Effect of neurosurgical residency programs on neurosurgical patient outcomes in a single health care system: a cohort study.

BACKGROUND: The evidence on the benefits and drawbacks of involving neurosurgical residents in the care of patients who undergo neurosurgical procedures is heterogeneous. We assessed the effect of neurosurgical residency programs on the outcomes of such patients in a large single-payer public health care system. METHODS: Ten population-based cohorts of adult patients in Ontario who received neurosurgical care from 2013 to 2017 were identified on the basis of procedural codes, and the cohorts were followed in administrative health data sources. Patient outcomes by the status of the treating hospital (with or without a neurosurgical residency program) within each cohort were compared with models adjusted for a priori confounders and with adjusted multilevel models (MLMs) to also account for hospital-level factors. RESULTS: A total of 46 608 neurosurgical procedures were included. Operative time was 8%-30% longer in hospitals with neurosurgical residency programs in 9 out of 10 cohorts. Thirty-day mortality was lower in hospitals with neurosurgical residency programs for aneurysm repair (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.20-0.44), cerebrospinal fluid shunting (OR 0.52, 95% CI 0.34-0.79), intracerebral hemorrhage evacuation (OR 0.66, 95% CI 0.52-0.84), and posterior lumbar decompression (OR 0.32, 95% CI 0.15-0.65) in adjusted models. The mortality rates remained significantly different only for aneurysm repair (OR 0.19, 95% CI 0.05-0.69) and cerebrospinal shunting (OR 0.42, 95% CI 0.21-0.85) in MLMs. Length of stay was mostly shorter in hospitals with neurosurgical residents, but this finding did not persist in MLMs. Thirty-day reoperation rates did not differ between hospital types in MLMs. For 30-day readmission rates, only extracerebral hematoma decompression was significant in MLMs (OR 1.41, 95% CI 1.07-1.87). CONCLUSION: Hospitals with neurosurgical residents had longer operative times with similar to better outcomes. Most, but not all, of the differences between hospitals with and without residency programs were explained by hospital-level variables rather than direct effects of residents.

Editor's Choice - Peri-Operative Outcomes of Carotid Endarterectomy are Not Improved on Dual Antiplatelet Therapy vs. Aspirin Monotherapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis of the peri-operative outcomes of carotid endarterectomy (CEA) on dual antiplatelet therapy (DAPT) vs. aspirin monotherapy was carried out, to determine optimal peri-operative management with these antiplatelet agents. DATA SOURCES: The Web of Science, Pubmed, and Embase databases were searched from inception to July 2021. The corresponding authors of excluded articles were contacted to obtain additional data for possible inclusion. REVIEW METHODS: The main outcomes included ischaemic complications (stroke, transient ischaemic attack [TIA], and transcranial Doppler [TCD] measured micro-emboli), haemorrhagic complications (haemorrhagic stroke, neck haematoma, and re-operation for bleeding), and composite outcomes. Pooled estimates using odds ratios (ORs) were combined using a random or fixed effects model based on the results of the chi square test and calculation of I2. RESULTS: In total, 47 411 patients were included in 11 studies, with 14 345 (30.2%) receiving DAPT and 33 066 (69.7%) receiving aspirin only. There was no significant difference in the rates of peri-operative stroke (OR 0.87, 95% confidence interval [CI] 0.72 - 1.05) and TIA (OR 0.78, 95% CI 0.52 - 1.17) despite a significant reduction in TCD measured micro-emboli (OR 0.19, 95% CI 0.10 - 0.35) in the DAPT compared with the aspirin monotherapy group. Subgroup analysis did not reveal any significant difference in ischaemic stroke risk between patients with asymptomatic and symptomatic carotid artery stenosis. DAPT was associated with an increased risk of neck haematoma (OR 2.79, 95% CI 1.87 - 4.18) and re-operation for bleeding (OR 1.98, 95% CI 1.77 - 2.23) vs. aspirin. Haemorrhagic stroke was an under reported outcome in the literature. CONCLUSION: This meta-analysis found that CEA while on DAPT increased the risk of haemorrhagic complications, with similar rates of ischaemic complications, vs. aspirin monotherapy. This suggests that the risks of performing CEA on DAPT outweigh the benefits, even in patients with symptomatic carotid stenosis. The overall quality of studies was low, and improved reporting of CEA outcomes in the literature is necessary.

Endovascular and Antithrombotic Treatment in Blunt Cerebrovascular Injuries: A Systematic Review and Meta-Analysis.

OBJECTIVES: Ischemic stroke has been estimated to occur in up to 26% of patients with blunt cerebrovascular injury (BCVI). Antithrombotic therapy (AT) may be used for stroke prevention, but the role of endovascular treatment (ET) remains unclear. We systematically reviewed the literature on AT and ET for the treatment of patients with BCVIs. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting the use of ET in BCVI patients. Post-ET neurologic outcomes, radiographic responses, and complication rates were assessed. A fixed-effect model meta-analysis was performed to compare treatment-related post-BCVI ischemic stroke rates between AT and ET protocols. RESULTS: We included 16 studies comprising 352 patients undergoing ET for BCVI. Mean post-ET rates of good neurologic outcomes and radiologic responses were 86.9% (range, 63.6-100%) and 94.0% (range 57.1-100%), respectively. Mean post-ET complication rate was 5.2% (range, 0-66.7%). Seven studies compared the roles of AT (delivered in 805 patients) and ET (performed in 235 patients) for preventing the onset of post-BCVI ischemic strokes. No significant difference in rates of post-BCVI ischemic stroke was found between patients receiving AT vs patients undergoing ET (OR 0.71, 95% CI: 0.35-1.42, p = 0.402). CONCLUSION: AT and ET may be comparable in preventing the occurrence of ischemic stroke following BCVIs. AT may be preferred as the less-invasive first-line therapy, but ET showed favorable rates of post-treatment clinical and radiologic outcomes, coupled with low rates of treatment-related complications.

Nutrition and lung cancer: a case control study in Iran.

BACKGROUND: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors. METHOD: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups. RESULT: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001). CONCLUSION: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran.

Transient elastography in hepatitis C virus-infected patients with beta-thalassemia for assessment of fibrosis.

AIM: We sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta-thalassemia. METHODS: Seventy-six CHC patients with beta-thalassemia underwent TE, liver biopsy, T2 -weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed. RESULTS: TE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2 -weighted MRI-LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log-transformed TE score(standardized ß = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized ß = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59-100%). A cut-off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut-off values for "TE-FIB-4 cirrhosis score" comprising TE and FIB-4 and "TE-APRI cirrhosis score" combining TE with aspartate aminotransferase-to-platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis. CONCLUSION: Regardless of LIC, TE alone or when combined with FIB-4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta-thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB-4 should be interpreted cautiously.

Opium could be considered an independent risk factor for lung cancer: a case-control study.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, and half of all incident lung cancers are believed to occur in the developing countries, including Iran. OBJECTIVE: We investigated the association of opium with the risk of lung cancer in a case-control study. METHODS: We enrolled 242 cases and 484 matched controls in this study. A questionnaire was developed, containing questions on basic demographic characteristics, as well as lifelong history of smoking cigarettes, exposure to passive smoking, opium use and alcohol consumption. For smoking cigarettes and opium and also oral opium intake frequency, duration and cumulative use were categorized into three groups: no use, low use and high use. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Multivariate analysis in men showed that after adjusting for the effect of ethnicity, education and pack years of smoking cigarettes, smoking opium remained as a significant independent risk factor with an OR of 3.1 (95% CI 1.2-8.1). In addition, concomitant heavy smoking of cigarettes and opium dramatically increased the risk of lung cancer to an OR of 35.0 (95% CI 11.4-107.9). CONCLUSION: This study demonstrated that smoking opium is associated with a high risk of lung cancer as an independent risk factor.

Ondansetron in patients with tinnitus: randomized double-blind placebo-controlled study.

The aim of this study was to assess the effect of ondansetron on symptoms of patients with subjective tinnitus accompanied by sensorineural hearing loss or normal hearing. Sixty patients with a chief complaint of tinnitus (with duration of more than 3 months) were equally randomized to ondansetron or placebo for 4 weeks. The dose of ondansetron was gradually increased from 4 mg/day (one tablet) to 16 mg/day (4 tablets) during 12 days and then continued up to 4 weeks. The exact number of tablets was prescribed in the placebo group. Patients underwent audiologic examinations and filled questionnaires at baseline and after 4 weeks of treatment. Our primary outcomes were changes in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Severity Index (TSI) and visual analog scale (VAS) scores. Our secondary outcomes were the changes in depression and anxiety based on Hospital Anxiety and Depression (HADS) questionnaire, side effects, tinnitus loudness matching, tinnitus pitch matching, pure tone audiometry and speech recognition threshold (SRT). In the ondansetron and placebo groups, 27 and 26 patients completed the study, respectively. The changes in VAS (P = 0.934), THI (P = 0.776), anxiety (P = 0.313) and depression (P = 0.163) scores were not different between the groups. TSI score decreased significantly in the ondansetron compared with the placebo group (P = 0.004). Changes in tinnitus loudness matching (P = 0.75) and pitch matching (P = 0.56) did not differ between the two groups. Ondansetron, but not placebo, decreased the SRT threshold (right, P < 0.001; left, P = 0.043) and mean PTA (right, P = 0.006; left, P < 0.001). In conclusion, ondansetron reduces the severity of tinnitus hypothetically through cochlear amplification.

Outcomes of Hypofractionated Stereotactic Radiotherapy for Small and Moderate-Sized Brain Metastases: A Single-Institution Analysis.

Background: Stereotactic radiosurgery (SRS) is the standard treatment for limited intracranial metastases. With the advent of frameless treatment delivery, fractionated stereotactic radiotherapy (FSRT) has become more commonly implemented given superior control and toxicity rates for larger lesions. We reviewed our institutional experience of FSRT to brain metastases without size restriction. Methods: We performed a retrospective review of our institutional database of patients treated with FSRT for brain metastases. Clinical and dosimetric details were abstracted. All patients were treated in 3 or 5 fractions using LINAC-based FSRT, did not receive prior cranial radiotherapy, and had at least 6 months of MRI follow-up. Overall survival was estimated using the Kaplan-Meier method. Local failure and radionecrosis cumulative incidence rates were estimated using a competing risks model with death as the competing risk. Univariable and multivariable analyses using Fine and Gray's proportional subdistribution hazards regression model were performed to determine covariates predictive of local failure and radionecrosis. Results: We identified 60 patients and 133 brain metastases treated at our institution from 2016 to 2020. The most common histologies were lung (53%) and melanoma (25%). Most lesions were >1 cm in diameter (84.2%) and did not have previous surgical resection (88%). The median duration of imaging follow-up was 9.8 months. The median survival for the whole cohort was 20.5 months. The local failure at 12 months was 17.8% for all lesions, 22.1% for lesions >1 cm, and 13.7% for lesions ≤1 cm (p = 0.36). The risk of radionecrosis at 12 months was 7.1% for all lesions, 13.2% for lesions >1 cm, and 3.2% for lesions ≤1 cm (p = 0.15). Conclusions: FSRT is safe and effective in the treatment of brain metastases of any size with excellent local control and toxicity outcomes. Prospective evaluation against single-fraction SRS is warranted for all lesion sizes.

Comparative Efficacy of Treatments for Brain Metastases from Non-Small Cell Lung Cancer without an EGFR-Mutation/ALK-Rearrangement: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: As many as 30% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BMs) over the course of their illness. Here, we quantitatively compare the efficacy of the various emerging regimens for NSCLC BMs without a definitive targetable epidermal growth factor receptor mutation/ALK rearrangement. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL, and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs that included ≥10 patients were included. We used a frequentist fixed or random-effects model for network meta-analysis. The outcomes of interest included intracranial progression-free survival (iPFS), overall survival (OS), and overall progression-free survival. RESULTS: In total, 18 studies representing 17 trials (n = 2726 patients) were identified. Immune checkpoint inhibitor regimens showed significant improvement in OS compared with chemotherapy alone, including pembrolizumab and chemotherapy (6 studies, hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21-0.62), atezolizumab alone (HR 0.54, 95% CI 0.33-0.89), and nivolumab and ipilimumab (HR 0.64, 95% CI 0.42-0.97). An improvement in overall PFS was seen with use of pembrolizumab and chemotherapy compared with chemotherapy alone (3 studies, HR 0.42, 95% CI 0.26-0.68). Studies evaluating checkpoint inhibitors did not report iPFS data, and we did not find improvement in iPFS or OS with the addition of any chemotherapy regimen to whole-brain radiation therapy. CONCLUSIONS: In this network meta-analysis, we demonstrate the promising survival benefit with use of checkpoint inhibitor-based regimens in NSCLC BMs without a targetable epidermal growth factor receptor mutation/ALK rearrangement. Moving forward, large-scale BM-focused RCTs are necessary to establish the iPFS benefit of immune checkpoint inhibitor-based immunotherapy in this patient population.

Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 newly diagnosed disease.

BACKGROUND: Glioblastoma (GB) is the most common malignant brain tumor with a dismal prognosis despite standard of care (SOC). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) beyond the SOC. METHODS: We included RCTs that investigated the addition of a new treatment to the SOC in patients with newly diagnosed GB. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) regarding OS and PFS were extracted from each paper. We utilized a frequentist network meta-analysis. We planned a subgroup analysis based on O6-methylguanine-DNA methyl-transferase (MGMT) status. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses. RESULTS: Twenty-one studies were included representing a total of 7403 patients with GB. There was significant heterogeneity among studies impacting important factors such as timing of randomization and sample size. A confidence analysis on the network meta-analysis results revealed a score of low or very low for all treatment comparisons, across subgroups. Allowing for the heterogeneity within the study population, alkylating nitrosoureas (Lomustine and ACNU) and tumor-treating field improved both OS (HR = 0.53, 95% CI 0.33-0.84 and HR = 0.63 95% CI 0.42-0.94, respectively) and PFS (HR = 0.88, 95% CI 0.77-1.00 and HR = 0.63 95% CI 0.52-0.76, respectively). CONCLUSIONS: Our analysis highlights the numerous studies performed on newly diagnosed GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity raises the need for better standardization in neuro-oncology studies.

Optimal Management of Calvarial Lymphoma: A Meta-Analysis.

BACKGROUND: Calvarial lymphoma is an exceedingly rare phenomenon; the clinical presentation and imaging pattern mimic many diseases of the central nervous system. Several treatment approaches have been undertaken with variable use of surgery plus adjuvant chemotherapy and radiation; an optimal treatment algorithm has yet to be defined. The aim of this study was to better characterize management strategies and patient outcomes. METHODS: An illustrative case was presented and a meta-analysis was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MEDLINE and Embase were searched for cases of calvarial lymphoma. Outcomes between patients who underwent open surgery and biopsy only were compared directly. RESULTS: In an analysis from 1976 to 2019, 62 patients with a median age of 60 were included. The most common presentations were subcutaneous scalp mass (89%), headaches (26%), and focal neurological deficits (21%). Osteolytic changes on computed tomography were seen in 69% of patients with extension into either the intracranial or extracranial space in 97% of cases. Surgical excision was performed in 41 patients with a remission rate of 85% and a recurrence rate of 5%, which did not vary significantly from patients treated nonsurgically (remission in 75%, P = 0.479; recurrence in 0%, P = 1.000) CONCLUSIONS: In patients presenting with a progressively enlarging scalp mass, calvarial lymphoma should be in the differential diagnosis, as it can be effectively managed with a biopsy followed by chemotherapy and radiation. The role for open surgery may be limited.

Erratum to: Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 1 newly diagnosed disease.

[This corrects the article DOI: 10.1093/noajnl/vdab028.].

Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 recurrent glioblastoma.

BACKGROUND: There exists no consensus standard of treatment for patients with recurrent glioblastoma (GB). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) to determine if any consensus treatment can be determined for recurrent GB. METHODS: We included all recurrent GB RCTs with at least 20 patients in each arm, and for whom patients underwent standard of care at the time of their GB initial diagnosis. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) of the comparison of study arms regarding OS and PFS were extracted from each paper. For comparative efficacy analysis, we utilized a frequentist network meta-analysis, an extension of the classic pair-wise meta-analysis. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses. RESULTS: Fifteen studies were included representing 29 separate treatment arms and 2194 patients. In our network meta-analysis, combination treatment with tumor-treating field and Vascular endothelial growth factor (VEGF) inhibitor ranked first in improving OS (P = .80). Concomitant anti-VEGF and Lomustine treatment was superior to Lomustine alone for extending PFS (HR 0.57, 95% CI 0.41-0.79) and ranked first in improving PFS compared to other included treatments (P = .86). CONCLUSIONS: Our analysis highlights the numerous studies performed on recurrent GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity precludes drawing strong conclusions, and confidence analysis was low to very low. Further confirmation by future trials is recommended for our exploratory results.

Antithrombotic choice in blunt cerebrovascular injuries: Experience at a tertiary trauma center, systematic review, and meta-analysis.

BACKGROUND: Blunt cerebrovascular injuries (BCVIs) may occur following trauma and lead to ischemic stroke if untreated. Antithrombotic therapy decreases this risk; however, the optimal agent has yet to be determined in this population. The aim of this study was to compare the risk-benefit profile of antiplatelet (AP) versus anticoagulant (AC) therapy in rates of ischemic stroke and hemorrhagic complications in BCVI patients. METHODS: We performed a retrospective review of BCVI patients at our tertiary care Trauma hospital from 2010 to 2015, and a systematic review and meta-analysis of the literature. The OVID Medline, Embase, Web of Science, and Cochrane Library databases were searched from inception to September 16, 2019. References of included publications were searched manually for other relevant articles. The search was limited to articles in humans, in patients 18 years or older, and in English. Studies that reported treatment-stratified clinical outcomes following AP or AC treatment in BCVI patients were included. Exclusion criteria included case reports, case series with n < 5, review articles, conference abstracts, animal studies, and non-peer-reviewed publications. Data were extracted from each study independently by two reviewers, including study design, country of origin, sex and age of patients, Injury Severity Score, Biffl grade, type of treatment, ischemic stroke rate, and hemorrhage rate. Pooled estimates using odds ratio (OR) were combined using a random-effects model using a Mantel-Hanzel weighting. The main outcome of interest was rate of ischemic stroke due to BCVI, and the secondary outcome was hemorrhage rate based on AC or AP treatment. RESULTS: In total, there were 2044 BCVI patients, as reported in the 22 studies in combination with our institutional data. The stroke rate was not significantly different between the two treatment groups (OR, 1.27; 95% confidence interval, 0.40-3.99); however, the hemorrhage rate was decreased in AP versus AC treated groups (OR, 0.38; 95% confidence interval, 0.15-1.00). CONCLUSION: Based on this meta-analysis, both AC and AP seem similarly effective in preventing ischemic stroke, but AP is better tolerated in the trauma population. This suggests that AP therapy may be preferred, but this should be further assessed with prospective randomized trials. LEVEL OF EVIDENCE: Review article, level II.

Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Brain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS). RESULTS: We included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24). CONCLUSIONS: In patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060.

Determining the Optimal Adjuvant Therapy for Improving Survival in Elderly Patients with Glioblastoma: A Systematic Review and Network Meta-analysis.

PURPOSE: Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis. EXPERIMENTAL DESIGN: MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients >60 years of age with histologically confirmed GBM were included. Primary outcome of interest was the pooled HR from randomized controlled trials (RCTs). Secondary outcomes of interest included pooled HR from studies controlling for MGMT promoter methylation status, and safety. RESULTS: Fourteen studies, including 5 RCTs, reporting 4,561 patients were included. Using highest quality data from RCTs, our network-based approach demonstrated that standard radiotherapy (SRT) and temozolomide (TMZ) provided similar survival benefit when compared with hypofractionated radiotherapy (HRT) and TMZ [HR = 0.90; 95% confidence interval (CI), 0.43-1.87], TMZ alone (HR 1.25; 95% CI, 0.69-2.26), HRT alone (HR = 1.34; 95% CI, 0.73-2.45), or SRT alone (HR = 1.43; 95% CI, 0.87-2.36). HRT-TMZ had the highest probability (85%) of improving survival in older patients with GBM followed by SRT-TMZ (72%). Pooled analysis of trials controlling for MGMT promoter methylation status demonstrated that TMZ monotherapy confers similar survival benefit to combined chemoradiotherapy. CONCLUSIONS: Statistical comparisons using a network approach demonstrates that the common treatment regimens for older patients with GBM in previous RCTs confer similar survival benefits. Adjustments for MGMT promoter methylation status demonstrated that radiotherapy alone was inferior to TMZ-based approaches. Head-to-head comparison of TMZ monotherapy to combined TMZ and radiation is warranted.

Hemorrhage, Seizures, and Dynamic Changes of Familial versus Nonfamilial Cavernous Malformation: Systematic Review and Meta-analysis.

BACKGROUND: Cerebral cavernous malformations (CCMs) may be familial or nonfamilial. This systematic review compared the natural history of CCMs in familial compared with nonfamilial cases. METHODS: We searched MEDLINE, Web of Science, and EMBASE for natural history studies on CCMs up to September 2018. We included studies that followed at least 20 untreated patients. Primary outcomes were hemorrhage, seizures, and neuroimaging changes in familial and nonfamilial cases. Incidence rate per person-year (PY) or lesion-year (LY) of follow-up were used to pool the data using fixed-effects or random-effects models. We used the incidence rate ratio for comparison. RESULTS: We could not compare hemorrhage rates between familial and nonfamilial cases mainly owing to mixtures of subgroups of patients. The seizure rate was similar in familial and nonfamilial cases with pooled incidence rate of 1.5%/PY (95% confidence interval 1.1%-2.2%). The reseizure rate was higher than the seizure rate (P < 0.001). New lesion development was higher in familial cases (32.1%/PY vs. 0.7%/PY, P < 0.001). Signal change on neuroimaging ranged from 0.2%/LY to 2.4%/LY in familial cases. In familial cases, incidence rate of size change was 8%/PY (95% confidence interval 5.2%-12.2%) and 1.1%/LY (95% confidence interval 0.6%-1.6%). CONCLUSIONS: Familial CCMs show higher dynamic changes than nonfamilial cases. However, the presence of actual dynamic changes needs further assessment in nonfamilial cases. CCMs demonstrate a low incidence of seizure. First-time seizure increases the chance of recurrent seizure. Seizure rate based on the location and type of the lesion should be investigated further.

Acupuncture-Induced Cranial Epidural Abscess: Case Report and Review of the Literature.

BACKGROUND: Acupuncture is a common form of alternative medicine that is used for pain control among other modalities of treatment. It is a relatively safe procedure, but complications, including those of infectious etiology, may still occur. CASE DESCRIPTION: A 47-year-old immunosuppressed woman presented with fever, altered level of consciousness, dysphasia, and a left occipital subgaleal fluctuant mass after acupuncture for headaches in the same area. Imaging demonstrated subgaleal and epidural collection localized in the left occipital region. She underwent urgent surgical evacuation of both collections. Cultures from intraoperative specimens grew Streptococcus anginosus. The patient started targeted antibiotic treatment leading to complete recovery. CONCLUSIONS: To our knowledge, this is the first report of intracranial abscess after acupuncture. Given the worldwide application of this alternative treatment, physicians, acupuncturists, and the general public should be aware of the possibility of this rare but serious complication.

Novel Statistical Analyses to Assess Hearing Outcomes After ABI Implantation in NF2 Patients: Systematic Review and Individualized Patient Data Analysis.

BACKGROUND: Patients with neurofibromatosis type 2 develop bilateral vestibular schwannomas with progressive hearing loss. Auditory brainstem implants (ABIs) stimulate hearing in the cochlear nuclei and show promise in improving hearing. Here, we assess the impact of ABI on hearing over time by systematically reviewing the literature and re-analyzing available individual patient data. METHODS: A multidatabase search identified 3 studies with individual patient data of longitudinal hearing outcomes after ABI insertion in adults. Data were collected on hearing outcomes of different sound complexities from sound to speech using an ABI ± lip reading ability plus demographic data. Because of heterogeneity each study was analyzed separately using random effects multilevel mixed linear modeling. RESULTS: Across all 3 studies (n = 111 total) there were significant improvements in hearing over time from ABI placement (P < 0.000 in all). Improvements in comprehension of sounds, words, sentences, and speech occurred over time with ABI use + lip reading but lip reading ability did not improve over time. All categories of hearing complexity had over 50% comprehension after over 1 year of ABI use and some subsets had over 75% or near 100% comprehension. Vowel comprehension was greater than consonant, and word comprehension was greater than sentence comprehension (P < 0.0001 in both). Age and sex did not predict outcomes. CONCLUSIONS: ABIs improve hearing beyond lip reading alone, which represents baseline patient function prior to treatment, and the benefits continue to improve with time. These findings may be used to guide patient counseling regarding ABI insertion, rehabilitation course after insertion, and future studies.

Chronic subdural collection overlying an intra-axial hemorrhagic lesion in chronic myelomonocytic leukemia: special report and review of the literature.

Introduction: Chronic myelomonocytic leukaemia (CMML) is a clonal hematopoietic stem cell disorder characterized by the presence of an absolute monocytosis in the peripheral blood (>1 x 109/L) and the presence of myelodysplastic and myeloproliferative features in the bone marrow. Involvement of the central nervous system (CNS) is uncommon in CMML.Areas covered: Herein described is a case report of a CMML patient who presents with symptomatic chronic subdural collection overlying a haemorrhagic brain lesion, along with diffuse dural infiltration, after two cycles of azacytidine. Surgical intervention was performed to alleviate the mass effect on the brain, and obtain a tissue sample for diagnosis. Histopathological report confirmed brain infiltration with myeloid leukemic cells.Expert commentary: Despite its rarity, cerebral dissemination should be considered even in patients with CMML. A multidisciplinary approach, lead by a hematologist, is mandatory in order to correct the underlying haematological disorder, with specific attention to the coagulation profile. Surgical intervention is necessary for symptomatic patients, and should be performed once an improvement of clinical conditions has been achieved. Despite appropriate surgical and medical therapy, the prognosis remains poor with high risk of perioperative complications, such as rebleeding, and progressive systemic involvement.