Safety and efficacy of bone marrow mononuclear cell therapy for ischemic stroke recovery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cell-based therapy represents a potential treatment for ischemic stroke (IS). Here, we performed a systematic review and meta-analysis to summarize the evidence provided by randomized controlled trials (RCTs) for the transplantation of bone marrow mononuclear cells (BMMNCs) in patients with IS in any phase after stroke. METHODS: We searched several databases for relevant articles up to the 10th of March 2023, including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov. Subgroup analyses were implemented to evaluate the dose and route of BMMNC administration. Statistical data were analyzed by Review Manager version 5.3 software. RESULTS: Six RCTs were included in this article, including 177 patients who were treated by the transplantation of BMMNCs and 166 patients who received medical treatment. The three-month National Institutes of Health Stroke Scale (NIHSS) score indicated a favorable outcome for the BMMNC transplantation group (standardized mean difference (SMD), - 0.34; 95% confidence interval (CI), - 0.57 to - 0.11; P = 0.004). There were no significant differences between the two groups at six months post-transplantation with regards to NIHSS score (SMD 0.00; 95% CI - 0.26 to 0.27; P = 0.97), modified Rankin Scale (risk ratio (RR) 1.10; 95% CI 0.75 to 1.63; P = 0.62), Barthel Index change (SMD 0.68; 95% CI - 0.59 to 1.95; P = 0.29), and infarct volume change (SMD - 0.08; 95% CI - 0.42 to 0.26; P = 0.64). In addition, there was no significant difference between the two groups in terms of safety outcome (RR 1.24; 95% CI 0.80 to 1.91; P = 0.33). CONCLUSION: Our meta-analysis demonstrated that the transplantation of BMMNCs was safe; however, the efficacy of this procedure requires further validation in larger RTCs.

Bridging therapy improves functional outcomes and reduces 90-day mortality compared with direct endovascular thrombectomy in patients with acute posterior ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: It remains unclear whether bridging therapy can achieve better neurologic outcomes than direct endovascular thrombectomy (EVT) in patients with posterior ischemic stroke. METHODS: We systematically searched PubMed, EMBASE, and Cochrane databases with posterior artery occlusion treated with bridging therapy vs. EVT. Efficacy was assessed based on functional independence at 90 days and successful recanalization, whereas safety was assessed by mortality, rate of symptomatic intracranial hemorrhage (sICH), and occurrence of any hemorrhage. All data were analyzed with Review Manager software v5.3 and the risk of bias was determined using the Methodological Index for Non-randomized Studies. RESULTS: We included 17 studies with a total of 3278 patients (1211 in the bridging therapy group and 2067 in the EVT group). Patients in the bridging group had a better functional outcome at 90 days, as evidenced by a higher proportion with a Modified Rankin Scale (mRS) score of 0-2 compared with the EVT group (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.54-2.19, P < 0.01), while no difference in mRS score of 0-3 (OR = 1.18, 95% CI: 0.96-1.45, P = 0.11). Patients in the bridging therapy group also had lower 90-day mortality rate (OR = 0.75, 95% CI: 0.59-0.95, P = 0.02). There were no significant differences between groups in rates of successful recanalization (OR = 0.96, 95% CI: 0.74-1.25, P = 0.77), sICH (OR = 1.27, 95% CI: 0.86-1.89, P = 0.24), and hemorrhage (OR = 1.22, 95% CI: 0.60-2.50, P = 0.58). CONCLUSIONS: Among patients with posterior ischemic stroke, bridging therapy may be superior to EVT in achieving a good functional outcome and lowering the mortality without increasing the risks of hemorrhage.

Integrative analysis of multi-omics data reveals a pseudouridine-related lncRNA signature for prediction of glioma prognosis and chemoradiotherapy sensitivity.

BACKGROUND: Glioblastoma is the most common type of glioma with a high incidence and poor prognosis, and effective medical treatment remains challenging. Pseudouridine (Ψ) is the first post-transcriptional modification discovered and one of the most abundant modifications to RNA. However, the prognostic value of Ψ-related lncRNAs (ΨrLs) for glioma patients has never been systematically evaluated. This study aims to construct a risk model based on ΨrLs signature and to validate the predictive efficiency of the model. METHOD: Transcriptomic data, genomic data, and relevant clinical data of glioma patients were extracted from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). ΨrLs with significant correlation with Ψ-related genes were identified, and univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were used to further select biomarkers and construct a ΨrLs signature risk model. Then, the expression of lncRNAs of ΨrLs signature in multiple glioma cell lines was detected by qPCR. Further, ROC analysis, stratification analysis, correlation analysis, survival analysis, nomogram, enrichment analysis, immune infiltration analysis, chemoradiotherapy sensitivity analysis, somatic mutation, and recurrent copy number variation (CNV) analysis were used to validate the predictive efficiency of ΨrLs signature in TCGA and CGGA datasets. RESULTS: A four-lncRNA ΨrLs signature (DNAJC27-AS1, GDNF-AS1, ZBTB20-AS4, and DNMBP-AS1) risk model was constructed. By ROC analysis, stratified analysis, correlation analysis, survival analysis, and nomogram, the signature showed satisfactory predictive efficiency. Functional enrichment analysis revealed the differences in immune-related biological processes between high- and low-risk groups. Immune infiltration analysis showed that the high-risk group had lower tumor purity and higher stromal, immune and ESTIMATE scores. Mitoxantrone was identified as effective drug for low-risk group of glioma patients. Key genes in glioma development, including IDH1, EGFR, PTEN, etc., were differentially mutated between risk groups. The main recurrent CNVs in low-risk groups were 19q13.42 deletion and 7q34 amplification; 10q23.31 deletion and 12q14.1 in the high-risk group. CONCLUSIONS: Our study identified a four-lncRNA ΨrLs signature that effectively predicts the prognosis of glioma patients and may serve as a diagnostic tool. Risk scores of glioma patients generated by the signature is associated with immune-related biological processes and chemoradiotherapy sensitivity. These findings may inform the development of more targeted and effective therapies for glioma patients.

The impact of COVID-19 on clinical outcomes in people undergoing neurosurgery: a systematic review and meta-analysis.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has created a global crisis unique to the healthcare system around the world. It also had a profound impact on the management of neurosurgical patients. In our research, we investigated the effect of the COVID-19 pandemic on clinical outcomes in people undergoing neurosurgery, particularly vascular and oncological neurosurgery. METHOD: Two investigators independently and systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrail.Gov, and Web of Science to identify relevant studies respecting the criteria for inclusion and exclusion published up to June 30, 2022. The outcomes of our research included mortality rate, length of stay, modified Rankin Score, delay in care, Glasgow outcome scale, and major complications. The risk of bias was assessed using the Methodological Index for Non-randomized Studies (MINORS) checklist. RESULTS: Two investigators independently and systematically searched 1378 results from MEDLINE, EMBASE, Cochrane database, ClinicalTrail.Gov, and Web of Science and extracted the detailed data from 13 studies that met the review's eligibility criteria. Two articles reported on patients with intracerebral hemorrhages, five on patients with subarachnoid hemorrhages, four on patients undergoing surgery for neuro-oncology, and in two studies the patients' conditions were unspecified. A total of 26,831 patients were included in our research. The number who died was significantly increased in the COVID-19 pandemic group (OR 1.52, 95% CI 1.36-1.69, P < 0.001). No significant difference was found between the two groups in terms of length of stay (SMD - 0.88, 95% CI - 0.18-0.02, P = 0.111), but it differed between regions, according to our subgroup analysis. CONCLUSION: Compared to the pre-pandemic group, the number who died was significantly increased in the COVID-19 pandemic group. Meanwhile, the effect of the pandemic on clinical outcomes in people undergoing neurosurgery might differ in different regions, according to our subgroup analysis.

Mechanical thrombectomy with intra-arterial alteplase provided better functional outcomes for AIS-LVO: a meta-analysis.

Background: Several clinical trials have shown that intra-arterial thrombolysis using alteplase during mechanical thrombectomy (MT) has a better outcome than MT alone in ischemic stroke management. We performed the current meta-analysis to estimate the efficacy and safety of MT with intra-arterial alteplase therapy. Methods: The MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched up to Mar. 2022 to identify the clinical trials that compared MT alone versus MT with intra-arterial alteplase therapy. STATA 16.0 was used for statistical analysis. The odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated with a random effect model. Results: Seven studies involving 1,083 participants were included. The primary outcomes were better functional outcomes, defined as a modified Rankin Scale (mRS) score between 0 and 2 at 90 days, and successful recanalization, defined as a modified thrombolysis in cerebral infarction (mTICI) score ≥ 2b. Compared to MT alone, MT with intra-arterial alteplase did not lead to higher mTICI scores (OR 1.58, 95%CI 0.94 to 2.67, p = 0.085, I2 = 16.8%) but did lead to better mRS (OR 1.37, 95%CI 1.01 to 1.86, p = 0.044). There was no increase in mortality or bleeding events in the overall or subgroup analyses. Conclusion: MT with intra-arterial alteplase did not improve the recanalization rate but provided better functional outcomes. The intervention did not increase adverse effects in any subgroup at the same time. Clinical trial registration: http://inplasy.com, identifier INPLASY202240027.

A glycosylation-related gene signature predicts prognosis, immune microenvironment infiltration, and drug sensitivity in glioma.

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype-Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)-regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy.

Efficacy and safety of stereotactic body radiotherapy for painful bone metastases: Evidence from randomized controlled trials.

Background: Pain relief is one of the main objectives of radiotherapy for cancer patients with bone metastases. Stereotactic body radiotherapy (SBRT) enables precise delivery of a higher dosage to the target area. Several trials have reported comparisons between SBRT and conventional radiotherapy (cRT) in patients with painful bone metastasis. However, the results of those investigations were inconsistent, and no systematic review or meta-analysis has been done till now. Methods: We systematically searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov up to May 1, 2022 for relevant studies. Patients with painful bone metastasis who received SBRT or cRT were included. The primary outcome was the patients' pain response rate at three months. The secondary outcomes included the rate of pain responders at one month and six months, oral morphine equivalent dose (OMED) use, and any adverse events. STATA software 12.0 was used for the statistical analysis. Results: We collected 533 patients' data from 4 randomized controlled trials (RCTs), there was a significant difference of pain response rate at 3 months between two groups (RR = 1.41, 95% CI: 1.12-1.77, I2 = 0.0%, P = 0.003). However, no significant difference was found in pain response rate at 1 month (RR = 1.19, 95% CI: 0.91-1.54, I2 = 31.5%, P = 0.201) and 6 months (RR = 1.25, 95% CI: 0.93-1.69, I2 = 0.0%, P = 0.140). OMED consumption was not significantly different in patients treated with SBRT compared with control group (WMD = -1.11, 95% CI: -17.51-15.28, I2 = 0.0%, P = 0.894). For safety outcome, no statistical difference was found between SBRT and cRT (RR = 0.72, 95% CI: 0.46-1.14, I2=20.1%, P = 0.162). Conclusion: This study shows that for painful bone metastases, patients with SBRT experienced better pain relief 3 months after radiation than patients with cRT, and SBRT did not increase the incidence of adverse events. Systematic review registration: https://inplasy.com/inplasy-2022-6-0099/, identifier INPLASY202260099.

Efficacy and safety of recanalization therapy for acute ischemic stroke with COVID-19: A systematic review and meta-analysis.

Background: The novel coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and created a tremendous threat to global health. Growing evidence suggests that patients with COVID-19 have more severe acute ischemic stroke (AIS). However, the overall efficacy and safety of recanalization therapy for AIS patients infected by the SARS-CoV-2 virus is unknown. Methods: The PRISMA guideline 2020 was followed. Two independent investigators systematically searched databases and ClinicalTrials.gov to identify relevant studies published up to 31 March 2022. AIS patients who received any recanalization treatments were categorized into those with COVID-19 and those without COVID-19. The main efficacy outcomes were patients' functional independence on discharge and successful recanalization, and the safety outcomes were in-hospital mortality and symptomatic intracranial hemorrhage. Subgroup analyses were implemented to assess the influence of admission National Institutes of Health Stroke Scale and different recanalization treatments on the outcomes. STATA software 12.0 was used for the statistical analysis. Results: This systematic review and meta-analysis identified 10 studies with 7,042 patients, including 596 COVID-19 positive patients and 6,446 COVID-19 negative patients. Of the total patients, 2,414 received intravenous thrombolysis while 4,628 underwent endovascular thrombectomy. COVID-19 positive patients had significantly lower rates of functional independence at discharge [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.15 to 0.59, P = 0.001], lower rates of successful recanalization (OR 0.40, 95% CI 0.24 to 0.68, P = 0.001), longer length of hospital stay (weighted mean difference 5.09, 95% CI 1.25 to 8.94, P = 0.009) and higher mortality rates (OR 3.38, 95% CI 2.43 to 4.70, P < 0.0001). Patients with COVID-19 had a higher risk of symptomatic intracranial hemorrhage than the control group, although the difference did not reach statistical significance (OR 2.34, 95% CI 0.99 to 5.54, P = 0.053). Conclusions: Compared with COVID-19 negative AIS patients who received recanalization treatments, COVID-19 positive patients turned out to have poorer outcomes. Particular attention needs to be paid to the treatments for these COVID-19 patients to decrease mortality and morbidity. Long-term follow-up is necessary to evaluate the recanalization treatments for AIS patients with COVID-19. Systematic review registration: https://inplasy.com/inplasy-2022-4-0022/, identifier: INPLASY202240022.

Contribution of Rs780094 and Rs1260326 Polymorphisms in GCKR Gene to Non-alcoholic Fatty Liver Disease: A Meta-Analysis Involving 26,552 Participants.

BACKGROUND: Many published studies attempted to elucidate the implication of glucokinase regulator gene (GCKR) polymorphisms in the susceptibility to non-alcoholic fatty liver disease (NAFLD), but the results among them were still controversial. OBJECTIVE: This meta-analysis aims to precisely assess the relationship between the GCKR polymorphisms and the risk of NAFLD. METHODS: Systematic computerized searches in six databases were performed and updated on April 6, 2020. Meta-analyses were conducted by calling the R programs based on accumulated epidemiological data. Odds ratio (OR) and 95% confidential interval (CI) were calculated to summarize the effect estimates. RESULTS: In total, 25 studies including 6,598 cases and 19,954 controls were included. The pooled estimates indicated that the T allele carrier of the GCKR rs780094 polymorphism has predisposition to NAFLD (allele model: OR: 1.20, 95% CI: 1.11~1.29; homozygote model: OR: 1.38, 95% CI: 1.15~1.67; heterozygote model: OR: 1.25, 95% CI: 1.12~1.39; dominant model: OR: 1.29, 95% CI: 1.13~1.47; recessive model: OR: 1.18, 95% CI: 1.06~1.31), and the same as the rs1260326 polymorphism (allele model: OR: 1.32, 95% CI: 1.22~1.42; homozygote model: OR: 1.65, 95% CI: 1.40~1.94; heterozygote model: OR: 1.24, 95% CI: 1.07~1.43; dominant model: OR: 1.39, 95% CI: 1.21~1.59; recessive model: OR: 1.44, 95% CI: 1.28~1.62). Further stratified analyses according to age and ethnicity confirmed the statistical existence in most subgroups. CONCLUSION: This meta-analysis suggested that both of the GCKR rs780094 and rs1260326 polymorphisms are significantly associated with the increased risk of NAFLD.

Clinical Presentation of Sporadic Creutzfeldt-Jakob Disease in Han-Chinese.

The clinical presentation in Chinese patients with sporadic Creutzfeldt-Jakob disease (sCJD) may be unique due to the big difference in the codon 129 polymorphism of the prion protein gene (PRNP). This study retrospectively reviewed 26 cases of sCJD diagnosed in a single center in recent years. All 26 sCJD patients received brain magnetic resonance imaging scan, cerebrospinal fluid 14-3-3 protein detection, electroencephalogram, and PRNP gene screening. The codon 129 polymorphism were all homozygous MM in 26 sCJD patients. The main onset symptoms of sCJD patients were rapidly progressive dementia, visual impairment, and cerebellar ataxia. At the time of diagnosis, the incidence of myoclonus and akinetic mutism were relatively low (<50%). For auxiliary examinations, the positive rate of the typical magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid 14-3-3 protein, and electroencephalogram-periodic sharp wave complex was 96%, 64%, and 50%, respectively. As MM genotype is dominant and brain MRI is sensitive, brain MRI seems to play a major role in diagnosis of sCJD in Chinese.

Health status and burden of health care costs among urban elderly in China.

This study evaluates health status among elderly residents in urban China and medical insurance schemes for them. A total of 931 urban elderly individuals aged 60 years or above in 3 cities were interviewed. The survey gathered data on individual sociodemographic characteristics, self-reported health status, chronic disease diagnoses, use of and expenditure related to health care services, satisfaction with medical insurance, and so on. The prevalence of chronic disease was 79.1% among the respondents, and medical expenditure on chronic disease per patient was 4656 Yuan in half a year. Over the 2 earlier weeks, 27.4% of respondents had felt sick, and 63.5% of them had had outpatient visits; 29.5% of respondents had been hospitalized in the past year. Among different groups, the inpatient reimbursement rate ranged from 45.5% to 81.2%, and the outpatient reimbursement rate was between 4.1% and 100%. The health care demand had not been met for many elderly individuals because of the lack of general outpatient coverage in the basic medical insurance scheme.

[Therapeutic efficacy analysis of bronchoscopic interventional therapy on severe tuberculous main bronchial stenosis complicated with unilateral atelectasis].

OBJECTIVE: To observe the therapeutic efficacy of bronchoscopic interventional therapy on severe tuberculous main bronchial stenosis or atresia complicated with unilateral atelectasis. METHODS: Ninety patients with severe tuberculous main bronchial stenosis or atresia complicated with unilateral atelectasis, who had received bronchoscopic interventional therapy, were divided into group A and B according to whether stents had been implanted or not. Patients in group A had been treated with electrocautery, balloon dilatation and cryotherapy. Group B had been treated with metallic stent implantation on the basis of the above interventional management. In order to observe the effectiveness, the time needed for taking effect and restenosis rate were noted. The efficacy between patients with different disease courses, radiology, bronchoscopy and dyspnea index were evaluated before treatment and after the patients' conditions were stable. RESULTS: Three months after treatment, the good response rate and the total effective rate of group B were higher than those of group A, 97% vs 42% (χ(2) = 29.595, P < 0.05), 100% vs 81% (χ(2) = 6.060, P < 0.05), respectively. The time needed for taking effect in group B was significantly shorter than that in group A, 0.25 month vs 1.6 month. The dyspnea indexes of both groups were significantly improved after treatment, but the improvement of group B was more significant than that of group A (u = -2.478, P < 0.05). The disease course of patients with different therapeutic efficacy was evaluated, and the median disease course was 2 months in good response efficacy patients, 3.5 months in improved patients, and 5 months in ineffective patients; the difference being significant between ineffective and good response efficacy patients (u = -3.079, P < 0.01). The restenosis rate of group B was significantly higher than that of group A, 72% vs 32% (χ(2) = 9.090, P < 0.01). The median restenosis time was 4 months in group A, and 6 months in group B. Bronchoscopy follow-up 12 months after the initial effective treatment showed that the good response rate and the total effective rate of group B were better than those of group A, 60% vs 29% (χ(2) = 10.559, P < 0.01), 88% vs 60% (χ(2) = 10.261, P < 0.01, respectively), and the total effective rate of main bronchial atresia patients in group B was significantly higher than that in group A, 90% vs 50% (Fisher's exact test, P < 0.05). There was no significant difference in effectiveness between severe stenosis and atresia patients in group A and B. CONCLUSION: Electrocautery, balloon dilatation, cryotherapy and stent implantation were effective methods to treat severe tuberculous main bronchial stenosis or atresia complicated with unilateral atelectasis. Among them, the therapeutic efficacy was better and the symptoms improved more quickly in patients with stent implantation. The efficacy of stent implantation was better than that of conventional interventional therapy, but the incidence of restenosis was also higher. Following-up should be emphasized in this group of patients. Disease courses were associated with the therapeutic efficacy; longer disease course was related to worse therapeutic efficacy, and restenosis occurred earlier. So interventional therapy should be initiated earlier for bronchial tuberculosis with dyspnea, especially for that complicated by atelectasis.