scholarly journals Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Juan Marta-Enguita ◽  
Manuel Navarro-Oviedo ◽  
Idoia Rubio-Baines ◽  
Nuria Aymerich ◽  
Maria Herrera ◽  
...  

Abstract Background Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi. Methods Among the 748 patients treated at a comprehensive stroke center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24 h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3 months (defined as modified Rankin Scale < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44). Results Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13–4.73)]. Patients with calprotectin ≥ 2.26 μg/mL were 4 times more likely to die [OR 4.34 (1.95–9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87–0.95) vs 0.89 (0.85–0.93); p < 0.05]. A multimarker approach demonstrated that patients with increased calprotectin, CRP, and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p = 0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p < 0.002), leukocytes (0.45, p < 0.01), and neutrophil elastase (0.70, p < 0.001) thrombus content. Conclusions Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. The presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation, and further studies are needed to determine its influence in resistance to reperfusion.

2020 ◽  
Author(s):  
Juan Marta-Enguita ◽  
Manuel Navarro-Oviedo ◽  
Idoia Rubio-Baines ◽  
Nuria Aymerich ◽  
Maria Herrera ◽  
...  

Abstract Background- Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi.Methods- Among the 748 patients treated at a comprehensive stroke centre between 2015-2017, 413 patients with confirmed acute ischemic injury were evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3-months (defined as modified Rankin Scale<2), and intracranial haemorrhage (ICH) after stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n=44). Results- Higher calprotectin levels were associated with 3-month mortality and ICH, while lower calprotectin levels were documented in patients with 3-month FI. After adjusting for potential confounders, plasma calprotectin levels remained associated with 3-month mortality [OR (95%CI); 3.06, (1.67-5.61)]. Patients with calprotectin≥2.26 µg/mL were 4-times more likely to die [OR 3.98, (1.88-8.41)]. Likewise, Neutrophil-Lymphocyte Ratio (NLR) and C-Reactive Protein (CRP) were also associated with 3-month mortality [OR 1.98, (1.17-3.35); and 1.39, (1.02-1.89) respectively]. A multimarker approach demonstrated that patients with increased calprotectin, CRP and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p=0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p<0.002); leukocytes (0.45, p<0.01) and neutrophil elastase (0.70, p<0.001) thrombi content. Conclusions- Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. Presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation and further studies are needed to determine its influence in resistance to reperfusion.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Susan Deveikis ◽  
Karen Albright ◽  
John Deveikis ◽  
Kara Sands ◽  
Harn Shiue ◽  
...  

Background and Purpose: Minimizing time from symptom onset to recanalization is crucial to maximizing outcome. Approaches to save time in ET cases including processes to reduce door-to-recanalization times need to be explored. Methods: We performed a retrospective review of consecutive ischemic stroke patients transferred to our comprehensive stroke center (CSC) from March 2014 to April 2015. Demographic and clinical data were collected. We compared adverse events (hemorrhagic transformation [HT], DVT, PE, urinary tract infection [UTI], pneumonia [PNA], bacteremia), door-to-recanalization time, and short-term outcomes in patients that were evaluated in the emergency department (ED) prior to ET and patients that were transferred directly to the endovascular suite, bypassing the ED. Results: Among the 776 consecutive ischemic stroke patients admitted to our center during the 14-month period, 7% (n=49) received acute ET. Twenty-six of these patients (53%) were transferred to our CSC for ET. Among transfers, 58% (n=15) bypassed the ED. Patients that bypassed the ED had a higher frequency of adverse events (53% vs. 27%, p=0.246), but shorter arrival to recanalization times when compared to patients that did not skip the ED (median 89 vs. 109 minutes p=0.637). Poor functional outcome, as measured by modified Rankin scale (mRS) score of 4-6, was similar between groups (67% vs. 64%, p=1.000), but in-hospital mortality was more frequent in the ED bypass group (33% vs. 18%, p=0.658). Conclusions: In our sample of acute ischemic patients transferred for acute ET, nearly 60% of patients bypassed the ED, reducing time to recanalization. This time savings was associated with a clinically higher proportion of adverse events. Standardized protocols for patients transferred to acute ET are needed to reduce time to recanalization without increasing adverse event rates.


2019 ◽  
Vol 47 (3-4) ◽  
pp. 112-120 ◽  
Author(s):  
David Weisenburger-Lile ◽  
Raphaël Blanc ◽  
Maeva Kyheng ◽  
Jean-Philippe Desilles ◽  
Julien Labreuche ◽  
...  

Background: To date, thrombectomy for large vessel occlusion (LVO) strokes can be performed only in comprehensive stroke centers with thrombectomy capacity. We compared the clinical outcome of patients first referred to a primary stroke center to those admitted directly to a comprehensive stroke center and treated on site in the multicentric observational Endovascular Treatment in Ischemic Stroke (ETIS) registry. Methods: From our perspective, multicenter, observational ETIS registry, we analyzed anterior circulation stroke patients, treated within 8 h, who underwent thrombectomy after thrombolysis and were admitted to a comprehensive stroke center either with drip and ship or mothership. Clinical and safety outcomes were compared between 2 groups. Results: A total of 971 patients were analyzed: 298 were treated with the mothership approach and 673 with drip and ship. Significantly more functional independence (90-day modified Rankin Scale [mRS] 0–2) was achieved in mothership (60.1%) than in drip and ship patients (52.6%; adjusted relative risk [RR] 0.87, 95% CI 0.77–0.98, p = 0.018). Excellent outcome (90-day mRS 0–1) was achieved in 45.3% of the mothership group, compared to 37.9% of the drip and ship group (RR 0.84, 95% CI 0.71–0.98; p = 0.026). According to the distance between the primary stroke center and the comprehensive stroke center, greater functional independence was achieved in mothership than in drip and ship >12.5 miles patients (adjusted RR 0.82; 95% CI 0.71–0.94). Results in the drip-ship group stratified according to time between cerebral imaging and groin puncture (categorized according to the median cut-off: 140 min) were similar. Symptomatic intracerebral hemorrhage rate and mortality within 90 days was similar in both groups (7.5 vs. 5.9%, p = 0.40; 17.4 vs. 16.1%, p = 0.63). Conclusions: Our study suggests that LVO stroke patients directly admitted to a comprehensive stroke center present a higher chance of functional independence, especially when the distance between the primary stroke center and comprehensive stroke center is >12.5 miles or when the time between cerebral imaging and groin puncture is ≥140 min.


2018 ◽  
Vol 11 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Mohammad Ismail ◽  
Xavier Armoiry ◽  
Noam Tau ◽  
François Zhu ◽  
Udi Sadeh-Gonik ◽  
...  

BackgroundThe effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke due to large vessel occlusion is time-dependent. While only stroke centers with endovascular capabilities perform MT, many patients who had a stroke initially present to the closest primary stroke centers capable of administering earlier intravenous thrombolysis, and then require to be transferred to a comprehensive stroke center for MT.PurposeTo compare the outcomes of this care pathway (drip and ship (DS)) with that whereby patients are directly transferred to a comprehensive stroke center (mothership (MS)).MethodsWe performed a systematic review and meta-analysis of published studies using several electronic databases to determine whether successful reperfusion (modified Thrombolysis In Cerebral Infarction ≥2b), functional independence at 90 days (modified Rankin Scale score ≤2), symptomatic intracranial hemorrhage, and 90-day mortality differed between those who underwent MT with the DS or the MS treatment pathway. Outcomes were meta-analyzed and the results expressed as adjusted relative risk (aRR) for the primary analysis and unadjusted relative risk (uRR) for secondary analysis.ResultsEight studies including 2068 patients were selected, including one study reporting results fully adjusted for baseline characteristics. Patients undergoing MS had better functional independence than those undergoing DS (uRR=0.87, 95% CI 0.81 to 0.93; aRR=0.87, 95% CI 0.77 to 0.98). No difference was found between the treatment pathways in successful reperfusion (uRR=1.05, 95% CI 0.95 to 1.15; aRR=1.00, 95% CI 0.92 to 1.10), symptomatic intracranial hemorrhage (uRR=1.37, 95% CI 0.91 to 2.06; aRR, 1.53, 95% CI 0.79 to 2.98), and 90-day mortality (uRR=1.00, 95% CI 0.84 to 1.19; aRR=1.21, 95% CI 0.89 to 1.64).ConclusionsPatients who had an acute ischemic stroke admitted directly to a comprehensive stroke center (MS patients) with endovascular capacities may have better 90-day outcomes than those receiving DS treatment. However, major limitations of current evidence (ie, retrospective studies and selection bias) suggest a need for adequately powered studies. Multicenter randomized controlled trials are expected to answer this question.


2021 ◽  
Vol 12 ◽  
Author(s):  
Christian A. Taschner ◽  
Alexandra Trinks ◽  
Jürgen Bardutzky ◽  
Jochen Brich ◽  
Ralph Hartmann ◽  
...  

Introduction: Organizing regional stroke care considering thrombolysis as well as mechanical thrombectomy (MTE) remains challenging in light of a wide range of regional population distribution. To compare outcomes of patients in a stroke network covering vast rural areas in southwestern Germany who underwent MTE via direct admission to a single comprehensive stroke center [CSC; mothership (MS)] with those of patients transferred from primary stroke centers [PSCs; drip-and-ship (DS)], we undertook this analysis of consecutive stroke patients with MTE.Materials and Methods: Patients who underwent MTE at the CSC between January 2013 and December 2016 were included in the analysis. The primary outcome measure was 90-day functional independence [modified Rankin score (mRS) 0–2]. Secondary outcome measures included time from stroke onset to recanalization/end of MTE, angiographic outcomes, and mortality rates.Results: Three hundred and thirty-two consecutive patients were included (MS 222 and DS 110). Median age was 74 in both arms of the study, and there was no significant difference in baseline National Institutes of Health Stroke Scale scores (median MS 15 vs. 16 DS). Intravenous (IV) thrombolysis (IVT) rates differed significantly (55% MS vs. 70% DS, p = 0.008). Time from stroke onset to recanalization/end of MTE was 112 min shorter in the MS group (median 230 vs. 342 min, p &lt; 0.001). Successful recanalization [thrombolysis in cerebral infarction (TICI) 2b-3] was achieved in 72% of patients in the MS group and 73% in the DS group. There was a significant difference in 90-day functional independence (37% MS vs. 24% DS, p = 0.017), whereas no significant differences were observed for mortality rates at 90 days (MS 22% vs. DS 17%, p = 0.306).Discussion: Our data suggest that patients who had an acute ischemic stroke admitted directly to a CSC may have better 90-day outcomes than those transferred secondarily for thrombectomy from a PSC.


Author(s):  
Marie-Claude Beaulieu ◽  
Ahmad Nehme ◽  
Francis Fortin ◽  
Fatine Karkri ◽  
Nicole Daneault ◽  
...  

ABSTRACT:Introduction:The benefit of late window endovascular treatment (EVT) for anterior circulation ischemic stroke has been demonstrated using perfusion-based neuroimaging. We evaluated whether non-contrast CT (NCCT) and CT-angiogram (CTA) alone can select late-presenting patients for EVT.Methods:We performed a retrospective comparison of all patients undergoing EVT at a single comprehensive stroke center from January 2016 to April 2017. Patients planned for EVT were divided into early (<6 hours from onset) and late (≥6 hours from onset or last time seen normal) window groups. Incidence of symptomatic hemorrhagic transformations (sHTs) at 24 hours and 3-month modified Rankin scores (mRSs) were compared.Results:During the study period, 204 (82%) patients underwent EVT in the early and 44 (18%) in the late window. Median (interquartile range) NIH Stroke Scale Score was similar between groups (early: 18 [15–23] vs. late: 17 [13–21]), as were median ASPECT scores (early: 9 [8–10] vs. late: 9 [7–9]). In the late window, 42 (95%) strokes were of unknown onset. Similar proportions of sHT occurred at 24 hours (early: 12 [6%] vs. late: 4 [9%], p = 0.43). At 3 months, the proportion of patients achieving functional independence (mRS 0–2) were comparable in the early (80/192 [42%]) and late (16/41 [39%]) windows (p = 0.76).Conclusion:NCCT- and CTA-based patient selection led to similar functional independence outcomes and low proportions of sHT in the early and late windows. In centers without access to perfusion-based neuroimaging, this pragmatic approach could be safe, particularly for strokes of unknown onset.


2021 ◽  
pp. 028418512110068
Author(s):  
Yu Hang ◽  
Zhen Yu Jia ◽  
Lin Bo Zhao ◽  
Yue Zhou Cao ◽  
Huang Huang ◽  
...  

Background Patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) were usually transferred from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (drip-and-ship [DS]), while driving the doctor from a CSC to a PSC to perform a procedure is an alternative strategy (drip-and-drive [DD]). Purpose To compare the efficacy and prognosis of the two strategies. Material and Methods From February 2017 to June 2019, 62 patients with LVO received endovascular treatment via the DS and DD models and were retrospectively analyzed from the stroke alliance based on our CSC. Primary endpoint was door-to-reperfusion (DTR) time. Secondary endpoints included puncture-to-recanalization (PTR) time, modified Thrombolysis in Cerebral Infarction (mTICI) rates at the end of the procedure, and modified Rankin Scale (mRS) at 90 days. Results Forty-one patients received the DS strategy and 21 patients received the DD strategy. The DTR time was significantly longer in the DS group compared to the DD group (315.5 ± 83.8 min vs. 248.6 ± 80.0 min; P < 0.05), and PTR time was shorter (77.2 ± 35.9 min vs. 113.7 ± 69.7 min; P = 0.033) compared with the DD group. Successful recanalization (mTICI 2b/3) was achieved in 89% (36/41) of patients in the DS group and 86% (18/21) in the DD group ( P = 1.000). Favorable functional outcomes (mRS 0–2) were observed in 49% (20/41) of patients in the DS group and 71% (15/21) in the DD group at 90 days ( P = 0.089). Conclusion Compared with the DS strategy, the DD strategy showed more effective and a trend of better clinical outcomes for AIS patients with LVO.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Saqib A Chaudhry ◽  
Gustavo J Rodriguez ◽  
M. Fareed K Suri ◽  
Adnan I Qureshi

Background: “Drip-and-ship” denotes patients in whom intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is initiated at the emergency department (ED) of a community hospital, followed by transfer within 24 hours to a comprehensive stroke center. Although drip-and-ship paradigm has the potential to increase the number of patients who receive IV rt-PA, comparative outcomes have not been assessed at a population based level. Methods: State-wide estimates of thrombolysis, associated in-hospital outcomes and mortality were obtained from 2008-2009 Minnesota Hospital Association (MHA) data. Patient numbers and frequency distributions were calculated for state-wide sample of patients hospitalized with a primary diagnosis of ischemic stroke. Patients outcomes were analyzed after stratification into patients treated with IV rt-PA through primary ED arrival or drip-and-ship paradigm. Results: Of the 21,024 admissions, 602 (2.86%) received IV rt-PA either through primary ED arrival (n=473) or drip-and-ship paradigm (n=129). The rates of secondary intracerebral or subarachnoid hemorrhage were higher in patients treated with IV rt-PA through primary ED arrival compared with those treated with drip-and-ship paradigm (8.5% versus 3.1, p=0.038). The in-hospital mortality rate was similar among ischemic stroke patients receiving IV rt-PA through primary ED arrival or drip-and-ship paradigm (5.9% versus 7.0%). The mean hospital charges were $65,669 for primary ED arrival and $47,850 for drip-and-ship treated patients (p<0.001). Conclusions: The results of drip-and-ship paradigm compare favorably with IV rt-PA treatment through primary ED arrival in this state-wide study.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Adam de Havenon ◽  
Anne Moore ◽  
Nicholas Freeberg ◽  
Ali Sultan-Qurraie ◽  
David Tirschwell

Background: An echocardiogram or transcranial Doppler (TCD) bubble study to test for a right-to-left shunt (RLS) is a standard component of an ischemic stroke workup. Because the pathway for an intracradiac RLS, such as a patent foramen ovale (PFO), is more direct, it has been proposed that the late appearance of a RLS suggests an extracardiac pathway. We sought to characterize a cohort of ischemic stroke patients with late RLS (LRLS) on TCD. Methods: We searched the medical record of a Comprehensive Stroke Center for patients with ischemic stroke who had a TCD and echocardiogram bubble study during 2011-2013. LRLS was defined as TCD bubbles appearing more than 18 cardiac cycles after contrast injection. TOAST stroke etiology classification was performed by a vascular neurologist blinded to TCD results. Results: 124 patients met inclusion criteria, of which 67/124 (54%) had RLS on TCD; and 32/67 (48%) had LRLS. In the 35/67 patients with normal RLS on TCD, 23% did not have RLS on echocardiography, consistent with prior reports of TCD’s superiority for detecting RLS. In the 32/67 patients with LRLS on TCD, 56% were negative for RLS by echocardiography. In the cohort of 124 patients, the percentage of TOAST classification 4 (stroke of other determined cause) was 26%, while in the 32 patients with LRLS the percentage of TOAST 4 was significantly higher at 52%(p=0.005) (Table 1). The increase in TOAST 4 in LRLS patients was created by an even distribution of decreases in the other TOAST categories. The most common TOAST 4 stroke etiology in LRLS patients was PFO with concurrent deep venous thrombosis. Conclusion: This preliminary data supports prior studies that have shown superiority of TCD over echocardiography for detection of RLS, and challenge the prevailing notion that extracardiac shunt, such as pulmonary AVM, is the most common cause of LRLS in ischemic stroke patients. This subgroup of patients warrants further research to clarify mechanisms of ischemic stroke in patients with RLS.


2017 ◽  
Vol 10 (9) ◽  
pp. 828-833 ◽  
Author(s):  
Abhi Pandhi ◽  
Georgios Tsivgoulis ◽  
Rashi Krishnan ◽  
Muhammad F Ishfaq ◽  
Savdeep Singh ◽  
...  

BackgroundFew data are available regarding the safety and efficacy of antiplatelet (APT) pretreatment in acute ischemic stroke (AIS) patients with emergent large vessel occlusions (ELVO) treated with mechanical thrombectomy (MT). We sought to evaluate the association of APT pretreatment with safety and efficacy outcomes following MT for ELVO.MethodsConsecutive ELVO patients treated with MT during a 4-year period in a tertiary stroke center were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), successful recanalization (SR; modified TICI score 2b/3), mortality, and functional independence (modified Rankin Scale scores of 0–2).ResultsThe study population included 217 patients with ELVO (mean age 62±14 years, 50% men, median NIH Stroke Scale score 16). APT pretreatment was documented in 71 cases (33%). Patients with APT pretreatment had higher SR rates (77% vs 61%; P=0.013). The two groups did not differ in terms of sICH (6% vs 7%), 3-month mortality (25% vs 26%), and 3-month functional independence (50% vs 48%). Pretreatment with APT was independently associated with increased likelihood of SR (OR 2.18, 95% CI1.01 to 4.73; P=0.048) on multivariable logistic regression models adjusting for potential confounders. A significant interaction (P=0.014) of intravenous thrombolysis (IVT) pretreatment on the association of pre-hospital antiplatelet use with SR was detected. APT pretreatment was associated with SR (OR 2.74, 95% CI 1.15 to 6.54; P=0.024) in patients treated with combination therapy (IVT and MT) but not in those treated with direct MT (OR 1.78, 95% CI 0.63 to 5.03; P=0.276).ConclusionAPT pretreatment does not increase the risk of sICH and may independently improve the odds of SR in patients with ELVO treated with MT. The former association appears to be modified by IVT.


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