Bedside Optic Nerve Ultrasonography for Diagnosing Increased Intracranial Pressure: A Systematic Review and Meta-analysis.

Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure. Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults. Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings. Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard. Data Extraction: 3 reviewers independently abstracted data and performed quality assessment. Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm. Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes. Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests. Primary Funding Source: None. (PROSPERO: CRD42017055485).

Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults. METHODS: In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697. FINDINGS: 25 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO2] across trials, 96% [range 94-99%, IQR 96-98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03-1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01-1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00-1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses. INTERPRETATION: In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94-96%. These results support the conservative administration of oxygen therapy. FUNDING: None.

Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis.

BACKGROUND: Atraumatic needles have been proposed to lower complication rates after lumbar puncture. However, several surveys indicate that clinical adoption of these needles remains poor. We did a systematic review and meta-analysis to compare patient outcomes after lumbar puncture with atraumatic needles and conventional needles. METHODS: In this systematic review and meta-analysis, we independently searched 13 databases with no language restrictions from inception to Aug 15, 2017, for randomised controlled trials comparing the use of atraumatic needles and conventional needles for any lumbar puncture indication. Randomised trials comparing atraumatic and conventional needles in which no dural puncture was done (epidural injections) or without a conventional needle control group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of postdural-puncture headache incidence and additional safety and efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42016047546. FINDINGS: We identified 20 241 reports; after exclusions, 110 trials done between 1989 and 2017 from 29 countries, including a total of 31 412 participants, were eligible for analysis. The incidence of postdural-puncture headache was significantly reduced from 11·0% (95% CI 9·1-13·3) in the conventional needle group to 4·2% (3·3-5·2) in the atraumatic group (relative risk 0·40, 95% CI 0·34-0·47, p<0·0001; I2=45·4%). Atraumatic needles were also associated with significant reductions in the need for intravenous fluid or controlled analgesia (0·44, 95% CI 0·29-0·64; p<0·0001), need for epidural blood patch (0·50, 0·33-0·75; p=0·001), any headache (0·50, 0·43-0·57; p<0·0001), mild headache (0·52, 0·38-0·70; p<0·0001), severe headache (0·41, 0·28-0·59; p<0·0001), nerve root irritation (0·71, 0·54-0·92; p=0·011), and hearing disturbance (0·25, 0·11-0·60; p=0·002). Success of lumbar puncture on first attempt, failure rate, mean number of attempts, and the incidence of traumatic tap and backache did not differ significantly between the two needle groups. Prespecified subgroup analyses of postdural-puncture headache revealed no interactions between needle type and patient age, sex, use of prophylactic intravenous fluid, needle gauge, patient position, indication for lumbar puncture, bed rest after puncture, or clinician specialty. These results were rated high-quality evidence as examined using the grading of recommendations assessment, development, and evaluation. INTERPRETATION: Among patients who had lumbar puncture, atraumatic needles were associated with a decrease in the incidence of postdural-puncture headache and in the need for patients to return to hospital for additional therapy, and had similar efficacy to conventional needles. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of atraumatic needles as a superior option for patients who require lumbar puncture. FUNDING: None.

Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk in the critically ill. METHODS: We searched the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015 without language or publication date restrictions. Only randomized controlled trials (RCTs) of PPIs vs H2RAs for stress ulcer prophylaxis in critically ill adults for clinically important bleeding, overt gastrointestinal (GI) bleeding, nosocomial pneumonia, mortality, ICU length of stay and Clostridium difficile infection were included. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess our confidence in the evidence for each outcome. RESULTS: In 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important GI bleeding (RR 0.39; 95 % CI 0.21, 0.71; P = 0.002; I (2) = 0 %, moderate confidence) and overt GI bleeding (RR 0.48; 95 % CI 0.34, 0.66; P < 0.0001; I (2) = 3 %, moderate confidence). PPI use did not significantly affect risk of pneumonia (RR 1.12; 95 % CI 0.86, 1.46; P = 0.39; I (2) = 2 %, low confidence), mortality (RR 1.05; 95 % CI 0.87, 1.27; P = 0.61; I (2) = 0 %, moderate confidence), or ICU length of stay (mean difference (MD), -0.38 days; 95 % CI -1.49, 0.74; P = 0.51; I (2) = 30 %, low confidence). No RCT reported Clostridium difficile infection. CONCLUSIONS: PPIs were superior to H2RAs in preventing clinically important and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality. Their impact on Clostridium difficile infection is yet to be determined.

Cervical spine clearance in obtunded patients after blunt traumatic injury: a systematic review.

BACKGROUND: Cervical spine clearance protocols are controversial for unconscious patients after blunt traumatic injury and negative findings on computed tomography (CT). PURPOSE: To review evidence about the utility of different cervical spine clearance protocols in excluding significant cervical spine injury after negative CT results in obtunded adults with blunt traumatic injury. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library were searched from January 2000 through November 2014. STUDY SELECTION: English-language studies that examined patients with negative CT results having confirmatory routine testing with magnetic resonance imaging (MRI), dynamic radiography, or clinical examination and that reported outcome measures of missed cervical spine injury, need for operative stabilization, or prolonged use of cervical collars. DATA EXTRACTION: Independent reviewers evaluated the quality of studies and abstracted the data according to a predefined protocol. DATA SYNTHESIS: Of 28 observational studies (3627 patients) that met eligibility criteria, 7 were prospective studies (1686 patients) with low risk of bias and well-interpreted, high-quality CT scans. These 7 studies showed that 0% of significant injuries were missed after negative CT results. The overall studies using confirmatory routine testing with MRI showed incidence rates of 0% to 1.5% for cervical spine instability (16 studies; 1799 patients), 0% to 7.3% for need for operative fixation (17 studies; 1555 patients), and 0% to 29.5% for prolonged collar use (16 studies; 1453 patients). LIMITATIONS: Most studies were retrospective. Approaches to management of soft tissue changes with collars varied markedly. CONCLUSION: Cervical spine clearance in obtunded adults after blunt traumatic injury with negative results from a well-interpreted, high-quality CT scan is probably a safe and efficient practice. PRIMARY FUNDING SOURCE: None.

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis.

IMPORTANCE: Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. OBJECTIVE: To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES: We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION: Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS: Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES: Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS: Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

Chronic subdural hematoma management: a systematic review and meta-analysis of 34,829 patients.

OBJECTIVE: To compare the efficacy and safety of multiple treatment modalities for the management of chronic subdural hematoma (CSDH) patients. BACKGROUND: Current management strategies of CSDHs remain widely controversial. Treatment options vary from medical therapy and bedside procedures to major operative techniques. METHODS: We searched MEDLINE (PubMed and Ovid), EMBASE, CINAHL, Google scholar, and the Cochrane library from January 1970 through February 2013 for randomized and observational studies reporting one or more outcome following the management of symptomatic patients with CSDH. Independent reviewers evaluated the quality of studies and abstracted the data on the safety and efficacy of percutaneous bedside twist-drill drainage, single or multiple operating room burr holes, craniotomy, corticosteroids as a main or adjuvant therapy, use of drains, irrigation of the hematoma cavity, bed rest, and treatment of recurrences following CSDH management. Mortality, morbidity, cure, and recurrence rates were examined for each management option. Randomized, prospective, retrospective, and overall observational studies were analyzed separately. Pooled estimates, confidence intervals (CIs), and relative risks (RRs) were calculated for all outcomes using a random-effects model. RESULTS: A total of 34,829 patients from 250 studies met our eligibility criteria. Sixteen trials were randomized, and the remaining 234 were observational. We included our unpublished single center series of 834 patients. When comparing percutaneous bedside drainage to operating room burr hole evacuation, there was no significant difference in mortality (RR, 0.69; 95% CI, 0.46-1.05; P = 0.09), morbidity (RR, 0.45; 95% CI, 0.2-1.01; P = 0.05), cure (RR, 1.05; 95% CI, 0.98-1.11; P = 0.15), and recurrence rates (RR, 1; 95% CI, 0.66-1.52; P = 0.99). Higher morbidity was associated with the adjuvant use of corticosteroids (RR, 1.97; 95% CI, 1.54-2.45; P = 0.005), with no significant improvement in recurrence and cure rates. The use of drains following CSDH drainage resulted in a significant decrease in recurrences (RR, 0.46; 95% CI, 0.27-0.76; P = 0.002). Craniotomy was associated with higher complication rates if considered initially (RR, 1.39; 95% CI, 1.04-1.74; P = 0.01); however, craniotomy was superior to minimally invasive procedures in the management of recurrences (RR, 0.22; 95% CI, 0.05-0.85; P = 0.003). CONCLUSIONS: Percutaneous bedside twist-drill drainage is a relatively safe and effective first-line management option. These findings may result in potential health cost savings and eliminate perioperative risks related to general anesthetic.

Minimal access to deep intracranial lesions using a serial dilatation technique: case-series and review of brain tubular retractor systems.

Surgical access to deep intracranial lesions causing the least amount of iatrogenic trauma to the surrounding brain tissue remains a challenging task. In this article, we evaluate the use of a set of sequential tubes that dilate and provide retraction of the overlying brain tissue acting as a surgical corridor for deep-seated brain lesions resection. In addition, we conducted a comprehensive review of the literature of previously described techniques using variable brain tubular retractor systems. We discuss the adaptation of a system designed for spinal use to intracranial pathologies and evaluate the outcomes for the patients involved in the study. Moreover, the advantages and limitations of the described technique were presented. Between August 2005 and 2011, a total of 30 patients with deep brain lesions were operated on using an incremental increase of tubing size for brain retraction guided by a frameless navigation device. Of these, seven cases were intraventricular, and 23 were intraparenchymal. Gross total resection was achieved in 70 % of cases, and the remaining had planned subtotal resections due to involvement of an eloquent area. In conclusion, the technique of serial dilatation of the brain tissue can be used in conjunction with a microscope or endoscope to provide satisfactory access to deep intracranial pathologies. It appears to minimize the associated retraction injury to the surrounding tissue by gradually dilating the white fiber tracts. This operative approach may be considered as an effective and safe alternative for brain tumor resections in selected cases, especially deep-seated lesions.

The Role of Anterior Cervical Discectomy and Fusion on Relieving Axial Neck Pain in Patients With Single-Level Disease: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: This study aims to evaluate the effects of anterior cervical decompression and fusion (ACDF) on axial neck pain in adult patients receiving surgery for myelopathy, radiculopathy, or a combination of both. METHODS: Two independent reviewers completed a librarian-assisted search of 4 databases. Visual Analogue Scale (VAS) and Neck Disability Index (NDI) scores were extracted preoperatively and at 3, 6, 12, 24, 36, 48, and 48+ months postoperatively for ACDF groups and pooled using a random-effects model. RESULTS: Of 17 850 eligible studies, 37 were included for analysis, totaling 2138 patients analyzed with VAS and 2477 with NDI score. Individual VAS mean differences were reduced at 6 weeks (-2.5 [95% confidence interval (CI): -3.5 to -1.6]), 3 months (-2.9 [-3.7 to -2.2]), 6 months (-3.2 [-3.9 to -2.6]), 12 months (-3.7 [-4.3 to -3.1]), 24 months (-4.0 [-4.4 to -3.5]), 48 months (-4.6 [-5.5 to -3.8]), and >48 months (-4.7 [-5.8 to -3.6]) follow-up (P < .0001 for all endpoints). Individual NDI mean differences were reduced at 6 weeks (-26.7 [-30.9 to -22.6]), 3 months (-29.8 [-32.7 to -26.8]), 6 months (-31.2 [-35.5 to -26.8)], 12 months (-29.3 [-33.2 to -25.4]), 24 months (-28.9 [-32.6 to -25.2]), 48 months (-33.1 [-37.4 to -28.7]), and >48 months (-37.6 [-45.9 to -29.3]) follow-up (P < .0001 for all endpoints). CONCLUSIONS: ACDF is associated with a significant reduction in axial neck pain compared with preoperative values in patients being treated specifically for myelopathy or radiculopathy. This influences the preoperative discussions surgeons may have with patients regarding their expectations for surgery. The effects seen are stable over time and represent a clinically significant reduction in axial neck pain.

Predicting Outcomes After Surgical Decompression for Mild Degenerative Cervical Myelopathy: Moving Beyond the mJOA to Identify Surgical Candidates.

BACKGROUND: Patients with mild degenerative cervical myelopathy (DCM) represent a heterogeneous population, and indications for surgical decompression remain controversial. OBJECTIVE: To dissociate patient phenotypes within the broader population of mild DCM associated with degree of impairment in baseline quality of life (QOL) and surgical outcomes. METHODS: This was a post hoc analysis of patients with mild DCM (modified Japanese Orthopedic Association [mJOA] 15-17) enrolled in the AOSpine CSM-NA/CSM-I studies. A k-means clustering algorithm was applied to baseline QOL (Short Form-36 [SF-36]) scores to separate patients into 2 clusters. Baseline variables and surgical outcomes (change in SF-36 scores at 1 yr) were compared between clusters. A k-nearest neighbors (kNN) algorithm was used to evaluate the ability to classify patients into the 2 clusters by significant baseline clinical variables. RESULTS: One hundred eighty-five patients were eligible. Two groups were generated by k-means clustering. Cluster 1 had a greater proportion of females (44% vs 28%, P = .029) and symptoms of neck pain (32% vs 11%, P = .001), gait difficulty (57% vs 40%, P = .025), or weakness (75% vs 59%, P = .041). Although baseline mJOA correlated with neither baseline QOL nor outcomes, cluster 1 was associated with significantly greater improvement in disability (P = .003) and QOL (P < .001) scores following surgery. A kNN algorithm could predict cluster classification with 71% accuracy by neck pain, motor symptoms, and gender alone. CONCLUSION: We have dissociated a distinct patient phenotype of mild DCM, characterized by neck pain, motor symptoms, and female gender associated with greater impairment in QOL and greater response to surgery.

Investigating the utility of intraoperative neurophysiological monitoring for anterior cervical discectomy and fusion: analysis of over 140,000 cases from the National (Nationwide) Inpatient Sample data set.

OBJECTIVE: Intraoperative neurophysiological monitoring (IONM) is a useful adjunct in spine surgery, with proven benefit in scoliosis-correction surgery. However, its utility for anterior cervical discectomy and fusion (ACDF) is unclear, as there are few head-to-head comparisons of ACDF outcomes with and without the use of IONM. The authors sought to evaluate the impact of IONM on the safety and cost of ACDF. METHODS: This was a retrospective analysis of data from the National (Nationwide) Inpatient Sample of the Healthcare Cost and Utilization Project from 2009 to 2013. Patients with a primary procedure code for ACDF were identified, and diagnosis codes were searched to identify cases with postoperative neurological complications. The authors performed univariate and multivariate logistic regression for postoperative neurological complications with use of IONM as the independent variable; additional covariates included age, sex, surgical indication, multilevel fusion, Charlson Comorbidity Index (CCI) score, and admission type. They also conducted propensity score matching in a 1:1 ratio (nearest neighbor) with the use of IONM as the treatment indicator and the aforementioned variables as covariates. In the propensity score-matched cohort, they compared neurological complications, length of stay (LOS), and hospital charges (in US dollars). RESULTS: A total of 141,007 ACDF operations were identified. IONM was used in 9540 cases (6.8%). No significant association was found between neurological complications and use of IONM on univariate analysis (OR 0.80, p = 0.39) or multivariate regression (OR 0.82, p = 0.45). By contrast, age ≥ 65 years, multilevel fusion, CCI score > 0, and a nonelective admission were associated with greater incidence of neurological complication. The propensity score-matched cohort consisted of 18,760 patients who underwent ACDF with (n = 9380) or without (n = 9380) IONM. Rates of neurological complication were comparable between IONM and non-IONM (0.17% vs 0.22%, p = 0.41) groups. IONM and non-IONM groups had a comparable proportion of patients with LOS ≥ 2 days (19% vs 18%, p = 0.15). The use of IONM was associated with an additional $6843 (p < 0.01) in hospital charges. CONCLUSIONS: The use of IONM was not associated with a reduced rate of neurological complications following ACDF. Limitations of the data source precluded a specific assessment of the effectiveness of IONM in preventing neurological complications in patients with more complex pathology (i.e., ossification of the posterior longitudinal ligament or cervical deformity).

Diagnosis of elevated intracranial pressure in critically ill adults: systematic review and meta-analysis.

OBJECTIVES: To summarise and compare the accuracy of physical examination, computed tomography (CT), sonography of the optic nerve sheath diameter (ONSD), and transcranial Doppler pulsatility index (TCD-PI) for the diagnosis of elevated intracranial pressure (ICP) in critically ill patients. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Six databases, including Medline, EMBASE, and PubMed, from inception to 1 September 2018. STUDY SELECTION CRITERIA: English language studies investigating accuracy of physical examination, imaging, or non-invasive tests among critically ill patients. The reference standard was ICP of 20 mm Hg or more using invasive ICP monitoring, or intraoperative diagnosis of raised ICP. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality using the quality assessment of diagnostic accuracy studies tool. Summary estimates were generated using a hierarchical summary receiver operating characteristic (ROC) model. RESULTS: 40 studies (n=5123) were included. Of physical examination signs, pooled sensitivity and specificity for increased ICP were 28.2% (95% confidence interval 16.0% to 44.8%) and 85.9% (74.9% to 92.5%) for pupillary dilation, respectively; 54.3% (36.6% to 71.0%) and 63.6% (46.5% to 77.8%) for posturing; and 75.8% (62.4% to 85.5%) and 39.9% (26.9% to 54.5%) for Glasgow coma scale of 8 or less. Among CT findings, sensitivity and specificity were 85.9% (58.0% to 96.4%) and 61.0% (29.1% to 85.6%) for compression of basal cisterns, respectively; 80.9% (64.3% to 90.9%) and 42.7% (24.0% to 63.7%) for any midline shift; and 20.7% (13.0% to 31.3%) and 89.2% (77.5% to 95.2%) for midline shift of at least 10 mm. The pooled area under the ROC (AUROC) curve for ONSD sonography was 0.94 (0.91 to 0.96). Patient level data from studies using TCD-PI showed poor performance for detecting raised ICP (AUROC for individual studies ranging from 0.55 to 0.72). CONCLUSIONS: Absence of any one physical examination feature is not sufficient to rule out elevated ICP. Substantial midline shift could suggest elevated ICP, but the absence of shift cannot rule it out. ONSD sonography might have use, but further studies are needed. Suspicion of elevated ICP could necessitate treatment and transfer, regardless of individual non-invasive tests. REGISTRATION: PROSPERO CRD42018105642.

Dendritic cell vaccines for high-grade gliomas.

Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To date, various promising chemotherapeutic regimens have been trialed for use in GBM; however, temozolomide (TMZ) therapy remains the only US Food and Drug Administration-approved first-line chemotherapeutic option for newly diagnosed GBM. Despite maximal therapy with surgery and combined concurrent chemoradiation and adjuvant TMZ therapy, the median overall survival remains approximately 14 months. Given the failure of conventional chemotherapeutic strategies in GBM, there has been renewed interest in the role of immunotherapy in GBM. Dendritic cells are immune antigen-presenting cells that play a role in both the innate and adaptive immune system, thereby making them prime vehicles for immunotherapy via dendritic cell vaccinations (DCVs) in various cancers. There is great enthusiasm surrounding the use of DCVs for GBM with multiple ongoing trials. In this review, we comprehensively summarize the safety, efficacy, and quality of life results from 33 trials reporting on DCV for high-grade gliomas.

Surgical outcomes for medically intractable epilepsy in low- and middle-income countries: a systematic review and meta-analysis.

OBJECTIVEThe aim of this study was to describe the current state of epilepsy surgery and establish estimates of seizure outcomes following surgery for medically intractable epilepsy (MIE) in low- and middle-income countries (LMICs).METHODSThe MEDLINE and Embase databases were searched without publication date restriction. This search was supplemented by a manual screen of key epilepsy and neurosurgical journals (January 2005 to December 2016). Studies that reported outcomes for at least 10 patients of any age undergoing surgery for MIE in LMICs over a defined follow-up period were included. A meta-analysis with a random-effects model was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. Pooled estimates of seizure freedom and favorable seizure outcomes following anterior temporal lobectomy with or without amygdalohippocampectomy (ATL ± AH) were reported.RESULTSTwenty studies were selected, of which 16 were from Asian centers. The average age at surgery in all studies was less than 30 years, and the average preoperative duration of epilepsy ranged from 3 to 16.1 years. Mesial temporal sclerosis accounted for 437 of 951 described pathologies, and 1294 of the 1773 procedures were ATL ± AH. Based on 7 studies (646 patients) the pooled seizure freedom estimate following ATL ± AH was 68% (95% CI 55%-82%). Based on 8 studies (1096 patients), the pooled estimate for favorable seizure outcomes was 79% (95% CI 74%-85%).CONCLUSIONSSurgery for MIE in LMICs shows a high percentage of seizure freedom and favorable outcomes. These findings call for a concerted global effort to improve timely access to surgery for MIE patients in these regions, including investments aimed at refining existing and establishing additional centers.

Highly Cited Works in Spinal Disorders: The Top 100 Most Cited Papers Published in Spine Journals.

STUDY DESIGN: Bibliometric analysis. OBJECTIVE: To identify, and summarize the key findings of, the top 100 most highly cited works published in spinal disorder topic-specific journals. SUMMARY OF BACKGROUND DATA: There is an abundance of published articles pertaining to spine surgery and spinal disorders. The number of citations a work receives provides a useful measure of its scientific impact. An understanding of the most cited works in spine surgery can identify literature that surgeons and researchers should be familiar with, point to the most active areas of research, inform the design of educational curricula, and help guide future research efforts. METHODS: Journals relating to spinal disorders were identified using the Journal Citation Reports database. We then searched the Web of Science database for articles appearing in each of these journals. The top 100 most cited works were selected for analysis. RESULTS: The top 100 most cited articles appeared in seven of eight journals dedicated to spinal disorders, with 84 in Spine and seven in the European Spine Journal. The citation count for individual articles ranged from 343 to 1949. Most works (73) were published between 1990 and 2004. The greatest number of articles (22) focused on low back pain, followed by biomechanics (13), degenerative disc disease (12), and lumbar spinal stenosis/lumbar fusion (9). With regard to study design, laboratory investigations were the most common (12), followed by guideline documents (11), reviews (10), and retrospective cohort studies (10). CONCLUSION: The most cited works in spinal disorder journals are guidelines for low back pain, descriptions of quality of life (QOL) metrics, or laboratory investigations into spinal biomechanics. A gap exists for work relating to neck pain or cervical spinal pathology (e.g., cervical myelopathy), representing opportunity for future work. Time of publication, topic of study, study design, and journal are possible determinants of likelihood of citation. LEVEL OF EVIDENCE: N/A.