Eosinophil: A New Circulating Biomarker for Risk of Poor Outcome in Stroke Patients Undergoing Mechanical Thrombectomy.

Objective: Acute ischemic stroke (AIS), caused by occlusion of large vessel, is a serious life-threatening disease. This study aimed to comprehensively investigate the association of 14 common and readily available circulating biomarkers with the 90-day modified Rankin Scale (mRS) score in patients undergoing mechanical thrombectomy (MT). Methods: This study included patients with anterior circulation large vessel occlusive stroke treated with MT from 05/2017 to 12/2021. Baseline comparisons of poor outcome were performed among enrolled patients. Factors that may be associated with the mRS score were assessed using correlation analysis. Univariate and multivariate logistic regression analyses were used to evaluate the predictive value of circulating biomarkers and poor outcome. Results: The mRS score has a strong correlation with neutrophil to lymphocyte ratio (NLR) and eosinophil levels (all rs>0.4 in absolute value and all P<0.001) in addition to a high correlation with National Institute of Health Stroke Scale (NIHSS) score (rs=0.40, P<0.001). There was also a high correlation between NLR and eosinophil (rs=-0.58, P<0.001). In the multivariate regression analysis, only neutrophil (adjusted OR=1.301, 95% CI: 1.155-1.465, P<0.001), eosinophil (adjusted OR<0.001, 95% CI: <0.001-0.016, P<0.001), and NLR (adjusted OR=1.158, 95% CI: 1.082-1.241, P<0.001) were independently associated with poor outcome. Conclusion: This study evaluated a series of circulating biomarkers and found that neutrophil, eosinophil, and NLR independently predicted poor outcome after MT in AIS patients. There was a significant negative correlation between eosinophil and NLR levels.

Value of angiographic regional circulation signs in predicting hemorrhagic transformation after endovascular thrombectomy.

OBJECTIVE: The aim of this study was to evaluate the predictive value of the early venous filling (EVF) sign, the basal ganglia blush (BGB) sign and both the EVF and BGB signs for the hemorrhagic transformation (HT) and parenchymal hematoma (PH) in patients after endovascular thrombectomy. METHODS: This study included patients with anterior circulation large vessel occlusive stroke treated with endovascular thrombectomy from May 2017 to December 2021. The predictive value of regional circulation signs for HT and PH were assessed using logistic regression models adjusted for confounders, and further a multiplicative interaction term was added to investigate the effect of different stroke severity on its predictive value. RESULTS: Among the 350 patients included and after adjusting for confounders, those with the EVF sign (adjusted OR=3.934, 95% CI:2.326-6.655), the BGB sign (adjusted OR=3.776, 95% CI:2.341-6.089), and both the EVF and BGB signs (adjusted OR=3.250, 95% CI: 1.886-5.600) were more likely to have HT. The EVF sign (adjusted OR=3.545, 95% CI:2.036-6.170), the BGB sign (adjusted OR=3.742, 95% CI:2.110-6.639), and both the EVF and BGB signs (adjusted OR=3.139, 95% CI: 1.776-5.549) were also significantly correlated with PH. When stratified according to stroke severity, we further found there were significant interactions between regional circulation signs and stroke severity on postoperative HT and PH (all P for interaction < 0.001). CONCLUSIONS: Regional circulation signs were independently associated with HT and PH after endovascular thrombectomy and had a higher predictive value in patients with severe stroke compared with mild to moderate stroke.

Influences of different referral modes on clinical outcomes after endovascular therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: As endovascular thrombectomy (EVT) is time-dependent, it is crucial to refer patients promptly. Current referral modes include Mothership (MS), Drip and Ship (DS) and Drive the Doctor (DD). The purpose of this study was to investigate the influences of different referral modes on the clinical outcomes of patients with acute ischemic stroke after EVT.  METHODS: A total of 349 patients from 15 hospitals between April 2017 and March 2020 were enrolled. The primary outcomes include poor outcome (modified Rankin Scale score of 3 to 6), symptomatic intracranial hemorrhage transformation (sICH), mortality and cost. Regression analysis was used to assess the association of referral modes with poor outcome, sICH, mortality and cost in acute ischemic stroke patients. RESULTS: Among the 349 patients, 83 were in DD group (23.78%), 85 in MS group (24.36%) and 181 in DS group (51.86%). There were statistically significant differences in intravenous thrombolysis, onset-to-door time, onset-to-puncture time, puncture-to-recanalization time, door-to-puncture time, door-to-recanalization time, and cost among the DD, MS, and DS groups (59.04% vs 35.29% vs 33.15%, P<0.001; 90 vs 166 vs 170 minutes, P<0.001; 230 vs 270 vs 270 minutes, P<0.001; 82 vs 54 vs 51 minutes, P<0.001; 110 vs 85 vs 96 minutes, P=0.004; 210 vs 146 vs 150 minutes, P<0.001; 64258 vs 80041 vs 70750 Chinese Yuan, P=0.018). In terms of sICH, mortality and poor outcome, there was no significant difference among the DD, MS, and DS groups (22.89% vs 18.82% vs 19.34%, P=0.758; 24.10% vs 24.71% vs 29.83%, P=0.521; 64.47% vs 64.71% vs 68.51%, P=0.827). The results of multiple regression analysis indicated that there was no independent correlation between different referral modes regarding sICH (ORMS: 0.50, 95%CI: 0.18, 1.38, P=0.1830; ORDS: 0.47, 95%CI: 0.19, 1.16, P=0.1000), mortality (ORMS: 0.56, 95%CI: 0.19, 1.67, P=0.2993; ORDS: 0.65, 95%CI: 0.25, 1.69, P=0.3744) and poor outcome (ORMS: 0.61, 95%CI: 0.25, 1.47, P=0.2705; ORDS: 0.53, 95%CI: 0.24, 1.18, P=0.1223). However, there was a correlation between MS group and cost (ß=30449.73, 95%CI: 11022.18, 49877.29; P=0.0023). The multiple regression analysis on patients finally admitted in comprehensive stroke center (MS+DS) versus patients finally admitted in primary stroke center (DD) showed that DD mode was independently associated with lower costs (ß=-19438.86, 95%CI: -35977.79, -2899.94; P=0.0219). CONCLUSION: There was no independent correlation between three referral modes and sICH, mortality, poor outcome correspondingly. Different referral modes can be implemented in clinical practice according to the situations encountered. Compared to MS and DS modes, DD mode is more economical.

Predictors and Dynamic Nomogram to Determine the Individual Risk of Malignant Brain Edema After Endovascular Thrombectomy in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). METHODS: We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. RESULTS: MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell's concordance index) of 0.925 (95% confidence interval=0.890-0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of <1.5 and tolerances of >0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). CONCLUSIONS: Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.

Treatment of Donor-derived Carbapenem-resistant Klebsiella pneumoniae Infection after Renal Transplantation with Tigecycline and Extended-infusion Meropenem.

OBJECTIVE: Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation. METHODS: From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed. RESULTS: Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18-129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33-55) showed no recurrence of new CRKP infection in the 7 surviving recipients. CONCLUSION: It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.

Circ-RNA Expression Pattern and circ-RNA-miRNA-mRNA Network in The Pathogenesis of Human Intervertebral Disc Degeneration.

OBJECTIVE: The present study aimed to screen the differentially expressed (DE) circular RNAs (circ-RNAs) between lumbar intervertebral disc degeneration (IVDD) and normal tissues. MATERIALS AND METHODS: In this experimental study, microarray hybridization was performed to evaluate circ-RNA expression, and the DE circ-RNAs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Host genes of DE circ-RNAs were predicted, and their functions were evaluated. Further, a competitive endogenesis (ce) RNA network among 4 DE circ-RNAs-miRNA-mRNA was constructed by Cytoscape. RESULTS: A total of 2636 circ-RNAs were detected in all samples; among them, 89.23% were exonic circ-RNAs. There were 138 DE circ-RNAs, including 134 up-regulated circ-RNAs and 4 downregulated circ-RNAs in IVDD samples. qRT-PCR validation experiments showed that expression trends of hsa_circ_0003239, hsa_circ_0003162, hsa_circ_0005918, and hsa_circ_0005556 were in line with the microarray analysis results. Functional enrichment analysis showed that host genes of DE circ-RNAs significantly disturbed pathways of regulation of actin cytoskeleton, propanoate metabolism, and ErbB signaling pathway. The four DE circ-RNAs related ceRNA network was constructed. CONCLUSION: Our results revealed that circ-RNAs can function as miRNA sponges and regulate parent gene expression to affect IVDD.

[Effect of substance K on the contractility of cardiomyocytes].

AIM: To investigate the influence and the mechanism of SK on the contractility of cultured cardiomyocytes of rats. METHODS: The primary cultured single myocardial cell was treated with SK and the contraction frequency and size of cardiomyocyte were determined by a computer image analysis system. At the same time the effects of propranolol (a beta receptor antagonist), phentolamine (a alpha receptor antagonist), DSP (a tachykinin receptor antagonist) on the action of SK were investigated. RESULTS: SK increased contractive extend of the cardiomyocyte, in which a dose-response relationship of SK at 1.78 x 10(-8) - 1.78 x 10(-5) mol/L exists. But the frequency of contraction did not change, pretreatment with propranolol, phentolamine had no action on the effect of SK, but DSP markedly attenuated the effects of SK. CONCLUSION: SK may directly enhance the contractility of single cardiomyocyte, which may be related with the tachykinin receptor.