Assessing the Fractional Curve for Proper Management of Adult Degenerative Scoliosis.

Adult degenerative scoliosis (ADS) is a coronal plane deformity often accompanied by sagittal plane malalignment. Surgical correction may involve the major and/or distally-located fractional curves (FCs). Correction of the FC has been increasingly recognized as key to ameliorating radicular pain localized to the FC levels. The present study aims to summarize the literature on the rationale for FC correction in ADS. Three databases were systematically reviewed to identify all primary studies reporting the rationale for correcting the FC in ADS. Articles were included if they were English full-text studies with primary data from ADS ( ≥ 18 years old) patients. Seventy-four articles were identified, of which 12 were included after full-text review. Findings suggest FC correction with long-segment fusion terminating at L5 increases the risk of distal junctional degeneration as compared to constructs instrumenting the sacrum. Additionally, circumferential fusion offers greater FC correction, lower reoperation risk, and shorter construct length. Minimally invasive surgery (MIS) techniques may offer effective radiographic correction and improve leg pain associated with foraminal stenosis on the FC concavity, though experiences are limited. Open surgery may be necessary to achieve adequate correction of severe, highly rigid deformities. Current data support major curve correction in ASD where the FC concavity and truncal shift are concordant, suggesting that the FC contributes to the patient's overall deformity. Circumferential fusion and the use of kickstand rods can improve correction and enhance the stability and durability of long constructs. Last, MIS techniques show promise for milder deformities but require further investigation.

Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas.

The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05-10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.

Evaluating the incidence and predictors of anti-NMDAR encephalitis in a contemporary cohort of patients diagnosed with dermoid tumors: A national inpatient sample analysis.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a form of encephalitis previously associated with dermoid tumors. However, most studies in the literature evaluating the disease are case reports and small patient cohorts, limiting robust statistical analysis. Here, we demonstrate predictors of anti-NMDAR encephalitis in a large cohort of US patients. METHODS: We used the 2016 National Inpatient Sample (NIS) to identify a cohort of 24,270 admitted for an ovarian dermoid tumor. Of these patients, 50 (0.21%) were diagnosed with anti-NMDAR encephalitis. Patient demographics, hospital characteristics, length of stay (LOS), and complications were collected. Statistical analysis consisted of odds ratios with chi-square testing to compare categorical variables. RESULTS: The mean age of all patients with dermoid tumors was 45.5 ± 18.0 years, and the mean age of patients with diagnosed anti-NMDAR encephalitis was 27.4 ± 4.9 years. The mean LOS in the dermoid tumor cohort was 3.5 ± 4.9 days, while the mean LOS in the anti-NMDAR encephalitis cohort was 31.9 ± 25.9 days (p < 0.001). The mean cost in the dermoid tumor cohort was $44,813.18±$54,305.90, while the mean cost in the anti-NMDAR encephalitis cohort was $445,628.60±$665,423.40 (p < 0.001). Patients with age above 30 years with dermoid tumors had significantly lower odds of developing anti-NMDAR encephalitis compared to patients younger than 30 years (OR: 0.19; 95%CI: 0.045-0.67; p-value: 0.003). White patients had significantly lower odds of developing anti-NMDAR encephalitis (OR: 0.19; 95%CI: 0.026-0.77; p-value: 0.013), and Black patients had significantly higher odds of developing anti-NMDAR encephalitis (OR: 3.45; 95%CI: 1.00-12.46; p-value: 0.044). CONCLUSION: Patient predictors of developing anti-NMDAR encephalitis include age, race, ethnicity and patients who go on to develop anti-NMDAR encephalitis have a significantly increased hospital LOS and cost compared to those who do not. Future research, including multi-center clinical trials and longitudinal data, is necessary to fully cement the findings of this manuscript.

Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review.

Although hypothermia has shown to protect against ischemic and traumatic neuronal death, its potential role in neurologic recovery following traumatic spinal cord injury (TSCI) remains incompletely understood. Herein, we systematically review the safety and efficacy of hypothermia therapy for TSCI. The English medical literature was reviewed using PRISMA guidelines to identify preclinical and clinical studies examining the safety and efficacy of hypothermia following TSCI. Fifty-seven articles met full-text review criteria, of which twenty-eight were included. The main outcomes of interest were neurological recovery and postoperative complications. Among the 24 preclinical studies, both systemic and local hypothermia significantly improved neurologic recovery. In aggregate, the 4 clinical studies enrolled 60 patients for treatment, with 35 receiving systemic hypothermia and 25 local hypothermia. The most frequent complications were respiratory in nature. No patients suffered neurologic deterioration because of hypothermia treatment. Rates of American Spinal Injury Association (AIS) grade conversion after systemic hypothermia (35.5%) were higher when compared to multiple SCI database control studies (26.1%). However, no statistical conclusions could be drawn regarding the efficacy of hypothermia in humans. These limited clinical trials show promise and suggest therapeutic hypothermia to be safe in TSCI patients, though its effect on neurological recovery remains unclear. The preclinical literature supports the efficacy of hypothermia after TSCI. Further clinical trials are warranted to conclusively determine the effects of hypothermia on neurological recovery as well as the ideal means of administration necessary for achieving efficacy in TSCI.

Bony fixation in the era of spinal robotics: A systematic review and meta-analysis.

BACKGROUND: Accurate spinal screw placement in spinal instrumentation is of utmost importance to avoid injury to surrounding neurovascular structures. This study was performed to investigate differences in accuracy, operating room time, length of stay, and operative blood loss across studies involving all types of spinal fixation. METHODS: PubMed, EMBASE, and Scopus were systematically queried to identify articles that fit the inclusion and exclusion criteria. Meta-analysis was performed using R software, and odds ratios and 95% CIs were calculated. RESULTS: Sixty-nine articles were included in qualitative synthesis, and 35 studies in the meta-analysis, for a total of 8,174 robotically placed screws in 1,492 patients compared to 9,791 conventionally placed screws in 1,638 patients. A total of 9 screw trajectories were studied in the literature, although only 4 had enough evidence to be included in the meta-analysis. Robotic screw placement was more accurate than conventional screw placement (OR 2.24; 95% CI, 1.71-2.94). Robotic placement was not associated with significantly different postoperative length of stay (SMD -0.32; 95% CI, -1.20, 0.51), operative blood loss (SMD -0.25; 95% CI, -0.79, 0.19), or operative duration (SMD 0.08; 95% CI -1.00, 1.39). A total of 8 robotic platforms were found in the literature with accuracy rates above 93%. CONCLUSION: Robotic spinal fixation is associated with increased screw placement accuracy and similar operative blood loss, length of stay, and operative duration. These findings support the safety and cost-effectiveness of robotic spinal surgery across the spectrum of robotic systems and screw types.

Association of tranexamic acid with decreased blood loss in patients undergoing laminectomy and fusion with posterior instrumentation: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) is an antifibrinolytic agent associated with reduced blood loss and mortality in a wide range of procedures, including spine surgery, traumatic brain injury, and craniosynostosis. Despite this wide use, the safety and efficacy of TXA in spine surgery has been considered controversial due to a relative scarcity of literature and lack of statistical power in reported studies. However, if TXA can be shown to reduce blood loss in laminectomy with fusion and posterior instrumentation, more surgeons may include it in their armamentarium. The authors aimed to conduct an up-to-date systematic review and meta-analysis of the efficacy of TXA in reducing blood loss in laminectomy and fusion with posterior instrumentation. METHODS: A systematic review and meta-analysis, abiding by PRISMA guidelines, was performed by searching the databases of PubMed, Web of Science, and Cochrane. These platforms were queried for all studies reporting the use of TXA in laminectomy and fusion with posterior instrumentation. Variables retrieved included patient demographics, surgical indications, involved spinal levels, type of laminectomy performed, TXA administration dose, TXA route of administration, operative duration, blood loss, blood transfusion rate, postoperative hemoglobin level, and perioperative complications. Heterogeneity across studies was evaluated using a chi-square test, Cochran's Q test, and I2 test performed with R statistical programming software. RESULTS: A total of 7 articles were included in the qualitative study, while 6 articles featuring 411 patients underwent statistical analysis. The most common route of administration for TXA was intravenous with 15 mg/kg administered preoperatively. After the beginning of surgery, TXA administration patterns were varied among studies. Blood transfusions were increased in non-TXA cohorts compared to TXA cohorts. Patients administered TXA demonstrated a significant reduction in blood loss (mean difference -218.44 mL; 95% CI -379.34 to -57.53; p = 0.018). TXA administration was not associated with statistically significant reductions in operative durations. There were no adverse events reported in either the TXA or non-TXA patient cohorts. CONCLUSIONS: TXA can significantly reduce perioperative blood loss in cervical, thoracic, and lumbar laminectomy and fusion procedures, while demonstrating a minimal complication profile.

Citation analysis of the most influential ependymoma research articles illustrates improved knowledge of the molecular biology of ependymoma.

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, including a mix of basic science and clinical journals. The three institutions with the most papers in the top 100 were St. Jude Children's Research Hospital (16%), the University of Texas MD Anderson Cancer Center (6%), and the German Cancer Research Center (5%). We analyzed the publications that may be considered the most influential in the understanding and treatment management of ependymoma. Studies focused on the molecular classification of ependymomas were well-represented among the most cited articles, reflecting the field's current area of focus and its future directions. Additionally, this article also offers a reference for further studies in the ependymoma field.

Getting Down to the Bare Bones: Does laminoplasty or laminectomy With Fusion Provide Better Outcomes for Patients With Multilevel Cervical Spondylotic Myelopathy?

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a degenerative disorder leading to progressive decline in spinal cord function. Cervical laminoplasty (CLP) and cervical laminectomy with fusion (CLF) are standard treatments for multilevel CSM. However, it is still unclear whether one procedure over the other provides better outcomes. Here, we performed a comprehensive review of published articles that compare the clinical outcomes and costs between CLP and CLF for CSM. METHODS: A literature search was performed using PubMed, Web of Science, and Cochrane databases. Strict exclusion criteria were applied, and included articles were then assessed for publication year, study design, and significant differences in outcome variables. RESULTS: From 519 studies identified with search terms, 38 studies were included for the qualitative analysis. Statistically significant differences in the clinical outcomes and costs were found in 18 studies. Eleven studies were prospective or retrospective, and 8 studies were meta-analyses. For the outcome variables of interest, results were reported by classifying into prospective studies, retrospective studies, and meta-analyses. CONCLUSION: CLP and CLF are 2 of the most commonly performed surgical procedures for the treatment of CSM. Although CLP and CLF each provide satisfactory clinical outcomes for patients with CMS, CLP may result in better cervical range of motion and less cost, length of stay, operation time, blood loss, paraspinal muscular atrophy, and rate of nerve palsies as compared to CLF. The major limitation of CLP versus CLF comparison studies includes the heterogeneity in techniques and preoperative criteria. Thus, further validation and investigations in larger cohorts will be required.

Ethical considerations and patient safety concerns for cancelling non-urgent surgeries during the COVID-19 pandemic: a review.

At the time of writing of this article, there have been over 110 million cases and 2.4 million deaths worldwide since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, postponing millions of non-urgent surgeries. Existing literature explores the complexities of rationing medical care. However, implications of non-urgent surgery postponement during the COVID-19 pandemic have not yet been analyzed within the context of the four pillars of medical ethics. The objective of this review is to discuss the ethics of elective surgery cancellation during the COVID-19 pandemic in relation to beneficence, non-maleficence, justice, and autonomy. This review hypothesizes that a more equitable decision-making algorithm can be formulated by analyzing the ethical dilemmas of elective surgical care during the pandemic through the lens of these four pillars. This paper's analysis shows that non-urgent surgeries treat conditions that can become urgent if left untreated. Postponement of these surgeries can cause cumulative harm downstream. An improved algorithm can address these issues of beneficence by weighing local pandemic stressors within predictive algorithms to appropriately increase surgeries. Additionally, the potential harms of performing non-urgent surgeries extend beyond the patient. Non-maleficence is maintained through using enhanced screening protocols and modifying surgical techniques to reduce risks to patients and clinicians. This model proposes a system to transfer patients from areas of high to low burden, addressing the challenge of justice by considering facility burden rather than value judgments concerning the nature of a particular surgery, such as cosmetic surgeries. Autonomy can be respected by giving patients the option to cancel or postpone non-urgent surgeries. However, in the context of limited resources in a global pandemic, autonomy is not absolute. Non-urgent surgeries can ethically be postponed in opposition to the patient's preference. The proposed algorithm attempts to uphold the four principles of medical ethics in rationing non-urgent surgical care by building upon existing decision models, using additional measures of resource burden and surgical safety to increase health care access and decrease long-term harm as much as possible. The next global health crisis will undoubtedly present its own unique challenges. This model may serve as a comprehensive starting point in determining future guidelines for non-urgent surgical care.

Predictors of Patient Satisfaction in Spine Surgery: A Systematic Review.

BACKGROUND: Recently, there has been increased interest in patient satisfaction measures such as Press Ganey and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys. In this systematic review, the spine surgery literature is analyzed to evaluate factors predictive of patient satisfaction as measured by these surveys. METHODS: A thorough literature search was performed in PubMed/MEDLINE, Google Scholar, and Cochrane databases. All English-language articles from database inception to July 2020 were screened for study inclusion according to PRISMA guidelines. RESULTS: Twenty-four of the 1899 published studies were included for qualitative analysis. There has been a statistically significant increase in the number of publications across years (P = 0.04). Overall, the studies evaluated the relationship between patient satisfaction and patient demographics (71%), preoperative and intraoperative clinical factors (21%), and postoperative factors (33%). Top positive predictors of patient satisfaction were patient and nursing/medical staff relationship (n = 4; 17%), physician-patient relationship (n = 4; 17%), managerial oversight of received care (n = 3; 13%), same sex/ethnicity between patient and physician (n = 2; 8%), and older age (n = 2; 8%). Top negative predictors of patient satisfaction were high Charlson Comorbidity Index/high disability/worse overall health functioning (n = 7; 29%), increased length of hospital stay (n = 4; 17%), high rating for pain/complications/readmissions (n = 4; 17%), and psychosocial factors (n = 3; 13%). CONCLUSIONS: There is heterogeneity in terms of different factors, both clinical and nonclinically related, that affect patient satisfaction ratings. More research is warranted to investigate the role of hospital consumer surveys in the spine surgical patient population.

Indication-based analysis of patient outcomes following deep brain stimulation surgery.

BACKGROUND: While considered a safe operation, deep brain stimulation (DBS) has been associated with various morbidities. We assessed differences in postsurgical complication rates in patients undergoing the most common types of neurostimulation surgery. METHODS: The National Readmission Database (NRD) was queried to identify patients undergoing neurostimulation placement with the diagnosis of Parkinson disease (PD), epilepsy, dystonia, or essential tremor (ET). Demographics and complications, including infection, pneumonia, and neurostimulator revision, were queried for each cohort and compiled. Readmissions were assessed in 30-, 90-, and 180-day intervals. We implemented nearest-neighbor propensity score matching to control for demographic and sample size differences between groups. RESULTS: We identified 3230 patients with Parkinson disease, 1289 with essential tremor, 965 with epilepsy, and 221 with dystonia. Following propensity score matching, 221 patients remained in each cohort. Readmission rates 30-days after hospital discharge for PD patients (15.5 %) were significantly greater than those for ET (7.8 %) and seizure patients (4.4 %). Pneumonia was reported for PD (1.6 %), seizure (3.3 %) and dystonia (1.7 %) patients but not individuals ET. No PD patients were readmitted at 30-days due to dysphagia while individuals treated for ET (6.5 %), seizure (1.6 %) and dystonia (5.2 %) were. DBS-revision surgery was performed for 11.48 % of PD, 6.52 % of ET, 1.64 % of seizure and 6.90 % of dystonia patients within 30-days of hospital discharge. CONCLUSION: 30-day readmission rates vary significantly between indications, with patients receiving DBS for PD having the highest rates. Further longitudinal studies are required to describe drivers of variation in postoperative outcomes following DBS surgery for different indications.

The 100 Most Influential Publications on Medulloblastoma: Areas of Past, Current, and Future Focus.

BACKGROUND: This article is the first to identify the most influential articles on medulloblastoma using the citation analysis methodology. OBJECTIVE: To perform a bibliometric analysis of the 100 most-cited articles on medulloblastoma. METHODS: Using the Web of Science database, search criteria included the title-specific keyword "medulloblastoma" OR "cerebellar primitive neuroectodermal tumor (PNET)" OR "cerebellar PNET." Publications from 1900 to 2020 labeled "article," "review," "data set," or "clinical trial" were chosen and ranked based on total number of citations in descending order. Each article was evaluated based on the following variables: total citations, average citations per year, first author, institution of first author, title, publication year, country of origin, SCImago Journal Rank, and Scopus SNIP (Source Normalized Impact per Paper). RESULTS: Our search yielded 4928 articles on medulloblastoma. The 100 most-cited articles ranged from 192 to 2017 across 42 unique journals; Journal of Clinical Oncology accounted for the most publications (16%). Paul A. Northcott was first author of the most articles on the list (n = 7.7%), and the most widely cited article was "Altered neural cell fates and medulloblastoma in mouse patched mutants" by Goodrich et al., published in Science (1997). CONCLUSIONS: Because medulloblastoma represents the most common form of pediatric cancerous brain tumor, it is important to identify works that have significantly contributed to the body of knowledge regarding this disease. The 100 most-cited medulloblastoma articles comprise a significant collection of data regarding the histopathologic and molecular classification of medulloblastoma as well as clinical outcomes of therapeutics used to treat this disease.

Spinal pathologies and management strategies associated with cervical angina (pseudoangina): a systematic review.

OBJECTIVE: Cervical angina, or pseudoangina pectoris, is a noncardiac syndrome of chest pain that often mimics angina pectoris but is a disease of the spine. Diagnosis of cervical angina can be difficult and is often overlooked, although once identified, it can be successfully managed through conservative therapies and/or a variety of surgical interventions. Ultimately, cervical angina is an important component of the list of differential diagnoses in noncardiac chest pain. In the present study, the authors report the first comprehensive systematic review of the range of cervical and thoracic pathologies associated with cervical angina, as well as the different treatment methods used to manage this condition. METHODS: A systematic review was performed according to PRISMA guidelines and using PubMed, Web of Science, and Cochrane databases from database inception to April 29, 2020, to identify studies describing spinal pathologies related to cervical angina. The following Boolean search was performed: ("cervical" OR "thoracic") AND ("angina" OR "chest pain") AND ("herniation" OR "OPLL"). Variables extracted included patient demographics, cervical angina pain location, pathology and duration of symptoms, treatment and/or management method, and posttreatment pain relief. RESULTS: Upon careful screening, 22 articles published between 1976 and 2020 met the study's inclusion/exclusion criteria, including 5 case series, 12 case reports, and 5 retrospective cohort studies. These studies featured a total of 1100 patients, of which 95 met inclusion criteria (mean patient age 51.7 years, age range 24-86 years; 53.6% male). Collectively, symptom durations ranged from 1.5 days to 90 months. Cervical herniation (72.6%) accounted for the majority of cervical angina cases, and surgical interventions (84.4%) predominated over physical therapy (13.0%) and medical management strategies (9.1%). Every patient assessed at follow-up reported relief from symptoms related to cervical angina. CONCLUSIONS: Cervical angina is a noncardiac syndrome of chest pain associated with a broad range of cervical and thoracic spinal pathologies, the most common of which is cervical disc herniation. Although difficult to diagnose, it can be successfully treated when identified through first-line conservative management or surgical interventions in refractory cases.

The role of frailty in geriatric cranial neurosurgery for primary central nervous system neoplasms.

OBJECTIVE: Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Geriatric patients have a higher risk of frailty, higher incidence of brain cancer, and increased postoperative complication rates compared to nongeriatric patients. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. METHODS: The authors conducted a retrospective cohort study of geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Complications of interest included infection, anemia, infarction, kidney injury, CSF leak, urinary tract infection, and mortality. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. RESULTS: A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23-1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70-6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07-1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71-2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17-2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22-2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at the time of primary admission. However, no significant difference was found between frail and nonfrail patients with regard to rates of infection, thromboembolism, CSF leak, dural tear, cerebral infarction, acute kidney injury, and mortality at all readmission time points. CONCLUSIONS: Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients. Further research is warranted to understand the effects and timeline of frailty in geriatric patients.

Translational Approaches to Electrical Stimulation for Peripheral Nerve Regeneration.

BACKGROUND: Achieving functional repair after peripheral nerve injury (PNI) remains problematic despite considerable advances in surgical technique. Therein, questions lie regarding the variable capacity of peripheral nerves to regenerate based on environmental influence. In-depth analyses of multiple therapeutic strategies have ensued to overcome these natural obstacles. Of these candidate therapies, electrical stimulation has emerged a frontrunner. Extensive animal studies have reported the ability of brief intraoperative electrical stimulation (BES) to enhance functional regeneration after PNI. Despite these reports, the exact mechanisms by which BES enhances regeneration and its effects on long nerve lesions are largely unknown. Indeed, clinical translation of this seemingly simple therapeutic has not been so simple, but a few studies performed in humans have yielded highly encouraging results. OBJECTIVE: We aimed to help bridge this translational gap by presenting the latest clinical trials on electrical stimulation for PNIs in combination with relevant etiologies, treatments and nonclinical findings. METHODS: To do so, a systematic search was performed on PubMed, IEEE, and Web of Science databases up to February 2020 using keywords significant to our study. References of each manuscript were screened for additional manuscripts of relevance to our study. RESULTS: We found multiple BES clinical studies reporting enhanced functional recovery or increased nerve regeneration. Although improved outcomes were reported, high variability after BES is seen between and within species likely due to injury severity, location and timeline along with other factors. CONCLUSION: Further clinical studies and introduction of novel delivery platforms are vital to uncover the true regenerative potential of electrical stimulationtherapy.

Enhancing peripheral nerve regeneration with neurotrophic factors and bioengineered scaffolds: A basic science and clinical perspective.

Despite the peripheral nervous systems (PNS) capacity to regenerate, functional restoration is highly variable following peripheral nerve injury (PNI), oftentimes leading to persistent functional deficits. In the preclinical arena, advances in the therapeutic use of exogenous neurotrophic factors and synthetic neural scaffold technology hold promise in augmenting endogenous PNS regeneration following PNI. Clinical trials utilizing neurotrophic factors for other indications (eg, peripheral neuropathy) may provide insight into their role in PNI. Here we provide an updated review of progress made toward enhancing regeneration after PNI with a focus on neurotrophic factors and bioengineered scaffolds.

Staged Cranial Surgery for Intracranial Lesions: Historical Perspective.

We follow the development of staged resection from its first description by Walter E. Dandy, one of the founding fathers of neurosurgery, in 1925 in which he removed a large vestibular schwannoma.This historical vignette cites neurosurgical case reports and literature to demonstrate the evolution of staged resection of intracranial lesions, from Dandy's initial use to its becoming a more viable and safe option for the treatment of meningiomas, vestibular schwannomas, and skull base lesions (among numerous other intracranial pathologies). We also discuss the current advancements and future perspectives of staged resection that may show promise in effectively treating a wide range of pathologies while simultaneously reducing morbidity rates-a warrant for further exploration of staged cranial surgery as an important tool in neurosurgery.

Indicators of responsiveness to immune checkpoint inhibitors.

Modulation of the immune system can produce anti-tumor responses in various cancer types, including melanoma. Recently, immune checkpoint inhibitors (ICI), in single agent and combination regimens, have produced durable and long-lasting clinical responses in a subset of metastatic melanoma patients. These monoclonal antibodies, developed against CTLA-4 and PD-1, block immune-inhibitory receptors on activated T-cells, amplifying the immune response. However, even when using anti-CTLA-4 and anti-PD-1 in combination, approximately half of patients exhibit innate resistance and suffer from disease progression. Currently, it is impossible to predict therapeutic response. Here, we report the first proteomic and histone epigenetic analysis of patient metastatic melanoma tumors taken prior to checkpoint blockade, which revealed biological signatures that can stratify patients as responders or non-responders. Furthermore, our findings provide evidence of mesenchymal transition, a known mechanism of immune-escape, in non-responding melanoma tumors. We identified elevated histone H3 lysine (27) trimethylation (H3K27me3), decreased E-cadherin, and other protein features indicating a more mesenchymal phenotype in non-responding tumors. Our results have implications for checkpoint inhibitor therapy as patient specific responsiveness can be predicted through readily assayable proteins and histone epigenetic marks, and pathways activated in non-responders have been identified for therapeutic development to enhance responsiveness.