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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Patients with severe COVID-19 related acute respiratory distress syndrome &#40;ARDS&#41; may benefit from V-V ECMO support&#46; However&#44; this technique remains associated with frequent complications and high mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> The early identification of patients with V-V ECMO who are likely to survive on ICU discharge therefore seems of major interest&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Endocan is a circulating proteoglycan secreted by the pulmonary vasculature under inflammatory conditions such as ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Recent data suggest that monitoring of blood endocan during 1st week following intensive care unit &#40;ICU&#41; admission may correlate with the severity of ARDS in Covid-19&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Thus&#44; we aimed in this study to assess whether plasma endocan measurements performed on the day of V-V ECMO implantation &#40;D0&#41; and repeated seven days later &#40;D7&#41; may be effective in predicting mortality on ICU discharge&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">This study was conducted in a 50-bed mixed ICU&#44; from October 2020 to June 2021&#46; We included all consecutive COVID-19 patients undergoing V-V ECMO implantation and with available results of plasma endocan measured on day of ECMO implantation&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Endocan was measured weekly on EDTA plasma in the central laboratory of our hospital using the ENDOMARK H1 ELISA kit &#40;Biothelis&#44; France&#41; in COVID-19 patients admitted in our ICU as part as the routine assessment of prognosis in ARDS&#44;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">4&#8211;6</span></a> along with CRP and fibrinogen&#46; This research was examined by our local IRB&#44; and approved under the number HP 22&#47;01&#46; Because of the retrospective observational design&#44; written informed consent was not required&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patients&#8217; characteristics were obtained at D0&#46; We also retrospectively collected values on D0 and D7 for plasma endocan &#40;endocan<span class="elsevierStyleInf">D0</span> and endocan<span class="elsevierStyleInf">D7</span>&#41;&#44; CRP &#40;CRP<span class="elsevierStyleInf">D0</span> and CRP<span class="elsevierStyleInf">D7</span>&#41; and fibrinogen &#40;fibrinogen<span class="elsevierStyleInf">D0</span> and fibrinogen<span class="elsevierStyleInf">D7</span>&#41;&#46; Variations between D0 and D7 were respectively calculated for endocan &#40;endocan<span class="elsevierStyleInf">D0&#8211;D7</span>&#41;&#44; CRP &#40;CRP<span class="elsevierStyleInf">D0&#8211;D7</span>&#41; and fibrinogen &#40;fibrinogen<span class="elsevierStyleInf">D0&#8211;D7</span>&#41; as following&#58; &#40;value on D7<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>value on D0&#41;&#47;value on D0&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Categorical variables were expressed as numbers &#40;percentages&#41; and compared using Fisher&#39;s exact test&#44; given small sample sizes&#46; Skewed continuous variables were presented as median &#40;interquartile range&#41; and compared using Mann-Whitney U test&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Decision tree based on CART algorithm was generated using the <span class="elsevierStyleItalic">rpart</span> R package with default settings&#44; using endocan<span class="elsevierStyleInf">D0</span>&#44; endocan<span class="elsevierStyleInf">D7</span>&#44; endocan<span class="elsevierStyleInf">D0&#8211;D7</span>&#44; CRP<span class="elsevierStyleInf">D0</span>&#44; CRP<span class="elsevierStyleInf">D7</span>&#44; CRP<span class="elsevierStyleInf">D0&#8211;D7</span>&#44; fibrinogen<span class="elsevierStyleInf">D0</span>&#44; fibrinogen<span class="elsevierStyleInf">D7</span> and fibrinogen<span class="elsevierStyleInf">D0&#8211;D7</span> as covariates&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">All statistical tests were two-tailed&#44; and <span class="elsevierStyleItalic">p</span> values &#60;0&#46;05 were considered statistically significant&#46; Statistical analysis was performed using R version 3&#46;6 &#40;R foundation for statistical analysis&#44; Austria&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Eleven patients undergoing V-V ECMO implantation for COVID-19 related ARDS were included in this study&#44; of whom 5 &#40;45&#37;&#41; were discharged alive from ICU&#46; All patients underwent invasive mechanical ventilation &#40;MV&#41; during their stay in ICU&#44; although invasive MV was initiated right before ECMO implantation and maintained less than 24<span class="elsevierStyleHsp" style=""></span>h for 2 patients from the survivors group&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Compared to survivors&#44; non-survivors had higher endocan<span class="elsevierStyleInf">D7</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#46;9 &#91;6&#46;1&#59; 19&#93;<span class="elsevierStyleHsp" style=""></span>ng&#47;ml vs 4&#46;3 &#91;3&#46;9&#59; 5&#46;6&#93;<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;017&#41;&#44; and greater increase in endocan<span class="elsevierStyleInf">D0&#8211;D7</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>208 &#91;&#8722;1&#59; &#43;612&#93; &#37; vs &#8722;49 &#91;&#8722;65&#59; &#43;52&#93;&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46; Conversely&#44; no difference was found between non-survivors and survivors for endocan<span class="elsevierStyleInf">D0</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;7 &#91;3&#59; 5&#46;7&#93;<span class="elsevierStyleHsp" style=""></span>ng&#47;ml vs 7&#46;9 &#91;3&#46;8&#59; 12&#46;2&#93;<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;25&#41;&#44; CRP<span class="elsevierStyleInf">D0</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>94 &#91;68&#59; 200&#93;<span class="elsevierStyleHsp" style=""></span>mg&#47;l vs 118 &#91;26&#59; 150&#93;<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;66&#41;&#44; CRP<span class="elsevierStyleInf">D7</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>68 &#91;50&#59; 77&#93;<span class="elsevierStyleHsp" style=""></span>mg&#47;l vs 39 &#91;35&#59; 123&#93;<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;41&#41;&#44; CRP<span class="elsevierStyleInf">D0&#8211;D7</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;17 &#91;&#8722;72&#59; &#8722;5&#93;&#37; vs 4 &#91;&#8722;75&#59; &#43;484&#93;&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;54&#41;&#44; fibrinogen<span class="elsevierStyleInf">D0</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#46;1 &#91;4&#46;9&#59; 8&#46;1&#93;<span class="elsevierStyleHsp" style=""></span>g&#47;l vs 6&#46;1 &#91;3&#46;9&#59; 6&#46;8&#93;<span class="elsevierStyleHsp" style=""></span>g&#47;l&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;33&#41;&#44; fibrinogen<span class="elsevierStyleInf">D7</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#46;1 &#91;4&#46;3&#59; 5&#46;6&#93;<span class="elsevierStyleHsp" style=""></span>g&#47;l vs 4&#46;6 &#91;2&#46;7&#59; 5&#46;1&#93;<span class="elsevierStyleHsp" style=""></span>g&#47;l&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;23&#41;&#44; and fibrinogen<span class="elsevierStyleInf">D0&#8722;D7</span> &#40;median &#91;IQR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;26 &#91;&#8722;43&#59; &#43;9&#93; &#37; vs &#8722;28 &#91;&#8722;50&#59; &#43;15&#93;&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">According to a decision tree based on a CART algorithm&#44; a 2-nodes model combining endocan<span class="elsevierStyleInf">D0&#8211;D7</span> with static value of endocan<span class="elsevierStyleInf">D0</span> was able to correctly identify all survivors and non-survivors&#46; Indeed&#44; according to this decision tree&#44; 3&#47;3 patients with endocan<span class="elsevierStyleInf">D0&#8722;D7</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#8722;40&#37; survived&#44; while 4&#47;4 patients with endocan<span class="elsevierStyleInf">D0&#8722;D7</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>120&#37; died&#46; Regarding patients with endocan<span class="elsevierStyleInf">D0&#8722;D7</span> in the gray zone ranging between &#8722;40&#37; and &#43;120&#37;&#44; 2&#47;2 survivors had endocan<span class="elsevierStyleInf">D0</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; while 2&#47;2 non-survivors had endocan<span class="elsevierStyleInf">D0</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; These cut-offs were inferred from the CART algorithm&#44; and are not supported by any statistical test&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">We hereby report results from a pilot study exploring the potential usefulness of endocan in patients with Covid-19 related ARDS undergoing V-V ECMO&#46; Compared to survivors&#44; non-survivors from our cohort were older&#44; with greater RESP scores and longer time from invasive MV to ECMO implantation&#44; which was in line with previously published data&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Data from this pilot study suggest that among patients undergoing V-V ECMO for COVID-19 related ARDS&#44; survival on ICU discharge would be associated with significant fall in plasma endocan measured 1 week after ECMO implantation&#46; Indeed&#44; subjects experiencing marked fall in plasma endocan were all discharged alive from ICU&#44; while those with greatest rises did not survive&#46; Further&#44; it seems that patients with intermediate variations of plasma endocan might be segregated into 2 groups according to initial levels of plasma endocan&#58; subjects with baseline values lower than 5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml who survived&#44; in contrast with those exhibiting initial values higher than 5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml who were not discharged alive from ICU&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">These results are in line with previous data regarding the biological role of endocan in critically ill subjects&#46; Indeed&#44; secretion of endocan is upregulated by pro-inflammatory cytokines&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> and endocan has been widely reported as a marker of pulmonary endothelial stress&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Furthermore&#44; endocan is known as an inhibitor of leukocyte recruitment&#44; therefore regulating lung inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> Consistent data suggest that low circulating levels of endocan at the early phase of lung aggression&#44; followed by secondary rise in its plasmatic values&#44; would reflect insufficient initial protection against lung inflammation&#44; being thus associated with poor outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">5&#44;9&#8211;11</span></a> Interestingly&#44; both patients from our cohort who underwent ECMO implantation with a duration of invasive MV<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h experienced marked decreases of plasma endocan on D7&#44; respectively found at &#8722;69&#37; and &#8722;47&#37;&#46; Further studies are needed to investigate the significance of these results&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors&#8217; contributions</span><p id="par0080" class="elsevierStylePara elsevierViewall">AT&#44; SA and SBL designed the study&#46; AT wrote the manuscript&#46; FBL&#44; CA&#44; FD and YT contributed to data collection&#46; SA and SBL participated in its critical revision&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors listed on this publication have no conflict of interest&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">See <a class="elsevierStyleCrossRef" href="#sec0020">Appendix A</a> for the member of Lille Intensive Care COVID-19 group&#46;</p>"
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            "apendice" => "<p id="par0100" class="elsevierStylePara elsevierViewall">Erika Parmentier-Decrucq&#44; Julien Poissy&#44; Sylvain Dubucquoi&#44; Pauline Boddaert&#44; Morgan Caplan&#44; Julien Goutay&#44; Arthur Durand&#44; Benoit Graffin&#44; Myrtille Gaudel&#44; Charles Detollenaere&#44; Ines Gueguen&#44; Marine Van Ceunebroek&#44; Romain Tortuyaux&#44; Ouriel Saura&#44; Ahmed El Kalioubie&#44; Raphael Favory&#44; Patrick Girardie&#44; Marion Houard&#44; Emmanuelle Jaillette&#44; Mercedes Jourdain&#44; Geoffrey Ledoux&#44; Daniel Mathieu&#44; Anne Sophie Moreau&#44; Saad Nseir&#44; Thierry Onimus&#44; Sebastien Preau&#44; Laurent Robriquet&#44; Anahita Rouze&#44; Sophie Six&#44; Jerome Soquet&#44; Valentin Loobuyck&#44; Agnes Mugnier&#44; Andr&#233; Vincentelli&#46;</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Lille Intensive Care COVID-19 group"
            "identificador" => "sec0020"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Decision tree for prediction of survival on ICU discharge&#46; Endocan<span class="elsevierStyleInf">D0</span>&#44; endocan<span class="elsevierStyleInf">D7</span>&#44; endocan<span class="elsevierStyleInf">D0&#8211;D7</span>&#44; CRP<span class="elsevierStyleInf">D0</span>&#44; CRP<span class="elsevierStyleInf">D7</span>&#44; CRP<span class="elsevierStyleInf">D0&#8211;D7</span>&#44; fibrinogen<span class="elsevierStyleInf">D0</span>&#44; fibrinogen<span class="elsevierStyleInf">D7</span> and fibrinogen<span class="elsevierStyleInf">D0&#8211;D7</span> were tested as covariates for survival in ICU prediction model&#46; D0&#58; day of ECMO implantation&#46; D7&#58; day 7 following ECMO implantation&#59; D0&#8211;D7&#58; variation between D0 and D7&#44; calculated as &#40;value on D7<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>value on D0&#41;&#47;value on D0&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Data are presented as number &#40;&#37;&#41; or median &#91;IQR&#93;&#46; BMI&#58; Body Mass Index&#59; COPD&#58; Chronic Obstructive Pulmonary Disease&#59; D0&#58; day of ECMO implantation&#59; D7&#58; day 7 following ECMO implantation&#59; ECMO&#58; Extra Corporeal Membrane Oxygenation&#59; ICU&#58; Intensive Care Unit&#59; MV&#58; Mechanical Ventilation&#59; RESP&#58; Respiratory Extracorporeal Membrane Oxygenation Survival Prediction&#59; RPM&#58; Rounds Per Minute&#59; SOFA&#58; Sequential Organ Failure Assessment&#59; VAP&#58; Ventilator Associated Pneumonia&#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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Survivors</th><th class="td" title="\n
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                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\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">Yes &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" 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
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Demographical data</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sex&#44; male&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">4 &#40;80&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;83&#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
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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="elsevierStyleHsp" style=""></span>Age&#44; years&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">48 &#91;33&#59; 62&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">57 &#40;48&#59; 63&#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
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                  \t\t\t\t">0&#46;43&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>BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</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">37 &#91;32&#59; 40&#93;&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">34 &#91;28&#59; 42&#93;&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
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                  \t\t\t\t">0&#46;66&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">Severity score on ECMO implantation</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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SOFA&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">9 &#91;6&#59; 13&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">9 &#91;8&#59; 11&#93;&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;93&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>RESP&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 &#91;&#8722;6&#59; 2&#46;5&#93;&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">&#8722;4 &#91;&#8722;6&#59; &#8722;2&#93;&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;43&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">Comorbidities</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>Diabetes mellitus&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;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">1 &#40;17&#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;55&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>Chronic respiratory failure&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">0 &#40;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">0 &#40;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;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;33&#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;45&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>Coronary disease&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;20&#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;17&#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&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>Immunocompromised patients&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">0 &#40;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">0 &#40;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&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">Characteristics of ECMO</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>Time from onset of symptoms to ECMO&#44; days&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">21 &#91;10&#46;5&#59; 33&#46;5&#93;&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">18 &#91;13&#46;5&#59; 24&#93;&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;71&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>Time from ICU admission to ECMO&#44; days&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">13 &#91;6&#59; 28&#93;&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 &#91;6&#59; 17&#93;&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;58&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>Time from invasive MV to ECMO&#44; days&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 &#91;0&#46;5&#59; 20&#93;&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&#46;5 &#91;3&#59; 13&#93;&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;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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>Invasive MV initiated on the day of ECMO implantation and maintained for less than 24<span class="elsevierStyleHsp" style=""></span>h&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;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">0 &#40;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;18&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>RPM on day of ECMO implantation&#44; &#215;1000&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&#46;9 &#91;2&#46;5&#59; 4&#46;6&#93;&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&#46;7 &#91;3&#46;4&#59; 4&#46;1&#93;&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;93&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>ECMO blood flow on day of ECMO implantation&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">4&#46;8 &#91;3&#46;9&#59; 7&#46;1&#93;&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;2 &#91;4&#46;6&#59; 6&#46;3&#93;&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;85&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">Outcomes</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>Duration of ECMO&#44; days&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">18 &#91;12&#59; 34&#93;&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">27 &#91;19&#59; 33&#93;&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;2&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>Length of stay in hospital&#44; days&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">53 &#91;35&#59; 79&#93;&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">36 &#91;31&#59; 49&#93;&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;31&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>Length of invasive MV&#44; days&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">13 &#91;5&#59; 43&#93;&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">26 &#91;34&#59; 48&#46;5&#93;&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;25&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
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Vol. 47. Issue 1.
Pages 51-54 (January 2023)
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Vol. 47. Issue 1.
Pages 51-54 (January 2023)
Scientific Letter
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Assessment of plasma endocan for the prediction of mortality in COVID-19 patients undergoing veno-venous ECMO: A pilot study
Evaluación del endocan para la predicción de la mortalidad en pacientes COVID-19 sometidos a ECMO veno-venosa: un estudio piloto
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C. Levya,b,c,e, N. Dognona,b,c,e, S. Normandina,b,c,e, T. Duburcqa,b,c,e, A. Gaudeta,b,c,d,e,
Corresponding author
alexandre.gaudet@chru-lille.fr

Corresponding author.
, Lille Intensive Care COVID-19 group 1
a Department of Intensive Care Medicine, Critical Care Center, CHU Lille, F-59000 Lille, France
b University of Lille, U995-LIRIC-Lille Inflammation Research International Center, Lille, France
c CHU Lille, Immunology Institute, F-59000 Lille, France
d University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Centre d’Infection et d’Immunité de Lille, F-59000 Lille, France
e University Lille, Inserm, U1285, CNRS, UMR 8576 - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France
Lille Intensive Care COVID-19 group
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Dear Editor:

Patients with severe COVID-19 related acute respiratory distress syndrome (ARDS) may benefit from V-V ECMO support. However, this technique remains associated with frequent complications and high mortality.1 The early identification of patients with V-V ECMO who are likely to survive on ICU discharge therefore seems of major interest.

Endocan is a circulating proteoglycan secreted by the pulmonary vasculature under inflammatory conditions such as ARDS.2 Recent data suggest that monitoring of blood endocan during 1st week following intensive care unit (ICU) admission may correlate with the severity of ARDS in Covid-19.3

Thus, we aimed in this study to assess whether plasma endocan measurements performed on the day of V-V ECMO implantation (D0) and repeated seven days later (D7) may be effective in predicting mortality on ICU discharge.

This study was conducted in a 50-bed mixed ICU, from October 2020 to June 2021. We included all consecutive COVID-19 patients undergoing V-V ECMO implantation and with available results of plasma endocan measured on day of ECMO implantation.

Endocan was measured weekly on EDTA plasma in the central laboratory of our hospital using the ENDOMARK H1 ELISA kit (Biothelis, France) in COVID-19 patients admitted in our ICU as part as the routine assessment of prognosis in ARDS,4–6 along with CRP and fibrinogen. This research was examined by our local IRB, and approved under the number HP 22/01. Because of the retrospective observational design, written informed consent was not required.

Patients’ characteristics were obtained at D0. We also retrospectively collected values on D0 and D7 for plasma endocan (endocanD0 and endocanD7), CRP (CRPD0 and CRPD7) and fibrinogen (fibrinogenD0 and fibrinogenD7). Variations between D0 and D7 were respectively calculated for endocan (endocanD0–D7), CRP (CRPD0–D7) and fibrinogen (fibrinogenD0–D7) as following: (value on D7value on D0)/value on D0.

Categorical variables were expressed as numbers (percentages) and compared using Fisher's exact test, given small sample sizes. Skewed continuous variables were presented as median (interquartile range) and compared using Mann-Whitney U test.

Decision tree based on CART algorithm was generated using the rpart R package with default settings, using endocanD0, endocanD7, endocanD0–D7, CRPD0, CRPD7, CRPD0–D7, fibrinogenD0, fibrinogenD7 and fibrinogenD0–D7 as covariates.

All statistical tests were two-tailed, and p values <0.05 were considered statistically significant. Statistical analysis was performed using R version 3.6 (R foundation for statistical analysis, Austria).

Eleven patients undergoing V-V ECMO implantation for COVID-19 related ARDS were included in this study, of whom 5 (45%) were discharged alive from ICU. All patients underwent invasive mechanical ventilation (MV) during their stay in ICU, although invasive MV was initiated right before ECMO implantation and maintained less than 24h for 2 patients from the survivors group.

Compared to survivors, non-survivors had higher endocanD7 (median [IQR]=12.9 [6.1; 19]ng/ml vs 4.3 [3.9; 5.6]ng/ml; p=0.017), and greater increase in endocanD0–D7 (median [IQR]=+208 [−1; +612] % vs −49 [−65; +52]%; p=0.03). Conversely, no difference was found between non-survivors and survivors for endocanD0 (median [IQR]=4.7 [3; 5.7]ng/ml vs 7.9 [3.8; 12.2]ng/ml; p=0.25), CRPD0 (median [IQR]=94 [68; 200]mg/l vs 118 [26; 150]mg/l; p=0.66), CRPD7 (median [IQR]=68 [50; 77]mg/l vs 39 [35; 123]mg/l; p=0.41), CRPD0–D7 (median [IQR]=−17 [−72; −5]% vs 4 [−75; +484]%; p=0.54), fibrinogenD0 (median [IQR]=7.1 [4.9; 8.1]g/l vs 6.1 [3.9; 6.8]g/l; p=0.33), fibrinogenD7 (median [IQR]=5.1 [4.3; 5.6]g/l vs 4.6 [2.7; 5.1]g/l; p=0.23), and fibrinogenD0−D7 (median [IQR]=−26 [−43; +9] % vs −28 [−50; +15]%; p=1) (Table 1).

Table 1.

Characteristics of patients and biomarkers in survivors and non-survivors.

  Survivorsp value 
  Yes (n=5)  No (n=6)   
Demographical data
Sex, male  4 (80%)  5 (83%) 
Age, years  48 [33; 62]  57 (48; 63)  0.43 
BMI, kg/m2  37 [32; 40]  34 [28; 42]  0.66 
Severity score on ECMO implantation
SOFA  9 [6; 13]  9 [8; 11]  0.93 
RESP  1 [−6; 2.5]  −4 [−6; −2]  0.43 
Comorbidities
Diabetes mellitus  2 (40%)  1 (17%)  0.55 
Chronic respiratory failure  0 (0%)  0 (0%) 
COPD  0 (0%)  2 (33%)  0.45 
Coronary disease  1 (20%)  1 (17%) 
Immunocompromised patients  0 (0%)  0 (0%) 
Characteristics of ECMO
Time from onset of symptoms to ECMO, days  21 [10.5; 33.5]  18 [13.5; 24]  0.71 
Time from ICU admission to ECMO, days  13 [6; 28]  11 [6; 17]  0.58 
Time from invasive MV to ECMO, days  3 [0.5; 20]  9.5 [3; 13]  0.41 
Invasive MV initiated on the day of ECMO implantation and maintained for less than 242 (40%)  0 (0%)  0.18 
RPM on day of ECMO implantation, ×1000  3.9 [2.5; 4.6]  3.7 [3.4; 4.1]  0.93 
ECMO blood flow on day of ECMO implantation  4.8 [3.9; 7.1]  5.2 [4.6; 6.3]  0.85 
Outcomes
Duration of ECMO, days  18 [12; 34]  27 [19; 33]  0.2 
Length of stay in hospital, days  53 [35; 79]  36 [31; 49]  0.31 
Length of invasive MV, days  13 [5; 43]  26 [34; 48.5]  0.25 
Biomarkers
Endocan at D0, ng/ml  7.9 [3.8; 12.2]  4.7 [3; 5.7]  0.25 
Endocan at D7, ng/ml  4.3 [3.9; 5.6]  12.9 [6.1; 19]  0.017 
Variation of endocan between D0 and D7, %  −49 [−65; 52]  208 [−1; 612]  0.03 
CRP at D0, mg/l  118 [26; 150]  94 [68; 200]  0.66 
CRP at D7, mg/l  39 [35; 123]  68 [50; 77]  0.41 
Variation of CRP between D0 and D7, %  4 [−75; 484]  −17 [−72; −5]  0.54 
Fibrinogen at D0, g/l  6.1 [3.9; 6.8]  7.1 [4.9; 8.1]  0.33 
Fibrinogen at D7, g/l  4.6 [2.7; 5.1]  5.1 [4.3; 5.6]  0.23 
Variation of fibrinogen between D0 and D7, %  −28 [−50; 15]  −26 [−43; 9] 

Data are presented as number (%) or median [IQR]. BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; D0: day of ECMO implantation; D7: day 7 following ECMO implantation; ECMO: Extra Corporeal Membrane Oxygenation; ICU: Intensive Care Unit; MV: Mechanical Ventilation; RESP: Respiratory Extracorporeal Membrane Oxygenation Survival Prediction; RPM: Rounds Per Minute; SOFA: Sequential Organ Failure Assessment; VAP: Ventilator Associated Pneumonia.

According to a decision tree based on a CART algorithm, a 2-nodes model combining endocanD0–D7 with static value of endocanD0 was able to correctly identify all survivors and non-survivors. Indeed, according to this decision tree, 3/3 patients with endocanD0−D7<−40% survived, while 4/4 patients with endocanD0−D7>+120% died. Regarding patients with endocanD0−D7 in the gray zone ranging between −40% and +120%, 2/2 survivors had endocanD0<5ng/ml, while 2/2 non-survivors had endocanD0>5ng/ml (Fig. 1). These cut-offs were inferred from the CART algorithm, and are not supported by any statistical test.

Figure 1.

Decision tree for prediction of survival on ICU discharge. EndocanD0, endocanD7, endocanD0–D7, CRPD0, CRPD7, CRPD0–D7, fibrinogenD0, fibrinogenD7 and fibrinogenD0–D7 were tested as covariates for survival in ICU prediction model. D0: day of ECMO implantation. D7: day 7 following ECMO implantation; D0–D7: variation between D0 and D7, calculated as (value on D7value on D0)/value on D0.

(0.19MB).

We hereby report results from a pilot study exploring the potential usefulness of endocan in patients with Covid-19 related ARDS undergoing V-V ECMO. Compared to survivors, non-survivors from our cohort were older, with greater RESP scores and longer time from invasive MV to ECMO implantation, which was in line with previously published data.

Data from this pilot study suggest that among patients undergoing V-V ECMO for COVID-19 related ARDS, survival on ICU discharge would be associated with significant fall in plasma endocan measured 1 week after ECMO implantation. Indeed, subjects experiencing marked fall in plasma endocan were all discharged alive from ICU, while those with greatest rises did not survive. Further, it seems that patients with intermediate variations of plasma endocan might be segregated into 2 groups according to initial levels of plasma endocan: subjects with baseline values lower than 5ng/ml who survived, in contrast with those exhibiting initial values higher than 5ng/ml who were not discharged alive from ICU.

These results are in line with previous data regarding the biological role of endocan in critically ill subjects. Indeed, secretion of endocan is upregulated by pro-inflammatory cytokines,7 and endocan has been widely reported as a marker of pulmonary endothelial stress.2 Furthermore, endocan is known as an inhibitor of leukocyte recruitment, therefore regulating lung inflammation.8 Consistent data suggest that low circulating levels of endocan at the early phase of lung aggression, followed by secondary rise in its plasmatic values, would reflect insufficient initial protection against lung inflammation, being thus associated with poor outcomes.5,9–11 Interestingly, both patients from our cohort who underwent ECMO implantation with a duration of invasive MV<24h experienced marked decreases of plasma endocan on D7, respectively found at −69% and −47%. Further studies are needed to investigate the significance of these results.

Authors’ contributions

AT, SA and SBL designed the study. AT wrote the manuscript. FBL, CA, FD and YT contributed to data collection. SA and SBL participated in its critical revision. All authors read and approved the final manuscript.

Funding

None declared.

Conflict of interest

The authors listed on this publication have no conflict of interest.

Acknowledgements

None.

Appendix A
Lille Intensive Care COVID-19 group

Erika Parmentier-Decrucq, Julien Poissy, Sylvain Dubucquoi, Pauline Boddaert, Morgan Caplan, Julien Goutay, Arthur Durand, Benoit Graffin, Myrtille Gaudel, Charles Detollenaere, Ines Gueguen, Marine Van Ceunebroek, Romain Tortuyaux, Ouriel Saura, Ahmed El Kalioubie, Raphael Favory, Patrick Girardie, Marion Houard, Emmanuelle Jaillette, Mercedes Jourdain, Geoffrey Ledoux, Daniel Mathieu, Anne Sophie Moreau, Saad Nseir, Thierry Onimus, Sebastien Preau, Laurent Robriquet, Anahita Rouze, Sophie Six, Jerome Soquet, Valentin Loobuyck, Agnes Mugnier, André Vincentelli.

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N. De Freitas Caires, A. Gaudet, L. Portier, A. Tsicopoulos, D. Mathieu, P. Lassalle.
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T. Pascreau, C. Tcherakian, B. Zuber, E. Farfour, M. Vasse, P. Lassalle.
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I. Tsangaris, A. Tsantes, E. Vrigkou, P. Kopterides, A. Pelekanou, K. Zerva, et al.
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A. Gaudet, E. Parmentier, S. Dubucquoi, J. Poissy, T. Duburcq, P. Lassalle, et al.
Low endocan levels are predictive of Acute Respiratory Distress Syndrome in severe sepsis and septic shock.
J Crit Care, 47 (2018), pp. 121-126
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A. Ioakeimidou, E. Pagalou, M. Kontogiorgi, E. Antoniadou, K. Kaziani, K. Psaroulis, et al.
Increase of circulating endocan over sepsis follow-up is associated with progression into organ dysfunction.
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A. Gaudet, E. Parmentier, S. Dubucquoi, J. Poissy, T. Duburcq, L. Portier, et al.
The complex kinetics of blood endocan during the time course of sepsis and acute respiratory distress syndrome.
Crit Care Lond Engl, 23 (2019), pp. 86

See Appendix A for the member of Lille Intensive Care COVID-19 group.

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