Validity of the flap risk score in predicting nasoseptal flap use after endoscopic transsphenoidal pituitary mass resection.

Introduction: There remains a paucity of literature examining the decision algorithm for use of nasoseptal flap (NSF) after endoscopic endonasal approaches (EEA) to pituitary adenoma resection. In 2018, we published the first ever flap risk score (FRS) to predict the use of NSF. We present here a validity study examining the FRS as applied to our center. Methods: A retrospective review was completed of consecutive patients undergoing EEA from January 2015 to March 2021. The sensitivity, specificity, and predictive value of the FRS were calculated. A multivariate logistic model was used to determine the relative weight imaging characteristics in predicting need for NSF. The relative weighting of the FRS was then re-optimized. Results: A total of 376 patients underwent EEA for pituitary adenoma resection, with 113 (30.1%) requiring NSF. The FRS had a sensitivity and specificity of 43.4% and 94.7%, respectively. Sphenoid sinus extension increased the odds of needing a NSF equivalent to 19 mm of tumor height, as opposed to 6 mm in the original 2018 cohort. The re-optimized model had sensitivity and specificity of 79.6% and 76.4%, respectively. Conclusion: We present a validity study examining the utility of FRS in predicting the use of NSF after EEA for pituitary adenoma resection. Our results show that while FRS is still predictive of the need for NSF after EEA, it is not as predictive now as it was for its original cohort. Therefore, a more comprehensive model is necessary to more accurately stratify patients' preoperative risk for NSF.

The effect of limited healthcare access on poor outcomes among hospitalized COVID-19 patients in Honduras: A single center cohort study.

Background: The COVID-19 pandemic has had a severe impact on the Latin American subcontinent, particularly in areas with limited hospital resources and a restricted Intensive Care Unit (ICU) capacity. This study aimed to provide a comprehensive description of the clinical characteristics, outcomes, and factors associated with survival of COVID-19 hospitalized patients in Honduras. Research question: What were the characteristics and outcomes of COVID-19 patients in a large referral center in Honduras? Study design and methods: This study employed a retrospective cohort design conducted in a single center in San Pedro Sula, Honduras, between October 2020 to March 2021. All hospitalized cases of confirmed COVID-19 during this timeframe were included in the analysis. Univariable and multivariable survival analysis were performed using Kaplan-Meier curves and Cox proportional hazards model aiming to identify factors associated with decreased 30 day in-hospital survival, using a priori-selected factors. Results: A total of 929 confirmed cases were identified in this cohort, with males accounting for 55.4 % of cases. The case fatality rate among the hospitalized patients was found to be 50.1 % corresponding to 466 deaths. Patients with comorbidities such as hypertension, diabetes, obesity, chronic kidney disease, chronic obstructive pulmonary disease and cardiovascular disease had a higher likelihood of mortality. Additionally, non-survivors had a significantly longer time from illness onset to hospital admission compared to survivors (8.2 days vs 4.7 days). Among the cohort, 306 patients (32.9 %) met criteria for ICU admission. However, due to limited capacity, only 60 patients (19·6 %) were admitted to the ICU. Importantly, patients that were unable to receive level-appropriate care had lower likelihood of survival compared to those who received level-appropriate care (hazard ratio: 1.84). Interpretation: This study represents, the largest investigation of in-hospital COVID-19 cases in Honduras and Central America. The findings highlight a substantial case fatality rate among hospitalized patients. In this study, patients who couldn't receive level-appropriate care (ICU admission) had a significantly lower likelihood of survival when compared to those who did. These results underscore the significant impact of healthcare access during the pandemic, particularly in low- and middle-income countries.

Applicant Perceptions of Postinterview Communication During the 2022 to 2023 Neurosurgery Recruitment Cycle: A Cross-Sectional Survey Study.

OBJECTIVES: To evaluate and describe neurosurgery applicant perceptions of the postinterview communication (PIC) process during the US residency match. METHODS: A voluntary and anonymous postmatch web-based survey was developed and sent to 209 candidates who applied to 1 academic neurosurgery practice during the 2022-2023 recruitment cycle, approximately 1 week following match day. Survey questions focused on their perceptions of and participation behaviors with PIC and how this impacted their final rank list. RESULTS: Seventy-eight (37.3%) of the 209 candidates responded to the survey. Sixty-four (84.2%) respondents reported submitting a letter of intent (LOI) to their number 1 ranked program. Sixty-one (82%) felt pressured to send a LOI to improve their rank status, fearing that it may harm them if they did not. Fifty-four (73.0%) respondents felt pressured to send an early LOI despite not seeing the program in person to communicate interest before programs certified their rank lists. Fourteen (18.9%) respondents agreed that a second look experience impacted their rank list enough to where they regretted an early LOI. Fifty-five (76.4%) respondents disagreed that second-look attendance had no impact on their rank status with a program. Fifty (71.4%) respondents agreed that PIC causes undue stress during the match process. Sixty-one (84.7%) respondents agreed that aspects of PIC require universal guidelines. CONCLUSIONS: This is the first study to describe the perceptions of PIC and behaviors of neurosurgery applicants during the US residency match process. Standardized PIC practices may help to ensure transparency and relieve stress for applicants during the match process.

Endovascular Thrombectomy for the Treatment of Large Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Control Trials.

BACKGROUND AND OBJECTIVES: Endovascular thrombectomy has previously been reserved for patients with small to medium acute ischemic strokes. Three recent randomized control trials have demonstrated functional benefit and risk profiles for thrombectomy in large-volume ischemic strokes. The primary objective of the meta-analysis was to determine the combined benefit of endovascular thrombectomy in patients with large-volume ischemic strokes and to determine the risk of adverse events after treatment. METHODS: We systematically searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Scopus, the Cochrane Central Register, and Google Scholar for randomized trials published between January 1, 2010, and February 19, 2023. We included trials specifically comparing endovascular thrombectomy with medical therapy in adults with acute ischemic stroke with large-volume infarctions (defined by Alberta Stroke Program Early Computed Tomography Score 3-5 or a calculated infarct volume of >50 mL). Data were extracted based on prespecified variables on study methods and design, participant characteristics, analysis approach, and efficacy/safety outcomes. Results were combined using a restricted maximum-likelihood estimation random-effects model. Studies were assessed for potential bias and quality of evidence. The primary outcome was an overall ordinal shift across modified Rankin scale scores toward a better outcome at 90 days after either treatment arm. RESULTS: Three thousand forty-four studies were screened, and 29 underwent full-text review. Three randomized trials (N = 1011) were included in the analysis. The pooled random-effects model for the primary outcome favored endovascular thrombectomy over medical management, with a generalized odds ratio of 1.55 (95% CI 1.25-1.91, I 2 = 42.84%). There was a trend toward increased risk of symptomatic intracranial hemorrhage in the thrombectomy group, with a relative risk of 1.85 (95% CI 0.94-3.63, I 2 = 0.00%). CONCLUSION: In patients with large-volume ischemic strokes, endovascular thrombectomy has a clear functional benefit and does not confer increased risk of significant complications compared with medical management alone.

Early Voice and Swallowing Disturbance Incidence and Risk Factors After Revision Anterior Cervical Discectomy and Fusion Using a Multidisciplinary Surgical Approach: A Retrospective Cohort Evaluation of a Prospective Database.

BACKGROUND AND OBJECTIVES: Dysphagia and vocal cord palsy (VCP) are common otolaryngological complications after revision anterior cervical discectomy and fusion (rACDF) procedures. Our objective was to determine the early incidence and risk factors of VCP and dysphagia after rACDF using a 2-team approach. METHODS: Single-institution, retrospective analysis of a prospectively collected database of patients undergoing rACDF was enrolled from September 2010 to July 2021. Of 222 patients enrolled, 109 patients were included in the final analysis. All patients had prior ACDF surgery with planned revision using a single otolaryngologist and single neurosurgeon. MD Anderson Dysphagia Inventory and fiberoptic endoscopic evaluation of swallowing (FEES) were used to assess dysphagia. VCP was assessed using videolaryngostroboscopy. RESULTS: Seven patients (6.7%) developed new postoperative VCP after rACDF. Most cases of VCP resolved by 3 months postoperatively (mean time-to-resolution 79 ± 17.6 days). One patient maintained a permanent deficit. Forty-one patients (37.6%) reached minimum clinically important difference (MCID) in their MD Anderson Dysphagia Inventory composite scores at the 2-week follow-up (MCID decline of ≥6), indicating new clinically relevant swallowing disturbance. Forty-nine patients (45.0%) had functional FEES Performance Score decline. On univariate analysis, there was an association between new VCPs and the number of cervical levels treated at revision ( P = .020) with long-segment rACDF (≥4 levels) being an independent risk factor ( P = .010). On linear regression, there was an association between the number of levels treated previously and at revision for FEES Performance Score decline ( P = .045 and P = .002, respectively). However, on univariate analysis, sex, age, body mass index, operative time, alcohol use, smoking, and individual levels revised were not risk factors for reaching FEES Performance Score decline nor MCID at 2 weeks postoperatively. CONCLUSION: VCP is more likely to occur in long-segment rACDF but is often temporary. Clinically relevant and functional rates of dysphagia approach 37% and 45%, respectively, at 2 weeks postoperatively after rACDF.

Postoperative Cerebrospinal Fluid-Related Complications After Posterior Fossa and Posterolateral Skull Base Surgeries: Development of a Predictive Model and Clinical Risk Score.

BACKGROUND: Postoperative pseudomeningocele (PMC) and cerebrospinal fluid (CSF) leak are common complications following posterior fossa and posterolateral skull base surgeries. We sought to 1) determine the rate of CSF-related complications and 2) develop a perioperative model and risk score to identify the highest risk patients for these events. METHODS: We performed a retrospective cohort of 450 patients undergoing posterior fossa and posterolateral skull base procedures from 2016 to 2020. Logistic regressions were performed for predictor selection for 3 prespecified models: 1) a priori variables, 2) predictors selected by large effect sizes, and 3) predictors with P ≤ 0.100 on univariable analysis. A final model was created by elimination of nonsignificant predictors, and the integer-based postoperative CSF-related complications (POCC) clinical risk score was derived. Internal validation was done using 10-fold cross-validation and bootstrapping with uniform shrinkage. RESULTS: A total of 115 patients (25.6%) developed PMC and/or CSF leakage. Age >55 years (odds ratio [OR], 0.560; 95% confidence interval [CI], 0.328-0.954), body mass index >30 kg/m2 (OR, 1.88; 95% CI, 1.14-3.10), and postoperative CSF diversion (OR, 2.85; 95% CI, 1.64-5.00) were associated with CSF leak and PMC. Model 2 was the most predictive (cross-validated area under the receiver operating characteristic curve, 0.690). The final risk score was devised using age, body mass index class, dural repair technique, use of bone substitute, and duration of postoperative CSF diversion. The POCC score performed well (cross-validated area under the receiver operating characteristic curve, 0.761) and was highly specific (96.1%). CONCLUSIONS: We created the first generalizable and predictive risk score to identify patients at risk of CSF-related complications. The POCC score could improve surveillance, inform doctor-patient discussions regarding the risks of surgery, and assist in perioperative management.

Does subtotal resection ameliorate hypothalamic morbidity in pediatric craniopharyngioma? A 30-year retrospective cohort study.

OBJECTIVE: The optimal extent of resection of craniopharyngiomas to minimize the long-term risks of hypothalamic and endocrine dysfunction (obesity and panhypopituitarism) in children remains uncertain. The purpose of this study was to report long-term outcomes of pediatric patients with craniopharyngioma undergoing surgical treatment and to study rates of endocrinological and hypothalamic dysfunction in association with extent of resection. METHODS: This retrospective study was performed in a cohort of children who underwent resection for craniopharyngioma at Children's of Alabama between 1990 and 2020. The primary outcome was hypothalamic dysfunction defined as a 0.5 increase in body mass index (BMI) Z-score and as a BMI > 2 SDs with or without psychiatric disturbances. Univariable analysis was performed using ANOVA, Wilcoxon rank-sum test, Pearson's chi-square test, and Fisher's exact test as appropriate. Missing data on the primary outcome were handled via multiple imputations. Relative risks were estimated using a multivariable generalized linear model with a priori variables selected using a modified Poisson regression approach with robust error variance to estimate risk ratios. RESULTS: The cohort includes 39 patients (24 girls and 15 boys; age range 1 month-16 years) who underwent resection of craniopharyngioma at the authors' center between 1990 and 2020. The preoperative goal of treatment was cyst decompression (CD) in 5, subtotal resection (STR) in 13, and gross-total resection (GTR) in 21 patients. The median long-term follow-up after surgery was 8.11 years (average 8.21, range 0.4-24.33 years). Univariate analysis demonstrated a statistically significant increase in hypothalamic dysfunction in patients undergoing GTR when compared to those undergoing STR or CD at 1 month postoperatively (p = 0.006) and 6-11 months postoperatively (p = 0.010), but with this difference not persisting beyond 1 year. Multivariable analysis showed patients older than 10 years at time of surgery to be the most affected and at highest risk of developing significant hypothalamic dysfunction. There was no significant difference in pituitary or neurological function between the STR/CD and GTR groups at 12-24 months or at most recent follow-up. There was no significant difference in BMI Z-scores between the STR/CD and GTR groups at 6-12 months or at most recent follow-up. CONCLUSIONS: Both STR and GTR of craniopharyngioma were associated with significant endocrinological sequelae after 1 year. These potential complications should be discussed with patients and their families, and postoperative protocols should include early nutritional and endocrinological interventions with endocrinologist consultation.

Oncolytic virotherapies for pediatric tumors.

INTRODUCTION: Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by chemotherapy and radiation which may be associated with considerable long-term morbidity. The emergence of oncolytic virotherapy (OVT) may provide an alternative or adjuvant treatment for pediatric oncology patients. AREAS COVERED: We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). For each virus, we discuss the mechanism of tumor-specific replication and cytotoxicity as well as key findings of preclinical and clinical studies. EXPERT OPINION: Substantial progress has been made in the past 10 years regarding the clinical use of OVT. From our review, OVT has favorable safety profiles compared to chemotherapy and radiation treatment. However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future.

Hemispherectomy Outcome Prediction Scale: a validity study.

OBJECTIVE: Hemispherectomy is highly effective for patients with medically refractory epilepsy (MRE) arising from a single hemisphere. Recently, the Hemispherectomy Outcome Prediction Scale (HOPS) was developed as a prediction tool for seizure freedom after hemispherectomy. The authors' goal was to perform a validation study to determine the generalizability of the HOPS score. METHODS: The authors present an observational, retrospective, 20-year, single-institution, two-surgeon experience using the lateral peri-insular hemispherectomy approach to validate the HOPS score. Variables used to derive the HOPS score included seizure onset age, semiology, PET hypometabolism, seizure substrate, and history of prior epilepsy resection. Multivariable logistic regression, multiple imputation, and Bayesian analyses were used to determine validity. RESULTS: The authors' cohort comprised 60 patients; 55% of patients were male and 78% were Caucasian. The median age at first hemispherectomy surgery was 72 months. At 1 year postoperatively, 80% of patients had Engel class I outcomes, analogous to most contemporary series. All patients who experienced seizure recurrence after hemispherectomy did so within the first 2 years postoperatively. Sixteen (27%) and 10 (17%) patients had contralateral MRI findings and hypometabolism on PET, respectively. Both a multivariable logistic regression model using HOPS score variables (model p = 0.2588) and a revised model that included contralateral MRI findings (model p = 0.4715) were not statistically significant in this cohort. Bayesian analysis also did not validate the HOPS score. CONCLUSIONS: While seizure outcome prediction tools may be helpful for counseling patients about postoperative outcomes, rigorous validity and reliability testing are required. Prospective, standardized, and longitudinal evaluation of patients undergoing hemispherectomy are needed.

Racial and socioeconomic disparities in glioblastoma outcomes: A single-center, retrospective cohort study.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor. Emerging reports have suggested that racial and socioeconomic disparities influence the outcomes of patients with GBM. No studies to date have investigated these disparities controlling for isocitrate dehydrogenase (IDH) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) status. METHODS: Adult patients with GBM were retrospectively reviewed at a single institution from 2008 to 2019. Univariable and multivariable complete survival analyses were performed. A Cox proportional hazards model was used to assess the effect of race and socioeconomic status controlling for a priori selected variables with known relevance to survival. RESULTS: In total, 995 patients met inclusion criteria. Of these, 117 patients (11.7%) were African American (AA). The median overall survival for the entire cohort was 14.23 months. In the multivariable model, AA patients had better survival compared with White patients (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.2-0.69). The observed survival difference was significant in both a complete case analysis model and a multiple imputations model accounting for missing molecular data and controlling for treatment and socioeconomic status. AA patients with low income (HR, 2.17; 95% CI, 1.04-4.50), public insurance (HR, 2.25; 95% CI, 1.04-4.87), or no insurance (HR, 15.63; 95% CI, 2.72-89.67) had worse survival compared with White patients with low income, public insurance, or no insurance, respectively. CONCLUSIONS: Significant racial and socioeconomic disparities were identified after controlling for treatment, GBM genetic profile, and other variables associated with survival. Overall, AA patients demonstrated better survival. These findings may suggest the possibility of a protective genetic advantage in AA patients. PLAIN LANGUAGE SUMMARY: To best personalize treatment for and understand the causes of glioblastoma, racial and socioeconomic influences must be examined. The authors report their experience at the O'Neal Comprehensive Cancer Center in the deep south. In this report, contemporary molecular diagnostic data are included. The authors conclude that there are significant racial and socioeconomic disparities that influence glioblastoma outcome and that African American patients do better.

Endovascular thrombectomy for the treatment of large ischemic stroke: a systematic review and meta-analysis of randomized control trials.

Importance: Endovascular thrombectomy (ET) has previously been reserved for patients with small to medium acute ischemic strokes. Three recent randomized control trials (RCTs) have demonstrated functional benefit and risk profiles for ET in large volume ischemic strokes. Objective: The primary objective of the meta-analysis was to determine the combined benefit of ET in adult patients with large volume acute ischemic strokes and to better determine the risk of adverse events following ET. Data Sources: We systematically searched MEDLINE, EMBASE, SCOPUS, the Cochrane Central Register of Controlled, and Google Scholar for all RCTs published in English language between January 1, 2010, to February 19, 2023. Study Selection: We included only RCTs specifically comparing ET to medical therapy in patients with acute ischemic stroke with large volume infarctions as defined by Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5 or calculated infarct volume of > 50-70mL. Two independent reviewers screened potential studies for full text review and metaanalysis inclusion with conflicts being resolved by consensus or third reviewer. Data Extraction and Synthesis: Data was extracted based on pre-specified variables on study methods and design, participant characteristics, analysis approach, as well as efficacy and safety outcomes. Results were combined using a restricted maximum-likelihood estimation random-effects model. Studies were assessed for potential bias and quality of evidence. Main Outcomes and Measures: The prespecified primary outcome was an overall ordinal shift across the range of modified Rankin scale scores toward a better outcome at 90 days following either ET or medical management for patients with large volume ischemic strokes. Results: A total of 3044 studies were screened, and 29 underwent full text review. 3 RCTs (1011 patients) were included in the analysis. The pooled random effects model for the primary outcome of mRS improvement favored ET over medical management, generalized odds ratio 1.55 [95% CI 1.25 - 1.91, T 2 = 0.01, I 2 = 42.84%]. There was a trend toward increased risk of symptomatic ICH in the ET group, relative risk 1.85 [95% CI 0.94 - 3.63, T 2 = 0.00, I 2 = 0.00%]. Conclusions and Relevance: In patients with large volume ischemic strokes, ET has a clear functional benefit and does not confer increased risk of significant complications compared to medical management alone.

Morbid Obesity Increases Length of Surgery in Elective Anterior Cervical Discectomy and Fusion Procedures but Not Readmission or Reoperation Rates: A Cohort Study.

BACKGROUND: As the obesity epidemic grows, the number of morbidly obese patients undergoing anterior cervical discectomy and fusion (ACDF) continues to increase. Despite the association of obesity with perioperative complications in anterior cervical surgery, the impact of morbid obesity on ACDF complications remains controversial, and studies examining morbidly obese cohorts are limited. METHODS: A single-institution, retrospective analysis of patients undergoing ACDF from September 2010 to February 2022 was performed. Demographic, intraoperative, and postoperative data were collected via review of the electronic medical record. Patients were categorized as nonobese (body mass index [BMI] <30), obese (BMI 30-39.9), or morbidly obese (BMI ≥40). Associations of BMI class with discharge disposition, length of surgery, and length of stay were assessed using multivariable logistic regression, multivariable linear regression, and negative binomial regression, respectively. RESULTS: The study included 670 patients undergoing single-level or multilevel ACDF: 413 (61.6%) nonobese, 226 (33.7%) obese, and 31 (4.6%) morbidly obese patients. BMI class was associated with prior history of deep venous thrombosis (P < 0.01), pulmonary thromboembolism (P < 0.05), and diabetes mellitus (P < 0.001). In bivariate analysis, there was no significant association between BMI class and reoperation or readmission rates at 30, 60, or 365 days postoperatively. In multivariable analysis, greater BMI class was associated with increased length of surgery (P = 0.03), but not length of stay or discharge disposition. CONCLUSIONS: For patients undergoing ACDF, greater BMI class was associated with increased length of surgery, but not reoperation rate, readmission rate, length of stay, or discharge disposition.

Incidence and management of postoperative pseudomeningocele and cerebrospinal fluid leak after Chiari malformation type I decompression.

OBJECTIVE: The optimal surgical management of Chiari malformation type I (CM-I) remains controversial and heterogeneous. The authors sought to investigate patient-specific, technical, and perioperative features that may affect the incidence of CSF-related complications including pseudomeningocele and CSF leak at their institution. METHODS: The authors performed a single-center, retrospective review of all adult patients with CM-I who underwent posterior fossa decompression. Patient demographics, operative details, and perioperative factors were collected via electronic medical record review. The authors performed Fisher's exact test and independent Student t-tests for categorical and continuous variables, respectively. Univariate regression analysis was performed to determine odds ratios. A multivariable regression analysis was performed for those factors with p < 0.10 or large effect sizes (OR ≥ 2.0 or ≤ 0.50) by univariate analysis. The STROBE guidelines for observational studies were followed. RESULTS: A total of 59 adult patients were included. Most patients were female (78.0%), and the mean body mass index was 32.2 (± 9.0). Almost one-third (30.5%) of patients had a syrinx on preoperative imaging. All patients underwent expansile duraplasty, of which 47 (79.7%) were from autologous pericranium. Arachnoid opening for fourth ventricular inspection was performed in 26 (44.1%) cases. CSF-related complications were identified in 18 (30.5%) of cases. Thirteen (22.0%) patients required readmission and 11 (18.6%) required intervention such as wound revision (n = 5), wound revision with CSF diversion (n = 4), CSF diversion alone (n = 1), or blood patch (n = 1). Three (5.1%) patients required permanent CSF diversion. Male sex (OR 3.495), diabetes mellitus (OR 0.249), tobacco use (OR 2.53), body mass index more than 30 (OR 2.45), preoperative syrinx (OR 1.733), autologous duraplasty (OR 0.331), and postoperative steroids (OR 2.825) were included in the multivariable analysis. No factors achieved significance by univariate or multivariable analysis (all p > 0.05). CONCLUSIONS: The authors report a single-center, retrospective experience of posterior fossa decompression for 59 adults with CM-I. No perioperative or technical features were found to affect the CSF-related complication rate. More standardized practices within centers are necessary to better delineate the true risk factors and potential protective factors against CSF-related complications.

Postoperative seizure freedom after vagus nerve stimulator placement in children 6 years of age and younger.

OBJECTIVE: Food and Drug Administration (FDA) approval for vagus nerve stimulator (VNS) implantation is limited to patients older than 4 years of age with medically refractory partial-onset seizures. In younger children with severe generalized epilepsy, however, VNS implantation remains off-label. In this study, the authors followed up on their previously reported cohort to review the longer-term safety and efficacy of VNS placement in children younger than 6 years with generalized medically refractory epilepsy (MRE), providing the largest cohort with > 2 years of follow-up to date in this age group. METHODS: This was a retrospective observational cohort study of patients younger than 6 years of age with generalized MRE who underwent VNS implantation at a single institution between 2010 and 2020. Inclusion criteria encompassed failure of more than two antiepileptic drugs alone or in combination, neurologist referral for vagus nerve stimulation, informed consent with knowledge of the off-label status in young children, and > 1 year of follow-up. Outcome measures included seizure reduction rate ≥ 50% and postoperative morbidity defined nominally. Statistical analysis was conducted with Stata/SE. RESULTS: Forty-five patients were included: 11 patients younger than 4 years of age and 34 between 4 and 6 years of age. There were no intraoperative complications. Perioperative complications within 1 year occurred in 11% (n = 5) of the patients and included two wound infections, a mild cough, hyperactivity, hoarseness, and 1 patient with persistent surgical site pain. A seizure reduction ≥ 50% was observed in 36.4% (n = 4) of the patients younger than 4 years of age at the 6-month and 1-, 2-, and 5-year follow-ups. In the 4- to 6-year-old cohort, this was observed in 32.4% (n = 11) of the patients at 6 months, 41.2% (n = 14) at 1 year, 38.2% (n = 13) at 2 years, and 41.2% (n = 14) at 5 years. CONCLUSIONS: VNS implantation for patients younger than 4 years of age with generalized onset MRE has not been approved by the FDA. This retrospective study establishes feasibility, illustrates an acceptable safety profile in children younger than 6 years, and demonstrates efficacy comparable to that reported in older patients.

Immunotherapy for Pediatric Brain and Spine Tumors: Current State and Future Directions.

BACKGROUND: Brain tumors are the most common solid tumors and the leading cause of cancer-related deaths in children. Incidence in the USA has been on the rise for the last 2 decades. While therapeutic advances in diagnosis and treatment have improved survival and quality of life in many children, prognosis remains poor and current treatments have significant long-term sequelae. SUMMARY: There is a substantial need for the development of new therapeutic approaches, and since the introduction of immunotherapy by immune checkpoint inhibitors, there has been an exponential increase in clinical trials to adopt these and other immunotherapy approaches in children with brain tumors. In this review, we summarize the current immunotherapy landscape for various pediatric brain tumor types including choroid plexus tumors, embryonal tumors (medulloblastoma, AT/RT, PNETs), ependymoma, germ cell tumors, gliomas, glioneuronal and neuronal tumors, and mesenchymal tumors. We discuss the latest clinical trials and noteworthy preclinical studies to treat these pediatric brain tumors using checkpoint inhibitors, cellular therapies (CAR-T, NK, T cell), oncolytic virotherapy, radioimmunotherapy, tumor vaccines, immunomodulators, and other targeted therapies. KEY MESSAGES: The current landscape for immunotherapy in pediatric brain tumors is still emerging, but results in certain tumors have been promising. In the age of targeted therapy, genetic tumor profiling, and many ongoing clinical trials, immunotherapy will likely become an increasingly effective tool in the neuro-oncologist armamentarium.

Quantifying and reporting outcome measures in pediatric epilepsy surgery: A systematic review.

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery.

Assessing the Impact of Changes to USMLE Step 1 Grading on Evaluation of Neurosurgery Residency Applicants in the United States: A Program Director Survey.

BACKGROUND: Neurosurgery (NS) is among the most selective specialties in the United States. As the United States Medical Licensing Examination (USMLE) Step 1 transitions to a binary pass/fail score, residency programs face unclear challenges in screening and evaluating applicants. The aim of this study is to provide insights into the perceived impact of changes to the USMLE Step 1 grading in the applicant selection process. METHODS: We created a survey using questions regarding NS program demographics, the perceived predictive abilities of Step 1 and Step 2 clinical knowledge (CK), and several factors that programs consider when assessing applicants. We queried program directors (PDs), program coordinators (PCs), and assistant PDs at 117 NS residency programs. Respondents were asked to rank these factors in order of importance for selection at their respective training program. We used descriptive statistics and a Wilcoxon matched-pairs signed-rank test to evaluate the effects of these changes using STATA 17. RESULTS: A total of 35 (30%) residency programs responded with 26 (74%) completing the factor ranking questions. 86% (95% confidence interval, 71.5%-94.3%) disagreed that the changes will better prepare students clinically. USMLE Step 2 CK scores, class rank, and away rotations saw significant increases in priority in the absence of a graded Step 1, whereas letters of recommendation and surrogates for research productivity saw notable, but not significant, changes after adjusting for multiple testing. CONCLUSIONS: Reporting binary Step 1 grades marks a significant shift in assessing applicants for NS residency by emphasizing Step 2 CK, class rank, and research productivity.

Western Honduras Copán Population-Based Cancer Registry: Initial Estimates and a Model for Rural Central America.

PURPOSE: Population-based cancer registries (PBCRs) are critical for national cancer control planning, yet few low- and middle-income countries (LMICs) have quality PBCRs. The Central America Four region represents the principal LMIC region in the Western hemisphere. We describe the establishment of a PBCR in rural Western Honduras with first estimates for the 2013-2017 period. METHODS: The Western Honduras PBCR was established through a collaboration of academic institutions and the Honduras Ministry of Health for collection of incident cancer data from public and private health services. Data were recorded using the Research Electronic Data Capture (REDCap) web-based platform with data monitoring and quality checks. Crude and age-standardized rates (ASRs) were calculated at the regional level, following WHO methodology. RESULTS: The web-based platform for data collection, available ancillary data services (eg, endoscopy), and technical support from international centers (United States and Colombia) were instrumental for quality control. Crude cancer incidence rates were 112.2, 69.8, and 154.6 per 100,000 habitants overall, males, and females, respectively (excluding nonmelanoma skin cancer). The adjusted ASRs were 84.2, 49.6, and 118.9 per 100,000 overall habitants, males, and females, respectively. The most common sites among men were stomach (ASR 26.0, 52.4%), colorectal (ASR 5.11, 10.15%), and prostate (ASR 2.7, 5.4%). The most common sites in women were cervix (ASR 34.2, 36.7%), breast (ASR 11.2, 12.3%), and stomach (ASR 10.8, 11.7%). CONCLUSION: The Copán-PBCR represents a successful model to develop cancer monitoring in rural LMICs. Innovations included the use of the REDCap platform and leverage of Health Ministry resources. This provides the first PBCR data for Honduras and the Central America Four and confirms that infection-driven cancers, such as gastric and cervical, should be priority targets for cancer control initiatives.