Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.

MRI-based machine learning models predict the malignant biological behavior of meningioma.

BACKGROUND: The WHO grade and Ki-67 index are independent indices used to evaluate the malignant biological behavior of meningioma. This study aims to develop MRI-based machine learning models to predict the malignant biological behavior of meningioma from the perspective of the WHO grade, Ki-67 index, and their combination. METHODS: This multicenter, retrospective study included 313 meningioma patients, of which 70 were classified as high-grade (WHO II/III) and 243 as low-grade (WHO I). The Ki-67 expression was classified into low-expression (n = 216) and high-expression (n = 97) groups with a threshold of 5%. Among them, there were 128 patients with malignant biological behavior whose WHO grade or Ki-67 index increased either or both. Data from Center A and B are were utilized for model development, while data from Center C and D were used for external validation. Radiomic features were extracted from the maximum cross-sectional area (2D) region of Interest (ROI) and the whole tumor volume (3D) ROI using different paraments from the T1, T2-weighted, and T1 contrast-enhanced sequences (T1CE), followed by five independent feature selections and eight classifiers. 240 prediction models were constructed to predict the WHO grade, Ki-67 index and their combination respectively. Models were evaluated by cross-validation in training set (n = 224). Suitable models were chosen by comparing the cross-validation (CV) area under the curves (AUC) and their relative standard deviations (RSD). Clinical and radiological features were collected and analyzed; meaningful features were combined with radiomic features to establish the clinical-radiological-radiomic (CRR) models. The receiver operating characteristic (ROC) analysis was used to evaluate those models in validation set. Radiomic models and CRR models were compared by Delong test. RESULTS: 1218 and 1781 radiomic features were extracted from 2D ROI and 3D ROI of each sequence. The selected grade, Ki-67 index and their combination radiomic models were T1CE-2D-LASSO-LR, T1CE-3D-LASSO-NB, and T1CE-2D-LASSO-LR, with cross-validated AUCs on the training set were 0.857, 0.798, and 0.888, the RSDs were 0.06, 0.09, and 0.05, the validation set AUCs were 0.829, 0.752, and 0.904, respectively. Heterogeneous enhancement was found to be associated with high grade and Ki-67 status, while surrounding invasion was associated with the high grade status, peritumoral edema and cerebrospinal fluid space surrounding tumor were correlated with the high Ki-67 status. The Delong test showed that these significant radiological features did not significantly improve the predictive performance. The AUCs for CRR models predicting grade, Ki-67 index, and their combination in the validation set were 0.821, 0.753, and 0.906, respectively. CONCLUSIONS: This study demonstrated that MRI-based machine learning models could effectively predict the grade, Ki-67 index of meningioma. Models considering these two indices might be valuable for improving the predictive sensitivity and comprehensiveness of prediction of malignant biological behavior of meningioma.

Novel Variant Expands the Clinical Spectrum of CUX2-Associated Developmental and Epileptic Encephalopathies.

Developmental and epileptic encephalopathies (DEE) caused by heterozygous deleterious variants in Cut Like Homeobox2 (CUX2) is rare. To the best of our knowledge the only variant associated with a phenotype in this gene is the de novo missense variant c.1768G > A, p.Glu590Lys; however, further additional research is needed to characterize the relationship between disease and variants in this gene. In this study, we reported a patient from a non-consanguineous Chinese family presenting with epilepsy, developmental delay, and speech delay. Additionally, the patient responded well to levetiracetam, and at his last follow-up (5.5 years old), he had discontinued antiepileptic drug treatment and remained seizure-free for 6 months. To identify possible causative variants, trio-whole exome sequencing was performed. We identified a novel de novo missense CUX2 c.2834C > T, p. Thr945Met variant in the patient. Based on clinical and genetics information associated with the bioinformatics analyses, we hypothesized that this variant was the cause of the reported phenotype. AlphaFold and SWISS-MODEL homology modeling servers were used to predict the three-dimensional (3D) structure of CUX2 protein. Predictions based on the 3D-structure modeling indicated that the p.Thr945Met substitution was likely to alter the DNA-binding specificities and affect protein function. On the basis of clinical characteristics and genetic analysis, we presented one case diagnosed with DEE67. Our finding expanded the clinical and molecular spectrum of CUX2 variants.

Repetitive Transcranial Magnetic Stimulation Improves Amygdale Functional Connectivity in Major Depressive Disorder.

Emotional abnormality in major depressive disorder (MDD) is generally regarded to be associated with functional dysregulation in the affective network (AN). The present study examined the changes in characteristics of AN connectivity of MDD patients before and after repetitive transcranial magnetic stimulation (rTMS) treatment over the left dorsolateral prefrontal cortex, and to further assess how these connectivity changes are linked to clinical characteristics of patients. Functional connectivity (FC) in the AN defined by placing seeds in the bilateral amygdale was calculated in 20 patients with MDD before and after rTMS, and in 20 healthy controls (CN). Furthermore, a linear regression model was used to obtain correlations between FC changes and Hamilton depression scale (HAMD) changes in MDD before and after rTMS. Before rTMS, compared with CN, MDD exhibited significantly lower FC between left insula (INS.L), right superior and inferior frontal gyrus (SFG.R and IFG.R), right inferior parietal lobule (IPL.R), and amygdala, and showed an increment of FC between the bilateral precuneus and amygdala in AN. After rTMS, MDD exhibited a significant increase in FC in the INS.L, IFG.R, SFG.R, IPL.R, and a significant reduction in FC in the precuneus. Interestingly, change in FC between INS.L and left amygdala was positively correlated with change in HAMD scores before and after rTMS treatment. rTMS can enhance affective network connectivity in MDD patients, which is linked to emotional improvement. This study further suggests that the insula may be a potential target region of clinical efficacy for MDD to design rationale strategies for therapeutic trials.

[Effect of Biofeedback Combined with Task-oriented Training on Hand Function, Gesell Scale Score and Balance Ability in Children with Spastic Cerebral Palsy].

OBJECTIVE: To analyze the effects of biofeedback combined with task-oriented training on hand function, Gesell's infant development scale score (Gesell) and balance ability in children with spastic cerebral palsy (SCP). METHODS: 66 children with SCP admitted to our hospital from January 2016 to June 2018 were randomly divided into the control group and the observation group. The control group ( n=33) received conventional rehabilitation treatment, and the observation group ( n=33) received biofeedback combined with task-oriented training based on the treatment of control group. After 6-month treatment, Modified Ashworth scale (MAS) score, Berg balance scale (BBS) score, standing and walking function score in gross motor function scale (GMFM), assisting hand assessment scales (AHA) score, Gesell scale score and satisfaction of the children's parents were compared between the two groups. RESULTS: The MAS score after treatment was lower than that before treatment in both two groups ( P<0.05), and the BBS score after treatment was higher than that before treatment in both two groups ( P<0.05). After treatment, the MAS score in the observation group was lower than the control group, and the BBS score in the observation group was higher than the control group ( P<0.05). The scores of standing and walking function after treatment were higher than that before treatment in both two groups ( P<0.05). After treatment, the scores of standing and walking function in the observation group were higher than the control group ( P<0.05). The AHA score and Gesell developmental quotient (DQ) score after treatment were higher than that before treatment in both two groups ( P<0.05). After the treatment, the AHA score and Gesell DQ score in the observation group were higher than the control group ( P<0.05). The satisfaction rate of rehabilitation treatment in the observation group was higher than the control group (90.91% vs. 60.61%, P<0.05). CONCLUSION: Biofeedback combined with task-oriented training can improve balance ability, spasm relieve, hand function, development level, standing and walking function in the children with spastic cerebral palsy and increase the treatment satisfaction degree of children's guardians.

The effect of night shift on sleep quality and depressive symptoms among Chinese nurses.

PURPOSE: Night shift is associated with adverse physical and psychological health outcomes such as poor sleep quality and depressive symptoms. We aimed to compare sleep quality as well as depressive symptoms in nurses working night shifts to those working day shifts only and explore the association between sleep quality and depressive symptoms among nurses. PATIENTS AND METHODS: Eight hundred sixty-five nurses were enrolled in the current study. Sleep quality and depressive symptoms among nurses were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depressive Disorders Rating Scale (HADS), respectively. RESULTS: PSQI and HADS scores were both significantly higher in the nurses working night shifts (P<0.05) than in those working day shifts only. Besides, there was a positive correlation between PSQI and HADS scores. Binary logistic regression showed that night shift and poor sleep quality were independent risk factors of depressive symptoms among nurses. CONCLUSION: Higher rates of depression among Chinese nurses working night shifts may be associated with poor sleep quality induced by night shift.

Post-thrombolysis hemorrhage risk of unruptured intracranial aneurysms.

BACKGROUND/AIMS: It has been questioned whether patients with unruptured intracranial aneurysms (IAs) are at a greater risk for the development of intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients with acute ischemic stroke and incidental IAs. METHODS: We searched PubMed, Web of Science and EMBASE for studies assessing ICH risk in patients with acute ischemic stroke treated with thrombolysis, in relation to the presence of pretreatment IAs. A fixed-effects model meta-analysis was performed. RESULTS: We identified four studies totaling 707 participants receiving intravenous thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis demonstrates relative risk (RR) for the presence of unruptured IAs and the development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I(2) = 0.0%). The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I(2) = 28.1%). CONCLUSION: Intravenous thrombolysis was safe among patients with acute ischemic stroke and incidental unruptured IAs. Future prospective studies with much larger sample sizes are required to clarify the significance of the association between pre-existing unruptured IAs and the development of post-thrombolysis ICH.