Biomarkers of systemic inflammatory status as predictors of delayed cerebral ischemia after subarachnoid hemorrhage

Biomarkers of systemic inflammatory status as predictors of delayed cerebral ischemia after subarachnoid hemorrhage | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Biomarkers of systemic inflammatory status as predictors of delayed cerebral ischemia after subarachnoid hemorrhage Leidy Gaviria, Andrés Gempeler, Andrea Valencia, Alexandra Porras, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4802088/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Inflammatory biomarkers and derived indexes have been reported as useful prognostic tools in subarachnoid hemorrhage (SAH) to predict risk of vasospasm, delayed cerebral ischemia (DCI) or death. This study aimed to assess the prognostic value of platelet characteristics, the systemic inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume-to-platelet ratio (MPV:PLT) in patients with aneurysmal subarachnoid hemorrhage. Methods: This was a retrospective cohort study that included 309 adult patients with SAH admitted to the ICU of a tertiary care teaching hospital in Cali, Colombia between 2011 and 2022. Plasma inflammatory biomarkers were measured in patients up to 14 days after SAH. Platelet characteristics trajectory plots by occurrence of DCI were produced to look for trend changes in the first days after SAH that could suggest and underlying pathophysiologic mechanism useful for prediction of this outcome. Odds ratios with 95% confidence interval were calculated for all indexes and ratios in the first three days after SAH using the originally reported cut-off points for its association with DCI, vasospasm, favorable modified Rankin scale score (0-3) and death. The prognostic value of the indexes was assessed through area under the receiver operating characteristic curves (AU-ROC). Results: 309 patients were included in this study (mean age 58.3 years, 68% women). DCI was detected in 137 patients; 44.3%. Vasospasm was detected in 111; 35.9%. During the hospitalization rebleeding occurred in 54 patients (17.5%), hydrocephalus in 107 patients (34.6%) and cerebral ischemia in 77 patients (24.9%). For the cut-off points of SII >1.92, SIRI>3.2, NLR>4, LMR145 during the first three days after admission we did not find association with DCI, vasospasm, neurologic outcome or death. The AU-ROC estimates of these indexes did not surpass a pre-stablished usefulness threshold of 75% and thus no new cut-off points were proposed. Conclusions Previously reported results of the prognostic value of inflammatory indexes and biomarkers in patients with SAH or other cerebrovascular diseases were not reproducible in this cohort of patients with aneurysmal subarachnoid hemorrhage. Our findings call into question the reproducibility and applicability of proposed prognostic biomarkers and indexes and should prompt efforts to verify their value in clinical settings, as well as prompt efforts to identify the best prognostic tools available in these patients. "Subarachnoid Hemorrhage"[Mesh] "Intracranial Aneurysm"[Mesh] "Aneurysm Ruptured"[Mesh] "Delayed cerebral ischemia"[Mesh] "Inflammatory indexes"[Mesh] Figures Figure 1 Figure 2 Figure 3 BACKGROUND Aneurysmal subarachnoid hemorrhage (aSAH) represents approximately 5% of all strokes and is a significant cause of morbidity and mortality worldwide(1). Re-bleeding, vasospasm, poor neurologic status at admission, thick SAH, and delayed cerebral ischemia are known predictive factors for poor outcome after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia (DCI) is among the most dreaded complications following SAH(2, 3). The severity of SAH, the presence of vasospasm, the inflammatory response, and microthrombosis events have been reported as factors associated with DCI (4). Because activated platelets participate in several other pathophysiologic mechanisms including inflammation and could be implicated in microcirculatory ischemic events that contribute to the cerebral atrophy and cognitive deficits observed during follow-up after aSAH (4, 5), platelet aggregation and inflammatory markers could be useful in the prognosis of DCI or death after SAH. Blood count and platelet parameters cutoff points have been assessed for their ability to identify patients at risk of vasospasm (4). Ratios like the mean platelet volume (MPV) to platelet count (PLT) ratio (MPV:PLT) have been proposed as tools to predict platelet-related systemic thrombogenicity(5), a process that could be involved in the pathophysiology of DCI(6). Currently, clinically relevant events that determine the recovery and functional outcome of the patients such as DCI and death are preferred over the occurrence of vasospasm, which is not associated with DCI in a third or even half of the affected patients, and thus the value of its predictors are to be evaluated for the patient-oriented outcomes (7). Neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported as predictors of outcomes in cerebrovascular diseases(4). The systemic immune-inflammation (SII) index and the systemic inflammation response index (SIRI) as biomarkers of systemic inflammation could reflect clinical outcomes of patients with various diseases, and have been shown to predict poor outcomes following intracerebral hemorrhage (8, 9). The reliable identification of tools for prognosis of relevant outcomes allows to inform patients and families, and suggests brain monitoring needs and therapy intensity level. The aim of this study was to assess the prognostic value of multiple inflammatory indexes and biomarkers measured in the first three days after ictus in patients with aneurysmal SAH. METHODS Design and population We conducted a prognostic factor cohort study based on clinical records that followed the PROGRESS methodological framework for prognosis studies of type 2. We included adult patients with a diagnosis of spontaneous SAH either with brain imaging and/or lumbar puncture, and a baseline complete blood count (CBC) admitted to the neurocritical care unit between January 15, 2011, and November 30, 2022. We excluded patients with non-aneurismal SAH, anticoagulant and antiplatelet drug use before SAH; history of hematological disease that alters platelet function, previous neurological or neurosurgical conditions other than SAH that alter consciousness, and patients who died within the first 24 hours of admission or were admitted more than 48 hours after the initial subarachnoid hemorrhage. This study was approved by the Institutional Review Board/Ethics Committee in Biomedical Research (number of approval 1345). Because the study involved chart review with no risk to the subjects, patients’ consent was waived. Measurements We recorded baseline clinical characteristics as well as laboratory parameters upon admission and during the first seven days, on day 10 and on day 14, to assess early phenomena and trends overtime during typical length of ICU stay. Based on head computed tomography images and reports we measured radiological hemorrhage grade with the modified Fisher scale(10), and used WFNS for clinical grading. Laboratory parameters were available from laboratory records routinely taken in the critical care unit during the study period. Inflammatory biomarkers ratios and indexes were calculated according to the formulas displayed in table 1. Parameters included the MPV cutoff points of 9.5 and 12.3 fL from normal laboratory values, and 14.5% for RDW(11). The MPV:PLT ratio (2018 Ray), the neutrophil / lymphocyte ratio -NLR(12); platelet-lymphocyte ratio-PLR, the systemic inflammation index-SII(13). Cut-off points reported in the literature were used as following: SII>1.92; NLR>4; PLR>145; and MPV:PLT ratio increase>0.33; SIRI>3.2; LMR<2. Odds ratios (OR) with 95% confidence intervals and ROC curves were obtained to assess their prognostic value for DCI and/or death. Table 1. Formulas for calculation of inflammatory indexes and ratios. We defined DCI as focal neurological impairment, such as hemiparesis, aphasia, apraxia, hemianopia, or neglect; or a decrease of at least 2 points on the Glasgow Coma Scale (either on the total score or on one of its individual components [eye, motor on either side, verbal]), this impairment should last for at least 1 hour, not be apparent immediately after aneurysm occlusion, and not be attributable to other causes by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies (14). We measured rebleeing, sonographic or angiographic vasospasm and death during ICU and hospital stay. We used the modified Rankin Scale to assess neurological status at discharge. Statistical Analysis For description of baseline clinical characteristics, distribution of continuous variables values was assessed to determine the use of mean and standard deviation (SD) or median and interquartile range (IQR). The categorical variables are presented with absolute and relative frequencies. Categorical variables are expressed as frequency with percentage. Differences in proportions were analyzed with X 2 test or Fisher’s exact test as suited, and differences in quantitative variables were analyzed with Student t-tests or Mann-Whitney U test according to their distribution. Odds ratios (OR) with 95% confidence intervals (95%CI) were calculated for each index at day 1, 2 and 3 using the proposed cut-off points in original publications to assess their association with DCI. Receiver operating characteristic (ROC) curves were used to assess the prognostic value of each index or ratio in the first three days after SAH. We used the area under the ROC curve (AUC) to determine discrimination performance. We determined a priori that for any index or ratio with AUC>0.75 a cut-off point for our data would be determined. Platelet and blood count parameters were assessed by comparing graphical trends between patients with and without DCI. Analyses were conducted in the statistical softwares RStudio and SPSS. Significant difference was considered at two-tailed p-value <0.05. RESULTS Three-hundred and nine patients fulfilled the selection criteria and were included in the study. The patients screened and reasons for exclusion are displayed in Figure 1. Baseline clinical features and interventions during hospital stay are displayed in Table 2. Most patients were around 58 years of age and the majority were women. Half of patients had hypertension as a comorbidity. High grade SAH according to WFNS was determined in 59.2% of patients. Most patients had their aneurysm controlled endovascularly (47.7%) Table 2. Demographic and clinical characteristics of patients. Characteristics Overall N = 309 No DCI n = 172 1 DCI n = 137 1 Women 210 (68.0%) 117 (68.0%) 93 (67.9%) Men 99 (32.0%) 55 (32.0%) 44 (32.1%) Age 58.3 (51.0; 67.0) 58.0 (48.6; 67.3) 59.5 (52.4; 66.0) Hypertension 159 (51.5%) 77 (44.8%) 82 (59.9%) Diabetes Mellitus 25 (8.1%) 12 (7.0%) 13 (9.5%) Coronary heart disease 7 (2.3%) 2 (1.2%) 5 (3.6%) Modified Fisher Scale 1, 2 39 (12.6%) 28 (16.3%) 11 (8.0%) 3, 4 270 (87.4%) 144 (83.7%) 126 (92.0%) World Federation of Neurosurgical Societies Scale Grades 1 - 3 126 (40.8%) 73 (42.4%) 53 (38.7%) Grades 4 - 5 183 (59.2%) 99 (57.6%) 84 (61.3%) Aneurysm management type Surgical 88 (29.3%) 50 (29.8%) 38 (28.8%) Endovascular 143 (47.7%) 72 (42.9%) 71 (53.8%) None 69 (23.0%) 46 (27.4%) 23 (17.4%) Discharge status Alive 182 (58.9%) 109 (62.2%) 75 (54.7%) Dead 127 (41.1%) 65 (37.8%) 62 (45.3%) Modified Rankin Scale at discharge 0 - 3 120 (38.8%) 87 (50.6%) 33 (24.1%) 4 - 6 189 (61.2%) 85 (49.4%) 104 (75.9%) 1 n (%); Median (IQR); DCI, delayed cerebral ischemia. DCI was detected in 137 patients; 44.3%. Vasospasm was detected in 111; 35.9%. The frequency of other complications recorded during ICU stay is presented in Table 3. The overall mortality was 41.1%; 127 deaths. The median time from admission to death or withdrawal of care was 15 days (IQR). Table 3. Complications during hospitalization Diagnosis n = 235 (%) Rebleeding 54 (17.5%) Vasospasm 111 (35.9%) Delayed cerebral ischemia 137 (44.3%) Hydrocephalus 107 (34.6%) Cerebral infarction 77 (24.9%) Table 4 displays the association of delayed cerebral ischemia for the cutoff points evaluated for SII, SIRI, NLR, LMR, and PLR during the first three days. None of the measured indices were associated with delayed cerebral ischemia. Table 4. Analysis of inflammatory indices in patients with or without delayed cerebral ischemia. No DCI n, (%) DCI n, (%) OR (IC95%) P- value SII >1.92 First day 32 (50.8) 31 (49.2) 1.23 (0.64-2.38) 0.535 Second day 34 (43.0) 45 (57.0) 1.58 (0.86-2.90) 0.141 Third day 19 (52.8) 17 (47.2) 0.89 (0.42-1.91) 0.773 SIRI >3.2 First day 40 (48.8) 42 (51.2) 1.46 (0.76-2.82) 0.252 Second day 58 (45.7) 69 (54.3) 1.78 (0.90-3.61) 0.100 Third day 70 (44.9) 86 (55.1) 2.08 (0.99-4.52) 0.057 NLR >4 First day 43 (46.2) 50 (53.8) 2.09 (1.07-4.19) 0.034 Second day 69 (47.9) 75 (52.1) 1.45 (0.64-3.34) 0.373 Third day 73 (45.9) 86 (54.1) 1.72 (0.80-3.80) 0.167 LMR 145 First day 37 (52.1) 34 (47.9) 1.14 (0.59-2.18) 0.702 Second day 54 (48.6) 57 (51.4) 1.06 (0.56-1.98) 0.866 Third day 39 (42.4) 53 (57.6) 1.57 (0.89-2.79) 0.124 Association of inflammatory indexes during the first 3 days after admission. Values considered abnormal were determined by the following cutoff points: SII index >1.92, SIRI > 3.2, NLR >4.0, LMR 145, (5-9) Table 5 displays the association of cerebral ischemia for the cutoff points evaluated for SII, SIRI, NLR, LMR and PLR during the first three days; SII value on the third day (OR 3.11 (IC95% 1.34 – 7.24) p=0.008), SIRI at first day (OR 2.15 (IC95% 1.02-4.71) p=0.047), NLR at first and third day (OR 2.30 (IC95% 1.05-5.37) p=0.033) are associated with cerebral ischemia Table 5. Analysis of laboratory values to predict cerebral infarct. Controls n, (%) Cerebral infarct n, (%) OR (IC95%) P- value SII >1.92 First day 42 (66.7) 21 (33.3) 1.60 (0.77-3.32) 0.204 Second day 60 (75.9) 19 (24.1) 0.80 (0.40-1.59) 0.533 Third day 22 (61.1) 14 (38.9) 3.11 (1.34-7.24) 0.008 SIRI >3.2 First day 54 (65.9) 28 (34.1) 2.15 (1.02-4.71) 0.047 Second day 91 (71.7) 36 (28.3) 1.58 (0.72-3.79) 0.276 Third day 107 (68.6) 49 (31.4) 2.21 (0.92-6.21) 0.098 NLR >4 First day 62 (66.7) 31 (33.3) 2.30 (1.05-5.37) 0.043 Second day 105 (72.9) 39 (27.1) 1.36 (0.54-3.92) 0.535 Third day 108 (67.9) 51 (32.1) 3.31 (1.22-11.60) 0.033 LMR 145 First day 49 (69.0) 22 (31.0) 1.35 (0.65-2.79) 0.419 Second day 83 (74.8) 28 (25.2) 0.85 (0.42-1.75) 0.660 Third day 64 (69.6) 28 (30.4) 1.17 (0.62-2.19) 0.660 Association of inflammatory indexes during the first 3 days after admission. Values considered abnormal were determined by the following cutoff points: SII index >1.92, SIRI > 3.2, NLR >4.0, LMR 145, (5-9) Table 6 displays the association of death for the cutoff points evaluated for SII, SIRI, NLR, LMR and PLR during the first three days; SII at third day (OR 2.43 (IC95% 1.06-5.51) p=0.033), SIRI at second day (OR 2.5 (IC95% 1.22-5.35) p=0.014), and LMR at second day (OR 2.78 (IC95% 1.50-5.23) p=0.001) are associated with death. Table 6. Analysis of laboratory values to predict death. Alive n, (%) Death n, (%) OR (IC95%) P- value SII >1.92 First day 28 (44.4) 35 (55.6) 1.75 (0.91-3.41) 0.096 Second day 44 (55.7) 35 (44.3) 0.95 (0.52-1.73) 0.860 Third day 22 (61.1) 14 (38.9) 2.43 (1.06-5.51) 0.033 SIRI >3.2 First day 39 (47.6) 43 (52.4) 1.54 (0.80-2.96) 0.196 Second day 63 (49.6) 64 (50.4) 2.50 (1.22-5.35) 0.014 Third day 91 (58.3) 65 (41.7) 1.56 (0.73-3.52) 0.266 NLR >4 First day 45 (48.4) 48 (51.6) 1.53 (0.79-3.01) 0.213 Second day 76 (52.8) 68 (47.2) 1.89 (0.82-4.64) 0.146 Third day 93 (58.5) 66 (41.5) 1.56 (0.71-3.65) 0.282 LMR 145 First day 37 (52.1) 34 (47.9) 1.02 (0.53-1.95) 0.950 Second day 59 (53.2) 52 (46.8) 1.23 (0.66-2.34) 0.516 Third day 55 (59.8) 37 (40.2) 1.03 (0.58-1.85) 0.908 Association of inflammatory indexes during the first 3 days after admission. Values considered abnormal were determined by the following cutoff points: SII index >1.92, SIRI > 3.2, NLR >4.0, LMR 145, (5-9) Figure 2 and 3 displays the ROC curves used to assess the performance and potential prognosis value of all the considered indexes and ratios during the first three days after SAH for DCI and for death. These show a poor performance of all the indexes and ratios as indicated by low AUC values, close to 0.5 (similar to a coin toss) and the absence of parameter values with useful sensitivity and specificity. DISCUSSION Summary of findings In this study we assessed inflammatory indexes (MPV:PLT ratio, systemic immune inflammation index, neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, platelet to lymphocyte ratio) in 309 aSAH patients as potential prognostic tools for DCI or death during ICU stay. We could not reproduce the results of previous studies that have proposed these as useful in SAH patients or in critical care patients with other types of stroke. The performance of these parameters as assessed by ROC curves and association with the events of interest based on proposed cut-off points did not suggest any as a valuable prognostic tool in our cohort. Limitations This was a single center retrospective study with the inherent limitations, including missing data for some patients regarding laboratory values. The statistical methodology used in this study analyzed trajectory and trends of individual patients while assessing the infliction point of the biomarkers. Also, we could only assess the prognostic value of the proposed indexes in hospital outcomes, as long term mortality and functional outcomes were not available to us. Implications for care and future research Delayed cerebral ischemia is a major event that affects survival and functional outcome following subarachnoid hemorrhage and has been a focus of recent research(3, 15-17). Early clinical parameters such as lower modified Fisher grade, WFNS scale, the absence of intracerebral hematoma and pupillary light reflexes can be used as early clinical predictors of functional outcome and favorable or non-favorable prognosis. The pathophysiology of DCI has been extensively discussed in recent reviews and we know that bleeding in subarachnoid space triggers a rapid activation of inflammatory cascades, leading to leukocytosis and activation of an innate immune response characterized by increased neutrophil counts and platelets, which induce micro thrombosis, and can increase the probability to DCI(6, 18). Previous studies reported that inflammatory markers are associated with the development of DCI. Ray B, et al (2018), measured the MPV:PLT ratio after aSAH and found a significant early increase in the reactive platelet population after aHSA in patients who developed DCI, Geraghty J, et al (2021), calculated the SII index and concluded that an early elevation of the SII index predicts the development of late cerebral vasospasm in aneurysmal SAH. Although we found several studies reporting different prognostic indexes or ratios, most results were not reproduced in subsequent studies. A potential explanation for this finding and for the discrepancy between our results and some previous studies is that of publications bias. It could be that studies that have assessed these parameters have not found clinically relevant associations and therefore are not submitted to or accepted by journals, while those with significant findings do; leading to availability of studies that are difficult to reproduce as their findings could be a consequence of random error. Other explanations for the discrepancy are the differences in patients’ selection and exposure measurements which can lead to different results. Of course, the inability to reproduce some findings was also expected as some indexes have been proposed in different populations (not SAH patients) and for different outcomes (vasospasm). Future prospective multicenter studies are required to evaluate the prognostic value of the inflammatory index for the diagnosis of ICD in patients with SAH and to identify new ones. This would also allow for the incorporation of additional forward-looking metrics. CONCLUSION Proposed prognostic tools based on blood count parameters do not appear useful in patients with SAH, and we need better tools for prognosis of complications that allow improved selection of monitoring alternatives and guide therapeutic decisions. Prospective and multicenter studies are needed to evaluate the value of systemic inflammatory markers that given the understanding of SAH pathophysiology have a promising potential. Abbreviations aSAH Aneurysmal subarachnoid hemorrhage DCI Delayed cerebral ischemia PLT Platelet count MPV Mean platelet volume NeuroICU Neurologic intensive care unit SII Systemic immune inflammation index SIRI Systemic inflammation Response index NLR Neutrophil to lymphocyte ratio LMR Lymphocyte to monocyte ratio PLR Platelet to lymphocyte ratio NEU Neutrophil LYM Lymphocyte MONO Monocyte Declarations The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. Acknowledgements: The authors would like to thank Dr. Juan P. Díaz-Solórzano, M.D., for providing language editing to improve the manuscript. References Etminan N, Chang H-S, Hackenberg K, De Rooij NK, Vergouwen MD, Rinkel GJ, et al. 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J Neuroanaesthesiology Crit Care. 2024. Alsbrook DL, Di Napoli M, Bhatia K, Desai M, Hinduja A, Rubinos CA, et al. Pathophysiology of early brain injury and its association with delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a review of current literature. J Clin Med. 2023;12(3):1015. Supplementary Files COIAR.docx COIAV.docx COIAG.docx Checklist.docx Neurocriticalcare.pdf COIJM.docx COILG.docx COIME.docx COIAP.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4802088","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":347052736,"identity":"29b11eea-46ad-40d7-a1e6-30e81fadaa28","order_by":0,"name":"Leidy Gaviria","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIie3RsUrEMBzH8V8MpEtq14BH7xX+0klEfZbSl+hwHpVAN3EWD5/B6eaUQrv4AIJT9xs8cDhBwaTDoUjubnTId0r+8BmSPxAK/cOOwSo1njhgUKZ2sifxmzxndrKXAGp7Y/UhJNI3rxLXU+rjwXw8Ul6Dd+t3XKZeIht9LtGfPrURNbdLR0TxMEGReYnK6xOJjt1rARMvPzMBmXEFk1c+Mh1GcuVI87WgA4hijszyOy7QxhWljrC3XUTm+mxBphjJpLOEi4KD/G9Jon54WZXzizrp+Ho1I5lEumWb0v9jriNJ7Y+r3SmXtAvYBW4w/zMJhUKh0LZvCpVG04VuAicAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-5838-8680","institution":"Fundación Valle del Lili: Fundacion Valle del Lili","correspondingAuthor":true,"prefix":"","firstName":"Leidy","middleName":"","lastName":"Gaviria","suffix":""},{"id":347052737,"identity":"c806790c-8451-4a24-a6b8-ca61771c964d","order_by":1,"name":"Andrés Gempeler","email":"","orcid":"","institution":"Fundación Valle del Lili: Fundacion Valle del Lili","correspondingAuthor":false,"prefix":"","firstName":"Andrés","middleName":"","lastName":"Gempeler","suffix":""},{"id":347052738,"identity":"52ac96db-b976-40ba-95f8-deee07804ce3","order_by":2,"name":"Andrea Valencia","email":"","orcid":"","institution":"Fundación Valle del Lili: Fundacion Valle del Lili","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Valencia","suffix":""},{"id":347052739,"identity":"44019849-76b2-4133-9c28-5d6789483ec9","order_by":3,"name":"Alexandra Porras","email":"","orcid":"","institution":"Universidad El Bosque","correspondingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Porras","suffix":""},{"id":347052740,"identity":"52724946-2d54-4808-a8e2-13e74133585e","order_by":4,"name":"María Andrea Rico","email":"","orcid":"","institution":"Universidad El Bosque","correspondingAuthor":false,"prefix":"","firstName":"María","middleName":"Andrea","lastName":"Rico","suffix":""},{"id":347052741,"identity":"270c3434-de82-46d7-846e-6b9d74bdc778","order_by":5,"name":"Manuela Escalante","email":"","orcid":"","institution":"Fundación Valle del Lili: Fundacion Valle del Lili","correspondingAuthor":false,"prefix":"","firstName":"Manuela","middleName":"","lastName":"Escalante","suffix":""},{"id":347052742,"identity":"6637d852-c4a8-4662-a8f4-f598c41395da","order_by":6,"name":"Jorge Mejía-Mantilla","email":"","orcid":"","institution":"Fundación Valle del Lili: Fundacion Valle del Lili","correspondingAuthor":false,"prefix":"","firstName":"Jorge","middleName":"","lastName":"Mejía-Mantilla","suffix":""}],"badges":[],"createdAt":"2024-07-25 13:15:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4802088/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4802088/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66894399,"identity":"78e39a54-6420-4908-b485-3abff310cede","added_by":"auto","created_at":"2024-10-17 15:01:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14470,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart illustrating patient cohort for the study. aSAH, aneurysmal subarachnoid hemorrhage; PLT, platelet count.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/1e63a92ee8abff45c1af11bb.png"},{"id":66894404,"identity":"d0fee909-df2a-4583-b6cf-dc6e86ab10c3","added_by":"auto","created_at":"2024-10-17 15:01:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":222820,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves for prognosis of delayed cerebral ischemia in the first three days after SAH\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC\u003c/strong\u003e, Area under the receiver operating characteristic curves; \u003cstrong\u003eSAH,\u003c/strong\u003e Aneurysmal subarachnoid hemorrhage; \u003cstrong\u003ePLT,\u003c/strong\u003ePlatelet count; \u003cstrong\u003eMPV, \u003c/strong\u003eMean platelet volume; \u003cstrong\u003eSII,\u003c/strong\u003e Systemic immune inflammation index; \u003cstrong\u003eSIRI,\u003c/strong\u003e Systemic inflammation Response index; \u003cstrong\u003eNLR,\u003c/strong\u003eNeutrophil to lymphocyte ratio; \u003cstrong\u003eLMR\u003c/strong\u003e: Lymphocyte to monocyte ratio; \u003cstrong\u003ePLR\u003c/strong\u003e: Platelet to lymphocyte ratio\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/3c3935da103ab7eca8e07650.png"},{"id":66894403,"identity":"52422416-de49-469e-96f5-3a1d7fd02d22","added_by":"auto","created_at":"2024-10-17 15:01:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":234372,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves for prognosis of death in the first three days after SAH\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC\u003c/strong\u003e, Area under the receiver operating characteristic curves; \u003cstrong\u003eSAH,\u003c/strong\u003e Aneurysmal subarachnoid hemorrhage; \u003cstrong\u003ePLT,\u003c/strong\u003ePlatelet count; \u003cstrong\u003eMPV, \u003c/strong\u003eMean platelet volume; \u003cstrong\u003eSII,\u003c/strong\u003e Systemic immune inflammation index; \u003cstrong\u003eSIRI,\u003c/strong\u003e Systemic inflammation Response index; \u003cstrong\u003eNLR,\u003c/strong\u003eNeutrophil to lymphocyte ratio; \u003cstrong\u003eLMR\u003c/strong\u003e: Lymphocyte to monocyte ratio; \u003cstrong\u003ePLR\u003c/strong\u003e: Platelet to lymphocyte ratio\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/5bb03203132fe28e5ef1dc6e.png"},{"id":66896672,"identity":"0dba8021-f73f-4613-8486-da29c76cb8ae","added_by":"auto","created_at":"2024-10-17 15:33:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1135278,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/2501e0e0-f6e6-44cf-a7c3-6ddc9e00e1ce.pdf"},{"id":66895425,"identity":"895377c5-112b-45f9-af0c-1f29da8ce913","added_by":"auto","created_at":"2024-10-17 15:09:28","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":34958,"visible":true,"origin":"","legend":"","description":"","filename":"COIAR.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/0e397b09c5bf73a0ff83f49d.docx"},{"id":66894397,"identity":"13989d65-3791-473d-8efe-5f49110a0b6f","added_by":"auto","created_at":"2024-10-17 15:01:28","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":35044,"visible":true,"origin":"","legend":"","description":"","filename":"COIAV.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/6c63e165b489d4ad3c596aca.docx"},{"id":66895428,"identity":"97fbc9ea-c81d-48ca-bb26-bcb14afeee11","added_by":"auto","created_at":"2024-10-17 15:09:28","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":34997,"visible":true,"origin":"","legend":"","description":"","filename":"COIAG.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/3690eefc3609a42a67891455.docx"},{"id":66895426,"identity":"15f1e06d-a136-40d5-a46c-0c2e600517f9","added_by":"auto","created_at":"2024-10-17 15:09:28","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":30765,"visible":true,"origin":"","legend":"","description":"","filename":"Checklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/55b127587e0eacb3a87c2bfd.docx"},{"id":66894406,"identity":"6ef1561c-be58-4b55-a935-ade15097a5cd","added_by":"auto","created_at":"2024-10-17 15:01:28","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":25401,"visible":true,"origin":"","legend":"","description":"","filename":"Neurocriticalcare.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/32b25457a8defd660bdcf6a0.pdf"},{"id":66895682,"identity":"48f4a75f-ab49-4d55-b79a-2542b93b1446","added_by":"auto","created_at":"2024-10-17 15:17:28","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":34983,"visible":true,"origin":"","legend":"","description":"","filename":"COIJM.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/e62ae3b015afd8f927048669.docx"},{"id":66894400,"identity":"1feef2c1-8245-4062-a086-647265486cfc","added_by":"auto","created_at":"2024-10-17 15:01:28","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":34968,"visible":true,"origin":"","legend":"","description":"","filename":"COILG.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/b1ab175473f467643a182e4d.docx"},{"id":66895681,"identity":"c3a57bbc-88b6-4cca-aa95-61db921ffc3b","added_by":"auto","created_at":"2024-10-17 15:17:28","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":34970,"visible":true,"origin":"","legend":"","description":"","filename":"COIME.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/f33b7d49635eac414ce9db7c.docx"},{"id":66895430,"identity":"d57fa794-c02b-4b2d-93cd-f8b11ef39cda","added_by":"auto","created_at":"2024-10-17 15:09:28","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":34968,"visible":true,"origin":"","legend":"","description":"","filename":"COIAP.docx","url":"https://assets-eu.researchsquare.com/files/rs-4802088/v1/a6c759fdd3cc6a6559c52dbd.docx"}],"financialInterests":"","formattedTitle":"Biomarkers of systemic inflammatory status as predictors of delayed cerebral ischemia after subarachnoid hemorrhage","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eAneurysmal subarachnoid hemorrhage (aSAH) represents approximately 5% of all strokes and is a significant cause of morbidity and mortality worldwide(1). Re-bleeding, vasospasm, poor neurologic status at admission, thick SAH, and delayed cerebral ischemia are known predictive factors for poor outcome after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia (DCI) is among the most dreaded complications following SAH(2, 3).\u0026nbsp;The severity of SAH, the presence of vasospasm, the inflammatory response, and microthrombosis events have been reported as factors associated with DCI\u0026nbsp;(4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBecause activated platelets participate in several other pathophysiologic mechanisms including inflammation and could be implicated in microcirculatory ischemic events that contribute to the cerebral atrophy and cognitive deficits observed during follow-up after aSAH\u0026nbsp;(4, 5), platelet aggregation and inflammatory markers could be useful in the prognosis of DCI or death after SAH.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBlood count and platelet parameters cutoff points have been assessed for their ability to identify patients at risk of vasospasm\u0026nbsp;(4). Ratios like the mean platelet volume (MPV) to platelet count (PLT) ratio (MPV:PLT) have been proposed as tools to predict platelet-related systemic thrombogenicity(5), a process that could be involved in the pathophysiology of DCI(6). Currently, clinically relevant events that determine the recovery and functional outcome of the patients such as DCI and death are preferred over the occurrence of vasospasm, which is not associated with DCI in a third or even half of the affected patients, and thus the value of its predictors are to be evaluated for the patient-oriented outcomes\u0026nbsp;(7).\u003c/p\u003e\n\u003cp\u003eNeutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported as predictors of outcomes in cerebrovascular diseases(4). The systemic immune-inflammation (SII) index and the systemic inflammation response index (SIRI) as biomarkers of systemic inflammation could reflect clinical outcomes of patients with various diseases, and have been shown to predict poor outcomes following intracerebral hemorrhage (8, 9). The reliable identification of tools for prognosis of relevant outcomes allows to inform patients and families, and suggests brain monitoring needs and therapy intensity level. The aim of this study was to assess the prognostic value of multiple inflammatory indexes and biomarkers measured in the first three days after ictus in patients with aneurysmal SAH.\u0026nbsp;\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eDesign and population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a prognostic factor cohort study based on clinical records that followed the PROGRESS methodological framework for prognosis studies of type 2. We included adult patients with a diagnosis of spontaneous SAH either with brain imaging and/or lumbar puncture, and a baseline complete blood count (CBC) \u0026nbsp; admitted to the neurocritical care unit between January 15, 2011, and November 30, 2022. We excluded patients with non-aneurismal SAH, anticoagulant and antiplatelet drug use before SAH; history of hematological disease that alters platelet function, previous neurological or neurosurgical conditions other than SAH that alter consciousness, and patients who died within the first 24 hours of admission or were admitted more than 48 hours after the initial subarachnoid hemorrhage. This study was approved by the Institutional Review Board/Ethics Committee in Biomedical Research (number of approval 1345). Because the study involved chart review with no risk to the subjects, patients\u0026rsquo; consent was waived.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe recorded baseline clinical characteristics as well as laboratory parameters upon admission and during the first seven days, on day 10 and on day 14, to assess early phenomena and trends overtime during typical length of ICU stay. Based on head computed tomography images and reports we measured radiological hemorrhage grade with the modified Fisher scale(10), and used WFNS for clinical grading.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLaboratory parameters were available from laboratory records routinely taken in the critical care unit during the study period. Inflammatory biomarkers ratios and indexes were calculated according to the formulas displayed in table 1. Parameters included the MPV cutoff points of 9.5 and 12.3 fL from normal laboratory values, and 14.5% for RDW(11). The MPV:PLT ratio (2018 Ray), the neutrophil / lymphocyte ratio -NLR(12); platelet-lymphocyte ratio-PLR, the systemic inflammation index-SII(13). Cut-off points reported in the literature were used as following: SII\u0026gt;1.92; NLR\u0026gt;4; PLR\u0026gt;145; and MPV:PLT ratio increase\u0026gt;0.33; SIRI\u0026gt;3.2; LMR\u0026lt;2. Odds ratios (OR) with 95% confidence intervals and ROC curves were obtained to assess their prognostic value for DCI and/or death.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Formulas for calculation of inflammatory indexes and ratios.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003cimg 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\"\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eWe defined DCI as focal neurological impairment, such as hemiparesis, aphasia, apraxia, hemianopia, or neglect; or a decrease of at least 2 points on the Glasgow Coma Scale (either on the total score or on one of its individual components [eye, motor on either side, verbal]), this impairment should last for at least 1 hour, not be apparent immediately after aneurysm occlusion, and not be attributable to other causes by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies (14). We measured rebleeing, sonographic or angiographic vasospasm and death during ICU and hospital stay. We used the modified Rankin Scale to assess neurological status at discharge.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor description of baseline clinical characteristics, distribution of continuous variables values was assessed to determine the use of mean and standard deviation (SD) or median and interquartile range (IQR). The categorical variables are presented with absolute and relative frequencies.\u0026nbsp;Categorical variables are expressed as frequency with percentage. Differences in proportions were analyzed with X\u003csup\u003e2\u003c/sup\u003e test or Fisher\u0026rsquo;s exact test as suited, and differences in quantitative variables were analyzed with Student t-tests or Mann-Whitney U test according to their distribution. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOdds ratios (OR) with 95% confidence intervals (95%CI) were calculated for each index at day 1, 2 and 3 using the proposed cut-off points in original publications to assess their association with DCI. \u0026nbsp;Receiver operating characteristic (ROC) curves were used to assess the prognostic value of each index or ratio in the first three days after SAH. We used the area under the ROC curve (AUC) to determine discrimination performance. We determined a priori that for any index or ratio with AUC\u0026gt;0.75 a cut-off point for our data would be determined. Platelet and blood count parameters were assessed by comparing graphical trends between patients with and without DCI. Analyses were conducted in the statistical softwares RStudio and SPSS. Significant difference was considered at two-tailed p-value \u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThree-hundred and nine patients fulfilled the selection criteria and were included in the study. The patients screened and reasons for exclusion are displayed in Figure 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBaseline clinical features and interventions during hospital stay are displayed in Table 2. Most patients were around 58 years of age and the majority were women. Half of patients had hypertension as a comorbidity. High grade SAH according to WFNS was determined in 59.2% of patients. Most patients had their aneurysm controlled endovascularly (47.7%)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable 2. Demographic and clinical characteristics of patients.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"613\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003eN = 309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eNo DCI\u003c/p\u003e\n \u003cp\u003en = 172\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eDCI\u003c/p\u003e\n \u003cp\u003en = 137\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eWomen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e210 (68.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e117 (68.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e93 (67.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eMen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e99 (32.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e55 (32.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e44 (32.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e58.3 (51.0; 67.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e58.0 (48.6; 67.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e59.5 (52.4; 66.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e159 (51.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e77 (44.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e82 (59.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eDiabetes Mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e25 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e12 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e13 (9.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eCoronary heart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e7 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e5 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 613px;\"\u003e\n \u003cp\u003eModified Fisher Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003e1, 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e39 (12.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e28 (16.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e11 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003e3, 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e270 (87.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e144 (83.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e126 (92.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 613px;\"\u003e\n \u003cp\u003eWorld Federation of Neurosurgical Societies Scale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eGrades 1 - 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e126 (40.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e73 (42.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e53 (38.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eGrades 4 - 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e183 (59.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e99 (57.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e84 (61.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 613px;\"\u003e\n \u003cp\u003eAneurysm management type\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eSurgical\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e88 (29.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e50 (29.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e38 (28.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eEndovascular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e143 (47.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e72 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e71 (53.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e69 (23.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e46 (27.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e23 (17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 613px;\"\u003e\n \u003cp\u003eDischarge status\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eAlive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e182 (58.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e109 (62.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e75 (54.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003eDead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e127 (41.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e65 (37.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e62 (45.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 613px;\"\u003e\n \u003cp\u003eModified Rankin Scale at discharge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003e0 - 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e120 (38.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e87 (50.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e33 (24.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 273px;\"\u003e\n \u003cp\u003e4 - 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e189 (61.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e85 (49.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e104 (75.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 613px;\"\u003e\n \u003cp\u003e\u003csup\u003e1\u003c/sup\u003en (%); Median (IQR); DCI, delayed cerebral ischemia.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDCI was detected in 137 patients; 44.3%. Vasospasm was detected in 111; 35.9%. The frequency of other complications recorded during ICU stay is presented in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe overall mortality was 41.1%; 127 deaths. The median time from admission to death or withdrawal of care was 15 days (IQR).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 3. Complications during hospitalization\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"255\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62.7451%;\"\u003e\n \u003cp\u003eDiagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.2549%;\"\u003e\n \u003cp\u003en = 235 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62.7451%;\"\u003e\n \u003cp\u003eRebleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.2549%;\"\u003e\n \u003cp\u003e54 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62.7451%;\"\u003e\n \u003cp\u003eVasospasm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.2549%;\"\u003e\n \u003cp\u003e111 (35.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62.7451%;\"\u003e\n \u003cp\u003eDelayed cerebral ischemia\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.2549%;\"\u003e\n \u003cp\u003e137 (44.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62.7451%;\"\u003e\n \u003cp\u003eHydrocephalus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.2549%;\"\u003e\n \u003cp\u003e107 (34.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62.7451%;\"\u003e\n \u003cp\u003eCerebral infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.2549%;\"\u003e\n \u003cp\u003e77 (24.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 displays the association of delayed cerebral ischemia for the cutoff points evaluated for SII, SIRI, NLR, LMR, and PLR during the first three days. None of the measured indices were associated with delayed cerebral ischemia.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 4. Analysis of inflammatory indices in patients with or without delayed cerebral ischemia.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"572\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.6084%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo DCI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDCI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (IC95%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP- value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSII \u0026gt;1.92\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e32 (50.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e31 (49.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.23 (0.64-2.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.535\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e34 (43.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e45 (57.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.58 (0.86-2.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e19 (52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e17 (47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.89 (0.42-1.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.773\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSIRI \u0026gt;3.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e40 (48.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e42 (51.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.46 (0.76-2.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e58 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e69 (54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.78 (0.90-3.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e70 (44.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e86 (55.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.08 (0.99-4.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNLR \u0026gt;4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e43 (46.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e50 (53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.09 (1.07-4.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e69 (47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e75 (52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.45 (0.64-3.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.373\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e73 (45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e86 (54.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.72 (0.80-3.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLMR \u0026lt;2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e27 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e24 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.00 (0.51-1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.989\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e41 (46.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e47 (53.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.26 (0.69-2.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e57 (44.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e70 (55.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.48 (0.81-2.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLR \u0026gt;145\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e37 (52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e34 (47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.14 (0.59-2.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.702\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e54 (48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e57 (51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.06 (0.56-1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.866\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e39 (42.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e53 (57.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.57 (0.89-2.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003eAssociation of inflammatory indexes during the first 3 days after admission. Values considered abnormal were determined by the following cutoff points: SII index \u0026gt;1.92, SIRI \u0026gt; 3.2, NLR \u0026gt;4.0, LMR \u0026lt;2, PLR \u0026gt;145, (5-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 5 displays the association of cerebral ischemia for the cutoff points evaluated for SII, SIRI, NLR, LMR and PLR during the first three days; SII value on the third day (OR 3.11 (IC95% 1.34 \u0026ndash; 7.24) p=0.008), SIRI at first day (OR\u0026nbsp;2.15 (IC95%\u0026nbsp;1.02-4.71) p=0.047), NLR at first and third day (OR\u0026nbsp;2.30 (IC95%\u0026nbsp;1.05-5.37) p=0.033)\u0026nbsp;are associated with cerebral ischemia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Analysis of laboratory values to predict cerebral infarct.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"572\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.6084%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCerebral infarct\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (IC95%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP- value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSII \u0026gt;1.92\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e42 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e21 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.60 (0.77-3.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e60 (75.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e19 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.80 (0.40-1.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.533\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e22 (61.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e14 (38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e3.11 (1.34-7.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSIRI \u0026gt;3.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e54 (65.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e28 (34.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.15 (1.02-4.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e91 (71.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e36 (28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.58 (0.72-3.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.276\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e107 (68.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e49 (31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.21 (0.92-6.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNLR \u0026gt;4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e62 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e31 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.30 (1.05-5.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e105 (72.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e39 (27.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.36 (0.54-3.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.535\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e108 (67.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e51 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e3.31 (1.22-11.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLMR \u0026lt;2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e35 (68.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e16 (31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.33 (0.63-2.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e60 (68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e28 (31.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.84 (0.92-3.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e88 (69.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e39 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.33 (0.68-2.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.412\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLR \u0026gt;145\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e49 (69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e22 (31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.35 (0.65-2.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.419\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e83 (74.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e28 (25.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.85 (0.42-1.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e64 (69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e28 (30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.17 (0.62-2.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003eAssociation of inflammatory indexes during the first 3 days after admission. Values considered abnormal were determined by the following cutoff points: SII index \u0026gt;1.92, SIRI \u0026gt; 3.2, NLR \u0026gt;4.0, LMR \u0026lt;2, PLR \u0026gt;145, (5-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 6 displays the association of death for the cutoff points evaluated for SII, SIRI, NLR, LMR and PLR during the first three days; SII at third day (OR 2.43 (IC95% 1.06-5.51) p=0.033), SIRI at second day (OR 2.5 (IC95% 1.22-5.35) p=0.014), and LMR at second day (OR 2.78 (IC95% 1.50-5.23) p=0.001) are associated with death.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 6. Analysis of laboratory values to predict death.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"572\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.6084%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlive\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDeath\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en, (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (IC95%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP- value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSII \u0026gt;1.92\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e28 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e35 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.75 (0.91-3.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.096\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e44 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e35 (44.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.95 (0.52-1.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.860\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e22 (61.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e14 (38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.43 (1.06-5.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSIRI \u0026gt;3.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e39 (47.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e43 (52.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.54 (0.80-2.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.196\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e63 (49.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e64 (50.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.50 (1.22-5.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e91 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e65 (41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.56 (0.73-3.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.266\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNLR \u0026gt;4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e45 (48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e48 (51.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.53 (0.79-3.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.213\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e76 (52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e68 (47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.89 (0.82-4.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e93 (58.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e66 (41.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.56 (0.71-3.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.282\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLMR \u0026lt;2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e24 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e27 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.38 (0.70-2.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.352\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e38 (43.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e50 (56.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e2.78 (1.50-5.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e71 (55.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e56 (44.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.74 (0.93-3.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 77.6224%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLR \u0026gt;145\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eFirst day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e37 (52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e34 (47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.02 (0.53-1.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.950\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eSecond day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e59 (53.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e52 (46.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.23 (0.66-2.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.516\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.6084%;\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.5804%;\"\u003e\n \u003cp\u003e55 (59.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0559%;\"\u003e\n \u003cp\u003e37 (40.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e1.03 (0.58-1.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.3776%;\"\u003e\n \u003cp\u003e0.908\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003eAssociation of inflammatory indexes during the first 3 days after admission. Values considered abnormal were determined by the following cutoff points: SII index \u0026gt;1.92, SIRI \u0026gt; 3.2, NLR \u0026gt;4.0, LMR \u0026lt;2, PLR \u0026gt;145, (5-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eFigure 2 and 3 displays the ROC curves used to assess the performance and potential prognosis value of all the considered indexes and ratios during the first three days after SAH for DCI and for death. These show a poor performance of all the indexes and ratios as indicated by low AUC values, close to 0.5 (similar to a coin toss) and the absence of parameter values with useful sensitivity and specificity.\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e\u003cstrong\u003eSummary of findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study we assessed inflammatory indexes (MPV:PLT ratio,\u0026nbsp;systemic immune inflammation index, neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio,\u0026nbsp;platelet to lymphocyte ratio)\u0026nbsp;in 309 aSAH patients as potential prognostic tools for DCI or death during ICU stay. We could not reproduce the results of previous studies that have proposed these as useful in SAH patients or in critical care patients with other types of stroke. The performance of these parameters as assessed by ROC curves and association with the events of interest based on proposed cut-off points did not suggest any as a valuable prognostic tool in our cohort.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a single center retrospective study with the inherent limitations, including missing data for some patients regarding laboratory values. The statistical methodology used in this study analyzed trajectory and trends of individual patients while assessing the infliction point of the biomarkers. Also, we could only assess the prognostic value of the proposed indexes in hospital outcomes, as long term mortality and functional outcomes were not available to us.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplications for care and future research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDelayed cerebral ischemia is a major event that affects\u0026nbsp;survival and functional outcome following subarachnoid hemorrhage and has been a focus of recent research(3, 15-17). \u0026nbsp;Early clinical parameters such as lower modified Fisher grade, WFNS scale, the absence of intracerebral hematoma and pupillary light reflexes can be used as early clinical predictors of functional outcome and favorable or non-favorable prognosis. The pathophysiology of DCI has been extensively discussed in recent reviews and we know that bleeding in subarachnoid space triggers a rapid activation of inflammatory cascades, leading to leukocytosis and activation of an innate immune response characterized by increased neutrophil counts and platelets, which induce micro thrombosis, and can increase the probability to DCI(6, 18). Previous studies reported that inflammatory markers are associated with the development of DCI. Ray B, et al (2018), measured the MPV:PLT ratio after aSAH and found a significant early increase in the reactive platelet population after aHSA in patients who developed DCI, Geraghty J, et al (2021), calculated the SII index and concluded that an early elevation of the SII index predicts the development of late cerebral vasospasm in aneurysmal SAH.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough we found several studies reporting different prognostic indexes or ratios, most results were not reproduced in subsequent studies. A potential explanation for this finding and for the discrepancy between our results and some previous studies is that of publications bias. It could be that studies that have assessed these parameters have not found clinically relevant associations and therefore are not submitted to or accepted by journals, while those with significant findings do; leading to availability of studies that are difficult to reproduce as their findings could be a consequence of random error. Other explanations for the discrepancy are the differences in patients\u0026rsquo; selection and exposure measurements which can lead to different results. Of course, the inability to reproduce some findings was also expected as some indexes have been proposed in different populations (not SAH patients) and for different outcomes (vasospasm).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFuture prospective multicenter studies are required to evaluate the prognostic value of the inflammatory index for the diagnosis of ICD in patients with SAH and to identify new ones. This would also allow for the incorporation of additional forward-looking metrics.\u0026nbsp;\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eProposed prognostic tools based on blood count parameters do not appear useful in patients with SAH, and we need better tools for prognosis of complications that allow improved selection of monitoring alternatives and guide therapeutic decisions. Prospective and multicenter studies are needed to evaluate the value of systemic inflammatory markers that given the understanding of SAH pathophysiology have a promising potential.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eaSAH\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAneurysmal subarachnoid hemorrhage\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDCI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDelayed cerebral ischemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePLT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePlatelet count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMPV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMean platelet volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNeuroICU\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeurologic intensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSII\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSystemic immune inflammation index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSIRI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSystemic inflammation Response index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNLR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeutrophil to lymphocyte ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLMR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLymphocyte to monocyte ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePLR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePlatelet to lymphocyte ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNEU\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeutrophil\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLYM\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLymphocyte\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMONO\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMonocyte\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Dr. Juan P. D\u0026iacute;az-Sol\u0026oacute;rzano, M.D., for providing language editing to improve the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEtminan N, Chang H-S, Hackenberg K, De Rooij NK, Vergouwen MD, Rinkel GJ, et al. Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: a systematic review and meta-analysis. JAMA Neurol. 2019;76(5):588\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTreggiari MM, Rabinstein AA, Busl KM, Caylor MM, Citerio G, Deem S, et al. Guidelines for the neurocritical care management of aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2023;39(1):1\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMacdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Reviews Neurol. 2014;10(1):44\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcMahon CJ, Hopkins S, Vail A, King AT, Smith D, Illingworth KJ, et al. Inflammation as a predictor for delayed cerebral ischemia after aneurysmal subarachnoid haemorrhage. J neurointerventional Surg. 2013;5(6):512\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRay B, Tinsley L, Ford L, Thompson DM, Sidorov EV, Bohnstedt BN. Trends of platelet volume index predicts delayed cerebral ischemia after subarachnoid hemorrhage. World Neurosurg. 2018;111:e624\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBudohoski KP, Guilfoyle M, Helmy A, Huuskonen T, Czosnyka M, Kirollos R, et al. The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2014;85(12):1343\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDhar R, Diringer MN. The burden of the systemic inflammatory response predicts vasospasm and outcome after subarachnoid hemorrhage. Neurocrit Care. 2008;8(3):404\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGeraghty JR, Lung TJ, Hirsch Y, Katz EA, Cheng T, Saini NS, et al. Systemic Immune-Inflammation Index Predicts Delayed Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage. Neurosurgery. 2021;89(6):1071\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhorchid Y, Schirmer CM, Commentary. Systemic Immune-Inflammation Index Predicts Delayed Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage. Neurosurgery. 2021;89(6):E307\u0026ndash;E.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClaassen J, Bernardini GL, Kreiter K, Bates J, Du YE, Copeland D, et al. Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke. 2001;32(9):2012\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiegler JE, Marcaccio C, Nawalinski K, Quattrone F, Sandsmark DK, Maloney-Wilensky E, et al. Elevated red cell distribution width is associated with cerebral infarction in aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2017;26(1):26\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDowlati E, Mualem W, Carpenter A, Chang JJ, Felbaum DR, Sur S et al. Early Fevers and Elevated Neutrophil-to-Lymphocyte Ratio are Associated with Repeat Endovascular Interventions for Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2021:1\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYun S, Yi HJ, Lee DH, Sung JH. Systemic inflammation response index and systemic immune-inflammation index for predicting the prognosis of patients with aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2021;30(8):105861.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010;41(10):2391\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGeraghty JR, Testai FD. Delayed cerebral ischemia after subarachnoid hemorrhage: beyond vasospasm and towards a multifactorial pathophysiology. Curr Atheroscler Rep. 2017;19(12):1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVeldeman M, Rossmann T, Haeren R, Vossen LV, Weiss M, Conzen C, et al. Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage: Location, Distribution Patterns, Infarct Load, and Effect on Outcome. Neurology. 2024;103(3):e209607.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWiseman PN, Power S, MacNally S, Nolan D, Corr P, Curley G et al. Management and Outcomes of Delayed Cerebral Ischemia Associated with Vasospasm Post Nontraumatic Subarachnoid Hemorrhage: A Retrospective Cohort Study in the National Neurosurgical Center in Ireland. J Neuroanaesthesiology Crit Care. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlsbrook DL, Di Napoli M, Bhatia K, Desai M, Hinduja A, Rubinos CA, et al. Pathophysiology of early brain injury and its association with delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a review of current literature. J Clin Med. 2023;12(3):1015.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"\"Subarachnoid Hemorrhage\"[Mesh], \"Intracranial Aneurysm\"[Mesh], \"Aneurysm, Ruptured\"[Mesh], \"Delayed cerebral ischemia\"[Mesh], \"Inflammatory indexes\"[Mesh]","lastPublishedDoi":"10.21203/rs.3.rs-4802088/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4802088/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eInflammatory biomarkers and derived indexes have been reported as useful prognostic tools in subarachnoid hemorrhage (SAH) to predict risk of vasospasm, delayed cerebral ischemia (DCI) or death. This study aimed to assess the prognostic value of platelet characteristics, the systemic inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume-to-platelet ratio (MPV:PLT) in patients with aneurysmal subarachnoid hemorrhage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis was a retrospective cohort study that included 309 adult patients with SAH admitted to the ICU of a tertiary care teaching hospital in Cali, Colombia between 2011 and 2022. Plasma inflammatory biomarkers were measured in patients up to 14 days after SAH. Platelet characteristics trajectory plots by occurrence of DCI were produced to look for trend changes in the first days after SAH that could suggest and underlying pathophysiologic mechanism useful for prediction of this outcome. Odds ratios with 95% confidence interval were calculated for all indexes and ratios in the first three days after SAH using the originally reported cut-off points for its association with DCI, vasospasm, favorable modified Rankin scale score (0-3) and death. The prognostic value of the indexes was assessed through area under the receiver operating characteristic curves (AU-ROC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e309 patients were included in this study (mean age 58.3 years, 68% women). DCI was detected in 137 patients; 44.3%. Vasospasm was detected in 111; 35.9%. During the hospitalization rebleeding occurred in 54 patients (17.5%), hydrocephalus in 107 patients (34.6%) and cerebral ischemia in 77 patients (24.9%). For the cut-off points of SII \u0026gt;1.92, SIRI\u0026gt;3.2, NLR\u0026gt;4, LMR\u0026lt;2, and PLR\u0026gt;145 during the first three days after admission we did not find association with DCI, vasospasm, neurologic outcome or death. The AU-ROC estimates of these indexes did not surpass a pre-stablished usefulness threshold of 75% and thus no new cut-off points were proposed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePreviously reported results of the prognostic value of inflammatory indexes and biomarkers in patients with SAH or other cerebrovascular diseases were not reproducible in this cohort of patients with aneurysmal subarachnoid hemorrhage. Our findings call into question the reproducibility and applicability of proposed prognostic biomarkers and indexes and should prompt efforts to verify their value in clinical settings, as well as prompt efforts to identify the best prognostic tools available in these patients.\u003c/p\u003e","manuscriptTitle":"Biomarkers of systemic inflammatory status as predictors of delayed cerebral ischemia after subarachnoid hemorrhage","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-17 15:01:23","doi":"10.21203/rs.3.rs-4802088/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9182fb86-861a-4211-9484-923bd08f407f","owner":[],"postedDate":"October 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-17T15:01:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-17 15:01:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4802088","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4802088","identity":"rs-4802088","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}