Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Carbon fiber-reinforced PEEK instrumentation in the spinal oncology population: a retrospective series demonstrating technique, feasibility, and clinical outcomes.

OBJECTIVE: The authors aimed to demonstrate the feasibility and advantages of carbon fiber-reinforced PEEK (CFRP) composite implants in patients with both primary and secondary osseous spinal tumors. METHODS: Twenty-eight spinal tumor patients who underwent fixation with CFRP hardware were retrospectively identified in a Spine Tumor Quality Database at a single institution. Demographic, procedural, and follow-up data were retrospectively collected. RESULTS: The study population included 14 females and 14 males with a mean age of 60 years (range 30-86 years). Five patients had primary bone tumors, and the remaining patients had metastatic tumors. Breast cancer was the most common metastatic tumor. The most common presenting symptom was axial spine pain (25 patients, 89%), and the most common Spine Instability Neoplastic Score was 7 (range 6-14). Two patients in this series had anterior cervical procedures. The remaining patients underwent posterior thoracolumbar fixation. The average fusion length included 4.6 vertebral segments (range 3-8). The mean clinical follow-up time with surgical or oncology teams was 6.5 months (range 1-23 months), and the mean interval for last follow-up imaging (CT or MRI) was 6.5 months (range 1-22 months). Eighteen patients received postoperative radiation at the authors' institution (16 with photon therapy, 2 with proton therapy). Eleven of the patients (39%) in this series died. At the last clinical follow-up, 26 patients (93%) had stable or improved neurological function compared with their preoperative status. At the last imaging follow-up, local disease control was observed in 25 patients (89%). Two patients required reoperation in the immediate postoperative period, one for surgical site infection and the other for compressive epidural hematoma. One patient was noted to have lucencies around the most cephalad screws 3 months after surgery. No hardware fracture or malfunction occurred intraoperatively. No patients required delayed surgery for hardware loosening, fracture, or other failure. Early tumor recurrence was detected in 3 patients. Early detection was attributed to the imaging characteristics of the CFRP hardware. CONCLUSIONS: CFRP spinal implants appear to be safe and comparable to conventional titanium implants in terms of functionality. The imaging characteristics of CFRP hardware facilitate radiation planning and assessment of surveillance imaging. CFRP hardware may enhance safety and efficacy, particularly with particle therapy dosimetry. Larger patient populations with longer-term follow-up are needed to confirm the various valuable aspects of CFRP spinal implants.

High-Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Nonsurgical Refractory Back Pain: Design of a Pragmatic, Multicenter, Randomized Controlled Trial.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to provide pain relief for chronic back and leg pain due to failed back surgery syndrome. But many patients with chronic back pain have not had major back surgery or are not good candidates for surgery, and conventional medical management (CMM) provides limited relief. We have termed this condition nonsurgical refractory back pain (NSRBP). Level 1 evidence does not yet exist showing the therapeutic benefit of SCS for NSRBP. OBJECTIVE: To compare 10-kHz SCS plus CMM (10-kHz SCS + CMM) to CMM alone for treatment of NSRBP in terms of clinical and cost effectiveness. STUDY DESIGN: Multicenter, randomized controlled trial (RCT), with subjects randomized 1:1 to either 10-kHz SCS + CMM or CMM alone. Optional crossover occurs at 6 months if treatment does not achieve ≥50% pain relief. METHODS: Patients with NSRBP as defined above may be enrolled if they are ineligible for surgery based on surgical consultation. Subjects randomized to 10-kHz SCS + CMM will receive a permanent implant if sufficient pain relief is achieved in a temporary trial. Both groups will receive CMM per standard of care and will undergo assessments at baseline and at follow-ups to 12 months. Self-report outcomes include pain, disability, sleep, mental health, satisfaction, healthcare utilization, and quality of life. RESULTS: Enrollment was initiated on September 10, 2018. Prespecified independent interim analysis at 40% of the enrollment target indicated the sample size was sufficient to show superiority of treatment at the primary endpoint; therefore, enrollment was stopped at 211. CONCLUSIONS: This large multicenter RCT will provide valuable evidence to guide clinical decisions in NSRBP.

A Randomized, Controlled, Phase III Clinical Trial to Evaluate the Efficacy and Tolerability of Risorine with Conventional Rifampicin in the Treatment of Newly Diagnosed Pulmonary Tuberculosis Patients.

BACKGROUND: The overall goals for treatment of Tuberculosis (TB) are to cure individual patient and to minimize the transmission of Mycobacterium tuberculosis. At the time of study conduction, the standard treatment for newly diagnosed tuberculosis patients consisted of an intensive phase for two months with four drugs (HRZE), followed by continuation phase for four months with two drugs (HR). Rifampicin, which is very effective against Mycobacterium tuberculosis, in both the phases of treatment, has certain concerns, which includes, decreased bioavailability with chronic use and hepatotoxicity. To overcome these concerns a new boosted formulation of Rifampicin (Risorine) with bio-enhancer Piperine was developed. Piperine has been found to increase bioavailability of several drugs including Amoxicillin, Cefotaxime, Theophylline and Propranolol. Risorine is a fixed dose combination that contains Rifampicin 200 mg + Isoniazid 300 mg + Piperine 10 mg. AIM AND OBJECTIVE: The aim of the present study was to validate the therapeutic efficacy and tolerability of Risorine formulation containing regimen with a conventional regimen in the management of patients with newly diagnosed pulmonary tuberculosis. METHODS: Total 216 patients with sputum positive and treatment naïve pulmonary tuberculosis were enrolled in the study after fulfillment of inclusion / exclusion criteria. These patients were randomized to receive either a conventional anti-TB therapy (n = 117) or a similar regimen containing Risorine (n = 99) for 6 months. During the study period, symptomatic improvement, sputum conversion and radiological improvement were monitored at regular intervals. RESULTS: Of the 216 enrolled patients, 75% in the Risorine group and 79% in the control group completed the study. At 4 weeks the sputum conversion rate was significantly superior in Risorine group (93%) than the control group (84%), which was consistence throughout the study. Cure rate at the end of 24 weeks, was higher in Risorine group (92%) than in the control group (82%). Elevation of liver enzymes were observed in 3 patients in the Risorine group and in 9 patients in control group. CONCLUSIONS: Risorine, a novel formulation of low dose Rifampicin (200 mg), a bio enhancer Piperine (10 mg) and standard dose Isoniazid (300 mg) when given along with Ethambutol and Pyrazinamide was comparable in efficacy with standard WHO therapy using conventional formulation. Risorine provides more Rifampicin in blood compare to GI tract as well as maintaining higher blood levels on chronic therapy compared to conventional Rifampicin with better safety profile. Risorine gives higher sputum conversion rate during the Intensive Phase which is maintained till the end of study. Further a trend was also noticed towards better tolerability with newer formulation, Risorine. H = Isoniazid, R = Rifampicin, Z = Pyrazinamide and E = Ethambutol.

Postoperative Outcomes for Spinal Fusion Procedures in Pediatric Patients with Anemia: A Retrospective and Multivariate Analysis.

BACKGROUND: Preoperative anemia is known to be associated with perioperative complications in many surgical interventions. Here, we examine the effects of preoperative anemia on peri-operative complications and postoperative outcomes in pediatric patients undergoing spinal fusion. METHODS: Retrospective analysis was conducted using the American College of Surgeons Pediatric National Surgery Quality Improvement Program Database between 2012-2020. Current Procedural Terminology codes 22800, 22,802, 22,804, 22,840, 22,842, 22,843, and 22,844 were included to represent all primary spinal fusion procedures performed. Patients without preoperative hematocrit (HCT) levels were excluded. Classification of anemia was determined via age- and sex-adjusted HCT levels. Patient demographics, preoperative comorbidities and risk factors, and 30-day postoperative outcomes were compared between the 2 cohorts using univariate analysis. Multivariate logistic regressions were performed to determine if anemia severity was independently associated with worse postoperative outcomes. RESULTS: A total of 30,243 pediatric patients were included in this study, with 26,621 not having preoperative anemia and 3622 having preoperative anemia. Pediatric patients with anemia have increased length of stay (LOS) (6.7 ± 9.6 vs. 5 ± 6, P < 0.001), 30-day unplanned reoperation rate (4% vs. 2.8%, P < 0.001), and total blood transfused (489.9 ± 497.8 vs. 423.4 ± 452.6, P < 0.001). Multivariate analysis supported anemia and degree of its severity as an independent predictor of increased length of stay (LOS), reoperation rate, and postoperative complications. CONCLUSIONS: Preoperative anemia leads to worse outcomes in pediatric spinal fusion procedures. Utilizing HCT recordings could be factored into the equation for optimal patient selection and prevention of post-operative complications.

Demographics and PainDETECT as Predictors of 24-Month Outcomes for 10 kHz SCS in Nonsurgical Refractory Back Pain.

BACKGROUND: Nonsurgical refractory back pain (NSRBP) is broadly defined as chronic refractory back pain in patients who have not had previous spine surgery and, because they are deemed inappropriate candidates for surgery, are reliant on conventional medical management (CMM), which often provides poor long-term outcomes. High-frequency spinal cord stimulation (10kHz SCS) has demonstrated high rates of pain relief and improvements in functioning in patients with NSRBP. However, despite the use of temporary trial stimulation to select patients who will respond to therapy, some patients fail to achieve long-term therapy response with permanent implants. Prediction analysis founded on patients' baseline characteristics may enrich the appropriate selection of patients for permanent implantation. OBJECTIVES: To examine baseline patient characteristics to predict long-term pain and functional responses to treatment with 10 kHz SCS for NSRBP. STUDY DESIGN: A retrospective analysis of baseline patient characteristics as predictors of 24-month pain and functional outcomes from a previous multicenter randomized controlled trial of 10 kHz SCS in patients with NSRBP. PATIENTS: Patients diagnosed with chronic, neuropathic, axial, low back pain refractory to CMM who had had no previous spine surgery, were deemed unsuitable candidates for it according to a spine surgeon, were implanted with 10kHz SCS and continued with CMM for up to 24 months. METHODS: The baseline characteristics of and 24-month outcomes in the 125 implanted patients who participated in the NSRBP randomized controlled trial (RCT) were included in this analysis. The baseline characteristics included demographics, baseline pain on the visual analog scale (VAS), baseline function based on the Oswestry Disability Index (ODI), mental health according to the patient health questionnaire-9 (PHQ-9), neuropathic pain as measured by PainDETECT, and each patient's temporary trial response. Patient response at 24 months was defined as absolute change from the baseline on the VAS and ODI, and each patient was also classified as a pain responder (achieving at least a 50% decrease in VAS pain score from the baseline) and a function responder (at least a 10-point decrease in ODI or a 24-month score of no more than 20 points). Multivariate prediction models based on regression and classification and regression tree (CART) techniques were developed using the response variables discussed above as the dependent variables and the baseline characteristics as the independent variables. RESULTS: Different factors contributed to pain and functional outcomes. Patients presenting with neuropathic pain (PainDETECT >= 19) and female gender had higher odds of being pain responders to 10 kHz SCS therapy than did males and those without neuropathic pain. Both higher age and depression score (PHQ-9) independently reduced the odds that a patient would be an ODI responder. Years since diagnosis, the reason the patient was deemed unsuitable for spine surgery, and pain etiology were not predictive of pain or functional outcomes. LIMITATIONS: A retrospective sub-analysis of a single pragmatic randomized controlled trial. CONCLUSIONS: There may be an opportunity to increase pain relief and functional improvement if additional patient screening accompanies the temporary lead trial. The presence of neuropathic pain, female gender, age, and depression had some predictive value, but this analysis demonstrates the treatment efficacy of 10 kHz SCS across a wide range of patients with NSRBP.

Durable responses at 24 months with high-frequency spinal cord stimulation for nonsurgical refractory back pain.

OBJECTIVE: The objective of this study was to evaluate the 24-month durability of pain relief, function, quality of life, and safety outcomes for patients with nonsurgical refractory back pain (NSRBP) treated with high-frequency spinal cord stimulation (SCS) within a large, national, multicenter randomized controlled trial (RCT). METHODS: Following the completion of an RCT comparing high-frequency SCS plus CMM with CMM alone for the treatment of NSRBP, patients gave additional consent for a follow-up extension to 24 months. Presented is the cohort analysis of all patients treated with high-frequency SCS following the optional crossover at 6 months. The outcomes assessed to 24 months included responder rate of ≥ 50% pain relief measured according to the visual analog scale [VAS]), disability (Oswestry Disability Index [ODI]), quality of life (EQ-5D 5-level [EQ-5D-5L]), opioid reduction. RESULTS: Of the 125 patients who received a permanent implant, 121 completed the 12-month follow-up, 101 gave additional consent for extended follow-up, and 98 completed the 24-month follow-up. At 24 months after implantation, the mean back pain VAS score was reduced by 73% and the responder rate was 82%. ODI and EQ-5D-5L both improved by at least double the minimal clinically important difference for each measure. No unexpected adverse events were observed, and the rates of serious adverse events (3.4%) and device explantations (4.8%) were low. CONCLUSIONS: The addition of high-frequency SCS to CMM in patients with NSRBP offers profound improvements at 24 months in pain, function, quality of life, and reduced opioid use. This study provides much-needed evidence to inform current clinical practice for managing patients with NSRBP.

Hybrid approach combining deep learning and a rule based expert system for concept extraction from prescriptions.

Concept extraction from prescriptions is a very important task that provides a foundation for many of the downstream healthcare applications in decision making across the areas of pharmacovigilance, medication adherence, inventory management, and other matters of value-based care. Although short, these directions can sometimes be complex. With the increase in complexity of direction, it becomes harder to extract various concepts by only rule based expert system. It identifies major concepts like frequency, dosage, duration, etc. from the natural text direction using a combination of rules and deep learning (DL) based methods on a large real world data of a pharmacy chain. The DL module includes a fine-tuned BERT transformer and Gram CNN (Convolutional Neural Network) based NER (Named Entity Recognition) architecture. The proposed method utilizes the domain heuristics along with intelligent labelling and bootstrapping to help DL models extract concepts with high evaluation scores and thus provides a way for carrying out concept extraction using targeted methods instead of one single method. To the best of our knowledge, this is the best performance reported in the literature for concept extraction from doctor's prescription.

Cross-Sectional Analysis of Neurosurgical Residency Websites During the Virtual Interview Cycle.

BACKGROUND: The loss of in-person interviews during the COVID-19 pandemic warrants an investigation into what information is provided to applicants through neurosurgery residency program websites (NRPWs). This study examines NRPWs across the United States and Canada to determine what details are provided to applicants through their respective websites. METHODS: Accreditation Council for Graduate Medical Education accredited neurologic surgery residency programs were identified through the American Association of Neurological Surgeons (AANS) website. NRPWs were searched for 48 criteria, including program overview, application requirements, and curriculum information. Small programs were defined as 1-2 residents per class, while large programs were classified as those with 3-4 residents per year. Content differences were analyzed between the top 20 and remaining programs per the Doximity Residency Navigator Rankings. RESULTS: The most prevalent information among 122 NRPWs was the neurosurgery residency overview (95%), names of faculty members (95%), and names of current residents (94%). Top-20 NRPWs were more likely to include post PGY-7 fellowships (90% vs. 61% P = 0.0108), operating room virtual reality experience (35% vs. 12% P = 0.0160), and faculty research (90% vs. 62% P = 0.0182) than the remainder of the programs. CONCLUSIONS: This study investigates NRPW content after the COVID-19 pandemic. We report broad variability in content provided by various neurosurgical training programs. Higher-ranked neurosurgery programs are more likely to include fellowship information, operating room virtual reality experience, and faculty research than lower-ranked programs.

Characterization of neurosurgery fellowship directors: strengths and room for improvement.

BACKGROUND: While many current and aspiring neurosurgeons are looking to supplement their clinical practices with leadership positions, there has not been research characterizing current leadership positions such as fellowship directors (FDs) in neurosurgery to provide insight into objective qualities that distinguish these individuals from the rest of the workforce. This study aims to outline the current characterization of spine, endovascular, pediatric, and stereotactic and functional neurosurgery fellowship directors. METHODS: A list of accredited neurosurgical fellowship programs located within the US and their respective directors was acquired through the AANS Neurosurgical Fellowship Training Program Directory. This study obtained educational, demographic, institutional, research, and professional background variables through curriculum vitae, institutional profiles, personal websites, emails, and the Scopus database. RESULTS: Of the 152 FDs analyzed, 143 (94%) were male, 9 (6%) were female, and the mean age was 52.2±8.5 years. The mean Scopus H-index and mean total citations for all FDs was 27±15.7 and 3782.1±4526.7, respectively. Furthermore, the majority of FDs were Caucasian (69.1%), followed by Asian (20.4%), Black or African American (5.3%), and Hispanic or Latino (5.3%). The mean number of years as FD was 8.9±7.2. CONCLUSIONS: This analysis showed neurosurgery fellowship directors are primarily Caucasian males. Neurosurgery training pedigree seems to play a role in FD attainment. In addition, these directors are largely distinguished by their research productivity. This analysis serves as an insight into the current climate for students aspiring to serve as academic leaders in the field of neurosurgery.

Cost-effectiveness of 10-kHz spinal cord stimulation therapy compared with conventional medical management over the first 12 months of therapy for patients with nonsurgical back pain: randomized controlled trial.

OBJECTIVE: This analysis evaluated if spinal cord stimulation (SCS) at 10 kHz plus conventional medical management (CMM) is cost-effective compared with CMM alone for the treatment of nonsurgical refractory back pain (NSRBP). METHODS: NSRBP subjects were randomized 1:1 into the 10-kHz SCS (n = 83) or CMM (n = 76) group. Outcomes assessed at 6 months included EQ-5D 5-level (EQ-5D-5L), medication usage, and healthcare utilization (HCU). There was an optional crossover at 6 months and follow-up to 12 months. The incremental cost-effectiveness ratio (ICER) was calculated with cost including all HCU and medications except for the initial device and implant procedure, and cost-effectiveness was analyzed based on a willingness-to-pay threshold of < $50,000 per quality-adjusted life-year. RESULTS: Treatment with 10-kHz SCS resulted in a significant improvement in quality of life (QOL) over CMM (EQ-5D-5L index score change of 0.201 vs -0.042, p < 0.001) at a lower cost, based on reduced frequency of HCU resulting in an ICER of -$4964 at 12 months. The ICER was -$8620 comparing the 6 months on CMM with postcrossover on 10-kHz SCS. CONCLUSIONS: Treatment with 10-kHz SCS provides higher QOL at a lower average cost per patient compared with CMM. Assuming an average reimbursement for device and procedure, 10-kHz SCS therapy is predicted to be cost-effective for the treatment of NSRBP compared with CMM within 2.1 years.

Procedural, workforce, and reimbursement trends in neuroendovascular procedures.

BACKGROUND: This study aims to define the proportion of Medicare neuroendovascular procedures performed by different specialists from 2013 to 2019, map the geographic distribution of these specialists, and trend reimbursement for these procedures. METHODS: The Medicare Provider Utilization Database was queried for recognized neuroendovascular procedures. Data on specialists and their geographic distribution were tabulated. Reimbursement data were gathered using the Physician Fee Schedule Look-Up Tool and adjusted for inflation using the United States Bureau of Labor Statistics' Consumer Price Index Inflation calculator. RESULTS: The neuroendovascular workforce in 2013 and 2019, respectively, was as follows: radiologists (46% vs 44%), neurosurgeons (45% vs 35%), and neurologists (9% vs 21%). Neurologists increased proportionally (p=0.03). Overall procedure numbers increased across each specialty: radiology (360%; p=0.02), neurosurgery (270%; p<0.01), and neurology (1070%; p=0.03). Neuroendovascular revascularization (CPT 61645) increased in all fields: radiology (170%; p<0.01), neurosurgery (280%; p<0.01), neurology (240%; p<0.01); central nervous system (CNS) permanent occlusion/embolization (CPT61624) in neurosurgery (67%; p=0.03); endovascular temporary balloon artery occlusion (CPT61623) in neurology (29%; p=0.04). In 2019, radiologists were the most common neuroendovascular specialists everywhere except in the Northeast where neurosurgeons predominated. Inflation adjusted reimbursement decreased for endovascular temporary balloon occlusion (CPT61623, -13%; p=0.01), CNS transcatheter permanent occlusion or embolization (CPT61624, -13%; p=0.02), non-CNS transcatheter permanent occlusion or embolization (CPT61626, -12%; p<0.01), and intracranial stent placement (CPT61635, -12%; p=0.05). CONCLUSIONS: The number of neuroendovascular procedures and specialists increased, with neurologists becoming more predominant. Reimbursement decreased. Coordination among neuroendovascular specialists in terms of training and practice location may maximize access to acute care.

Association between immunohistochemical markers and tumor progression following resection of spinal chordomas: a multicenter study.

OBJECTIVE: Chordomas are slow-growing tumors derived from notochord remnants. Despite margin-negative excision and postoperative radiation therapy, spinal chordomas (SCs) often progress. The potential of immunohistochemical (IHC) markers, such as epithelial membrane antigen (EMA), combined with machine learning algorithms to predict long-term (≥ 12 months) postoperative tumor progression, has been understudied. The authors aimed to identify IHC markers using trained tree-based algorithms to predict long-term (≥ 12 months) postoperative tumor progression. METHODS: The authors reviewed the records of patients who underwent resection of SCs between January 2017 and June 2021 across the Mayo Clinic enterprise. Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient's record. Low tumor progression was defined as more than a 94.3-mm3 decrease in the tumor size at the latest radiographic follow-up. Decision trees and random forest classifiers were trained and tested to predict the long-term volumetric progression after an 80/20 data split. RESULTS: Sixty-two patients diagnosed with and surgically treated for SC were identified, of whom 31 were found to have a more advanced tumor progression based on the tumor volume change cutoff of 94.3 mm3. The mean age was 54.3 ± 13.8 years, and most patients were male (62.9%) and White (98.4%). The most common treatment modality was subtotal resection with radiation therapy (35.5%), with proton beam therapy being the most common (71%). Most SCs were sacrococcygeal (41.9%), followed by cervical (32.3%). EMA-positive SCs had a postoperative progression risk of 67%. Pancytokeratin-positive SCs had a progression rate of 67%; however, patients with S100 protein-positive SCs had a 54% risk of progression. The accuracy of this model in predicting the progression of unseen test data was 66%. Pancytokeratin (mean minimal depth = 1.57), EMA (mean minimal depth = 1.58), cytokeratin A1/A3 (mean minimal depth = 1.59), and S100 protein (mean minimal depth = 1.6) predicted the long-term volumetric progression. Multiway variable importance plots show the relative importance of the top 10 variables based on three measures of varying significance and their predictive role. CONCLUSIONS: These IHC variables with tree-based machine learning tools successfully demonstrate a high capacity to identify a patient's tumor progression pattern with an accuracy of 66%. Pancytokeratin, EMA, cytokeratin A1/A3, and S100 protein were the IHC drivers of a low tumor progression. This shows the power of machine learning algorithms in analyzing and predicting outcomes of rare conditions in a small sample size.

Clinical Outcomes of Stereotactic Radiosurgery-Related Radiation Necrosis in Patients with Intracranial Metastasis from Melanoma.

Background: Radiation necrosis (RN) is a clinically relevant complication of stereotactic radiosurgery (SRS) for intracranial metastasis (ICM) treatments. Radiation necrosis development is variable following SRS. It remains unclear if risk factors for and clinical outcomes following RN may be different for melanoma patients. We reviewed patients with ICM from metastatic melanoma to understand the potential impact of RN in this patient population. Methods: Patients who received SRS for ICM from melanoma at Mayo Clinic Arizona between 2013 and 2018 were retrospectively reviewed. Data collected included demographics, tumor characteristics, radiation parameters, prior surgical and systemic treatments, and patient outcomes. Radiation necrosis was diagnosed by clinical evaluation including brain magnetic resonance imaging (MRI) and, in some cases, tissue evaluation. Results: Radiation necrosis was diagnosed in 7 (27%) of 26 patients at 1.6 to 38 months following initial SRS. Almost 92% of all patients received systemic therapy and 35% had surgical resection prior to SRS. Patients with RN trended toward having larger ICM and a prior history of surgical resection, although statistical significance was not reached. Among patients with resection, those who developed RN had a longer period between surgery and SRS start (mean 44 vs 33 days). Clinical improvement following treatment for RN was noted in 2 (29%) patients. Conclusions: Radiation necrosis is relatively common following SRS for treatment of ICM from metastatic melanoma and clinical outcomes are poor. Further studies aimed at mitigating RN development and identifying novel approaches for treatment are warranted.

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Image-localized biopsy mapping of brain tumor heterogeneity: A single-center study protocol.

Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease. Biopsies are required to obtain a pathological diagnosis and are predominantly taken from the tumor core, which often has different traits to the surrounding invasive tumor that typically leads to recurrent disease. One approach to solving this issue is to characterize the spatial heterogeneity of molecular, genetic, and cellular features of glioma through the intraoperative collection of multiple image-localized biopsy samples paired with multi-parametric MRIs. We have adopted this approach and are currently actively enrolling patients for our 'Image-Based Mapping of Brain Tumors' study. Patients are eligible for this research study (IRB #16-002424) if they are 18 years or older and undergoing surgical intervention for a brain lesion. Once identified, candidate patients receive dynamic susceptibility contrast (DSC) perfusion MRI and diffusion tensor imaging (DTI), in addition to standard sequences (T1, T1Gd, T2, T2-FLAIR) at their presurgical scan. During surgery, sample anatomical locations are tracked using neuronavigation. The collected specimens from this research study are used to capture the intra-tumoral heterogeneity across brain tumors including quantification of genetic aberrations through whole-exome and RNA sequencing as well as other tissue analysis techniques. To date, these data (made available through a public portal) have been used to generate, test, and validate predictive regional maps of the spatial distribution of tumor cell density and/or treatment-related key genetic marker status to identify biopsy and/or treatment targets based on insight from the entire tumor makeup. This type of methodology, when delivered within clinically feasible time frames, has the potential to further inform medical decision-making by improving surgical intervention, radiation, and targeted drug therapy for patients with glioma.

Dental light curing and its effects on color perception.

INTRODUCTION: Light curing has become increasingly popular for orthodontic bonding, partly as a result of improvements in light-curing unit technology and higher light intensities. The aim of this study was to determine orthodontists' knowledge of dental light-curing units, their safety aspects, and the possible effects on color perception. METHODS: Questionnaires were administered to 120 specialists or trainees to assess their knowledge of light curing and safety issues. In addition, 15 orthodontists and 15 nonorthodontists were asked to complete the Farnsworth Munsell 100 hue test to assess color perception. RESULTS: One hundred four questionnaires were returned, giving a response rate of 86.6%. Light-emitting diode lights were the most popular (73.4%), followed by quartz-halogen (9.2%) and plasma lights (5.5%); 11.9% were unsure of the type of light used, 84% did not know the intensity, and 67% did not know the wavelength of the lights. Although most used safety equipment-eg, paddles-7% used no safety measures. Seventy-six percent were either unsure or took no precautions during light curing for staff or patients who had previous cataract surgery, and up to 99% were either unsure or took no precautions during light curing for staff or patients taking photosensitizing medications. With the Farnsworth Munsell test, 28 participants had average color discrimination, with 2 demonstrating superior discrimination. There were no differences between the orthodontists and the controls, or between men and women. CONCLUSIONS: Orthodontists' knowledge of dental light-curing units and hazards is poor. Although potential risks are associated with the long-term use of these light-curing units, no effect on color discrimination was detected.

Trends in Peripheral Nerve Surgery: Workforce, Reimbursement, and Procedural Rates.

BACKGROUND: Peripheral nerve surgery is one of the smallest neurosurgical subspecialties. It is hypothesized that the number of neurosurgeons performing these procedures has declined over the last decade due to many factors, including limited training opportunities and lower compensation relative to other subspecialties. METHODS: Data for physicians who performed peripheral nerve surgical procedures (PNSPs) were obtained from the Medicare Provider Utilization Database and used to calculate the total number of procedures performed by physicians of each specialty for each year. The Physician Fee Schedule Look-Up Tool was used to determine reimbursement rates for the top 5 PNSPs for neurosurgeons, which were then adjusted for inflation using the U.S. Bureau of Labor's Consumer Price Index Inflation Calculator. RESULTS: From 2012 to 2019, the top 3 contributing specialties were orthopedic surgery, urology, and hand surgery. Both the percentage of PNSPs performed by neurosurgeons and the number of neurosurgeons performing PNSPs decreased. Between 2000 and 2020, the average reimbursement for the commonly identified codes 64721, 64718, 64722, and 64718 decreased, whereas the reimbursement for 64555 (implantation of peripheral nerve neurostimulator electrodes) increased. CONCLUSIONS: Despite an overall increase in number of PNSPs, the percentage of PNSPs performed by neurosurgeons decreased from 2012 to 2019. There was overall workforce exit among neurosurgical peripheral nerve specialists over time. From 2000 to 2020, the average reimbursement for most PNSPs has decreased. Further investigation is needed to establish factors contributing to these trends and how they may be mitigated.