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which can develop into acute respiratory distress syndrome &#40;ARDS&#41;&#44; metabolic acidosis&#44; and even liver&#44; kidney or heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">3</span></a> Comorbidities such as hypertension &#40;HT&#41;&#44; diabetes mellitus &#40;DM&#41;&#44; coronary heart disease &#40;CHD&#41;&#44; cerebrovascular disease&#44; chronic obstructive pulmonary disease&#44; and kidney disorders are risk factor for disease severity and fatality&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">4</span></a> The risk for COVID-19 death in patients with chronic kidney disease &#40;CKD&#41; is greater than the risk for COVID-19 death in patients with DM and CHD and the risk increases as the eGFR decreases&#44; with the highest risk in patients on renal replacement therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">5</span></a> Increased risk of infectious complications and more adverse outcomes in CKD patients can be attributed to older age&#44; additional comorbidities&#44; pro-inflammatory state and the alterations of the innate and adaptive immune response associated with uremia&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">6&#8211;9</span></a> Therefore&#44; early detection and accurate evaluation of the severity of SARS-CoV-2 infection in CKD patients may facilitate appropriate clinical decision making&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although&#44; primarily it was documented as a respiratory tract infection&#44; COVID-19 is a systemic disease with a significant impact on the hematopoietic and immune system&#46; The alterations in circulating blood cells related with inflammation and immune status of COVID-19 positive patients have been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">10</span></a> Hematological parameters&#44; such as white blood cells and their subpopulations&#44; red cell distribution width&#44; mean platelet volume&#44; and platelet&#44; and combined ratios of these parameters such as neutrophil-to-lymphocyte ratio &#40;NLR&#41;&#44; and platelet-to-lymphocyte ratio &#40;PLR&#41; are widely used for risk stratification&#44; diagnosis&#44; and determination of prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">10&#44;11</span></a> Systemic immune inflammation index &#40;SII&#41; based on peripheral lymphocyte&#44; neutrophil and platelet counts has been considered as a better index to reflect the local immune response and systemic inflammation&#46; Recently&#44; it was reported that the elevated SII was a prognostic indicator in predicting in-hospital mortality of COVID 19&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">To date&#44; few studies have assessed the prognostic capacity of blood cell count derived inflammation indexes in CKD patients&#46; Therefore&#44; we aimed to investigate changes in hematological parameters and indexes in CKD patients with SARS-CoV-2 infection&#44; in comparison with patients without CKD and to evaluate their utility as prognostic markers of disease mortality in CKD patients&#46; To the best of our knowledge&#44; this is the first time that these markers have been investigated simultaneously in a single study conducted on CKD patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and participants</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a retrospective study performed on COVID-19 patients with CKD&#44; including moderate and advanced CKD patients &#40;stage 3&#8211;5 CKD&#41; and maintenance hemodialysis &#40;HD&#41; patients&#46; CKD patients matched one to one to age and sex matched COVID-19 patients without biochemical and&#47;or radiological evidence of kidney disease&#46; All included patients were symptomatic and had either a positive result in real-time reverse transcriptase-polymerase chain reaction &#40;RT-PCR&#41; analysis of nasal and pharyngeal swab samples or chest computerized tomography findings compatible with COVID 19&#46; Exclusion criteria were acute kidney injury at admission&#44; presence of hematological malignancies and concurrent chemotherapy or immunosuppressive treatment&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Data collection and definitions</span><p id="par0025" class="elsevierStylePara elsevierViewall">Data were obtained from electronic medical records&#44; including demographics&#44; co-morbid diseases&#44; clinical features&#44; laboratory findings at admission&#44; length of hospitalization&#44; and outcomes&#46; Severity score of chest computerized tomography &#40;CT&#41; proposed by Pan et al&#46; were also recorded&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">13</span></a> Routine laboratory examination consisted of complete blood count analysis including hemoglobin&#44; leucocytes&#44; platelets&#44; absolute neutrophil and lymphocyte counts as well as serum biochemical tests &#40;including renal and liver function&#44; lactate dehydrogenase&#41;&#44; D-dimer&#44; fibrinogen&#44; ferritin&#44; C-reactive protein &#40;CRP&#41; and procalcitonin &#40;PCT&#41;&#46; Blood cell count derived inflammation indexes&#59; NLR &#40;Neutrophil count&#47;Lymphocyte count<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#37;&#41;&#44; PLR &#40;Platelet count&#47;Lymphocyte count<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#37;&#41;&#44; SII &#40;platelet counts<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>neutrophil counts&#47;lymphocyte counts&#41;&#44; and lymphocyte-to-CRP ratio &#40;LCR&#41; &#40;lymphocyte count&#47;CRP value&#41; were calculated&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Severe COVID-19 was defined as patients that met any of following criteria&#58; respiratory frequency more than 30&#47;minute&#44; oxygen saturation under 92&#37; and&#47;or the partial pressure of arterial oxygen and the inspiratory oxygen fraction &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span>&#41; ratio less than 300&#46; Intensive care need of those with severe disease were noted&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The primary endpoint was all-cause mortality&#46; We assessed in-hospital mortality defined by survival status at discharge&#46; All parameters and outcomes were compared between patients with CKD and without CKD&#46; Also&#44; blood cell derived inflammation indexes were compared between CKD patients who died and recovered&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Approval from the local ethics committee was obtained for this study &#40;confirmation date and number&#58; February 15&#44; 2020&#47;2021-04-10&#41;&#46; This study was conducted in accordance with the principles of the Declaration of Helsinki&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistics</span><p id="par0045" class="elsevierStylePara elsevierViewall">Statistical analyses were performed by NCSS &#40;Number Cruncher Statistical System&#41; with statistical significance set at two-tailed <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; Categorical variables were described as the total number and percentages and continuous variables were described as median interquartile range &#40;IQR&#41;&#46; A Kolmogorov&#8211;Smirnov test and Shapiro&#8211;Wilk test were used to evaluate the distribution of the sample data&#46; Qualitative data were compared by using Pearson Chi-Square test and Fisher&#8211;Freeman&#8211;Halton Exact test&#44; as appropriate&#46; Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test was used comparison of data that were not compatible with normal distribution&#46; A receiver operating characteristic &#40;ROC&#41; curve analysis was adopted to determine the optimal cut-off point for NLR&#44; PLR&#44; LCR and SII with respect to survival&#46; Forward logistic regression analysis was performed to identify variables associated with in-hospital mortality in terms of odds ratio and 95&#37; confidence intervals&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Baseline characteristics</span><p id="par0050" class="elsevierStylePara elsevierViewall">A total of 93 patients with CKD and 93 age and sex matched patients without CKD were included in the study&#46; Among the CKD group&#44; 38 patients &#40;40&#46;8&#37;&#41; underwent maintenance HD and 55 patients &#40;59&#46;2&#37;&#41; suffered stage 3&#8211;5 CKD&#46; A comparison of the demographic characteristics and clinical findings between non-CKD and CKD patients are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The median age of entire cohort was 70 years &#40;25&#8211;92 years&#41; and 50&#46;5&#37; were male&#46; The age of nondialysis CKD patients were significantly higher than those of HD patients &#91;72 &#40;25&#8211;92&#41; years vs 62 &#40;25&#8211;88&#41; years&#44; respectively&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93;&#46; Patients with CKD had higher prevalence rate of HT&#44; DM&#44; CHD&#44; and chronic obstructive pulmonary diseases compared to the patients without CKD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#44; respectively&#41;&#46; Notably&#44; 64&#46;5&#37; of non-CKD patients with COVID-19 did not have any comorbidity&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Dry cough and dyspnea were the most common symptoms at presentation in both groups but non-CKD patients were more likely to present with sore-throat &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; In subgroup analysis&#44; fever was more frequently detected in patients on maintenance HD compared to CKD patients not on-dialysis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; 48&#46;9&#37; of the patients was diagnosed by a positive RT-PCR and the others had symptoms and chest CT findings compatible with COVID 19&#46; There is no significant difference between either CKD patients and non-CKD patients or CKD subgroups in terms of RT-PCR positivity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;122&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;388&#44; respectively&#41;&#46; Compared with subjects in non-CKD group&#44; those in CKD group had higher rate of severe chest CT score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#41;&#46; However&#44; no difference was observed between CKD subgroups in terms of chest CT severity&#46; CKD patients had higher risk of severe disease&#44; and mortality compared to non-CKD patients &#40;72&#37; vs 50&#46;5&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; 36&#46;6&#37; vs 10&#46;8&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41;&#46; As expected&#44; the rates of ICU admission and the length of hospitalization were higher in CKD group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41;&#46; In subgroup analysis&#44; mortality rate was higher in patients with the non-dialysis CKD compared to the patients on HD but these results did not reach statistical significance &#40;40&#37; vs 31&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;542&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Laboratory results</span><p id="par0060" class="elsevierStylePara elsevierViewall">Laboratory findings at admission are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; We found that the inflammatory status was significantly elevated in CKD patients compared to non-CKD patients&#46; In this regard&#44; significantly higher levels of leucocytes&#44; neutrophils&#44; NLR&#44; SII&#44; CRP&#44; and PCT were observed in patients with CKD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;018&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41;&#46; On the contrary&#44; lymphocyte counts and LCR were much lower in CKD group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41;&#46; As expected&#44; hemoglobin level was lower in patients with CKD compared to non-CKD patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Notably&#44; serum levels of D-dimer and ferritin which have been associated with increased disease severity and higher mortality in patients with COVID-19&#44; were significantly higher in CKD group than in those without CKD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Since the significant differences in levels of the inflammatory markers were observed between non-CKD patients and CKD patients&#44; a subgroup analysis was performed to identify hematological parameters that could differentially affect mortality among patients with CKD&#46; CKD patients died had higher values of NLR &#40;13&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;65 vs&#46; 4&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;81&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; PLR &#40;324&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>292&#46;67 vs&#46; 174&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>81&#46;68&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41; and SII &#40;2403&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1999&#46;46 vs&#46; 831&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>517&#46;02&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and lower level of LCR &#40;27&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>50&#46;34 vs 70&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>145&#46;85&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; compared to those recovered&#46; There was no statistically significant difference in PLR levels between patients with CKD and those without CKD&#46; However&#44; among patients with CKD&#44; significantly higher level of PLR was observed in CKD patients who died&#44; in comparison to CKD patients who recovered &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Given that statistically significant difference was found between dead and recovered CKD patients in term of hematological parameters &#40;NLR&#44; PLR&#44; LCR and SII&#41;&#44; the optimal cutoff values were identified by ROC analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The cut off point was 5&#46;1 &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;830&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; CI&#58;0&#46;744&#8211;0&#46;916&#41;&#44; 1180&#46;5 &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;811&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; CI&#58;0&#46;719&#8211;0&#46;904&#41;&#44; 187&#46;5 &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;664&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#59; CI&#58;0&#46;540&#8211;0&#46;787&#41;&#44; 9 &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;712&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; CI&#58;0&#46;596&#8211;0&#46;828&#41; for NLR&#44; SII&#44; PLR&#44; and LCR&#44; respectively&#46; The ROC curve of NLR and SII gave us the best prediction for distinguishing patients with higher risk of death at an earlier stage&#46; Among these parameters&#44; the smallest area belonged to PLR&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">To identify the factors that may affect mortality rate of COVID-19 among CKD patients&#44; we obtained the crude odds ratio &#40;OR&#41; after conducting the logistic regression analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46; Step-wise variable selection led to a model with age &#40;&#62;72 years&#41; &#40;1051 &#91;95&#37; CI&#58; 0&#46;998&#8211;1&#46;108&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;06&#41;&#44; NLR &#40;&#8805;5&#46;1&#41; &#40;3&#46;148 &#91;95&#37; CI&#58; 0&#46;810&#8211;12&#46;234&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;098&#41;&#44; SII &#40;&#8805;1180&#46;5&#41; &#40;4&#46;419 &#91;95&#37; CI&#58; 1&#46;303&#8211;14&#46;992&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;017&#41; and LCR &#40;&#8804;9&#41; &#40;4&#46;984 &#91;95&#37; CI&#58; 1&#46;466&#8211;16&#46;945&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; as predictors for survival&#46; Conversely&#44; gender&#44; comorbidities &#40;DM&#44; HT&#44; CHD&#41; and PLR did not correlate with the survival outcome&#46; Our study demonstrated that NLR&#44; SII and LCR can be used as a predictor of mortality among CKD patients with COVID 19&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">This study is important because&#44; it is the first study to investigate association between SII and disease mortality in CKD patients with SARS-CoV-2 infection&#46; Recently&#44; SII has been shown to be a potential indicator of survival in COVID 19&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">12</span></a> We believe our study may extend the relevance of SII to predicting in-hospital mortality of COVID-19&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Viral nucleic acid test by RT-PCR assay plays a vital role in diagnosis and isolation of individuals with COVID 19&#46; However&#44; lower sensitivity&#44; insufficient stability&#44; and long processing time were detrimental to the control of the pandemic&#46; In the current study&#44; nearly half of the study population were diagnosed based on RT-PCR test&#46; RT-PCR negative patients were only included if the clinical and CT findings were strongly suggestive of COVID 19&#46; Since the previous studies demonstrated that the sensitivity of CT for diagnosis of COVID-19 infection was higher compared with RT-PCR sensitivity&#44;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">14&#44;15</span></a> chest CT was used at the first-line evaluation of the patients with a high clinical probability of COVID-19 pneumonia for rapid diagnosis&#44; isolation and administration of appropriate treatment&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">To date&#44; several studies have reported worse clinical outcomes&#44; including more ICU admissions and higher mortality rate among CKD patients with COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">16&#44;17</span></a> In agreement with previous reports&#44; the current study showed that mortality was significantly higher in CKD patients than in those without CKD &#40;36&#46;6 vs 10&#46;8&#37;&#41;&#46; This may be explained by a pro-inflammatory state with functional defects in the natural and adaptive immunity&#46; Although the highest mortality rate was observed in non-dialysis CKD group compared to HD group&#44; it didn&#8217;t reach statistical significance&#46; This difference may be attributed to older age of nondialysis-CKD patients&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Evidence from the global outbreak showed that individuals with older age&#44; male gender and CKD associated morbidities such as HT&#44; DM and CHD are at much greater risk of dying from COVID 19&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">18&#8211;20</span></a> On the contrary&#44; the distribution of risk factors for COVID-19 mortality was differed in patients with CKD from the general population&#46; Previous studies have suggested that some commonly reported comorbidities including HT&#44; DM&#44; chronic lung disease and CHD had no influence on mortality among CKD patients with COVID 19&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">21&#8211;23</span></a> On the other hand&#44; some studies conducted on hemodialysis patients with COVID 19 reported that only heart failure&#44; CHD and lung disease were risk factors for worse outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">24</span></a> In agreement with COVID-19 database analysis of Turkish Society of Nephrology and European Renal Association&#44;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">21&#44;22</span></a> we found that male sex&#44; HT&#44; CHD and DM do not confer an independent increased risk of mortality&#46; There were conflicting reports whether CKD is a risk factor for death in COVID 19&#46; While initial reports failed to assess the impact of CKD on severity of COVID 19&#44; OpenSAFELY project showed that the top three risk categories for death from COVID 19 were&#44; in order from the highest to the lowest risk&#44; dialysis patients &#40;aHR 3&#46;69&#41;&#44; transplant recipients &#40;aHR 3&#46;53&#41; and CKD &#40;aHR 2&#46;52 for patients with eGFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; CKD Grade 4&#8211;5&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">5</span></a> This finding emphasize the immunosuppressive nature of the uremic milieu in CKD patients&#44; resulting in increased vulnerability to hyperinflammation and cytokine storm upon SARS-CoV-2 infection&#44; eventually severe disease and death&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Cytokine storm has been linked to severity in COVID 19&#46; A rapid and coordinated innate immune response is the first line of defense mechanism against viral infections&#46; However&#44; when the immune response is dysregulated&#44; it leads to excessive systemic inflammation&#44; and even cause death&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">25</span></a> Previous researches on non-CKD patients with COVID-19 proposed several biomarkers for severe disease&#44; including lymphopenia and increased levels of CRP&#44; LDH&#44; PCT and cytokines &#40;IL-6&#44; IL-10 and tumor necrosis factor&#41;&#44; emphasizing the role of the immuno-inflammatory responses in the pathogenesis and progression of COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">26&#44;27</span></a> Similarly&#44; in our cohort&#44; higher leukocyte and neutrophil count as well as lower lymphocyte count were observed in CKD patients who died&#46; Blood cell count-derived inflammation indexes&#44; including NLR and PLR have been reported to be a more sensitive biomarker of inflammation than the individual levels of blood cell line&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">28</span></a> Up to now&#44; the potentials of blood cell count-derived inflammation indexes as a predictor of mortality in CKD patients with COVID 19 have been assessed in a few reports&#46; Davila-Collado et all have analyzed the impact of NLR&#44; monocyte to lymphocyte ratio &#40;MLR&#41;&#44; and PLR on 37 CKD patients with SARS-CoV-2 infection and noticed that only an elevation in MLR was consistently correlated with increased mortality among patients with CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">29</span></a> In a report of 10 maintenance HD patients&#44; NLR and LCR were associated with the severe form and mortality of COVID 19&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">30</span></a> Another study conducting on 62 HD patients showed that higher NLR was associated with the most severe form of COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">31</span></a> In line with the literature&#44; mortality was associated with a lower LCR but higher NLR in our study group&#46; It was also remarkable that SII was significantly higher in CKD cases developing mortality&#46; To the best of our knowledge&#44; to date&#44; no study has been carried out to evaluate the feasibility of SII to assess COVID-19 disease mortality in CKD patients&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">As a new systemic inflammation indicator&#44; SII&#44; based on lymphocyte&#44; neutrophile&#44; and platelet counts has been reported as prognostic factor in COVID 19&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">12</span></a> Utility of SII to identify COVID 19 patients at higher risk of death is given by the differential roles that lymphocyte&#44; neutrophil and platelet playing during immune response&#46; Lymphocytes are known to be responsible for eliminating virus infected cells&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">32</span></a> Although neutrophils are the most important cellular defense against infections&#44; it is not clear whether neutrophils play a role in anti-viral defense in viral pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">33</span></a> However&#44; neutrophil recruitment into the lungs has been observed only in pneumonia patients with ARDS&#44; support that neutrophils play a role defending the airway epithelium in the presence of severe SARS-CoV-2 virus infection&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">33</span></a> Platelets contribute to hemostasis and also participate in the inflammation and host defense&#46; Decreased platelet production and increased consumption due to diffuse alveolar damage are thought to cause thrombocytopenia in COVID-19 patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">34&#44;35</span></a> In consideration of these factors&#44; SII might be better able to reflect the balance of host inflammatory and immune status in COVID 19&#46; The current study revealed that the discriminative performance of SII and NLR were the highest among the hematological indexes evaluated&#44; in predicting disease mortality&#46; There seems to be some evidence to indicate that SII was not inferior to NLR which is widely used to predict the severity of COVID-19 disease&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">36</span></a> Our results are in line with recently published studies identifying the value of SII to predict the risk of in-hospital mortality of COVID-19 patients and confirms the reliability of SII as a powerful predictor of survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">37&#44;38</span></a> As SII is based on the results of complete blood count analysis&#44; it is inexpensive&#44; more simple&#44; easily applicable and more suitable for widespread use&#46; Quantification of SII at admission would guide the physician for early identification and timely management of the patients with worse survival&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In addition&#44; we found that the AUC was significant with the PLR and LCR&#46; Qu R&#46; et al&#46; reported that the PLR may predict mortality in COVID-19 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">39</span></a> Although PLR&#44; which increase thrombosis development and responsible for the cytokine and chemokine cascade&#44; was significantly higher in CKD patients developing mortality&#44; it didn&#8217;t predict disease mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">40</span></a> It can be explained by the relatively low number of the patients&#46; As such&#44; Fois et al&#46; observed higher value of PLR in deceased patients with COVID 19&#46; However&#44; after adjusting for confounders&#44; they found a borderline significance between worse survival and PLR &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">37</span></a> Since the SARS-CoV-2 viral load has been highly correlated with lymphocyte count and CRP value&#44; LCR can help to predict disease severity&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">41</span></a> In the current study LCR showed a reasonable ability to predict disease mortality&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">There were several limitations to our study that warrant consideration&#46; First&#44; it was a retrospective&#44; single-center study of CKD patients with COVID 19 admitted to the hospital&#46; Large- scale multicenter prospective studies should be performed to support our findings&#46; Second&#44; patients without a positive RT-PCR were also included in the study but all RT-PCR-negative patients had clinical features and chest CT findings strongly suggestive of COVID-19&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0115" class="elsevierStylePara elsevierViewall">We report for the first time that SII is able to distinguish COVID-19 infected CKD patients of worse survival and it is as powerful as NLR in this regard&#46; Since SII can be easily quantified from blood sample data&#44; it can provide significant benefits for early identification and timely management of CKD patients with worse survival&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0120" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interests</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and aim</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients with chronic kidney disease &#40;CKD&#41; are susceptible to SARS-CoV-2 infection and more prone to develop severe disease&#46; It is important to know predictors of poor outcomes to optimize the strategies of care&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">93 patients with CKD and 93 age-sex matched patients without CKD were included in the study&#46; Data on demographic&#44; clinical features&#44; hematological indices and outcomes were noted and compared between the groups&#46; Neutrophile to lymphocyte ratio &#40;NLR&#41;&#44; platelet-to-lymphocyte ratio &#40;PLR&#41;&#44; systemic immune inflammation index &#40;SII&#41; &#40;platelet counts<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>neutrophil counts&#47;lymphocyte counts&#41; and lymphocyte-to-CRP ratio &#40;LCR&#41; were calculated on admission and the association of these markers with disease mortality in CKD patients was identified&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">CKD patients had higher risk of severe disease&#44; and mortality compared to non-CKD patients &#40;72&#37; vs 50&#46;5&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; 36&#46;6&#37; vs 10&#46;8&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41; and were more likely to have higher values of immuno-inflammatory indices &#40;leukocyte count&#44; neutrophil&#44; NLR&#44; SII and C-reactive protein&#44; etc&#46;&#41; and lower level of lymphocyte and LCR&#46; Also&#44; higher levels of NLR&#44; SII&#44; PLR and lower level of LCR were seen in CKD patients who died compared to those recovered&#46; In a receiver operating characteristic curve analysis&#44; NLR&#44; SII&#44; PLR and LCR area under the curve for in-hospital mortality of CKD patients were 0&#46;830&#44; 0&#46;811&#44; 0&#46;664 and 0&#46;712&#44; respectively&#46; Among all parameters&#44; NLR and SII gave us the best ability to distinguish patients with higher risk of death&#46; Based on the cut-off value of 1180&#46;5&#44; the sensitivity and specificity of the SII for predicting in-hospital mortality were found to be 67&#46;5&#37; and 79&#46;6&#37;&#44; respectively&#46; The corresponding sensitivity and specificity of the NLR were 85&#46;2&#37; and 66&#46;1&#37;&#44; respectively&#44; at the cut-off value of 5&#46;1&#46; Forward stepwise logistic regression analysis showed that NLR &#40;&#8805;5&#46;1&#41;&#44; SII &#40;&#8805;1180&#46;5&#41; and LCR &#40;&#8804;9&#41; were predictors for in-hospital mortality&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We report for the first time that SII is able to distinguish COVID-19 infected CKD patients of worse survival and it is as powerful as NLR in this regard&#46; As SII is easily quantified from blood sample data&#44; it may assist for early identification and timely management of CKD patients with worse survival&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con enfermedad renal cr&#243;nica &#40;ERC&#41; son susceptibles a la infecci&#243;n por SARS-CoV-2 y m&#225;s propensos a desarrollar una enfermedad grave&#46; Es importante conocer los predictores de los malos resultados para optimizar las estrategias de atenci&#243;n&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron en el estudio 93 pacientes con ERC y 93 pacientes sin ERC&#44; emparejados por edad y sexo&#46; Los datos sobre las caracter&#237;sticas demogr&#225;ficas&#44; cl&#237;nicas&#44; &#237;ndices hematol&#243;gicos y resultados&#44; se anotaron y compararon entre los grupos&#46; La proporci&#243;n de neutr&#243;filos a linfocitos &#40;NLR&#41;&#44; la proporci&#243;n de plaquetas a linfocitos &#40;PLR&#41;&#44; el &#237;ndice de inflamaci&#243;n inmunitaria sist&#233;mica &#40;SII&#41; &#40;recuentos de plaquetas<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>recuentos de neutr&#243;filos&#47;recuentos de linfocitos&#41; y la proporci&#243;n de linfocitos a PCR &#40;LCR&#41; se calcularon en el momento de la admisi&#243;n y se identific&#243; la asociaci&#243;n de estos marcadores con la mortalidad por enfermedad en pacientes con ERC&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con ERC tuvieron un mayor riesgo de enfermedad grave y mortalidad en comparaci&#243;n con los pacientes sin ERC &#40;72&#37; vs 50&#44;5&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#44; 36&#44;6&#37; vs 10&#44;8&#37;&#44; p &#60; 0&#44;001&#44; respectivamente&#41; y tuvieron m&#225;s probabilidades de tener valores m&#225;s altos de &#237;ndices inmuno inflamatorios &#40;recuento de leucocitos&#44; neutr&#243;filos&#44; NLR&#44; SII y prote&#237;na C reactiva&#44; etc&#46;&#41; y niveles m&#225;s bajos de linfocitos y LCR&#46; Adem&#225;s&#44; se observaron niveles m&#225;s altos de NLR&#44; SII&#44; PLR y un nivel m&#225;s bajo de LCR en pacientes con ERC que murieron en comparaci&#243;n con los recuperados&#46; En un an&#225;lisis de la curva de caracter&#237;sticas operativas del receptor&#44; el &#225;rea NLR&#44; SII&#44; PLR y LCR bajo la curva de mortalidad hospitalaria de pacientes con ERC fueron de 0&#44;830&#44; 0&#44;811&#44; 0&#44;664 y 0&#44;712&#44; respectivamente&#46; Entre todos los par&#225;metros&#44; NLR y SII se di&#243; a conocer la mejor manera de distinguir a los pacientes con mayor riesgo de muerte&#46; Con base en el valor de corte de 1180&#44;5&#44; se encontr&#243; que la sensibilidad y especificidad del SII&#44; para predecir la mortalidad hospitalaria&#44; fue del 67&#44;5&#37; y 79&#44;6&#37;&#44; respectivamente&#46; La sensibilidad y especificidad correspondientes del NLR fueron del 85&#44;2&#37; y 66&#44;1&#37;&#44; respectivamente&#44; en el valor de corte de 5&#44;1&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El an&#225;lisis de regresi&#243;n log&#237;stica escalonada hacia adelante mostr&#243; que el NLR &#40;&#8805;5&#44;1&#41;&#44; SII &#40;&#8805;1180&#44;5&#41; y LCR &#40;&#8804;9&#41; fueron predictores de mortalidad hospitalaria&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Informamos&#44; por primera vez&#44; que el SII es capaz de distinguir pacientes con ERC infectados por COVID-19 de peor supervivencia y&#44; en este sentido&#44; es tan poderoso como el NLR&#46; Como el SII se cuantifica f&#225;cilmente a partir de los datos de las muestras de sangre&#44; puede ayudar a la identificaci&#243;n temprana y el manejo oportuno de los pacientes con ERC con peor supervivencia&#46;</p></span>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Receiver Operating Characteristic Curves &#40;ROC&#41; of blood cell count derived inflammation indexes and their respective areas under the curves &#40;AUC&#41; for in hospital mortality&#46; &#40;A&#41; ROC curves of PLR &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;664&#41; for in hospital mortality&#46; &#40;B&#41; ROC curves of NLR &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;830&#41;&#46; &#40;C&#41; ROC curves of SII &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;811&#41;&#46; &#40;D&#41; ROC curves of LCR &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;712&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Data were expressed as median &#40;IQR&#41; for quantitative variables and <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41; for nominal parameters&#46; COPD&#44; chronic obstructive pulmonary disease&#46; CKD&#44; chronic kidney disease&#46; CVO&#44; cerebrovascular disorders&#46; CT&#44; computed tomography&#46; ICU&#44; intensive care unit&#46; RT-PCR&#44; reverse transcription polymerase chain reaction&#46; RRT&#44; renal replacement therapy&#46; SpO<span class="elsevierStyleInf">2</span>&#44; oxygen saturation&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Sex</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Co-morbid diseases</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypertension&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;877&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Coronary heart disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Malignancy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;635&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CVO&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\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">Symptoms</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>Fever&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28 &#40;30&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">31 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;672&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;14&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyspnea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cough&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fatigue&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Myalgia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Headache&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;623&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sore throat&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diarrhea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;519&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Taste&#47;smell disorder&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;2&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;675&nbsp;\t\t\t\t\t\t\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  " colspan="7" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">COVID-19 diagnosis</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="7" align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">RT-PCR</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><span class="elsevierStyleHsp" style=""></span>Positive&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">51 &#40;54&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40 &#40;43&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;122&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;48&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;36&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;388&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">CT scan</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><span class="elsevierStyleHsp" style=""></span>Mild&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Moderate&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Severe&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Low saturation &#40;&#60;92&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">46 &#40;49&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">65 &#40;69&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38 &#40;69&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27 &#40;71&#46;1&#41;&nbsp;\t\t\t\t\t\t\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
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Outcomes</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>Severe disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">67 &#40;72&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40 &#40;72&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27 &#40;71&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;000&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ICU care need&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16 &#40;17&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;34&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;26&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;253&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Secondary infection&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;10&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">37 &#40;39&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19 &#40;34&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18 &#40;47&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;305&nbsp;\t\t\t\t\t\t\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-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="elsevierStyleItalic">Length of stay &#40;days&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;2&#8211;40&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;2&#8211;57&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;2&#8211;57&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;2&#8211;31&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;161&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mortality</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;10&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;36&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Data were expressed as median &#40;IQR&#41;&#46; AST&#44; aspartate aminotransferase&#46; ALT&#44; alanine aminotransferase&#46; PCT&#44; Procalcitonin&#46; CRP&#44; C-reactive protein&#46; Hb&#44; hemoglobin&#46; WBC&#44; leukocyte&#46; CT&#44; computed tomography&#46; LDH&#44; lactate dehydrogenase&#46; LCR&#44; lymphocyte-C-reactive protein ratio&#46; NLR&#44; neutrophils to lymphocytes ratio&#46; PLR&#44; platelet to lymphocyte ratio&#46; SII&#44; systemic immune-inflammation index&#46;</p>"
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            0 => array:1 [
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                0 => """
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Spesifisite&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positive predictive value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Negative predictive value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; confidence interval&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PLR&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">&#8805;187&#46;5&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\ttop\n
                  \t\t\t\t">61&#46;76&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#46;10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">NLR&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">&#8805;5&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \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">66&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;18&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\ttop\n
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                  \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;830&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;744&#8211;0&#46;916&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;001&#42;&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
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                  \t\t\t\t">SII&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8805;1180&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">67&#46;65&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#46;71&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">0&#46;719&#8211;0&#46;904&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;001&#42;&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">LCR&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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                  """
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">HT&#44; hypertension&#46; DM&#44; diabetes mellitus&#46; CHD&#44; coronary heart disease&#46; PLR&#44; platelet to lymphocyte ratio&#46; NLR&#44; neutrophils to lymphocytes ratio&#46; SII&#44; systemic immune-inflammation index&#46; LCR&#44; lymphocyte-C-reactive protein ratio&#46; ODDS&#44; odds ratio&#46;</p>"
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