41; and had better 1-year survival &#40;95&#37; vs 82&#37;&#41;&#46; It would be interesting to perform a study with a similar design in lung transplant recipients&#44; where infection plays an even more important role&#46; In fact&#44; reducing the number of infections is essential if we are to improve the outcomes of lung transplantation&#46; Randomized clinical trials in which immunosuppressive therapy is adjusted according to ImmuKnow&#174; or other immunological monitoring assays are needed&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Studies on acute rejection performed in liver transplantation<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">4&#44;16&#8211;18</span></a> have shown high specificity &#40;94&#8211;100&#37;&#41; and low sensitivity &#40;9&#8211;50&#37;&#41; for ImmuKnow&#174; with a cut-off point of ATP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>525<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; The results are poorer in kidney transplantation&#44; with a specificity of 65&#8211;80&#37; and a sensitivity of 33&#8211;23&#37;&#46; In lung transplantation&#44; Shino et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> reported a sensitivity of 45&#37; and a specificity of 79&#37; with this cut-off point&#46; In our study&#44; we cannot draw conclusions because only two samples out of 271 were above this limit&#59; we did however observe the same acute rejection rate in patients with mean ImmuKnow&#174; values of ATP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and &#60;225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL during the study period&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">With respect to pulmonary function&#44; there were no differences between patients with ATP levels<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and patients with lower levels&#46; However&#44; follow-up was too short to draw conclusions on changes in pulmonary function&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The main limitations of the present study are those of multicenter observational studies&#46; Although we attempted to collect all variables prospectively in order to minimize potential bias&#44; some variables are difficult to record and analyze&#46; For example&#44; one physician may address a particular clinical situation differently from another&#44; or there may be differences between centers in terms of prophylaxis&#44; immunosuppression&#44; and patient follow-up&#46; Our study is also limited by the short follow-up period&#44; although this was during a period when the patient is still very susceptible to infections&#44; i&#46;e&#46;&#44; between 6 and 12 months after surgery&#46; We excluded the first 6 months because some postoperative variables can also play a role in the development of infection &#40;for example problems in bronchial anastomosis&#44; leukopenia due to valganciclovir prophylaxis&#44; and different fungal or bacterial prophylaxis between centers&#41;&#46; Therefore&#44; the predictive value of ImmuKnow&#174; in these first 6 months is unclear&#46; Finally&#44; our study was limited by potential variability in the immunoassays used&#59; we attempted to minimize this variability by using a central laboratory&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In conclusion&#44; ImmuKnow&#174; does not seem useful to predict episodes of non-CMV infection in lung transplant recipients&#44; but could identify patients with a very low risk&#46; ImmuKnow&#174; could help us to adjust the immunosuppressive treatment&#44; reducing the dose of immunosuppressants when the ImmuKnow&#174; values are very low&#46; However&#44; this should be evaluated with clinical trials designed for this purpose&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Author contributions</span><p id="par0150" class="elsevierStylePara elsevierViewall">VM&#44; SGO&#44; RC&#44; VLP&#44; JMC&#44; JR&#44; AS contributed to the design&#59; VM&#44; SGO&#44; HS&#44; RC&#44; PU coordinated the study&#59; VM&#44; CB&#44; MLM&#44; PJM&#44; JPO&#44; VLP&#44; RA&#44; JMC&#44; JMV&#44; JR&#44; RL&#44; PU&#44; JE&#44; AS contributed to the data collection&#59; SR&#44; RC&#44; ILA contributed to sample analysis&#59; VM&#44; SGO&#44; HS&#44; ILA&#44; AM contributed to data analysis&#59; VM wrote the manuscript&#59; VM&#44; VLP&#44; JMC&#44; DI&#44; JR&#44; PU&#44; AS contributed to the revision of the manuscript&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding source</span><p id="par0155" class="elsevierStylePara elsevierViewall">This work was supported by <span class="elsevierStyleGrantSponsor" id="gs1">Roche Farma S&#46;A</span>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests related to this manuscript to disclose&#46;</p></span></span>"
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              "titulo" => "Immune cell functional assay &#40;ImmuKnow&#174;&#41;"
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              "titulo" => "Antimicrobial prophylaxis"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Immune cell functional assay &#40;ImmuKnow&#174;&#41; is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients&#46; We studied the prognostic value of the assay for predicting non-cytomegalovirus &#40;CMV&#41; infections in lung transplant recipients&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed&#46; Immune cell functional assay was carried out at 6&#44; 8&#44; 10&#44; and 12 months&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Twenty-three patients &#40;25&#37;&#41; developed 29 non-CMV infections between 6 and 12 months post-transplant&#46; At 6 months&#44; the immune response was moderate &#40;ATP 225&#8211;525<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; in 14 &#40;15&#46;2&#37;&#41; patients and low &#40;ATP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; in 78 &#40;84&#46;8&#37;&#41;&#59; no patients had a strong response &#40;ATP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>525<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#46; Only 1 of 14 &#40;7&#46;1&#37;&#41; patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 &#40;28&#46;2&#37;&#41; patients with low response&#44; indicating sensitivity of 95&#46;7&#37;&#44; specificity of 18&#46;8&#37;&#44; positive predictive value &#40;PPV&#41; of 28&#46;2&#37;&#44; and negative predictive value &#40;NPV&#41; of 92&#46;9&#37; &#40;AUC 0&#46;64&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#41;&#46; Similar acute rejection rates were recorded in patients with mean ATP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>225 vs&#46; &#60;225<span class="elsevierStyleHsp" style=""></span>ng&#47;mL during the study period &#40;7&#46;1&#37; vs&#46; 9&#46;1&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;81&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Although ImmuKnow&#174; does not seem useful to predict non-CMV infection&#44; it could identify patients with a very low risk and help us define a target for an optimal immunosuppression&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El test de funci&#243;n de la inmunidad celular &#40;ImmuKnow&#174;&#41; es un m&#233;todo que mide el estado de la inmunidad celular en pacientes inmunosuprimidos&#46; Se estudi&#243; su valor pron&#243;stico para predecir infecciones diferentes a citomegalovirus &#40;CMV&#41; en receptores de un trasplante pulmonar&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio observacional prospectivo multic&#233;ntrico de 92 pacientes seguidos desde los 6 a los 12 meses postrasplante&#46; El test se realiz&#243; a los 6&#44; 8&#44; 10 y 12 meses&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Veintitr&#233;s pacientes &#40;25&#37;&#41; desarrollaron 29 infecciones no debidas a CMV entre los 6 y los 12 meses posteriores al trasplante&#46; A los 6 meses&#44; la respuesta inmune fue moderada &#40;ATP 225-525<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; en 14 &#40;15&#44;2&#37;&#41; pacientes y baja &#40;ATP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; en 78 &#40;84&#44;8&#37;&#41;&#59; ning&#250;n paciente tuvo una respuesta fuerte &#40;ATP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>525<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; Solo uno de 14 &#40;7&#44;1&#37;&#41; pacientes con una respuesta moderada desarroll&#243; una infecci&#243;n diferente a CMV en los 6 meses siguientes a la realizaci&#243;n del test en comparaci&#243;n con 22 de 78 &#40;28&#44;2&#37;&#41; con respuesta baja&#44; indicando una sensibilidad del 95&#44;7&#37;&#44; una especificidad del 18&#44;8&#37;&#44; un valor predictivo positivo del 28&#44;2&#37; y un valor predictivo negativo del 92&#44;9&#37; &#40;AUC 0&#44;64&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;043&#41;&#46; Se registraron tasas de rechazo agudo similares en pacientes con ATP medio &#62;<span class="elsevierStyleHsp" style=""></span>225 frente a &#60;<span class="elsevierStyleHsp" style=""></span>225<span class="elsevierStyleHsp" style=""></span>ng&#47;ml durante el per&#237;odo de estudio &#40;7&#44;1 frente al 9&#44;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;81&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusi&#243;n</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Aunque el test ImmuKnow&#174; no parece &#250;til para predecir infecciones diferentes al CMV&#44; podr&#237;a identificar pacientes con riesgo muy bajo y ayudarnos a definir un objetivo de inmunosupresi&#243;n &#243;ptima&#46;</p></span>"
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      2 => array:7 [
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                  \t\t\t\t" scope="col">Non-CMV infection &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>69&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Non-CMV infection &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Absent&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Present&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">54&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">55&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;752&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Body mass index</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">22&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Underlying disease</span></td><td class="td" title="\n
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                  \t\t\t\t">0&#46;861&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pulmonary fibrosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;34&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;43&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>COPD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">20 &#40;29&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;30&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cystic fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;13&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;8&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pulmonary hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;10&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Type of transplant &#40;single&#47;double&#41; immunosuppression&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#47;47 &#40;31&#46;9&#37;&#47;68&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#47;12 &#40;47&#46;8&#47;52&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;167&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Induction &#40;no&#47;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;47&#46;8&#37;&#41;&#47;36 &#40;52&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;43&#46;5&#37;&#41;&#47;13 &#40;56&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;717&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Basiliximab &#40;no&#47;yes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;8&#37;&#41;&#47;35 &#40;97&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;7&#46;7&#37;&#41;&#47;12 &#40;92&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;960&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Primary graft dysfunction&#58; Grade 0&#47;1&#47;2&#47;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#47;9&#47;7&#47;8 &#40;65&#46;2&#37;&#47;13&#46;0&#37;&#47;10&#46;1&#37;&#47;11&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#47;1&#47;3&#47;4 &#40;63&#46;6&#37;&#47;4&#46;5&#37;&#47;13&#46;6&#37;&#47;18&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;607&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Donor CMV serology&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;80&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;80&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Recipient CMV serology&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">CMV infection at 6&#8211;12 months &#40;no&#47;yes&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;59&#46;4&#37;&#41;&#47;28 &#40;40&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;47&#46;8&#37;&#41;&#47;12 &#40;52&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;331&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">CMV disease at 6&#8211;12 months &#40;no&#47;yes&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66 &#40;95&#46;7&#37;&#41;&#47;3 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;95&#46;7&#37;&#41;&#47;1 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Respiratory function at 6 months &#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#41;&#58;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FVC &#40;liters&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;124&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span> &#40;liters&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;373&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#46;70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;244&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Blood results at 6 months &#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#41;&#58;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Leukocytes 10<span class="elsevierStyleSup">9</span>&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;02<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lymphocytes 10<span class="elsevierStyleSup">9</span>&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;363&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glucose &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>37&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93&#46;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;180&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glomerular filtration rate &#40;CKD-EPI&#44; mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#46;01<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;532&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical data of patients who developed a non-CMV infection between 6 and 12 months after transplant surgery and those who did not&#46;</p>"
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                            0 => "B&#46;D&#46; Alexander"
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                      "doi" => "10.1034/j.1399-3062.2001.003003128.x"
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                        "tituloSerie" => "Transpl Infect Dis"
                        "fecha" => "2001"
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