Dexamethasone and overall survival and progression free survival in patients with newly diagnosed glioblastoma: a meta-analysis.

PURPOSE: Glioblastomas, the most common primary malignant brain tumors in adults, still hold poor prognosis. Corticosteroids, such as dexamethasone, are usually prescribed to reduce peritumoral edema and limit neurological symptoms, although potential detrimental effects of these drugs have been described. The present meta-analysis aimed to explore the association of dexamethasone with overall survival (OS) and progression free survival (PFS) in patients with newly diagnosed glioblastoma. METHODS: PubMed, Cochrane Library, Embase, and ClinicalTrials.gov were searched for pertinent studies following the Preferred Reporting Items of Systematic Review and Meta-Analysis checklist. Pooled multivariable-adjusted hazard ratios (HR) for OS and PFS and their associated 95% confidence intervals (CIs) were calculated using the random-effects model and the heterogeneity among studies was assessed using I2. The quality of evidence was assessed using the GRADE criteria. RESULTS: Seven studies were included, pooling data of 1,257 patients, with age varying from 11 to 81 years. Glioblastoma patients on pre- or peri-operative dexamethasone were associated with a significantly poorer overall survival (HR: 1.33, 95% CI: 1.15, 1.55; 7 studies; I2: 59.9%) and progression free survival (HR: 1.77, 95% CI: 1.05, 2.97; 3 studies; I2: 71.1%) compared to patients not on dexamethasone. The quality of evidence was moderate for overall survival and low for progression free survival. CONCLUSION: Dexamethasone appeared to be associated with poor survival outcomes of glioblastoma patients.

Exercise training restores weight gain and attenuates hepatic inflammation in a rat model of non-celiac gluten sensitivity.

Gluten intolerance is associated with several disorders in the body. Although research has grown in recent years, the understanding of its impact on different tissues and the effects of physical exercise in mitigating health problems in the condition of gluten intolerance are still limited. Therefore, our objective was to test whether gliadin would affect metabolism and inflammation in liver tissue and whether aerobic physical exercise would mitigate the negative impacts of gliadin administration in rodents. Wistar rats were divided into exercised gliadin, gliadin, and control groups. Gliadin was administered by gavage from birth to 60 days of age. The rats in the exercised gliadin group performed an aerobic running exercise training protocol for 15 days. At the end of the experiments, physiological, histological, and molecular analyzes were performed in the study. Compared to the control group, the gliadin group had impaired weight gain and increased gluconeogenesis, lipogenesis, and inflammatory biomarkers in the liver. On the other hand, compared to the gliadin group, animals in the exercise-gliadin group had a recovery in body weight, improved insulin sensitivity, and a reduction in some gluconeogenesis, lipogenesis, and inflammatory biomarkers in the liver. In conclusion, our results revealed that the administration of gliadin from birth impaired weight gain and induced an increase in hepatic inflammatory cytokines, which was associated with an impairment of glycemic homeostasis in the liver, all of which were attenuated by adding aerobic exercise training in the gliadin group.

Time-restricted feeding combined with resistance exercise prevents obesity and improves lipid metabolism in the liver of mice fed a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat in the liver, is estimated to be the most common liver disease worldwide. Obesity is a major risk factor and contributor, and, accordingly, weight loss can improve NAFLD. Previous studies in preclinical models of diet-induced obesity and fatty liver disease have shown the independent benefits of resistance exercise training (RT) and time-restricted feeding (TRF) in preventing weight gain and hepatic build-up of fat. Here, we tested the combined effect of TRF and RT on obesity and NAFLD in mice fed a high-fat diet. Our results showed that both TRF-8-h food access in the active phase-and RT-consisting of three weekly sessions of ladder climbing-attenuated body weight gain, improved glycemic homeostasis, and decreased the accumulation of lipids in the liver. TRF combined with RT improved the respiratory exchange rate, energy expenditure, and mitochondrial respiration in the liver. Furthermore, gene expression analysis in the liver revealed lower mRNA expression of lipogenesis and inflammation genes along with increased mRNA of fatty acid oxidation genes in the TRF + RT group. Importantly, combined TRF + RT was shown to be more efficient in preventing obesity and metabolic disorders. In conclusion, TRF and RT exert complementary actions compared with isolated interventions, with significant effects on metabolic disorders and NAFLD in mice.NEW & NOTEWORTHY Whether time-restricted feeding (TRF) combined with resistance exercise training (RT) may be more efficient compared with these interventions alone is still unclear. We show that when combined with RT, TRF provided additional benefits, being more effective in increasing energy expenditure, preventing weight gain, and regulating glycemic homeostasis than each intervention alone. Thus, our results demonstrate that TRF and RT have complementary actions on some synergistic pathways that prevented obesity and hepatic liver accumulation.

Vitamin D protects against depression: Evidence from an umbrella meta-analysis on interventional and observational meta-analyses.

Meta-analyses of interventional and observational studies investigating the efficacy and the relationship between vitamin D and depression provided inconsistent results. The current umbrella meta-analysis was conducted to assess the available evidence and provide a conclusive outcome in this regard. The following international databases were systematically searched till March 2022: PubMed, Scopus, Embase, Web of Science, and Google Scholar. Random-effects model was carried out to calculate the pooled point estimates and their respective 95 % confidence intervals (CI). Ten meta-analyses of randomised controlled trials (RCTs) revealed significant reduction in depression symptoms comparing participants on vitmain D supplements to those on placebo (Pooled standardised mean difference: - 0.40; 95 % CI: - 0.60, - 0.21, p < 0.01: I2 = 89.1 %, p < 0.01). Four meta-analyses of cohort studies (with one having two subgroups) revealed that participants with lower levels of serum vitamin D were at increased odds of depression than those with higher levels of serum vitamin D (Pooled odds ratio: 1.60; 95 % CI: 1.08, 2.36, p < 0.01; I2 = 91.3 %, p < 0.01). The present umbrella meta-analysis confirms the potential benefits of vitamin D supplementation and higher serum vitamin D levels in reducing the development and symptoms of depression.

Efficacy and Safety of Direct Oral Anticoagulants (DOACs) Versus Warfarin in Atrial Fibrillation Patients with Prior Stroke: a Systematic Review and Meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke. METHODS: Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims) as the randomization was broken. RESULTS: Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance: for ischemic stroke, 0.84 (0.66-1.07) in claims; 0.90 (0.77-1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62-0.96) in claims; 0.86 (0.77-0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33-0.99) in claims; 0.87 (0.79-0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39-1.33) in claims; 0.51 (0.38-0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71-1.03) in claims; 0.90 (0.76-1.08) for non-claims and RCT subgroups. CONCLUSION: DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.

Effects of probiotics supplementation on blood pressure: An umbrella meta-analysis of randomized controlled trials.

AIMS: Several meta-analyses have revealed that probiotics could lower blood pressure (BP), but the findings were inconsistent. In this regard, an umbrella meta-analysis was carried out to provide a more accurate estimate of the overall impacts of probiotics supplementation on BP. DATA SYNTHESIS: We searched the following international databases till November 2021: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar. A random-effects model was applied to evaluate the effects of probiotics on BP. Sensitivity analysis was performed by using the leave-one-out method. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. Pooled effect size of 14 meta-analyses with 15,494 participants indicated significant decreases in both systolic (Weighted mean difference (WMD) = -1.96 mmHg; 95% confidence interval (CI): -2.78, -1.14, p < 0.001, and standardized mean difference (SMD) = -2.62; 95% CI: -4.96, -0.28, p < 0.001) and diastolic BP (WMD = -1.28 mmHg; 95% CI: -1.76, -0.79, p < 0.001, and SMD = -0.60 mmHg; 95% CI: -1.08, -0.12, p = 0.014) following probiotics supplementation. Greater effects on SBP were revealed in trials with a mean age of >50 years and the duration of intervention ≤10 weeks. DBP was also more reduced in studies with a dosage of ≥1010 colony forming unit (CFU), and SBP was decreased in patients with hypertension or diabetes analyzing WMD. CONCLUSION: The present umbrella meta-analysis suggests probiotics supplementation to improve BP and claims that probiotics could be used as a complementary therapy for controlling high BP. PROSPERO ID: CRD42022306560.

The optimal treatment of type II and III odontoid fractures in the elderly: an updated meta-analysis.

PURPOSE: Odontoid fractures are the most common cervical spine fractures in the elderly, with a controversial optimal treatment. The objective of this review was to compare the outcome of surgical and conservative treatments in elderly (≥ 65 years), by updating a systematic review published by the authors in 2013. METHODS: A comprehensive search was conducted in seven databases. Clinical outcome was the primary outcome. Fracture union- and stability were secondary outcomes. Pooled point estimates and their respective 95% confidence intervals (CIs) were derived using the random-effects model. A random-effects multivariable meta-regression model was used to correct for baseline co-variates when sufficiently reported. RESULTS: Forty-one studies met the inclusion criteria, of which forty were case series and one a cohort study. No clinical differences in outcomes including the Neck Disability Index (NDI, 700 patients), Visual Analogue Scale pain (VAS, 180 patients), and Smiley-Webster Scale (SWS, 231 patients) scores were identified between surgical and conservative treatments. However, fracture union was higher in surgically treated patients (pooled incidence 72.7%, 95% CI 66.1%, 78.5%, 31 studies, 988 patients) than in conservatively treated patients (40.2%, 95% CI 32.0%, 49.0%, 22 studies, 912 patients). This difference remained after correcting for age and fracture type. Fracture stability (41 studies, 1917 patients), although numerically favoring surgery, did not appear to differ between treatment groups. CONCLUSION: While surgically treated patients showed higher union rates than conservatively treated patients, no clinically relevant differences were observed in NDI, VAS pain, and SWS scores and stability rates. These results need to be further confirmed in well-designed comparative studies with proper adjustment for confounding, such as age, fracture characteristics, and osteoporosis degree.

Effect of awake craniotomy in glioblastoma in eloquent areas (GLIOMAP): a propensity score-matched analysis of an international, multicentre, cohort study.

BACKGROUND: Awake mapping has been associated with decreased neurological deficits and increased extent of resection in eloquent glioma resections. However, its effect within clinically relevant glioblastoma subgroups remains poorly understood. We aimed to assess the benefit of this technique in subgroups of patients with glioblastomas based on age, preoperative neurological morbidity, and Karnofsky Performance Score (KPS). METHODS: In this propensity score-matched analysis of an international, multicentre, cohort study (GLIOMAP), patients were recruited at four tertiary centres in Europe (Erasmus MC, Rotterdam and Haaglanden MC, The Hague, Netherlands, and UZ Leuven, Leuven, Belgium) and the USA (Brigham and Women's Hospital, Boston, MA). Patients were eligible if they were aged 18-90 years, undergoing resection, had a histopathological diagnosis of primary glioblastoma, their tumour was in an eloquent or near-eloquent location, and they had a unifocal enhancing lesion. Patients either underwent awake mapping during craniotomy, or asleep resection, as per treating physician or multidisciplinary tumour board decision. We used propensity-score matching (1:3) to match patients in the awake group with those in the asleep group to create a matched cohort, and to match patients from subgroups stratified by age (<70 years vs ≥70 years), preoperative National Institute of Health Stroke Scale (NIHSS) score (score of 0-1 vs ≥2), and preoperative KPS (90-100 vs ≤80). We used Cox proportional hazard regressions to analyse the effect of awake mapping on the primary outcomes including postoperative neurological deficits (measured by deterioration in NIHSS score at 6 week, 3 months, and 6 months postoperatively), overall survival, and progression-free survival. We used logistic regression to analyse the predictive value of awake mapping and other perioperative factors on postoperative outcomes. FINDINGS: Between Jan 1, 2010, and Oct 31, 2020, 3919 patients were recruited, of whom 1047 with tumour resection for primary eloquent glioblastoma were included in analyses as the overall unmatched cohort. After propensity-score matching, the overall matched cohort comprised 536 patients, of whom 134 had awake craniotomies and 402 had asleep resection. In the overall matched cohort, awake craniotomy versus asleep resection resulted in fewer neurological deficits at 3 months (26 [22%] of 120 vs 107 [33%] of 323; p=0·019) and 6 months (30 [26%] of 115 vs 125 [41%] of 305; p=0·0048) postoperatively, longer overall survival (median 17·0 months [95% CI 15·0-24·0] vs 14·0 months [13·0-16·0]; p=0·00054), and longer progression-free survival (median 9·0 months [8·0-11·0] vs 7·3 months [6·0-8·8]; p=0·0060). In subgroup analyses, fewer postoperative neurological deficits occurred at 3 months and at 6 months with awake craniotomy versus asleep resection in patients younger than 70 years (3 months: 22 [21%] of 103 vs 93 [34%] of 272; p=0·016; 6 months: 24 [24%] of 101 vs 108 [42%] of 258; p=0·0014), those with an NIHSS score of 0-1 (3 months: 22 [23%] of 96 vs 97 [38%] of 254; p=0·0071; 6 months: 27 [28%] of 95 vs 115 [48%] of 239; p=0·0010), and those with a KPS of 90-100 (3 months: 17 [19%] of 88 vs 74 [35%] of 237; p=0·034; 6 months: 24 [28%] of 87 vs 101 [45%] of 223, p=0·0043). Additionally, fewer postoperative neurological deficits were seen in the awake group versus the asleep group at 3 months in patients aged 70 years and older (two [13%] of 16 vs 15 [43%] of 35; p=0·033; no difference seen at 6 months), with a NIHSS score of 2 or higher (3 months: three [13%] of 23 vs 21 [36%] of 58; p=0·040) and at 6 months in those with a KPS of 80 or lower (five [18%] of 28 vs 34 [39%] of 88; p=0·043; no difference seen at 3 months). Median overall survival was longer for the awake group than the asleep group in the subgroups younger than 70 years (19·5 months [95% CI 16·0-31·0] vs 15·0 months [13·0-17·0]; p<0·0001), an NIHSS score of 0-1 (18·0 months [16·0-31·0] vs 14·0 months [13·0-16·5]; p=0·00047), and KPS of 90-100 (19·0 months [16·0-31·0] vs 14·5 months [13·0-16·5]; p=0·00058). Median progression-free survival was also longer in the awake group than in the asleep group in patients younger than 70 years (9·3 months [95% CI 8·0-12·0] vs 7·5 months [6·5-9·0]; p=0·0061), in those with an NIHSS score of 0-1 (9·5 months [9·0-12·0] vs 8·0 months [6·5-9·0]; p=0·0035), and in those with a KPS of 90-100 (10·0 months [9·0-13·0] vs 8·0 months [7·0-9·0]; p=0·0010). No difference was seen in overall survival or progression-free survival between the awake group and the asleep group for those aged 70 years and older, with NIHSS scores of 2 or higher, or with a KPS of 80 or lower. INTERPRETATION: These data might aid neurosurgeons with the assessment of their surgical strategy in individual glioblastoma patients. These findings will be validated and further explored in the SAFE trial (NCT03861299) and the PROGRAM study (NCT04708171). FUNDING: None.

Time-restricted feeding combined with aerobic exercise training can prevent weight gain and improve metabolic disorders in mice fed a high-fat diet.

KEY POINTS: Time-restricted feeding (TRF, in which energy intake is restricted to 8 h/day during the dark phase) alone or combined with aerobic exercise (AE) training can prevent weight gain and metabolic disorders in Swiss mice fed a high-fat diet. The benefits of TRF combined with AE are associated with improved hepatic metabolism and decreased hepatic lipid accumulation. TRF combined with AE training increased fatty acid oxidation and decreased expression of lipogenic and gluconeogenic genes in the liver of young male Swiss mice. TRF combined with AE training attenuated the detrimental effects of high-fat diet feeding on the insulin signalling pathway in the liver. ABSTRACT: Time-restricted feeding (TRF) or physical exercise have been shown to be efficient in the prevention and treatment of metabolic disorders; however, the additive effects of TRF combined with aerobic exercise (AE) training on liver metabolism have not been widely explored. In this study TRF (8 h in the active phase) and TRF combined with AE (TRF+Exe) were compared in male Swiss mice fed a high-fat diet, with evaluation of the effects on insulin sensitivity and expression of hepatic genes involved in fatty acid oxidation, lipogenesis and gluconeogenesis. As in previous reports, we show that TRF alone (eating only between zeitgeber time 16 and 0) was sufficient to reduce weight and adiposity gain, increase fatty acid oxidation and decrease lipogenesis genes in the liver. In addition, we show that mice of the TRF+Exe group showed additional adaptations such as increased oxygen consumption ( V̇O2${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ ), carbon dioxide production ( V̇CO2${\dot V_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ ) and production of ketone bodies (ß-hydroxybutyrate). Also, TRF+Exe attenuated the negative effects of high-fat diet feeding on the insulin signalling pathway (insulin receptor, insulin receptor substrate, Akt), and led to increased fatty acid oxidation (Ppara, Cpt1a) and decreased gluconeogenic (Fbp1, Pck1, Pgc1a) and lipogenic (Srebp1c, Cd36) gene expression in the liver. These molecular results were accompanied by increased glucose metabolism, lower serum triglycerides and reduced hepatic lipid content in the TRF+Exe group. The data presented in this study show that TRF alone has benefits but TRF+Exe has additive benefits and can mitigate the harmful effects of consuming a high-fat diet on body adiposity, liver metabolism and glycaemic homeostasis in young male Swiss mice.

The effect of smoking on survival in lung carcinoma patients with brain metastasis: a systematic review and meta-analysis.

The effects of smoking on survival in BM patients have yet to be reviewed and meta-analysed. However, previous studies have shown that smokers had a greater risk of dying from lung cancer compared to non-smokers. This meta-analysis, therefore, aimed to analyse the effects of cigarette smoking on overall survival (OS) and progression-free survival (PFS) in lung cancer BM patients. PubMed, Embase, Web of Science, Cochrane and Google Scholar were searched for comparative studies regarding the effects of smoking on incidence and survival in brain metastases patients up to December 2020. Three independent reviewers extracted overall survival (OS) and progression-free survival data (PFS). Random-effects models were used to pool multivariate-adjusted hazard ratios (HR). Out of 1890 studies, fifteen studies with a total of 2915 patients met our inclusion criteria. Amongst lung carcinoma BM patients, those who were smokers (ever or yes) had a worse overall survival (HR: 1.34, 95% CI 1.13, 1.60, I2: 72.1%, p-heterogeneity < 0.001) than those who were non-smokers (never or no). A subgroup analysis showed the association to remain significant in the ever/never subgroup (HR: 1.34, 95% CI 1.11, 1.63) but not in the yes/no smoking subgroup (HR: 1.30, 95% CI 0.44, 3.88). This difference between the two subgroups was not statistically significant (p = 0.91). Amongst lung carcinoma BM patients, smoking was associated with a worse OS and PFS. Future studies examining BMs should report survival data stratified by uniform smoking status definitions.

Transcranial Doppler and computed tomography angiography for detecting cerebral vasospasm post-aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm is a life-threatening complication following aneurysmal subarachnoid hemorrhage (aSAH). While digital subtraction angiography (DSA) is the current gold standard for detection, the diagnostic performance of computed tomography angiography (CTA) and transcranial Doppler (TCD) remains controversial. We aimed to summarize the available evidence and provide recommendations for their use based on GRADE criteria. A literature search was conducted for studies comparing CTA or TCD to DSA for adults ≥ 18 years with aSAH for radiographic vasospasm detection. The DerSimonian-Laird random-effects model was used to pool sensitivity and specificity and their 95% confidence intervals (CI) and derive positive and negative pooled likelihood ratios (LR + /LR -). Out of 2070 studies, seven studies (1646 arterial segments) met inclusion criteria and were meta-analyzed. Compared to the gold standard (DSA), CTA had a pooled sensitivity of 82% (95%CI, 68-91%) and a specificity of 97% (95%CI, 93-98%), while TCD had lower sensitivity 38% (95%CI, 19-62%) and specificity of 91% (95%CI, 87-94%). Only the LR + for CTA (27.3) reached clinical significance to rule in diagnosis. LR - for CTA (0.19) and TCD (0.68) approached clinical significance (< 0.1) to rule out diagnosis. CTA showed higher LR + and lower LR - than TCD for diagnosing radiographic vasospasm, thereby achieving a strong recommendation for its use in ruling in or out vasospasm, based on the high quality of evidence. TCDs had very low LR + and a reasonably low LR - , thereby achieving a weak recommendation against its use in ruling in vasospasm and weak recommendation for its use in ruling out vasospasm.

Efficacy and safety of flexible versus rigid endoscopic third ventriculostomy in pediatric and adult populations: a systematic review and meta-analysis.

Endoscopic third ventriculostomy (ETV) is a well-established surgical procedure for hydrocephalus treatment, but there is sparse evidence on the optimal choice between flexible and rigid approaches. A meta-analysis was conducted to compare efficacy and safety profiles of both techniques in pediatrics and adults. A comprehensive search was conducted on PubMED, EMBASE, and Cochrane until 11/10/2019. Efficacy was evaluated comparing incidence of ETV failure, while safety was defined by the incidence of perioperative complications, intraoperative bleedings, and deaths. Random-effects models were used to pool the incidence. Out of 1365 studies, 46 case series were meta-analyzed, yielding 821 patients who underwent flexible ETV and 2918 who underwent rigid ETV, with an age range of [5 days-87 years]. Although flexible ETV had a higher incidence of failure in adults (flexible: 54%, 95%CI: 22-82% vs rigid: 20%, 95%CI: 22-82%) possibly due to confounding due to etiology in adults treated with flexible, a smaller difference was seen in pediatrics (flexible: 36%, pediatric: 32%). Safety profiles were acceptable for both techniques, with a certain degree of variability for complications (flexible 2%, rigid 18%) and death (flexible 1%, rigid 3%) in pediatrics as well as complications (rigid 9%, flexible 13%), death (flexible 4%, rigid 6%) and intra-operative bleeding events (rigid 6%, flexible 8%) in adults. No clear superiority in efficacy could be depicted between flexible and rigid ETV for hydrocephalus treatment. Safety profiles varied by age but were acceptable for both techniques. Well-designed comparative studies are needed to assess the optimal endoscopic treatment option for hydrocephalus.

Complications and cosmetic outcomes of materials used in cranioplasty following decompressive craniectomy-a systematic review, pairwise meta-analysis, and network meta-analysis.

BACKGROUND: Optimal reconstruction materials for cranioplasty following decompressive craniectomy (DC) remain unclear. This systematic review, pairwise meta-analysis, and network meta-analysis compares cosmetic outcomes and complications of autologous bone grafts and alloplasts used for cranioplasty following DC. METHOD: PubMed, Embase, and Cochrane were searched from inception until April 2021. A random-effects pairwise meta-analysis was used to compare pooled outcomes and 95% confidence intervals (CIs) of autologous bone to combined alloplasts. A frequentist network meta-analysis was subsequently conducted to compare multiple individual materials. RESULTS: Of 2033 articles screened, 30 studies were included, consisting of 29 observational studies and one randomized control trial. Overall complications were statistically significantly higher for autologous bone compared to combined alloplasts (RR = 1.56, 95%CI = 1.14-2.13), hydroxyapatite (RR = 2.60, 95%CI = 1.17-5.78), polymethylmethacrylate (RR = 1.50 95%CI = 1.08-2.08), and titanium (Ti) (RR = 1.56 95%CI = 1.03-2.37). Resorption occurred only in autologous bone (15.1%) and not in alloplasts (0.0%). When resorption was not considered, there was no difference in overall complications between autologous bone and combined alloplasts (RR = 1.00, 95%CI = 0.75-1.34), nor between any individual materials. Dehiscence was lower for autologous bone compared to combined alloplasts (RR = 0.39, 95%CI = 0.19-0.79) and Ti (RR = 0.34, 95%CI = 0.15-0.76). There was no difference between autologous bone and combined alloplasts with respect to infection (RR = 0.85, 95%CI = 0.56-1.30), migration (RR = 1.36, 95%CI = 0.63-2.93), hematoma (RR = 0.98, 95%CI = 0.53-1.79), seizures (RR = 0.83, 95%CI = 0.29-2.35), satisfactory cosmesis (RR = 0.88, 95%CI = 0.71-1.08), and reoperation (RR = 1.66, 95%CI = 0.90-3.08). CONCLUSIONS: Bone resorption is only a consideration in autologous cranioplasty compared to bone substitutes explaining higher complications for autologous bone. Dehiscence is higher in alloplasts, particularly in Ti, compared to autologous bone.

Audiovestibular symptoms and facial nerve function comparing microsurgery versus SRS for vestibular schwannomas: a systematic review and meta-analysis.

OBJECTIVE: Surgery and radiosurgery represent the most common treatment options for vestibular schwannoma. A systematic review and meta-analysis were conducted to compare the outcomes of surgery versus stereotactic radiosurgery (SRS). METHODS: The Cochrane library, PubMed, Embase, and clinicaltrials.gov were searched through 01/2021 to find all studies on surgical and stereotactic procedures performed to treat vestibular schwannoma. Using a random-effects model, pooled odds ratios (OR) and their 95% confidence intervals (CI) comparing post- to pre-intervention were derived for pre-post studies, and pooled incidence of adverse events post-intervention were calculated for case series and stratified by intervention type. RESULTS: Twenty-one studies (18 pre-post design; three case series) with 987 patients were included in the final analysis. Comparing post- to pre-intervention, both surgery (OR: 3.52, 95%CI 2.13, 5.81) and SRS (OR: 3.30, 95%CI 1.39, 7.80) resulted in greater odds of hearing loss, lower odds of dizziness (surgery OR: 0.10; 95%CI 0.02, 0.47 vs. SRS OR: 0.22; 95%CI 0.05, 0.99), and tinnitus (surgery OR: 0.23; 95%CI 0.00, 37.9; two studies vs. SRS OR: 0.11; 95%CI 0.01, 1.07; one study). Pooled incidence of facial symmetry loss was larger post-surgery (14.3%, 95%CI 6.8%, 22.7%) than post-SRS (7%, 95%CI 1%, 36%). Tumor control was larger in the surgery (94%, 95%CI 83%, 98%) than the SRS group (80%, 95%CI 31%, 97%) for small-to-medium size tumors. CONCLUSION: Both surgery and SRS resulted in similar odds of hearing loss and similar improvements in dizziness and tinnitus among patients with vestibular schwannoma; however, facial symmetry loss appeared higher post-surgery.

The effect of weight loss on hypothalamus structure and function in obese individuals: a systematic review and meta-analysis.

INTRODUCTION: Obesity presents with structural and functional hypothalamic dysfunction. However, it is unclear whether weight loss can lead to hypothalamic changes. We therefore aimed to conduct a systematic review and meta-analysis to determine the effect of body mass reduction in obese individuals on hypothalamic structure and function. METHODS: PubMed, Embase and Cochrane databases were searched for studies that reported the change in hypothalamic structure and function after weight loss. Qualitative and quantitative analyses were performed on magnetic resonance imaging techniques, medio-basal hypothalamus T2-relaxation time, blood oxygen level dependent (BOLD) contrast, voxel-based morphometry (VBM) and biomarkers including glucose, insulin, leptin, ghrelin and inflammatory markers of interleukins. Mean differences between pre- and post-weight loss and 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS: Thirteen pre-post studies were included, of which six accounted for the meta-analysis. Studies showed a favorable decrease in T2-relaxation time (n = 1), favorable change in hypothalamic activity after weight loss on BOLD contrast (n = 4), with higher peak activities after surgical weight loss (n = 2). No differences were found in the gray matter density of the hypothalamus on VBM (n = 1). Pooled mean differences between pre- and post-surgical weight loss revealed a decrease of 8.53 mg/dl (95% CI: 5.17, 11.9) in glucose, 7.73 pmol/l (95% CI: 5.07, 10.4) in insulin, 15.5 ng/ml (95% CI: 9.40, 21.6) in leptin, 142.9 pg/ml (95% CI: 79.0, 206.8) in ghrelin and 9.43 pg/ml (95% CI: -6.89, 25.7) in IL-6 level. CONCLUSIONS: Our study showed weight reduction in obesity led to limited structural change and significant functional changes in the hypothalamus.

Differences in outcomes of mandatory motorcycle helmet legislation by country income level: A systematic review and meta-analysis.

BACKGROUND: The recent Lancet Commission on Legal Determinants of Global Health argues that governance can provide the framework for achieving sustainable development goals. Even though over 90% of fatal road traffic injuries occur in low- and middle-income countries (LMICs) primarily affecting motorcyclists, the utility of helmet laws outside of high-income settings has not been well characterized. We sought to evaluate the differences in outcomes of mandatory motorcycle helmet legislation and determine whether these varied across country income levels. METHODS AND FINDINGS: A systematic review and meta-analysis were completed using the PRISMA checklist. A search for relevant articles was conducted using the PubMed, Embase, and Web of Science databases from January 1, 1990 to August 8, 2021. Studies were included if they evaluated helmet usage, mortality from motorcycle crash, or traumatic brain injury (TBI) incidence, with and without enactment of a mandatory helmet law as the intervention. The Newcastle-Ottawa Scale (NOS) was used to rate study quality and funnel plots, and Begg's and Egger's tests were used to assess for small study bias. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were stratified by high-income countries (HICs) versus LMICs using the random-effects model. Twenty-five articles were included in the final analysis encompassing a total study population of 31,949,418 people. There were 17 retrospective cohort studies, 2 prospective cohort studies, 1 case-control study, and 5 pre-post design studies. There were 16 studies from HICs and 9 from LMICs. The median NOS score was 6 with a range of 4 to 9. All studies demonstrated higher odds of helmet usage after implementation of helmet law; however, the results were statistically significantly greater in HICs (OR: 53.5; 95% CI: 28.4; 100.7) than in LMICs (OR: 4.82; 95% CI: 3.58; 6.49), p-value comparing both strata < 0.0001. There were significantly lower odds of motorcycle fatalities after enactment of helmet legislation (OR: 0.71; 95% CI: 0.61; 0.83) with no significant difference by income classification, p-value: 0.27. Odds of TBI were statistically significantly lower in HICs (OR: 0.61, 95% CI 0.54 to 0.69) than in LMICs (0.79, 95% CI 0.72 to 0.86) after enactment of law (p-value: 0.0001). Limitations of this study include variability in the methodologies and data sources in the studies included in the meta-analysis as well as the lack of available literature from the lowest income countries or from the African WHO region, in which helmet laws are least commonly present. CONCLUSIONS: In this study, we observed that mandatory helmet laws had substantial public health benefits in all income contexts, but some outcomes were diminished in LMIC settings where additional measures such as public education and law enforcement might play critical roles.

Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric and adult population: a systematic review and meta-analysis.

Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety, and efficacy for these procedures in different clinical scenarios. The objective of the present study was to pool the available evidence to compare outcomes among patients with hydrocephalus undergoing ETV versus VPS. A systematic search of the literature was conducted via PubMed, EMBASE, and Cochrane Library through 11/29/2018 to identify studies evaluating failure and complication rates, following ETV or VPS. Pooled effect estimates were calculated using random effects. Heterogeneity was assessed by the Cochrane Q test and the I2 value. Heterogeneity sources were explored through subgroup analyses and meta-regression. Twenty-three studies (five randomized control trials (RCTs) and 18 observational studies) were meta-analyzed. Comparing ETV to VPS, failure rate was not statistically significantly different with a pooled relative risk (RR) of 1.48, 95%CI (0.85, 2.59) for RCTs and 1.17 (0.89, 1.53) for cohort studies; P-interaction: 0.44. Complication rates were not statistically significantly different between ETV and VPS in RCTs (RR: 1.34, 95%CI: 0.50, 3.59) but were statistically significant for prospective cohort studies (RR: 0.47, 95%CI: 0.30, 0.78); P-interaction: 0.07. Length of hospital stay was no different, when comparing ETV and VPS. These results remained unchanged when stratifying by intervention type and when regressing on age when possible. No significant differences in failure rate were observed between ETV and VPS. ETV was found to have lower complication rates than VPS in prospective cohort studies but not in RCTs. Further research is needed to identify the specific patient populations who may be better suited for one intervention versus another.

Safety and efficacy of prothrombin complex concentrate (PCC) for anticoagulation reversal in patients undergoing urgent neurosurgical procedures: a systematic review and metaanalysis.

Anticoagulant therapy poses a significant risk for patients undergoing emergency neurosurgery procedures, necessitating reversal with prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). Data on PCC efficacy lack consistency in this setting. This systematic review and metaanalysis aimed to evaluate efficacy and safety of PCC for anticoagulation reversal in the context of urgent neurosurgery. Articles from PubMed, Embase, and Cochrane databases were screened according to the PRISMA checklist. Adult patients receiving anticoagulation reversal with PCC for emergency neurosurgical procedures were included. When available, patients who received FFP were included as a comparison group. Pooled estimates of observational studies were calculated for efficacy and safety outcomes via random-effects modeling. Initial search returned 4505 articles, of which 15 studies met the inclusion criteria. Anticoagulants used included warfarin (83%), rivaroxaban (6.8%), phenprocoumon (6.1%), apixaban (2.2%), and dabigatran (1.5%). The mean International Normalized Ratio (INR) prePCC administration ranged from 2.3 to 11.7, while postPCC administration from 1.1 to 1.4. All-cause mortality at 30 days was 27% (95%CI 21, 34%; I2 = 44.6%; p-heterogeneity = 0.03) and incidence of thromboembolic events was 6.00% among patients treated with PCC (95%CI 4.00, 10.0%; I2 = 0%; p-heterogeneity = 0.83). Results comparing PCC and FFP demonstrated no statistically significant differences in INR reversal, mortality, or incidence of thromboembolic events. This metaanalysis demonstrated adequate safety and efficacy for PCC in the reversal of anticoagulation for urgent neurosurgical procedures. There was no significant difference between PCC and FFP, though further trials would be useful in demonstrating the safety and efficacy of PCC in this setting.

Minimally invasive versus open surgery for the correction of adult degenerative scoliosis: a systematic review.

While open surgery has been the primary surgical approach for adult degenerative scoliosis, minimally invasive surgery (MIS) represents an alternative option and appears to be associated with reduced morbidity. Given the lack of consensus, we aimed to conduct a systematic review on available literature comparing MIS versus open surgery for adult degenerative scoliosis. PubMed, Embase, and Cochrane databases were searched through December 16, 2019, for studies that compared both MIS and open surgery in patients with degenerative scoliosis. Four cohort studies reporting on 350 patients met the inclusion criteria. In two studies, patients undergoing open surgery were younger and had more severe disease at baseline as compared with MIS. Patients who underwent MIS had less blood loss, shorter length of stay, and a reduced rate of complications and infections. Both MIS and open surgery resulted in a significant change in pain and disability scores and both approaches provided significant correction of deformity in all studies, although open surgery was associated with a greater change in pelvic incidence-lumbar lordosis mismatch (PI-LL) and sagittal vertical axis (SVA) in two and three studies, respectively. In patients with adult degenerative scoliosis undergoing surgery, both MIS and open approaches appeared to offer comparable improvements in pain and function. However, MIS was associated with better safety outcomes, while open surgery provided greater correction of spinal deformity. Further studies are needed to identify specific subset of patients who may benefit from one approach versus the other.

The endoscope-assisted supraorbital "keyhole" approach for anterior skull base meningiomas: an updated meta-analysis.

INTRODUCTION: The gold-standard treatment for symptomatic anterior skull base meningiomas is surgical resection. The endoscope-assisted supraorbital "keyhole" approach (eSKA) is a promising technique for surgical resection of olfactory groove (OGM) and tuberculum sellae meningioma (TSM) but has yet to be compared with the microscopic transcranial (mTCA) and the expanded endoscopic endonasal approach (EEA) in the context of existing literature. METHODS: An updated study-level meta-analysis on surgical outcomes and complications of OGM and TSM operated with the eSKA, mTCA, and EEA was conducted using random-effect models. RESULTS: A total of 2285 articles were screened, yielding 96 studies (2191 TSM and 1510 OGM patients). In terms of effectiveness, gross total resection incidence was highest in mTCA (89.6% TSM, 91.1% OGM), followed by eSKA (85.2% TSM, 84.9% OGM) and EEA (83.9% TSM, 82.8% OGM). Additionally, the EEA group had the highest incidence of visual improvement (81.9% TSM, 54.6% OGM), followed by eSKA (65.9% TSM, 52.9% OGM) and mTCA (63.9% TSM, 45.7% OGM). However, in terms of safety, the EEA possessed the highest cerebrospinal fluid leak incidence (9.2% TSM, 14.5% OGM), compared with eSKA (2.1% TSM, 1.6% OGM) and mTCA (1.6% TSM, 6.5% OGM). Finally, mortality and intraoperative arterial injury were 1% or lower across all subgroups. CONCLUSIONS: In the context of diverse study populations, the eSKA appeared not to be associated with increased adverse outcomes when compared with mTCA and EEA and offered comparable effectiveness. Case-selection is paramount in establishing a role for the eSKA in anterior skull base tumours.