Objective
To explore the clinical efficacy and long-term outcomes of anticoagulants therapy in pediatric cerebral venous sinus thrombosis (CVST).
Methods
58 CVST children aged 1 month to 16 years received an standardized anticoagulant therapy of low molecular weight heparin, warfarin and urokinase.Initial and follow-up neuroimages were evaluated for associated intracranial hemorrhage, thrombus propagation rate and long-term quality-of-life.And clinical outcome was assessed by the modified Rankin scale (mRS).
Results
Among them, 38/58 received anticoagulants at diagnosis.Major anticoagulation-associated hemorrhage occurred in 5.3% (2/38) and clinical outcome was favorable.Early follow-up imaging demonstrated thrombus propagation in 5/58 children (1/38 with and 4/20 without anticoagulation[P=0.023]). Five deaths were associated with CVST (1 with anticoagulation). The decreasing rate of mortality in CVST with anticoagulation was 25%-30%.Clinical outcomes of death and long-term worse prognosis were unfavorable in 22%(11/50). The clinical risk factors of long-term outcomes were full-term infant (OR[odd ratio]0.12, P=0.045), neuroimaging of multiple lesions (OR 15.16, P=0.042) and anticoagulation (OR 0.007, P=0.024). Initial intracranial hypertension was associated with neonatal asphyxia (OR 0.35, P=0.025), neuroimaging of multiple lesion (OR 8.73, P=0.048) and onset time (OR 0.89, P=0.003). Furthermore anticoagulation was probably helpful for CVST children in controlling subacute intracranial pressure (P=0.048).
Conclusions
In pediatric CVST with mild intracranial hemorrhage, anticoagulation is both safe and effective.And it may reduce the rate of mortality, enhance quality-of-life and improve long-term outcomes.
Key words:
Cranium; Venous sinus; Thrombosis; Comparative Study
Importance Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. Objective To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. Design, Setting, and Participants This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Interventions Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. Main Outcomes and Measures The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Results Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P = .05) compared with the enoxaparin group. Conclusions and Relevance In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. Trial Registration ClinicalTrials.gov Identifier: NCT03363035
Abstract Lenvatinib is a type I tyrosine kinase inhibitor exhibiting powerful antiangiogenic activity in cancer therapy. Displaying activity in multiple solid tumors, it has been approved in differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma as single agent or in combination. In addition, lenvatinib has shown promise in several other tumor types including medullary, anaplastic thyroid, adenoid cystic, and endometrial cancer. Exploring synergy between angiogenic and immune checkpoint inhibitors, the lenvatinib/pembrolizumab combination is poised to become the next pair of active drugs in endometrial, lung, and gastrointestinal malignancies. Despite robust activity, the drug can be difficult to tolerate. Optimization of dose and biomarkers for prediction of efficacy and toxicities will be of great help.
Traumatic brain injury (TBI) impairs cognitive function. Systemic inflammation plays important role in cognitive deficits. It remains unclear if systemic inflammation in TBI is associated with poor cognitive function.
Abstract Background Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods Male Sprague-Dawley rats were established to type 2 diabetic model. After 6 weeks, diabetic rats and normal controls were intravitreally injected with. Cs-A (42 ng/2 μL) to the left eye, and 2 μL DMSO to the right eye for the control.. Another group of normal wild-type rats was subjected to intravitreal injections into. The left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus. Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with. Hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were. Detected by immunohistochemistry, ELISA or Western blot or RT-PCR. Results Retinal expression levels of IL-1β and TNF-α were upregulated in type 2. diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were. Attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in. diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions Intravitreal administration of Cs-A showed a protective effect on retina. of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α. via the suppression of HMGB-1.
The general aggression model (GAM) has suggested that the interaction between person factors (e.g., personality variables) and situation factors (e.g., playing violent video games [VVGs]) can increase individuals' aggressive behaviors through their cognition (e.g., hostile attributions), affect (e.g., negative affect), and/or arousal. The present study employed a modified competitive reaction time task to test the effects of shyness, violent (vs. nonviolent) gameplay, and shyness on individuals' positive-negative affect, hostile attributions, and aggressive behaviors. In addition, the present study also employed structural equation modeling (SEM) to test the mediation (by cognition and affect) and moderation (by shyness). Results showed that playing a VVG increased aggressive behaviors, negative affect, and hostile attributions primarily among shy participants. In addition, the results of SEM also revealed that this moderating role was mediated by negative affect and hostile attributions. The present study supported GAM and showed that individuals' aggressive behaviors are differentially susceptible to VVGs, depending on their level of shyness in a "for bad and for worse" manner.
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