Tyrosine kinase inhibitors in the treatment of leptomeningeal carcinomatosis.

Leptomeningeal carcinomatosis (LMC) is a devastating complication of advanced cancers, such as lung cancer and breast cancer, which is usually indicative of a poor prognosis. The current treatments for LMC include palliative care, with others aiming to prolong survival and relieve neurological symptoms. Traditional treatments for LMC include radiotherapy, systemic chemotherapy, and intrathecal injection. Furthermore, the application of molecularly targeted agents, such as antiepidermal growth factor receptor (anti-EGFR), antihuman epidermal growth factor receptor 2 (anti-HER2), and anti-PD-1 monoclonal antibody, have prolonged the survival of LMC patients. Targeted therapy with tyrosine kinase inhibitors has also been proven to be an effective treatment. Tyrosine kinases can be overactive or expressed at high levels in some cancer cells; therefore, the use of tyrosine kinase inhibitors may prevent the activation of tumor-related pathways, preventing cancer cell growth. The EGFR family are cell surface receptors directly related to tumor occurrence with tyrosine kinase activity; it is the most widely used target for tyrosine kinase inhibitors in the treatment of LMC. In this review, we introduced the clinical manifestation and diagnostic criteria of LMC, clarified the treatment mechanism of tyrosine kinase inhibitors for LMC with mutations in EGFR, HER2, or anaplastic lymphoma kinase, reviewed the current application of various generation tyrosine kinase inhibitors in patients with LMC, and discussed new clinical trials and the future directions of tyrosine kinase inhibitor therapy.

The efficacy and safety of FcRn inhibitors in patients with myasthenia gravis: a systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease that causes local or generalized muscle weakness. Complement inhibitors and targeting of the neonatal Fc receptor (FcRn) to block IgG cycling are two novel and successful mechanisms. METHODS: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before May 18, 2023. Review Manager 5.3 software was used to assess the data. RESULTS: We pooled 532 participants from six randomized controlled trials (RCTs). Compared to the placebo, the FcRn inhibitors were more efficacy in Myasthenia Gravis Activities of Daily Living (MG-ADL) (MD = - 1.69 [- 2.35, - 1.03], P < 0.00001), MG-ADL responder (RR = 2.01 [1.62, 2.48], P < 0.00001), Quantitative Myasthenia Gravis (QMG) (MD = - 2.45 [- 4.35, - 0.55], P = 0.01), Myasthenia Gravis Composite (MGC) (MD = - 2.97 [- 4.27, - 1.67], P < 0.00001), 15-item revised version of the Myasthenia Gravis Quality of Life (MGQoL15r) (MD = - 2.52 [- 3.54, - 1.50], P < 0.00001), without increasing the risk of safety. The subgroup analysis showed that efgartigimod was more effective than placebo in MG-ADL responders. Rozanolixizumab was more effective than the placebo except in QMG, and batoclimab was more effective than the placebo except in MG-ADL responder. Nipocalizumab did not show satisfactory efficacy in all outcomes. With the exception of rozanolixizumab, all drugs showed non-inferior safety profiles to placebo. CONCLUSION: FcRn inhibitors have good efficacy and safety in patients with MG. Among them, efgartigimod and nipocalimab were effective without causing an increased safety risk. Rozanolixizumab, despite its superior efficacy, caused an increased incidence of adverse events. Current evidence does not suggest that nipocalimab is effective in patients with MG.

Causal association of leisure sedentary behavior and cervical spondylosis, sciatica, intervertebral disk disorders, and low back pain: a Mendelian randomization study.

Background: Some studies suggest sedentary behavior is a risk factor for musculoskeletal disorders. This study aimed to investigate the potential causal association between leisure sedentary behavior (LSB) (including television (TV) viewing, computer use, and driving) and the incidence of sciatica, intervertebral disk degeneration (IVDD), low back pain (LBP), and cervical spondylosis (CS). Methods: We obtained the data of LSB, CS, IVDD, LBP, sciatica and proposed mediators from the gene-wide association studies (GWAS). The causal effects were examined by Inverse Variance Weighted (IVW) test, MR-Egger, weighted median, weighted mode and simple mode. And sensitivity analysis was performed using MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and MR-Egger intercept test. Multivariable MR (MVMR) was conducted to investigate the independent factor of other LSB; while two-step MR analysis was used to explore the potential mediators including Body mass index (BMI), smoking initiation, type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), schizophrenia, bipolar disorder between the causal association of LSB and these diseases based on previous studies. Results: Genetically associated TV viewing was positively associated with the risk of CS (OR = 1.61, 95%CI = 1.25 to 2.07, p = 0.002), IVDD (OR = 2.10, 95%CI = 1.77 to 2.48, p = 3.79 × 10-18), LBP (OR = 1.84, 95%CI = 1.53 to 2.21, p = 1.04 × 10-10) and sciatica (OR = 1.82, 95% CI = 1.45 to 2.27, p = 1.42 × 10-7). While computer use was associated with a reduced risk of IVDD (OR = 0.66, 95%CI = 0.55 to 0.79, p = 8.06 × 10-6), LBP (OR = 0.49, 95%CI = 0.40 to 0.59, p = 2.68 × 10-13) and sciatica (OR = 0.58, 95%CI = 0.46 to 0.75, p = 1.98 × 10-5). Sensitivity analysis validated the robustness of MR outcomes. MVMR analysis showed that the causal effect of TV viewing on IVDD (OR = 1.59, 95%CI = 1.13 to 2.25, p = 0.008), LBP (OR = 2.15, 95%CI = 1.50 to 3.08, p = 3.38 × 10-5), and sciatica (OR = 1.61, 95%CI = 1.03 to 2.52, p = 0.037) was independent of other LSB. Furthermore, two-step MR analysis indicated that BMI, smoking initiation, T2DM may mediate the causal effect of TV viewing on these diseases. Conclusion: This study provides empirical evidence supporting a positive causal association between TV viewing and sciatica, IVDD and LBP, which were potentially mediated by BMI, smoking initiation and T2DM.

Association Between Diverse Cell Death Patterns Related Gene Signature and Prognosis, Drug Sensitivity, and Immune Microenvironment in Glioblastoma.

Glioblastoma (GBM) is the most invasive type of glioma and is difficult to treat. Diverse programmed cell death (PCD) patterns have a significant association with tumor initiation and progression. A novel prognostic model based on PCD genes may serve as an effective tool to predict the prognosis of GBM. The study incorporated 11 PCD patterns, namely apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis, to develop the model. To construct and validate the model, both bulk and single-cell transcriptome data, along with corresponding clinical data from GBM cases, were obtained from the TCGA-GBM, REMBRANDT, CGGA, and GSE162631 datasets. A cell death-related signature containing 14 genes was constructed with the TCGA-GBM cohort and validated in the REMBRANDT and CGGA datasets. GBM patients with a higher cell death index (CDI) were significantly associated with poorer survival outcomes. Two separate clusters associated with clinical outcomes emerged from unsupervised analysis. A multivariate Cox regression analysis was conducted to examine the association of CDI with clinical characteristics, and a prognostic nomogram was developed. Drug sensitivity analysis revealed high-CDI GBM patients might be resistant to carmustine while sensitive to 5-fluorouracil. Less abundance of natural killer cells was found in GBM cases with high CDI and bulk transcriptome data. A cell death-related prognostic model that could predict the prognosis of GBM patients with good performance was established, which could discriminate between the prognosis and drug sensitivity of GBM.

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.

Efficacy and safety of the innovative monoclonal antibodies in adults with generalized myasthenia gravis: a Bayesian network analysis.

Background: A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among drugs remains unclear. Therefore, we conduct a frequentist network meta-analysis (NMA) to compare the relative effects of different drugs for generalized MG. Methods: PubMed, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched for eligible studies up to 1 June 2023. The primary outcome was efficacy (Myasthenia Gravis Activities of Daily Living [MG-ADL] score and Quantitative Myasthenia Gravis [QMG] score) and safety (adverse events [AEs]). Mean difference (MD) and risk ratio (RR) with their 95% credible intervals (95%CrIs) were used to show the effect size of continuous and categorical variables, respectively. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Thirteen studies involving 1167 individuals were identified for NMA. For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively). For safety outcomes, belimumab achieved the highest SUCRA value (89.8%) with significant statistical difference compared to rozanolixzumab 7mg/kg (RR 0.08, 95%CrI 0.01 to 0.94) and rozanolixzumab 10mg/kg (RR 0.08, 95%CrI 0.01 to 0.86). Conclusion: While all monoclonal antibodies were superior to the placebo, rozanolixzumab and batoclimab might be the most effective for generalized MG. However, rozanolixzumab was associated with higher incidence of AEs. Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings. Systematic review registration: https://inplasy.com/?s=202370112, identifier 202370112.

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.

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.

Non-Angry Superficial Draining Veins: A New Technique in Identifying the Extent of Nidus Excision during Cerebral Arteriovenous Malformation Surgery.

BACKGROUND: As essential techniques, intraoperative indocyanine green video angiography (ICG-VA) and FLOW 800 have been widely used in microsurgery for arteriovenous malformations (AVMs). In the present report, we introduced a supplementary technical trick for judging the degree of lesion resection when there were superficial drainage veins. FLOW 800 analysis is used to verify our conjecture. METHODS: A retrospective analysis of a 33 case cohort treated surgically from June 2020 to September 2022 was conducted and their lesions were removed by superficial drainage veins as a supplementary technical trick and analyzed with FLOW800. RESULTS: In our 33 AVMs, the feeding artery was visualized earlier than the draining vein. Intraoperatively, the T1/2 peak and slope of the draining vein were significantly higher than that of the lesion. However, the maximum fluorescence intensity (MFI) of the draining vein decreased as the procedure progressed (p < 0.001). After reducing the blood flow to the nidus by progressive dissection of the feeding artery, the arteriovenous transit time (AVTT) decreased from 0.64 ± 0.47 s, was prolonged to 2.38 ± 0.52 (p < 0.001), and the MFI and slope of the nidus decreased from the pre-resection 435.42 ± 43.90 AI and 139.77 ± 27.55 AI/s, and decreased to 386.70 ± 48.17 AI and 116.12 ± 17.46 AI/s (p < 0.001). After resection of the nidus, the T1/2 peak of the draining vein increased from 21.42 ± 4.70 s, prolonged to after dissection of the blood feeding artery, 23.07 ± 5.29 s (p = 0.424), and after resection of the lesion, 25.13 ± 5.46 s (p = 0.016), with a slope from 135.79 ± 28.17 AI/s increased to 210.86 ± 59.67 AI/s (p < 0.001). CONCLUSIONS: ICG-VA integrated with FLOW 800 is an available method for determining the velocity of superficial drainage veins. Whether the color of the superficial drainage veins on the cortical surface returns to normal can determine whether the lesion is completely resected and can reduce the possibility of residual postoperative lesions.

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.

Construction and Validation of a Necroptosis-Related lncRNA Signature in Prognosis and Immune Microenvironment for Glioma.

Background: Glioma is the most common primary brain tumor, representing approximately 80.8% of malignant tumors. Necroptosis triggers and enhances antitumor immunity and is expected to be a new target for tumor immunotherapy. The effectiveness of necroptosis-related lncRNAs as potential therapeutic targets for glioma has not been elucidated. Methods: We acquired RNA-seq data sets from LGG and GBM samples, and the corresponding clinical characteristic information is from TCGA. Normal brain tissue data is from GTEX. Based on TCGA and GTEx, we used univariate Cox regression to sort out survival-related lncRNAs. Lasso regression models were then built. Then, we performed a separate Kaplan-Meier analysis of the lncRNAs used for modeling. We validated different risk groups via OS, DFS, enrichment analysis, comprehensive immune analysis, and drug sensitivity. Results: We constructed a 12 prognostic lncRNAs model after bioinformatic analysis. Subsequently, the risk score of every glioma patient was calculated based on correlation coefficients and expression levels, and the patients were split into low- and high-risk groups according to the median value of the risk score. A nomogram was established for every glioma patient to predict prognosis. Besides, we found significant differences in OS, DFS, immune infiltration and checkpoints, and immune therapy between different risk subgroups. Conclusion: Predictive models of 12 necroptosis-related lncRNAs can facilitate the assessment of the prognosis and molecular characteristics of glioma patients and improve treatment modalities.

Efficacy and Safety of Different Bioactive Coils in Intracranial Aneurysm Interventional Treatment, a Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Bioactive coils have been used for nearly 20 years to improve aneurysm treatments. Previous studies are inadequate for comparing the efficacy and safety between different coils. The aim of this study was to investigate the safety and efficacy of different coils by comparing the percentage of people with different modified Raymond scale grades, re-rupture rates, and mortality in patients with intracranial aneurysms embolized with different coils. METHOD: Randomized controlled trials (RCTs) containing coils for aneurysm interventional treatment were collected from Web of Science, PubMed, and the Cochrane Library up to December 2021. Bayesian network meta-analysis with a randomized or fixed model was performed to compare the efficacy and safety among different bioactive coils and bare platinum coils. RESULTS: We pooled 3362 patients from eight RCTs. No significant differences were found between coils in the proportion of patients with a three-grade classification assessed with the modified Raymond scale immediately after surgery. Hydrogel coils did not show a significant difference in the percentage of patients with a modified Raymond scale grade I postoperatively compared with bare platinum coils (OR, -0.1080; 95% CI, -0.4201-0.2423), but at follow-up, the percentage of patients with modified Raymond scale grade I was significantly higher with hydrogel coils than with bare platinum coils (OR, 0.4957; 95% CI, 0.0060-0.9442). There were no statistical differences between these four coils in terms of aneurysm rupture or re-rupture rate and mortality. CONCLUSION: Though there was no significant difference in the embolization effect between the several coils in the postoperative period, complete embolization was more likely to be achieved with hydrogel coils compared to bare platinum coils at follow-up. There were no significant differences in safety between the several coil materials.

Utility of indocyanine green videoangiography with FLOW 800 analysis in brain tumour resection as a venous protection technique.

BACKGROUND: In regard to central nervous system tumour resection, preserving vital venous structures to avoid devastating consequences such as brain oedema and haemorrhage is important. However, in clinical practice, it is difficult to obtain clear and vivid intraoperative venous visualization and blood flow analyses. METHODS: We retrospectively reviewed patients who underwent brain tumour resection with the application of indocyanine green videoangiography (ICG-VA) integrated with FLOW 800 from February 2019 to December 2020 and present our clinical cases to demonstrate the process of venous preservation. Galen, sylvian and superior cerebral veins were included in these cases. RESULTS: Clear documentation of the veins from different venous groups was obtained via ICG-VA integrated with FLOW 800, which semiquantitatively analysed the flow dynamics. ICG-VA integrated with FLOW 800 enabled us to achieve brain tumour resection without venous injury or obstruction of venous flux. CONCLUSIONS: ICG-VA integrated with FLOW 800 is an available method for venous preservation, although further comparisons between ICG-VA integrated with FLOW 800 and other techniques of intraoperative blood flow monitoring is needed.

Diagnostic accuracy of intraoperative brainstem auditory evoked potential for predicting hearing loss after vestibular schwannoma surgery.

Objective: This meta-analysis evaluated the diagnostic value of intraoperative brainstem auditory evoked potential (BAEP) for predicting post-operative hearing loss. Methods: Research articles in MEDLINE, Embase, and Cochrane Library databases were searched and selected up to 20 January 2022, and data were extracted following a standard procedure. A diagnostic accuracy test meta-analysis was performed using a mixed-effect binary regression model. Results: A total of 693 patients from 15 studies were extracted. The change in intraoperative BAEP showed high sensitivity (0.95) but low specificity (0.37), with an area under the curve of 0.83. Diagnostic accuracy of the loss of potentials showed high sensitivity (0.82) and specificity (0.79). The area under the curve was 0.88. No factor was found to account for the heterogeneity of the results according to the meta-regression and subgroup analyses (all P-values > 0.05). Conclusions: Our results showed that the loss of BAEP has meaningful value for predicting hearing loss after vestibular schwannoma surgery. The change in BAEP is also important for its high sensitivity during hearing preservation surgery.

Clinical application of magnetic resonance-guided focused ultrasound in Parkinson's disease: a meta-analysis of randomized clinical trials.

BACKGROUND: To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of Parkinson's disease (PD). METHODS: The databases of Medline, EMBASE, and the Cochrane Library were searched for eligible randomized controlled trials comparing focused ultrasound surgery (FUS) group vs. sham procedure group in PD. Weighted mean differences and standardized mean differences with corresponding 95% confidence intervals were used to summarize the primary outcome, namely, the effect of MRgFUS to improve limb tremor in PD patients and adverse events, and the secondary outcome, which is the effect of MRgFUS in improving the quality of life, activities of daily living, and non-motor symptoms. RESULTS: The pooled analysis comprised 2 studies. The blinded phase lasted for 4 months in one experiment and up to 3 months in the other. The FUS group showed significant improvement in limb tremor on the treated side (SMD: - 1.20; 95% CI: - 2.06, - 0.34) and the ability to perform daily activities (SMD: - 0.86; 95% CI: - 1.41, - 0.32) compared to the sham group, but there were no significant group differences in other indicators. Of the process-related adverse events, dizziness (OR: 4.68; 95% CI: 1.20, 18.23) was more common in the treatment group, with no group differences in the remaining adverse events. CONCLUSIONS: These findings suggest beneficial effects of MRgFUS in PD patients with no serious side effects. Larger multicenter studies are needed in the future to select the most appropriate target and surgical device setup parameters.

Intraoperative indocyanine green video angiography (ICG-VA) with FLOW 800 software in complex intracranial aneurysm surgery.

BACKGROUND: Indocyanine green video angiography (ICG-VA) is a safe and effective instrument to assess changes in cerebral blood flow during cerebrovascular surgery. After ICG-VA, FLOW 800 provides a color-coded map to directly observe the dynamic distribution of blood flow and to calculate semiquantitative blood flow parameters later. The purpose of our study is to assess whether FLOW 800 is useful for surgery of complex intracranial aneurysms and to provide reliable evidence for intraoperative decision-making. METHODS: We retrospectively reviewed patients with complex aneurysms that underwent microsurgical and intraoperative evaluation of ICG-VA and FLOW 800 color-coded maps from February 2019 to May 2020. FLOW 800 data were correlated with patient characteristics, clinical outcomes, and intraoperative decision-making. RESULTS: The study included 32 patients with 42 complex aneurysms. All patients underwent ICG-VA FLOW 800 data provided semiquantitative data regarding localization, flow status in major feeding arteries; color maps confirmed relative adequate flow in parent, branching, and bypass vessels. CONCLUSIONS: FLOW 800 is a useful supplement to ICG-VA for intraoperative cerebral blood flow assessment. ICG-VA and FLOW 800 can help to determine the blood flow status of the parent artery after aneurysm clipping and the bypass vessels after aneurysm bypass surgery.

Different Doses of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis (RRMS) had been well verified in several large randomized controlled trials (RCTs) during the past decade. However, there are fewer systematic comparisons of different doses of fingolimod and whether the dose of 0.5 mg/d is the optimal one still remains to be solved. Objective: The objective of this systematic review was to evaluate the efficacy and safety of the four existing doses of fingolimod in the treatment of RRMS, especially the dose of 0.5 mg/d. Methods: MEDLINE, EMBASE, Cochrane Library, and clinicaltrials.gov were searched for RCTs which were performed to evaluate different doses of fingolimod and the corresponding control (placebo or DMTs) up to October 2020. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model. Results: We pooled 7184 patients from 11 RCTs. Fingolimod 0.5 mg/d was superior to control group in all eight efficacy outcomes including annualized relapse rate (ARR) (MD -0.22, 95%CI -0.29 to -0.14, p < 0.00001) but surprisingly showed a higher risk of basal-cell carcinoma (RR 4.40, 95%CI 1.58 to 12.24, p = 0.004). Although 1.25 mg/d is more than twice the dose of 0.5 mg/d, the effect size was almost similar between them. Dose of 5 mg/d obtained an unsatisfactory efficacy while showing a greater risk of adverse events than other three doses (RR 1.17, 95%CI 1.05 to 1.30, p = 0.003). Additionally, fingolimod 0.25 mg/d not only showed a better performance in delaying the disease progress of magnetic resonance imaging (MRI), but also achieved a certain degree of patient treatment satisfaction. Conclusion: At present, 0.5 mg/d remains to be the optimal dose of fingolimod for RRMS patients but trials of a lower dose are still of great clinical significance and should be paid more attentions.

Self-Assembly Iron Oxide Nanoclusters for Photothermal-Mediated Synergistic Chemo/Chemodynamic Therapy.

METHODS: Superparamagnetic iron oxide nanoclusters (SPIOCs) were located within the core, which resulted in high photothermal conversion and outstanding generation of reactive oxygen species (ROS). The shell consisted of a human serum albumin- (HSA-) paclitaxel (PTX) layer, which extended the blood circulation time and ensured the effectiveness of the chemotherapy. Arg-Gly-Asp peptides (RGD) were linked to the naked cysteine moieties in HSA to promote the specific targeting of human glioma U87 cells by α v ß 3 integrins. Continuous near-infrared light irradiation triggered and promoted the synergistic chemo/CDT therapy through the photothermal effect. RESULTS: Our SPIOCs@HSA-RGD nanoplatform showed well biocompatibility and could target glioma specifically. Photothermal conversion and ROS burst were detected after continuous 808 nm light irradiation, and a significant antitumor effect was achieved. CONCLUSION: Experimental in vitro and in vivo evaluations showed that our photothermal-mediated chemo/CDT therapy could efficiently inhibit tumor growth and is therefore promising for cancer therapy.

A new scoring system for predicting extent of resection in medial sphenoid wing meningiomas based on three-dimensional multimodality fusion imaging.

BACKGROUND: Three-dimensional (3D) fusion imaging has been proved to be a promising neurosurgical tool for presurgical evaluation of tumor removal. We aim to develop a scoring system based on this new tool to predict the resection grade of medial sphenoid wing meningiomas (mSWM) intuitively. METHODS: We included 46 patients treated for mSWM from 2014 to 2019 to evaluate their tumors' location, volume, cavernous sinus involvement, vascular encasement, and bone invasion by 3D multimodality fusion imaging. A scoring system based on the significant parameters detected by statistical analysis was created and evaluated. RESULTS: The tumor volumes ranged from 0.8 cm3 to 171.9 cm3. A total of 39 (84.8%) patients had arterial involvement. Cavernous sinus (CS) involvement was observed in 23 patients (50.0%) and bone invasion was noted in 10 patients (21.7%). Simpson I resection was achieved in 10 patients (21.7%) and Simpson II resection was achieved in 17 patients (37.0%). Fifteen patients (32.6%) underwent Simpson III resection and 4 patients (8.7%) underwent Simpson IV resections. A scoring system was created. The score ranged from 1 to 10 and the mean score of our patients was 5.3 ± 2.8. Strong positive monotonic correlation existed between the score and resection grade (Rs = 0.772, P < 0.001). The scoring system had good predictive capacity with an accuracy of 69.60%. CONCLUSIONS: We described a scoring system that enabled neurosurgeons to predict extent of resection and outcomes for mSWM preoperatively with 3D multimodality fusion imaging. TRIAL REGISTRATION: Retrospectively registered.