UNASSIGNED: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment.
UNASSIGNED: To elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms.
UNASSIGNED: We analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture.
UNASSIGNED: Nasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations.
UNASSIGNED: CHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.

UNASSIGNED: Biomarkers of fibrinolysis are elevated during acute immunologic reactions (allergic reactions and angioedema), although it is unclear whether fibrinolysis is associated with disease severity.
UNASSIGNED: We investigated a possible association between maximum lysis (ML) measured by thromboelastography and the severity of acute immunologic reactions.
UNASSIGNED: We recruited patients with acute immunologic reactions at a high-volume emergency department. Clinical disease severity at presentation and at the end of the emergency department stay was assessed using a 5-grade scale, ranging from local symptoms to cardiac arrest. We determined ML on admission by thromboelastography (ROTEM\'s extrinsic [EXTEM], and aprotinin [APTEM] tests), expressed as ML%. Hyperfibrinolysis was defined as an ML of >15% in EXTEM, which was reversed by adding aprotinin (APTEM). We used exact logistic regression to investigate an association between ML% and disease severity (grades 1 and 2 [mild] vs 3-5 [severe]) and between hyperfibrinolysis and disease severity.
UNASSIGNED: We included 31 patients (71% female; median age, 52 [IQR, 35-58] years; 10 [32%] with a severe reaction). ML% was higher in patients with severe symptoms (21 [IQR, 12-100] vs 10 [IQR, 4-17]). Logistic regression found a significant association between ML% and symptom severity (odds ratio, 1.07; 95% CI, 1.01-1.21; P = .003). Hyperfibrinolysis was detected in 6 patients and found to be associated with severe symptoms (odds ratio, 17.59; 95% CI, 1.52-991.09; P = .02). D-dimer, tryptase, and immunoglobulin E concentrations increased with the severity of immunologic reactions.
UNASSIGNED: ML, quantified by thromboelastography, is associated with the severity of acute immunologic reactions.

BACKGROUND: Antithrombotic therapy (AT) should generally be avoided within 24 hours after recombinant tissue-plasminogen activator (rt-PA) treatment but should be considered in patients with large-artery atherosclerosis (LAA) who undergo concomitant emergent endovascular treatment (EVT). The aim of the present study was to assess the safety of AT within 24 hours after rt-PA treatment in patients with hyperacute ischemic stroke due to LAA who received concomitant EVT.
METHODS: From January 2013 through July 2019, consecutive patients with acute ischemic cerebrovascular disease due to LAA who were admitted within 6 hours from symptom onset were recruited. The patients were classified into six groups based on the reperfusion treatment and early (within 24 hours) AT from rt-PA treatment. Safety outcomes were compared among the groups.
RESULTS: A total of 155 patients (35 women [23%], median age 74 [IQR 66-79] years; NIHSS score 3 [1-10]) were included in the present study. Of these, 73 (47%) received no reperfusion therapy, 24 (15%) received rt-PA treatment and early AT, seven (6%) received rt-PA without early AT, 26 (17%) received EVT only, six (4%) received both rt-PA and EVT without early AT, and 19 (12%) received rt-PA and EVT with early AT. AT was administered a median of 3.9 (1.6-8.0) hours after rt-PA in patients with rt-PA+EVT with early AT. AT within 24 hours after rt-PA and EVT treatment did not increase hemorrhagic complications (p > 0.05 for all).
CONCLUSIONS: In this retrospective analyses, early AT administration for patients with hyperacute stroke due to LAA treated with rt-PA plus EVT did not increase hemorrhagic events.

Central retinal artery occlusion (CRAO), a type of acute retinal arterial ischemia, analogous to an ocular stroke, is a medical emergency that warrants immediate diagnosis and treatment. CRAO usually presents with sudden, painless, monocular vision loss. Ipsilateral carotid artery disease is an important associated finding in these patients. The primary limitation to effective treatment of CRAO is that patients are rarely seen in the acute stage. Moreover, there are no guidelines for effective treatment. We report a patient with right CRAO whose treatment with intravenous thrombolysis with tenecteplase and anterior chamber paracentesis with ocular massage resulted in a good clinical outcome.

The relationship between demographic/clinical characteristics, clinical outcomes and the development of hemorrhagic complications in patients with ischemic stroke who underwent reperfusion therapy has not been studied sufficiently. We have aimed to compare genders and age groups in terms of clinical features and outcome; and types of reperfusion treatments and clinical features regarding the development of hemorrhagic complications in patients with ischemic stroke who underwent recombinant tissue plasminogen activator (rtPA) and/or thrombectomy. Patients with acute ischemic stroke undergoing rtPA and/or thrombectomy were divided into six age groups. Parameters including hemorrhagic complications, anticoagulant and antiaggregant use, hyperlipidemia, smoking status, biochemical parameters, and comorbidities were documented. National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Score (mRS) and Glasgow Coma Scale scores were recorded. Etiological classification of stroke was done. These parameters were compared in terms of age groups, genders, and hemorrhagic complications. Significant differences were found between age groups concerning hypertension, coronary artery disease, smoking status, and antiaggregant use. Rate of hemorrhagic complications in rtPA group was significantly lower when compared with other treatment groups. Hemorrhagic complications developed mostly in the rtPA+thrombectomy group. Among the patients who developed hemorrhagic complications, NIHSS scores on admission were found to be significantly lower in men than women. Admission, discharge, and 3rd month mRS values in men were significantly lower than those of women. Knowing demographic and clinical features of patients that may have an impact on the clinical course of ischemic stroke managed with reperfusion therapy will be useful in predicting the hemorrhagic complications and clinical outcomes.

OBJECTIVE: Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion.
METHODS: We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI).
RESULTS: rtPA increased neutrophil infiltration into the brain microvessels and worsened blood-brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI.
CONCLUSIONS: Neutrophils play a crucial role in promoting ischemic injury and blood-brain barrier disruption, making them potential therapeutic targets.

UNASSIGNED: Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA).
UNASSIGNED: This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors.
UNASSIGNED: Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall p = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], p = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH.
UNASSIGNED: This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.

Thrombolytic therapy with the tissue plasminogen activator (tPA) is a therapeutic option for acute ischemic stroke. However, this approach is subject to several limitations, particularly the increased risk of hemorrhagic transformation (HT). Lithium salts show neuroprotective effects in stroke, but their effects on HT mechanisms are still unknown. In our study, we use the models of photothrombosis (PT)-induced brain ischemia and oxygen-glucose deprivation (OGD) to investigate the effect of Li+ on tPA-induced changes in brain and endothelial cell cultures. We found that tPA did not affect lesion volume or exacerbate neurological deficits but disrupted the blood-brain barrier. We demonstrate that poststroke treatment with Li+ improves neurological status and increases blood-brain barrier integrity after thrombolytic therapy. Under conditions of OGD, tPA treatment increased MMP-2/9 levels in endothelial cells, and preincubation with LiCl abolished this MMP activation. Moreover, we observed the effect of Li+ on glycolysis in tPA-treated endothelial cells, which we hypothesized to have an effect on MMP expression.

Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.

BACKGROUND: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear.
METHODS: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset.
RESULTS: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).
CONCLUSIONS: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.).