Enduring Neuroprotective Effect of Subacute Neural Stem Cell Transplantation After Penetrating TBI

Traumatic brain injury (TBI) is the largest cause of death and disability of persons under 45 years old, worldwide. Independent of the distribution, outcomes such as disability are associated with huge societal costs. The heterogeneity of TBI and its complicated biological response have helped clarify the limitations of current pharmacological approaches to TBI management. Five decades of effort have made some strides in reducing TBI mortality but little progress has been made to mitigate TBI-induced disability. Lessons learned from the failure of numerous randomized clinical trials and the inability to scale up results from single center clinical trials with neuroprotective agents led to the formation of organizations such as the Neurological Emergencies Treatment Trials (NETT) Network, and international collaborative comparative effectiveness research (CER) to re-orient TBI clinical research. With initiatives such as TRACK-TBI, generating rich and comprehensive human datasets with demographic, clinical, genomic, proteomic, imaging, and detailed outcome data across multiple time points has become the focus of the field in the United States (US). In addition, government institutions such as the US Department of Defense are investing in groups such as Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug-screening consortium to address the barriers in translation. The consensus from such efforts including “The Lancet Neurology Commission” and current literature is that unmitigated cell death processes, incomplete debris clearance, aberrant neurotoxic immune, and glia cell response induce progressive tissue loss and spatiotemporal magnification of primary TBI. Our analysis suggests that the focus of neuroprotection research needs to shift from protecting dying and injured neurons at acute time points to modulating the aberrant glial response in sub-acute and chronic time points. One unexpected agent with neuroprotective properties that shows promise is transplantation of neural stem cells. In this review we present (i) a short survey of TBI epidemiology and summary of current care, (ii) findings of past neuroprotective clinical trials and possible reasons for failure based upon insights from human and preclinical TBI pathophysiology studies, including our group's inflammation-centered approach, (iii) the unmet need of TBI and unproven treatments and lastly, (iv) present evidence to support the rationale for sub-acute neural stem cell therapy to mediate enduring neuroprotection

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Prolonged tracheal extubation time after glioma surgery was associated with lack of familiarity between the anesthesia provider and the operating neurosurgeon. A retrospective, observational study

We consider the effect of the number of previous interactions between the anesthesia provider and a single neurosurgeon during neurosurgical procedures (“familiarity”) and occurrence of an interval ≥15 min from the end of surgery (i.e., dressings applied) to tracheal extubation (“prolonged extubation”) during subsequent glioma procedures by that neurosurgeon. The value of 15min is a threshold at which post-case activity by non-anesthesia personnel in the operating room ends.Historical observational study.Neurosurgical operating room suite in an academic teaching hospital.294 patients undergoing elective supratentorial glioma surgery between 2012 and 2017 by a single neurosurgeon.1) Time from end of surgery (“dressings applied”) to extubation; 2) number of previous cases where the anesthesia provider had been present at the end of a neurosurgical procedure performed by the neurosurgeon; 3) case duration.Anesthesia providers (nurse anesthetists or anesthesia residents) were considered “unfamiliar” with the neurosurgeon if they had been present at the time of extubation for <5 previous neurosurgical cases (including glioma and non-glioma surgery) performed by the neurosurgeon during the study interval. For approximately half the cases the anesthesia provider was unfamiliar with the neurosurgeon. There was an association between the provider's number of historical cases with the neurosurgeon and prolonged extubation (P = 0.0048); the adjusted odds ratio (by unadjusted logistic regression) for unfamiliarity was 2.10 (95% CI 1.28 to 3.44, P = 0.025). Consistent with previously shown associations between case duration and prolonged extubation, analyses were valid based on a near-linear relationship between the logit (prevalence of prolonged extubation) and the case duration quintile.Lack of familiarity between the anesthesia provider and neurosurgeon during previous anesthetics is associated with prolonged tracheal extubation following intracranial glioblastoma surgery.•Studied 294 patients undergoing elective glioblastoma surgery by one neurosurgeon.•Prolonged extubation occurred if ≥15 min after the end of surgery.•Unfamiliarity defined as <5 prior cases by the anesthetist-neurosurgeon pair•Prolonged extubation was associated with unfamiliarity.•Longer cases were also more likely to be associated with prolonged extubation

Analysis of intra-operative variables as predictors of 30-day readmission in patients undergoing glioma surgery at a single center

Reducing the time from surgery to adjuvant chemoradiation, by decreasing unnecessary readmissions, is paramount for patients undergoing glioma surgery. The effects of intraoperative risk factors on 30-day readmission rates for such patients is currently unclear. We utilized a predictive model-driven approach to assess the impact of intraoperative factors on 30-day readmission rates for the cranial glioma patient. Retrospectively, the intraoperative records of 290 patients who underwent glioma surgery at a single institution by a single surgeon were assessed. Data on operative variables including anesthesia specific factors were analyzed via univariate and stepwise regression analysis for impact on 30-day readmission rates. A predictive model was built to assess the capability of these results to predict readmission and validated using leave-one-out cross-validation. In multivariate analysis, end case hypothermia (OR 0.28, 95% CI [0.09, 0.84]), hypertensive time > 15 min (OR 2.85, 95% CI [1.21, 6.75]), and pre-operative Karnofsky performance status (KPS) (OR 0.63, 95% CI [0.41, 0.98] were identified as being significantly associated with 30-day readmission rates (chi-squared statistic vs. constant model 25.2, p < 0.001). Cross validation of the model resulted in an overall accuracy of 89.7%, a specificity of 99.6%, and area under the receiver operator curve (AUC) of 0.763. Intraoperative risk factors may help risk-stratify patients with a high degree of accuracy and improve postoperative patient follow-up. Attention should be paid to duration of hypertension and end-case final temperature as these represent potentially modifiable factors that appear to be highly associated with 30-day readmission rates. Prospective validation of our model is needed to assess its potential for implementation as a screening tool to identify patients undergoing glioma surgery who are at a higher risk of post-operative readmission within 30 days

Central Neurocytoma Treatment Modalities: A Systematic Review Assessing the Outcomes of Combined Maximal Safe Resection and Radiotherapy with Gross Total Resection

Central neurocytomas (CNCs) are rare intraventricular lesions comprising <1% of primary brain tumors. Their surgical and adjuvant management is unclear. Our goal was to update Rades et al.'s 2006 systematic review to assess the outcome differences among 3 fundamental therapies for CNC: gross total resection with and without radiation therapy (RT) versus maximal safe resection with adjuvant RT. Articles indexed on PubMed and Google Scholar and published between January 1, 2006 and December 31, 2019 were selected using the PRISMA criteria. Studies were excluded if they had fewer than 3 cases, did not categorize extent of resection, or were duplicate studies, technical reports, case reports, or studies without follow-up. Complication rates, recurrence rates, overall survival and progression-free survival were extracted where possible. χ proportionality tests were used for comparison (P values >0.05 suggested significance). On aggregation, 615 patients from 13 studies including ours were assessed. Although overall survival was not significantly different (χ  = 1.56; P = 0.46), the recurrence rate differed significantly between GTR + RT (6.9%, 92.11 months), GTR-RT (23.9%, 96.8 months), and MSR + RT (16.8%, 85 months) (χ  = 10.94; P = 0.004). Pooled complication rates for GTR and MSR + RT were 31.2% and 24% (P = 0.049), respectively. RT remains an important adjuvant treatment that can improve patient survival in the presence of MSR to levels comparable to those of GTR or GTR + RT. Where total resection carries too much risk, MSR + RT can be considered as the next best alternative for tumor control

Salvage craniotomy for treatment-refractory symptomatic cerebral radiation necrosis

Abstract Background The incidence of symptomatic radiation necrosis (RN) has risen as radiotherapy is increasingly used to control brain tumor progression. Traditionally managed with steroids, symptomatic RN can remain refractory to medical treatment, requiring surgical intervention for control. The purpose of our study was to assess a single institution’s experience with craniotomy for steroid-refractory pure RN. Methods The medical records of all tumor patients who underwent craniotomies at our institution from 2011 to 2016 were retrospectively reviewed for a history of preoperative radiotherapy or radiosurgery. RN was confirmed histopathologically and patients with active tumor were excluded. Preoperative, intraoperative, and outcome information was collected. Primary outcomes measured were postoperative KPS and time to steroid freedom. Results Twenty-four patients with symptomatic RN were identified. Gross total resection was achieved for all patients. Patients with metastases experienced an increase in KPS (80 vs 100, P < .001) and required a shortened course of dexamethasone vs patients with high-grade gliomas (3.4 vs 22.2 weeks, P = .003). RN control and neurological improvement at 13.3 months’ follow-up were 100% and 66.7%, respectively. Adrenal insufficiency after rapidly tapering dexamethasone was the only morbidity (n = 1). Overall survival was 93.3% (14/15) at 1 year. Conclusion In cases of treatment-refractory symptomatic RN, resection can lead to an overall improvement in postoperative health status and neurological outcomes with minimal RN recurrence. Craniotomy for surgically accessible RN can safely manage symptomatic patients, and future studies assessing the efficacy of resection vs bevacizumab may be warranted

The Role of Laser Interstitial Thermal Therapy in Surgical Neuro-Oncology: Series of 100 Consecutive Patients

Laser interstitial thermal therapy (LITT) is an adjuvant treatment for intracranial lesions that are treatment refractory or in deep or eloquent brain. Initial studies of LITT in surgical neuro-oncology are limited in size and follow-up. To present our series of LITT in surgical neuro-oncology to better evaluate procedural safety and outcomes. An exploratory cohort study of all patients receiving LITT for brain tumors by a single senior neurosurgeon at a single center between 2013 and 2018. Primary outcomes included extent of ablation (EOA), time to recurrence (TTR), local control at 1-yr follow-up, and overall survival (OS). Secondary outcomes included complication rate. Outcomes were compared by tumor subtype. Predictors of outcomes were identified. A total of 91 patients underwent 100 LITT procedures; 61% remain alive with 72% local control at median 7.2 mo follow-up. Median TTR and OS were 31.9 and 16.9 mo, respectively. For lesion subtypes, median TTR (months, not applicable [N/A] if 85% predicted longer TTR (P = .006, log-rank analysis). Complication rate was 4%. Our series of LITT in surgical neuro-oncology, 1 of the largest to date, further evidences its safety and outcomes profile

Ventriculostomy supply cart decreases time-to-external ventricular drain placement in the emergency department

Background: Minimizing time-to-external ventricular drain (EVD) placement in the emergency department (ED) is critical. We sought to understand factors affecting time-to-EVD placement through a quality improvement initiative. Methods: The use of process mapping, root cause analyses, and interviews with staff revealed decentralized supply storage as a major contributor to delays in EVD placement. We developed an EVD “crash cart” as a potential solution to this problem. Time-to-EVD placement was tracked prospectively using time stamps in the electronic medical record (EMR); precart control patients were reviewed retrospectively. Results: The final cohorts consisted of 33 precart and 18 postcart cases. The mean time-to-EVD in the precart group was 99.09 min compared to 71.88 min in the postcart group (two-tailed t -test, P = 0.023). Median time-to-EVD was 92 min in the precart group compared to 64 min in the postcart group (rank sum test, P = 0.0165). Postcart patients trended toward improved outcomes with lower modified Rankin score scores at 1 year, but this did not reach statistical significance (two-tailed t -test, P = 0.177). Conclusion: An EVD “crash cart” is a simple intervention that can significantly reduce time-to-EVD placement and may improve outcomes in patients requiring an EVD