S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Background and purposePost-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.MethodsWe analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.ResultsPTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.ConclusionsHigher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation

Minimal risk of contrast-induced kidney injury in a randomly selected cohort with mildly reduced GFR

Objectives: Previous large studies of contrast-induced or post-contrast acute kidney injury (CI-AKI/PC-AKI) have been observational, and mostly retrospective, often with patients undergoing non-enhanced CT as controls. This carries risk of inclusion bias that makes the true incidence of PC-AKI hard to interpret. Our aim was to determine the incidence of PC-AKI in a large, randomly selected cohort, comparing the serum creatinine (Scr) changes after contrast medium exposure with the normal intraindividual fluctuation in Scr. Methods: In this prospective study of 1009 participants (age 50–65 years, 48% females) in the Swedish CArdioPulmonary bioImage Study (SCAPIS), with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min, all received standard dose intravenous iohexol at coronary CT angiography (CCTA). Two separate pre-CCTA Scr samples and a follow-up sample 2–4 days post-CCTA were obtained. Change in Scr was statistically analyzed and stratification was used in the search of possible risk factors. Results: Median increase of Scr post-CCTA was 0–2 μmol/L. PC-AKI was observed in 12/1009 individuals (1.2%) according to the old ESUR criteria (> 25% or > 44 μmol/L Scr increase) and 2 individuals (0.2%) when using the updated ESUR criteria (≥ 50% or ≥ 27 μmol/L Scr increase). Possible risk factors (e.g., diabetes, age, eGFR, NSAID use) did not show increased risk of developing PC-AKI. The mean effect of contrast media on Scr did not exceed the intraindividual Scr fluctuation. Conclusions: Iohexol administration to a randomly selected cohort with mildly reduced eGFR is safe, and PC-AKI is very rare, occurring in only 0.2% when applying the updated ESUR criteria. Key Points: • Iohexol administration to a randomly selected cohort, 50–65 years old with mildly reduced eGFR, is safe and PC-AKI is very rare. • Applying the updated ESUR PC-AKI criteria resulted in fewer cases, 0.2% compared to 1.2% using the old ESUR criteria in this cohort with predominantly mild reduction of renal function. • The mean effect of CM on Scr did not exceed the intraindividual background fluctuation of Scr, regardless of potential risk factors, such as diabetes or NSAID use in our cohort of 1009 individuals

Revised Swedish guidelines on intravenous iodine contrast medium-induced acute kidney injury 2022 : A summary

The Swedish Society of Uroradiology has revised their computed tomography (CT) guidelines regarding iodine contrast media-induced acute kidney injury (CI-AKI). They are more cautious compared to the European Society of Urogenital Radiology and the American College of Radiology since the actual risk of CI-AKI remains uncertain in patients with moderate to severe kidney damage due to a lack of prospective controlled studies and mainly based on retrospective propensity score-matched studies with low-grade evidence. Another source of uncertainty is the imprecision of glomerular filtration rate (GFR) estimating equations. However, randomized hydration studies indictae an upper limit risk of CI-AKI of about 5% for outpatients with a GFR in the range of 30–44 or 45–59 mL/min/1.73m2 combined with multiple risk factors. Apart from GFR limits, the guideline also includes limits for systemic contrast medium exposure expressed in gram-iodine/GFR ratio

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman’s rho = 0.668 p p = 0.923) or in NT-proBNP expression (0.29 [0.11–0.58]% vs. 0.18 [0.05–0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Background and purpose: Post-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH. Methods: We analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis. Results: PTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots. Conclusions: Higher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation.This publication has emanated from research conducted with the financial support of Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant No. 13/RC/2073_2. Furthermore, the authors declare that this study received funding from Cerenovus. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.peer-reviewe