Decision system for extent of resection in WHO grade 3 gliomas: a Chinese Glioma Genome Atlas database analysis.

BACKGROUND: Extensive surgical resection has been found to be associated with longer survival in patients with gliomas, but the interactive prognostic value of molecular pathology of the surgical resection is unclear. This study evaluated the impact of molecular pathology and clinical characteristics on the surgical benefit in WHO grade 3 IDH-mutant gliomas. METHODS: Clinical and pathological information of 246 patients with WHO grade 3 IDH-mutant gliomas were collected from the Chinese Glioma Genome Atlas database (2006-2020). The role of the extent of resection on overall survival, stratified by molecular pathology and clinical characteristics, was investigated. We then assessed prognostic factors using a univariate log-rank test and multivariate Cox proportional hazards model in the subgroups. RESULTS: The extent of resection was an independent prognostic factor in the entire cohort, even when adjusted for molecular pathology. Gross total resection was found to be associated with longer survival in all patients and in the astrocytoma group but not in the oligodendroglioma group. Compared with subtotal resections, gross total resections resulted in a longer survival time for astrocytoma patients aged ≤ 45 years. However, there was no survival benefit from total resection in patients with astrocytoma aged > 45 years. CONCLUSIONS: Extensive resection benefits only a proportion of patients with WHO grade 3 IDH-mutant gliomas. Younger patients with astrocytomas had survival benefits from extensive resection. In addition to clinical characteristics (especially age), molecular pathology impacted prognosis in patients with gliomas. Our findings provide guiding information to neurosurgeons while planning surgeries.

High-dose versus low-dose inhaled levodopa (CVT-301) in patients with Parkinson disease for the treatment of OFF episodes: a meta-analysis of randomized controlled trials.

BACKGROUND: Levodopa is the most commonly used first-line drug for Parkinson's disease. However, during the period of medication, the generation of motor fluctuations affects the life quality of patients. CVT-301, as an inhaled levodopa for the treatment of OFF episodes, rose in response to this condition. METHODS: We systematically searched Medline, EMBASE, Cochrane Library, and Clinicaltrials.gov for relevant randomized controlled trials, from the earliest available date to February 12, 2022, to evaluate the efficacy of high and low dose of inhaled levodopa in patients with Parkinson's disease. RESULTS: A total of six multicenter, randomized controlled trials with 1166 patients were included. Compared with placebo, CVT-301 has a statistically significant effect on the treatment of Parkinson's patients with OFF episodes of medication interval. The UPDRS Part III score decreased more significantly in the high-dose group 30 minutes after administration than the low-dose group (WMD = - 4.51; 95% CI, - 7.34 to - 1.68; p = 0.002). More patients in the high-dose group achieved and maintained an on state up to 60 min after receiving study medication (RR = 1.17; 95% CI, 1.08 to 1.27; p < 0.001). And more patients were proved with improved PGIC scores in the high-dose group (RR = 1.13; 95% CI, 1.05 to 1.21; p = 0.001). CONCLUSIONS: High doses CVT-301 can improve the motor function of the patient to some extent. There seems no risk of increasing adverse reactions.

The efficacy and safety of atogepant for the prophylactic treatment of migraine: evidence from randomized controlled trials.

BACKGROUND: Migraine is a common neurovascular disorder that has a severe impact on the individual daily life. Atogepant (AGN-241689) is an orally ingested, small-molecule drugs belonging to calcitonin gene-related peptide receptor antagonist, which has been initiated for the prophylactic treatment of migraine. However, there is no comprehensive literature to study the efficacy and safety of atogepant for the treatment of migraine. In this article, we present a meta-analysis of the available studies. METHODS: MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched before October 20, 2021 for any relevant literature. Eventually, three randomized clinical trials (RCTs) with 2,466 patients were included in our study. RESULTS: We pooled 2,466 patients from 3 RCTs and primary outcome was mean monthly migraine days, the secondary endpoints were monthly headache days, acute medication use days per month and ≥ 50% reduction in monthly migraine days, baseline to end of trials. It was found that atogepant (10 mg, 30 mg, 60 mg once a day) led to a significant reduction in monthly migraine days (P < 0.00001, P < 0.00001, P = 0.007), monthly headache days (P < 0.00001, P < 0.00001, P = 0.001), and monthly medication use days (P < 0.00001, P < 0.00001, P = 0.0001), and an increase in the proportion of people with ≥ 50% reduction in monthly migraine days (P = 0.0008, P = 0.02, P = 0.04) in comparison with placebo. Moreover, there were no significant differences (P > 0.05) in outcomes of adverse events between atogepant and placebo. CONCLUSIONS: Atogepant has shown good efficacy and safety in the prophylactic treatment of migraine, and further studies are expected.

Different dosage regimens of Eptinezumab for the treatment of migraine: a meta-analysis from randomized controlled trials.

BACKGROUND: Migraine is one of the most common neurological diseases around the world and calcitonin gene-related peptide (CGRP) plays an important role in its pathophysiology. Therefore, in the present study, we evaluated the efficacy of monoclonal antibodies blocking the CGRP ligand or receptor in episodic and chronic migraine. OBJECTIVE: The objective of our study is implementing a meta-analysis to systematically evaluate the efficacy and safety of eptinezumab for the treatment of migraine compared with placebo. METHOD: We searched the Medline, Embase, Cochrane Library and Clinicaltrials.gov for randomized controlled trials (RCTs) which were performed to evaluate eptinezumab versus placebo for migraine up to September 2020. The data was assessed by Review Manager 5.3 software. The risk ratio (RR) and standard mean difference (SMD) were analyzed using dichotomous outcomes and continuous outcomes respectively with a random effect model. RESULT: We collected 2739 patients from 4 RCTs: the primary endpoint of efficacy was the change from baseline to week 12 in mean monthly migraine days (MMDs). We found that eptinezumab (30 mg, 100 mg, 300 mg) led to a significant reduction in MMDs (P = 0.0001,P < 0.00001, P < 0.00001) during 12 weeks compared with placebo, especially with 300 mg. For the safety, we compared and concluded the treatment emergent adverse events (TEAEs) of the 4 RCTs. This indicated no evident statistical difference between eptinezumab and placebo. CONCLUSIONS: In the present study, we found that eptinezumab is safe and has significant efficacy in the treatment of migraine, especially the dose of 300 mg.

Transcranial direct current stimulation with virtual reality versus virtual reality alone for upper extremity rehabilitation in stroke: A meta-analysis.

Background: Stroke is one of the most prevalent diseases. Motor impairment in patients with stroke frequently affects the upper extremities. Several randomized clinical trials (RCTs) have tried to prove whether or not the combination of transcranial direct current stimulation (tDCS) with virtual reality (VR) is superior to VR alone for upper extremity rehabilitation. Methods: We searched Embase, MEDLINE, the Cochrane Library database, and Clinicaltrials.gov for relevant RCTs published before June 10, 2022. The results were analyzed by using standard mean differences (SMD) and 95% confidence intervals (95% CI). Results: We pooled 120 patients from 4 RCTs. There were no significant improvements in the Fugl-Meyer Upper Extremity scale (SMD = 0.51; 95% CI, -0.04 to 1.06), the Box and Block Test (SMD = 0.42; 95% CI, -0.02 to 0.86), and the Modified Ashworth Scale after the combined treatment of tDCS and VR. But tDCS combined with VR could enhance the Barthel Index scores in patients with stroke compared to VR alone (SMD = 0.49; 95% CI, 0.04 to 0.94). Conclusions: The combination of tDCS and VR can improve the quality of daily living in patients with stroke. No more satisfactory efficacy has been demonstrated in terms of upper extremity function. However, we observe a distinct trend toward significance in some outcomes.

The efficacy and safety of ganaxolone for the treatment of refractory epilepsy: A meta-analysis from randomized controlled trials.

OBJECTIVE: Epilepsy is one of the most common and refractory neurological disorders globally. Ganaxolone, a neuroactive steroid that enhances GABAergic inhibition, has been tested in many trials for the resolution of refractory epilepsy. Based on these, our study implemented a meta-analysis to evaluate the general benefit of ganaxolone for refractory epilepsy. METHODS: EMBASE, Medline, Scopus, Cochrane Library, and Clinicaltrials.gov were searched for relevant randomized controlled trials (RCTs) up to June 20, 2022. The risk ratio (RR) and standard mean difference (SMD) were analyzed using dichotomous and continuous outcomes, respectively with a random effect model. Trial sequential analysis (TSA) was also performed to judge the reliability of results. RESULTS: We totally collected 659 patients from four RCTs to evaluate the efficacy and safety of ganaxolone. As results showed, ≥50% reduction in mean seizure frequency has improved significantly compared with placebo (RR = 1.60, 95%CI: 1.02-2.49, p = 0.04, I2  = 30%), which is supported by TSA. However, the percentage of seizure-free days shows no statistical significance (p = 0.36). For safety outcomes, adverse events (AEs), serious adverse events, and AE leading to study drug discontinuation all revealed no obvious difference between ganaxolone and placebo (p > 0.05). SIGNIFICANCE: Based on our research, we have observed that ganaxolone is safe and has potential efficacy in the treatment of refractory epilepsy, waiting for further studies.

Long-term survival of patients with intracranial metastases from thyroid cancer presenting with seizures: a case report and literature review.

Background: Thyroid cancer has low incidence and mortality. While metastatic cancer is the most common type of intracranial cancer, patients with intracranial metastases from thyroid cancer very rarely present with seizures. Here, we describe a case study and review the neurological symptoms and histopathology of intracranial metastases from thyroid cancer. Case Description: A 38-year-old woman was diagnosed with intracranial metastases from papillary thyroid cancer, with the chief symptom being generalized seizures. The bilateral frontal masses were completely resected in 2 operations, after which the patient was treated with whole-brain radiotherapy and tyrosine kinase inhibitors (TKIs). It has now been over 13 years since thyroid cancer resection and 51 months since she was diagnosed with intracranial metastases from papillary thyroid cancer. The long-term survival might be due to the effective and prompt treatment. Through literature review, we found the incidence of intracranial metastases from different subtypes of thyroid cancer to be inconsistent with epidemiological findings in thyroid cancer. Conclusions: Intracranial metastases of thyroid cancer should be considered when the patient has a history of thyroid cancer with seizures. A combination of surgery, radiation therapy, and TKI drugs may prolong survival.

Efficacy and safety of remote ischemic conditioning for acute ischemic stroke: A comprehensive meta-analysis from randomized controlled trials.

BACKGROUND AND PURPOSE: Remote ischemic conditioning (RIC) is a remote, transient, and noninvasive procedure providing temporary ischemia and reperfusion. However, there is no comprehensive literature investigating the efficacy and safety of RIC for the treatment of acute ischemic stroke. In the present study, we performed a comprehensive meta-analysis of the available studies. METHODS: MEDLINE, Embase, the Cochrane Library database (CENTRAL), and ClinicalTrials.gov were searched before Sep 7, 2022. The data were analyzed using Review Manager 5.4.1 software, Stata version 16.0 software, and R 4.2.0 software. Odds ratio (OR), mean difference (MD), and corresponding 95% CIs were pooled using fixed-effects meta-analysis. RESULTS: We pooled 6392 patients from 17 randomized controlled trials. Chronic RIC could reduce the recurrence of ischemic stroke at the endpoints (OR 0.67, 95% CI [0.51, 0.87]). RIC could also improve the prognosis of patients at 90 days as assessed by mRS score (mRS 0-1: OR 1.29, 95% CI [1.09, 1.52]; mRS 0-2: OR 1.22, 95% CI [1.01, 1.48]) and at the endpoints assessed by NIHSS score (MD -0.99, 95% CI [-1.45, -0.53]). RIC would not cause additional adverse events such as death (p = 0.72), intracerebral hemorrhage events (p = 0.69), pneumonia (p = 0.75), and TIA (p = 0.24) but would inevitably cause RIC-related adverse events (OR 26.79, 95% CI [12.08, 59.38]). CONCLUSIONS: RIC could reduce the stroke recurrence and improve patients' prognosis. Intervention on bilateral upper limbs, 5 cycles, and a length of 50 min in each intervention might be an optimal protocol for RIC at present. RIC could be an effective therapy for patients not eligible for reperfusion therapy. RIC would not cause other adverse events except for relatively benign RIC-related adverse events.

Comparative efficacy and safety of various mechanical thrombectomy strategies for patients with acute ischemic stroke: a Bayesian network meta-analysis.

Background: Stent retriever, contact aspiration, and combined treatment are crucial mechanical thrombectomy strategies for patients with acute ischemic stroke (AIS). Objectives: The aim of this study was to compare and rank three different mechanical thrombectomy strategies for AIS due to large vessel occlusion by means of a Bayesian network meta-analysis. Design: A systematic review and Bayesian network meta-analysis based on PRISMA guidelines. Data sources and methods: Relevant randomized controlled trials (RCTs) were identified in Embase, MEDLINE, the Cochrane Library database, and Clinicaltrials.gov from inception to 15 March 2022. We used random effect models to estimate corresponding odds ratios (ORs) and rank probabilities using pairwise and Bayesian network meta-analysis. We applied the grading of recommendations assessment, development, and evaluation (GRADE) methodology to rate the certainty of evidence. Results: We identified 10 RCTs enrolling 2098 participants. As for modified Rankin Scale (mRS) 0-2, moderate certainty evidence established all mechanical thrombectomy strategies that were more effective than standard medical treatment [combined: log OR 0.9288, 95% credibility intervals (CrI) 0.1268-1.7246; contact aspiration: log OR 0.9507, 95% CrI 0.3361-1.5688; stent retriever: log OR 1.0919, 95% CrI 0.6127-1.5702]. The same applied to mRS 0-3 (combined: log OR 0.9603, 95% CrI 0.2122-1.7157; contact aspiration: log OR 0.7554, 95% CrI 0.1769-1.3279; stent retriever: log OR 1.0046, 95% CrI 0.6001-1.4789). Combined treatment was superior to stent retriever in substantial reperfusion (log OR 0.8921, 95% CrI 0.2105-1.5907, high certainty). Stent retriever had the highest probability of being optimal for mRS 0-2 and mRS 0-3. Standard medical treatment had the lowest risk of subarachnoid hemorrhage. For all other outcomes, combined treatment was most likely the best treatment. Conclusion: Our results indicated that, with the exception of functional outcome, combined treatment might be the outstanding strategy. Apart from subarachnoid hemorrhage, all three mechanical thrombectomy strategies proved better strategies than standard medical treatment. Registration: PROSPERO (CRD42022351878).

The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis.

The efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia have been well verified in several large randomized controlled trials (RCTs) over the past several decades. However, there have been few systematic comparisons of different DORAs, and the best DORA for insomniacs has remained unclear. Here, Medline, Embase, Cochrane library, and clinicaltrials.gov were searched for RCTs (through December 31, 2020) to evaluate different DORAs versus a placebo. We pooled data from 13 RCTs. DORAs were superior to the placebo in all efficacy outcomes except the subjective number of awakenings (P = 0.90), but also showed higher risks of somnolence, abnormal dreams, fatigue, and dry mouth (somnolence: P < 0.00001; abnormal dreams: P = 0.03; fatigue: P = 0.001; dry mouth: P = 0.007). No statistical differences were found between any two of the DORAs in terms of primary efficacy outcomes. However, lemborexant yielded the three-highest surfaces under the curve ranking area (SUCRA) values (78.25%, 96.25% and 89.13%). Taken together, we conclude that DORAs are superior to the placebo in terms of efficacy and safety measures.

Safety and efficacy of tyrosine kinase inhibitors for the treatment of multiple sclerosis: A systematic review and meta-analysis from randomized controlled trials.

Background: Multiple sclerosis (MS), an autoimmune disease, is characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Drugs targeting tyrosine kinase, a critical component of immune cell receptor signaling, have been developed to treat MS. However, the exact efficacy and safety of tyrosine kinase inhibitors (TKIs) are still controversial, and comprehensive analysis with a high level of evidence is needed. Methods: Medline, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials (RCTs) evaluating TKIs versus placebo for MS were searched up to April 1st, 2022. The risk ratio (RR) and mean difference (MD) or standard mean difference (SMD) were analyzed using dichotomous outcomes and continuous outcomes, respectively, with a random effect model. Results: A total of 1,043 patients derived from four clinical trials were included to investigate the efficacy and safety of TKI therapy for MS. According to our analysis, TKIs decreased the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI with the application of high dose (SMD = -0.61, 95% CI: -0.93 to -0.30, P = 0.0001). Meanwhile, TKIs prevented the expanded disability status scale (EDSS) from rising (MD = -0.10, 95% CI: -0.19 to -0.00, P = 0.046). In terms of MS relapse, TKIs have not revealed an obvious statistical difference compared with placebo (RR = 0.96, 95% CI: 0.55-1.65, P = 0.8755). However, more adverse events seem to occur in the TKIs group, both for adverse events (RR = 1.12, 95% CI: 1.05-1.19, P = 0.0009) and serious adverse events (RR = 1.91, 95% CI: 1.30-2.81, P = 0.001). Conclusion: Tyrosine kinase inhibitors have shown promise in treating MS. Generally, TKIs that attain the effective dose demonstrate definite efficacy and have tolerable side effects. More clinical trials and validation are needed, and we anticipate that TKIs will be a viable alternative for MS patients.

Thrombectomy with or without thrombolysis in patients with acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Recently, several randomized controlled trials (RCTs) about direct mechanical thrombectomy (d-MT) vs. intravenous thrombolysis before MT (IVT + MT) for acute ischemic stroke (AIS) patients have been reported. This study aims to investigate the differences in efficacy and safety of MT with or without IVT for the treatment of patients with AIS. METHODS: MEDLINE, EMBASE, Cochrane Library and Clinicaltrials.gov from March 2011 to February 2021 were systematically searched for studies comparing the two strategies directly. Review Manager 5.3 software was used to assess the risk of bias and pool the data with a random effect model. RESULTS: We pooled 1633 patients from 4 RCTs. The primary outcome, proportion of patients achieving functional independence (mRS0-2) at 90 days, was not significantly different between the two groups (MT 46.02% vs. IVT + MT 45.47%, OR 1.02; 95% CI 0.84-1.25). However, the risk of developing any ICH was lower in the d-MT group (RR 0.75; 95% CI 0.63-0.89). In addition, the remaining secondary outcomes, such as successful reperfusion (eTICI scale, 2b-3) at final angiogram (OR 0.80; 95% CI, 0.62-1.03) and mortality at 90 days (RR 1.06; 95% CI 0.85-1.31), did not differ between the groups. CONCLUSIONS: Outcomes were similar for d-MT and IVT + MT, with d-MT having a lower risk of any ICH. We need to focus on precision medicine in the future. REGISTRATION: URL: http://inplasy.com ; Unique identifier: INPLASY202130094.

Microsurgical Management of Posterior Circulation Aneurysms: A Retrospective Study on Epidemiology, Outcomes, and Surgical Approaches.

Posterior circulation aneurysms have been regarded as the most challenging for endovascular coiling and microsurgical occlusion. The role of microsurgical treatment is gradually being overlooked and diminishing in the trend of endovascular treatment. As microsurgical occlusion of posterior circulation aneurysms is decreasing, we present our relevant experience to evaluate treatment options and surgical approaches. A retrospective study was conducted in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University between 2016 and 2021. Patients with posterior circulation aneurysms treated by clipping, bypass, and trapping were enrolled and followed up for at least six months. We included 50 patients carrying 53 posterior circulation aneurysms, 43 of whom had aneurysm ruptures. The posterior cerebral artery and posterior inferior cerebellar artery were the most common aneurysm locations. Direct clipping was performed in 43 patients, while bypass and trapping was performed in six patients. The retrosigmoid, far-lateral, and midline or paramedian suboccipital approaches were performed for those aneurysms in the middle and lower thirds. Aneurysms in the upper third required the lateral supraorbital approach, pterional approach, subtemporal approach, and occipital craniotomy. The lateral supraorbital approach was utilized in seven patients for aneurysms above the posterior clinoid process. Thirty-four patients recovered well with modified Rankin score 0-3 at discharge. No patient experienced aneurysm recurrence during the mean follow-up period of 3.57 years. Microsurgery clipping and bypass should be considered in conjunction with endovascular treatment as a treatment option in posterior circulation aneurysms. The lateral supraorbital approach is a feasible, safe, and simple surgical approach for aneurysms above the posterior clinoid process.

Efficacy of Neurostimulations for Upper Extremity Function Recovery after Stroke: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Neurostimulations for the post-stroke recovery of upper extremity function has been explored in previous research, but there remains a controversy about the superiority of different neurostimulations. METHODS: Randomized controlled trials (RCTs) were searched in MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov, from 1 January 2000 to 1 June 2022. A conventional pair-wise meta-analysis with a random-effect model was used to evaluate direct evidence. Bayesian random effect models were used for network meta-analysis. The grading of the recommendations assessment, development and evaluation (GRADE) approach was applied to assess the clinical quality of the results. RESULTS: A total of 88 RCTs, which enrolled 3491 participants, were included. For the Fugl-Meyer Assessment-Upper Extremity score change from the baseline to the longest follow-up, the following interventions showed a significant difference: VNS (MD = 4.12, 95%CrI: 0.54 to 7.80, moderate certainty), cNMES (MD = 3.98, 95%CrI: 1.05 to 6.92, low certainty), FES (MD = 7.83, 95%CrI: 4.42 to 11.32, very low certainty), drTMS (MD = 7.94, 95%CrI: 3.71 to 12.07, moderate certainty), LFrTMS (MD = 2.64, 95%CrI: 1.20 to 4.11, moderate certainty), HFrTMS (MD = 6.73, 95%CrI: 3.26 to 10.22, moderate certainty), and iTBS combined with LFrTMS (MD = 5.41, 95%CrI: 0.48 to 10.35, moderate certainty). CONCLUSIONS: The neurostimulations above the revealed significant efficacy for improving the upper limb function after stroke eased the suffering of the patient.

The Function of Tranexamic Acid to Prevent Hematoma Expansion After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis From Randomized Controlled Trials.

Objectives: The clinical results caused by spontaneous intracerebral hemorrhage (ICH) are disastrous to most patient. As tranexamic acid (TXA) has been proved to decrease the influence of ICH, we conducted this research to explore the function of TXA for the prognosis of ICH compared with placebo. Methods: We searched MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials (RCTs) that were performed to evaluate TXA vs. placebo for ICH up to February 2021. The data were assessed by Review Manager 5.3 software. The risk ratio (RR) and mean difference were analyzed using dichotomous outcomes and continuous outcomes, respectively, with a fixed effect model. Results: We collected 2,479 patients from four RCTs. Then, we took the change of hematoma volume, modified Rankin Scale (mRS), and adverse events as evaluation standard of the treatment for ICH. Through statistical analysis, we found that there is no obvious hematoma expansion effect after the application of TXA (RR = 1.05), and we proceeded the quantitative analysis of percentage change in hematoma volume from baseline, indicating that TXA could inhibit the expansion of hematoma volume (RR = -2.02) compared with placebo. However, according to the outcomes of mRS (0-1, RR = 1.04; 0-2, RR = 0.96), TXA cannot improve neurological functional prognosis. As for the security outcomes-mortality (RR = 1.02), thromboembolic events (RR = 0.99), neurological deterioration (RR = 0.92), infection (RR = 0.86), and craniotomy (RR = 0.41), there seems exist no statistical difference between TXA and placebo. Conclusions: TXA has an advantage in the aspect of preventing hematoma expansion compared with placebo for ICH, but cannot illustrate the efficacy of TXA in improving neurological functional prognosis, which still needs more researches with large sample sizes. Moreover, for safety, we did not find obvious statistical difference between TXA and placebo.

Different Monoclonal Antibodies in Myasthenia Gravis: A Bayesian Network Meta-Analysis.

Background: Myasthenia gravis (MG) is a common autoimmune disease with acquired neuromuscular transmission disorders. Recently, monoclonal antibodies have been shown to successfully treat a variety of diseases. Methods: In this meta-analysis, an appropriate search strategy was used to search eligible randomized controlled trials (RCTs) on different monoclonal antibodies to treat patients with MG published up to September 2021 from the embase, PubMed, and Cochrane Library. We assessed the average difference or odds ratio between each drug and placebo and summarized them as the average and 95% confidence interval (CI), respectively. Results: In indicators of efficacy, patients receiving eculizumab (MD, -1.9; 95% CI, -3.2-0.76) had decreases in MG-ADL scores compared to placebo. In addition, only eculizumab (MD, -3.1; 95% CI, -4.7-1.5) and efgartigimod (MD, -1.4; 95% CI, -2.1-0.68) showed a significant difference from placebo in the amount of reduction in QMG scores, while neither of the other two monoclonal antibodies was statistically significant. With regard to the safety of monoclonal antibody therapy, there was no significant difference in the probability of AE in subjects treated with any of the four monoclonal antibodies compared to placebo. Conclusions: eculizumab was effective in reducing MG-ADL scores and QMG scores in myasthenia gravis. Meanwhile, eculizumab also caused fewer AE. As an emerging therapy, monoclonal antibodies are prospective in the treatment of MG. However, more researches are required to be invested in the future as the results obtained from small sample sizes are not reliable enough.

Is Fluoxetine Good for Subacute Stroke? A Meta-Analysis Evidenced From Randomized Controlled Trials.

Background and Purpose: Fluoxetine is a drug commonly used to treat mental disorders, such as depression and obsessive-compulsive disorder, and some studies have shown that fluoxetine can improve motor and function recovery after stroke. Therefore, we performed a meta-analysis to investigate the efficacy and safety of fluoxetine in the treatment of post-stroke neurological recovery. Methods: PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) that were performed to assess the efficacy and safety of fluoxetine for functional and motor recovery in subacute stroke patients up to October 2020. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and standardized mean difference (SMD) were analyzed and calculated with a fixed effects model. Results: We pooled 6,788 patients from nine RCTs. The primary endpoint was modified Rankin Scale (mRS). Fluoxetine did not change the proportion of mRS ≤ 2 (P = 0.47). The secondary endpoints were Fugl-Meyer Motor Scale (FMMS), Barthel Index (BI), and National Institutes of Health Stroke Scale (NIHSS). Fluoxetine improved the FMMS (P < 0.00001) and BI(P < 0.0001) and showed a tendency of improving NIHSS (P = 0.08). In addition, we found that fluoxetine reduced the rate of new-onset depression (P < 0.0001) and new antidepressants (P < 0.0001). Conclusion: In post-stroke treatment, fluoxetine did not improve participants' mRS and NIHSS but improved FMMS and BI. This difference could result from heterogeneities between the trials: different treatment duration, clinical scales sensitivity, patient age, delay of inclusion, and severity of the deficit.