Tethered cord prevalence among patients with prenatal or postnatal myelomeningocele repair.

BACKGROUND: Myelomeningocele (MMC) is a severe form of spina bifida characterized by spinal cord extrusion into a cerebrospinal fluid (CSF) filled sac which may lead to lifelong disability. Repair of these lesions have classically occurred shortly after birth, but more recently, prenatal myelomeningocele repair techniques have been elucidated. This study aimed to investigate the outcome of surgery, particularly with subsequent spinal cord tethering, in patients with prenatal myelomeningocele closure and those with postnatal repair surgery. MATERIALS AND METHODS: In this retrospective study which assessed patients from April 2002 to April 2020, the data of 18 total patients with MMC were reviewed. Nine patients from each group were included, closed prenatally or postnatally, respectively. Demographic information including age and sex, birth week, infant comorbidities, presence of dermoid or lipoma, cutaneous stigmata, total number and timing of detethering procedures, presence of Chiari malformation, and need for VPS was obtained. RESULTS: Eighteen patients including nine infants closed prenatally and nine infants with myelomeningoceles closed postnatally were reviewed. The mean age was 4 ± 3 years and 6.22 ± 2.4 in prenatal and postnatal retrospectively. There was a significant relationship between the number of detethering procedures (p-value = 0.03) and the need for a ventriculoperitoneal shunt (VPS) (p-value = 0.01) between the groups, with the prenatal closure group having lower rates of each. There was no significant difference between the groups in regard to the mean age at the detethering procedure (p = 0.4), sex (p = 0.09), birth week (p = 0.8), comorbidities (p = 0.8), presence of intraspinal dermoid or lipoma (p = 0.09), presence of cutaneous stigma (p = 0.08), Chiari (p = 0.6), fatty filum (p = 0.08), syrinx (p = 0.4), bone anomaly (p = 0.4), and spina bifida neurological scale (p = 0.66). CONCLUSION: There was a significant relationship between the two groups in terms of the number of detethering procedures, and the need for VPS. Our data represents a possible difference in the need for detethering surgeries and ventriculoperitoneal shunt placements between patients with prenatal and postnatal myelomeningocele closures.

Linear pharmacokinetics of 3,4-methylenedioxypyrovalerone (MDPV) and its metabolites in the rat: relationship to pharmacodynamic effects.

3,4-Methylenedioxypyrovalerone (MDPV) is a commonly abused synthetic cathinone in the United States and is associated with dangerous side effects. MDPV is a dopamine transporter blocker that is 10-fold more potent than cocaine as a locomotor stimulant in rats. Previous in vitro and in vivo metabolism studies identified 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) as the two primary MDPV metabolites. This study examined MDPV pharmacokinetics and metabolism, along with associated pharmacodynamic effects in rats receiving 0.5, 1.0 and 2.0 mg/kg subcutaneous (s.c.) MDPV. Blood was collected by an indwelling jugular catheter before dosing and at 10, 20, 30, 60, 120, 240 and 480 minutes thereafter. Plasma specimens were analyzed by liquid chromatography coupled to high-resolution tandem mass spectrometry. Maximum concentrations (Cmax ) and area-under-the-curve (AUC) for MDPV and two metabolites increased proportionally with administered dose, showing linear pharmacokinetics. MDPV exhibited the highest Cmax at all doses (74.2-271.3 µg/l) and 4-OH-3-MeOH-PV the highest AUC (11 366-47 724 minutes per µg/l), being the predominant metabolite. MDPV time to Cmax (Tmax ) was 12.9-18.6 minutes, while 3,4-catechol-PV and 4-OH-3-MeO-PV peaked later with Tmax 188.6-240 minutes after s.c. dosing. Horizontal locomotor activity (HLA) and stereotypy correlated positively with plasma MDPV concentrations, while HLA correlated negatively with MDPV metabolites. These results suggest that the parent compound mediates motor stimulation after systemic MDPV administration, but additionally, metabolites may be inhibitory, may not be active or may not pass the blood brain barrier.

Studies toward the Development of Antiproliferative Neoclerodanes from Salvinorin A.

The success rate for central nervous system (CNS) drug candidates in the clinic is relatively low compared to the industry average across other therapeutic areas. Penetration through the blood-brain barrier (BBB) to reach the therapeutic target is a major obstacle in development. The rapid CNS penetration of salvinorin A has suggested that the neoclerodane nucleus offers an excellent scaffold for developing antiproliferative compounds that enter the CNS. The Liebeskind-Srogl reaction was used as the main carbon-carbon bond-forming step toward the synthesis of quinone-containing salvinorin A analogues. Quinone-containing salvinorin A analogues were shown to have antiproliferative activity against the MCF7 breast cancer cell line, but show no significant activity at the κ-opioid receptors. In an in vitro model of BBB penetration, quinone-containing salvinorin A analogues were shown to passively diffuse across the cell monolayer. The analogues, however, are substrates of P-glycoprotein, and thus further modification of the molecules is needed to reduce the affinity for the efflux transporter.

Clinical and socioeconomic predictors of shunt malfunction in the pediatric emergency department.

OBJECTIVE: The aim of this study was to delineate the clinical and socioeconomic variables associated with shunt revision in pediatric patients presenting to the emergency department (ED) with concerns of ventricular shunt malfunction. METHODS: A retrospective analysis of pediatric ED consultations for shunt malfunction over a 1-year period was conducted, examining clinical symptoms, radiographic findings, and socioeconomic variables. Sensitivities, specificities, and positive and negative predictive values were calculated for each presenting symptom collected. Logistic regression models were used to estimate the odds ratios for shunt revision based on these variables, and multivariate analyses were used to adjust for potential confounders. RESULTS: Of the 271 ED visits from 137 patients, 19.2% resulted in shunt revision. Increased ventricle size on imaging (OR 11.38, p < 0.001), shunt site swelling (OR 9.04, p = 0.01), bradycardia (OR 7.08, p < 0.001), and lethargy (OR 5.77, p < 0.001) were significantly associated with shunt revision. Seizure-like activity was inversely related to revision needs (OR 0.24, p < 0.001). Patients with private or self-pay insurance were more likely to undergo revision compared with those with public insurance (p = 0.028). Multivariate analysis further confirmed the significant associations of increased ventricle size, lethargy, and bradycardia with shunt revision, while also revealing that seizure-like activity inversely affected the likelihood of revision. Patients with severe cognitive and language disabilities were more likely to be admitted to the hospital from the ED but were not more likely to undergo revision. CONCLUSIONS: Clinical signs such as increased ventricle size, shunt site swelling, bradycardia, and lethargy may be strong predictors of the need for shunt revision in pediatric patients presenting to the ED with concerns of shunt malfunction. Socioeconomic factors play a less clear role in predicting shunt revision and admission from the ED; however, the nature of their influence is unclear. These findings can help inform clinical decision-making and optimize resource utilization in the ED.

Tethered spinal cord tension assessed via ultrasound elastography in computational and intraoperative human studies.

BACKGROUND: Tension in the spinal cord is a trademark of tethered cord syndrome. Unfortunately, existing tests cannot quantify tension across the bulk of the cord, making the diagnostic evaluation of stretch ambiguous. A potential non-destructive metric for spinal cord tension is ultrasound-derived shear wave velocity (SWV). The velocity is sensitive to tissue elasticity and boundary conditions including strain. We use the term Ultrasound Tensography to describe the acoustic evaluation of tension with SWV. METHODS: Our solution Tethered cord Assessment with Ultrasound Tensography (TAUT) was utilized in three sub-studies: finite element simulations, a cadaveric benchtop validation, and a neurosurgical case series. The simulation computed SWV for given tensile forces. The cadaveric model with induced tension validated the SWV-tension relationship. Lastly, SWV was measured intraoperatively in patients diagnosed with tethered cords who underwent treatment (spinal column shortening). The surgery alleviates tension by decreasing the vertebral column length. RESULTS: Here we observe a strong linear relationship between tension and squared SWV across the preclinical sub-studies. Higher tension induces faster shear waves in the simulation (R2 = 0.984) and cadaveric (R2 = 0.951) models. The SWV decreases in all neurosurgical procedures (p < 0.001). Moreover, TAUT has a c-statistic of 0.962 (0.92-1.00), detecting all tethered cords. CONCLUSIONS: This study presents a physical, clinical metric of spinal cord tension. Strong agreement among computational, cadaveric, and clinical studies demonstrates the utility of ultrasound-induced SWV for quantitative intraoperative feedback. This technology is positioned to enhance tethered cord diagnosis, treatment, and postoperative monitoring as it differentiates stretched from healthy cords.

Tethered spinal cord syndrome occurs when surrounding tissue attaches to and causes stretching across the spinal cord. People with a tethered cord can experience weakness, pain, and loss of bladder control. Although increased tension in the spinal cord is known to cause these symptoms, evaluating the amount of stretching remains challenging. We investigated the ability of an ultrasound imaging approach to measure spinal cord tension. We studied our method in a computer simulation, a benchtop validation model, and in six people with tethered cords during surgery that they were undergoing to reduce tension. In each phase, the approach could detect differences between stretched spinal cords and spinal cords in a healthy state. Our method could potentially be used in the future to improve the care of people with a tethered cord.

Cerebrospinal Fluid biomarkers in pediatric brain tumors: A systematic review.

Central nervous system (CNS) tumors are the leading cause of cancer death in pediatric patients. Though these tumors typically require invasive surgical procedures to diagnose, cerebrospinal fluid (CSF) liquid biopsy presents a potential method for rapid and noninvasive detection of markers of CNS malignancy. To characterize molecular biomarkers that can be used in the diagnosis, prognosis, and monitoring of pediatric cancer patients, a literature review was conducted in accordance with PRISMA guidelines. PubMed and EMBASE were searched for the terms biomarkers, liquid biopsy, cerebrospinal fluid, pediatric central nervous system tumor, and their synonyms. Studies including pediatric patients with CSF sampling for tumor evaluation were included. Studies were excluded if they did not have full text or if they were case studies, methodology reports, in languages other than English, or animal studies. Our search revealed 163 articles of which 42 were included. Proteomic, genomic, and small molecule markers associated with CNS tumors were identified for further analysis and development of detection tools.

Intracranial Gliosarcoma: A National Cancer Database Survey of Clinical Predictors for Overall Survival.

OBJECTIVE: Gliosarcoma (GSM) is a variant of glioblastoma, 1 of the most common and aggressive primary brain tumors in adults. Our study seeks to analyze a large cohort of patients with GSM in the National Cancer Database (NCDB) to elucidate clinical predictors of overall survival (OS). METHODS: Data was collected on patients diagnosed with histologically-confirmed GSM using the NCDB (2004-2016). OS was determined via univariate Kaplan-Meier analysis. Bivariate and multivariate Cox proportional-hazards analyses were also utilized. RESULTS: Our cohort of 1015 patients had a median age at diagnosis of 61 years. Six hundred thirty-one (62.2%) were male, 896 (89.0%) were Caucasian, and 698 (68.8%) lacked any comorbidities. Median OS was 11.5 months. Regarding treatment, 264 (26.5%) patients underwent surgery (S) only (OS = 5.19 months), 61 (6.1%) underwent surgery and radiotherapy (S + RT) (OS = 6.87 months), 20 (2.0%) underwent surgery and chemotherapy (S + CT); (OS = 15.51 months), and 653 (65.4%) underwent S + CT + RT (triple) combination therapy (OS = 13.8 months). Notably, on bivariate analysis, S + CT (Hazard ratio [HR] = 0.59, P-value = 0.04) and triple therapy (HR = 0.57, P < 0.01) were associated with increased OS. S + RT was not significantly associated with OS. Similarly, on multivariate Cox proportional-hazards analyses, gross total resection (HR = 0.76, P = 0.02), S + CT (HR = 0.46, P < 0.01), and triple therapy (HR = 0.52, P < 0.01) predicted significantly increased OS. Furthermore, age >60 years old (HR = 1.03, P < 0.01) and the presence of comorbidities (HR = 1.43, P < 0.01) predicted significantly decreased OS. CONCLUSIONS: Despite maximal multimodal treatment, GSMs have poor median OS. NCDB data suggest age, comorbidities, extent of resection, and adjuvant treatment each minimally delays poor outcomes.

Safety and Accuracy of Freehand Pedicle Screw Placement and the Role of Intraoperative O-Arm: A Single-Institution Experience.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim was to investigate the accuracy of pedicle screw placement by freehand technique and to compare revision surgery rates among three different imaging verification pathways. SUMMARY OF BACKGROUND DATA: Studies comparing different imaging modalities in freehand screw placement surgery are limited. MATERIALS AND METHODS: A single-institution retrospective chart review identified adult patients who underwent freehand pedicle screw placement in the thoracic, lumbar or sacral levels. Patients were stratified into three cohorts based on the intraoperative imaging modality used to assess the accuracy of screw position: intraoperative X-rays (cohort 1); intraoperative O-arm (cohort 2); or intraoperative computed tomography (CT)-scan (cohort 3). Postoperative CT scans were performed on all patients in cohorts 1 and 2. Postoperative CT scan was not required in cohort 3. Screw accuracy was assessed using the Gertzbein-Robbins grading system. RESULTS: A total of 9179 pedicle screws were placed in the thoracic or lumbosacral spine in 1311 patients. 210 (2.3%) screws were identified as Gertzbein-Robbins grades C-E on intraoperative/postoperative CT scan, 137 thoracic screws, and 73 lumbar screws ( P <0.001). Four hundred and nine patients underwent placement of 2754 screws followed by intraoperative X-ray (cohort 1); 793 patients underwent placement of 5587 screws followed by intraoperative O-arm (cohort 2); and 109 patients underwent placement of 838 screws followed by intraoperative CT scan (cohort 3). Postoperative CT scans identified 65 (2.4%) and 127 (2.3%) malpositioned screws in cohorts 1 and 2, respectively. Eleven screws (0.12%) were significantly malpositioned and required a second operation for screw revision. Nine patients (0.69%) required revision operations: eight of these patients were from cohort 1 and one patient was from cohort 2. CONCLUSION: When compared to intraoperative X-ray, intraoperative O-arm verification decreased the revision surgery rate for malpositioned screws from 0.37% to 0.02%. In addition, our analysis suggests that the use of intraoperative O-arm can obviate the need for postoperative CT scans.

Microsurgical Management of Complex Hypothalamic Hamartomas in the Era of Minimally Invasive Therapy: A Case Series and Narrative Review.

BACKGROUND: There has been a paradigm shift in the management of hypothalamic hamartoma (HH) from traditional microsurgical techniques to less invasive alternatives. However, large and extensive HH may fail to respond to these therapies, necessitating craniotomies. METHODS: All patients who underwent microsurgical resection of a complex HH by the 2 senior authors from 2011 to 2021 were included. Charts were retrospectively reviewed and demographic, clinical, imaging, and outcome data were recorded. RESULTS: Eight patients (mean age, 7 years) were included. Two had failed previous treatments. All 7 presented with gelastic seizures and cognitive dysfunction, 6 showed central precocious puberty, and 3 had behavioral problems. The mean lesion size was 21.6 mm and all had interpeduncular extension, 5 had intraventricular extension (Delalande type I, 3; type III, 4; type IV, 1). A frontotemporal orbitozygomatic approach with optic nerve decompression was used in all patients, supplemented by another approach in 3 (endoscopic transventricular, 3; transcallosal, 1). Gross total resection was achieved in 6 patients and subtotal resection in 2. Transient complications occurred in 3 patients (37.5%): self-limited sodium imbalance (n = 3), subdural hygroma (n = 2). Permanent complications occurred in 2 patients (25%): perforator infarct (n = 1) and short-term memory loss (n = 1). All patients experienced seizure resolution with preserved hypothalamic-pituitary axis function. After a mean follow-up of 41 months (range, 2-66 months), 7 patients remained seizure free, and 1 had rare seizures. Cognitive and behavioral symptoms improved in all patients. CONCLUSIONS: For large HH with interpeduncular extension, microsurgery via the frontotemporal orbitozygomatic approach is a safe and highly effective treatment modality.

Spinal cord untethering and midline myelotomy for delayed, symptomatic post-traumatic syringomyelia due to retained ballistic fragments: case report.

INTRODUCTION: Post-traumatic syringomyelia is an uncommon complication after traumatic spinal cord injury. This case study details our decision-making and surgical approach for a patient with symptomatic post-traumatic syringomyelia after sustaining a gunshot wound. CASE PRESENTATION: A 24-year-old man with past medical history of distant American Spinal Injury Association Impairment Grade B spinal cord injury due to ballistic injury developed delayed post-traumatic syringomyelia, resulting in unilateral sensory loss and left upper extremity weakness. CT and MR imaging revealed a syrinx spanning his cervical and thoracic spine causing significant spinal cord compression. To relieve achieve decompression and restore CSF flow dynamics, we performed a bony extradural decompression, bullet fragment extraction, spinal cord untethering, and midline myelotomy. Postoperatively, the patient demonstrated clinical and radiographical improvement. DISCUSSION: Post-traumatic syringomyelia is potentially morbid sequalae of spinal cord injuries. Suspicion for post-traumatic syringomyelia should be maintained in patients with delayed, progressive neurologic deficits. In this setting, surgical intervention may require extradural and intradural procedures to mitigate neural compression along the dilated central canal by the syrinx.

Advances in monitoring for acute spinal cord injury: a narrative review of current literature.

Spinal cord injury (SCI) is a devastating condition that affects about 17,000 individuals every year in the United States, with approximately 294,000 people living with the ramifications of the initial injury. After the initial primary injury, SCI has a secondary phase during which the spinal cord sustains further injury due to ischemia, excitotoxicity, immune-mediated damage, mitochondrial dysfunction, apoptosis, and oxidative stress. The multifaceted injury progression process requires a sophisticated injury-monitoring technique for an accurate assessment of SCI patients. In this narrative review, we discuss SCI monitoring modalities, including pressure probes and catheters, micro dialysis, electrophysiologic measures, biomarkers, and imaging studies. The optimal next-generation injury monitoring setup should include multiple modalities and should integrate the data to produce a final simplified assessment of the injury and determine markers of intervention to improve patient outcomes.

Narrative Review of Predictive Analytics of Patient-Reported Outcomes in Adult Spinal Deformity Surgery.

STUDY DESIGN: Narrative review. OBJECTIVE: Decision making in surgery for adult spinal deformity (ASD) is complex due to the multifactorial etiology, numerous surgical options, and influence of multiple medical and psychosocial factors on patient outcomes. Predictive analytics provide computational tools to analyze large data sets and generate hypotheses regarding new data. In this review, we examine the use of predictive analytics to predict patient-reported outcomes (PROs) in ASD surgery. METHODS: A search of PubMed, Web of Science, and Embase databases was performed to identify all potentially relevant studies up to February 1, 2020. Studies were included based on the use of predictive analytics to predict PROs in ASD. RESULTS: Of 57 studies identified and reviewed, 7 studies were included. Multiple algorithms including supervised and unsupervised methods were used. Significant heterogeneity was observed with choice of PROs modeled including ODI, SRS22, and SF36, assessment of model accuracy, and with the model accuracy and area under the receiver operating curve values (ranging from 30% to 86% and 0.57 to 0.96, respectively). Models were built with data sets of patients ranging from 89 to 570 patients with a range of 22 to 267 variables. CONCLUSIONS: Predictive analytics makes accurate predictions regarding PROs regarding pain, disability, and work and social function; PROs regarding satisfaction, self-image, and psychologic aspects of ASD were predicted with the lowest accuracy. Our review demonstrates a relative paucity of studies on ASD with limited databases. Future studies should include larger and more diverse databases and provide external validation of preexisting models.

Prediction Models in Degenerative Spine Surgery: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: To review the existing literature of prediction models in degenerative spinal surgery. METHODS: Review of PubMed/Medline and Embase databases was conducted to identify articles between January 1, 2000 and March 1, 2020 that reported prediction model performance for outcomes following elective degenerative spine surgery. RESULTS: Thirty-one articles were included. Twenty studies were of thoracolumbar, 5 were of cervical, and 6 included all spine patients. Five studies were externally validated. Prediction models were developed using machine learning (42%) and logistic regression (42%) as well as other techniques. Web-based calculators were included in 45% of published articles. Various outcomes were investigated, including complications, infection, length of stay, discharge disposition, reoperation, readmission, disability score, back pain, leg pain, return to work, and opioid dependence. CONCLUSIONS: Significant heterogeneity exists in methods used to develop prediction models of postoperative outcomes after degenerative spine surgery. Most internally validate their scores, but a few have been externally validated. Areas under the curve for most models range from 0.6 to 0.9. Techniques for development are becoming increasingly sophisticated with different machine learning tools. With further external validation, these models can be deployed online for patient, physician, and administrative use, and have the potential to optimize outcomes and maximize value in spine surgery.

Multidisciplinary approach for repair of a large ventral thoracic meningocele in neurofibromatosis-1; a systematic review of the literature and case report.

Thoracic meningoceles and dural ectasia are less commonly recognized manifestations of neurofibromatosis 1 (NF1). Rarely, large thoracic meningoceles may become compressive and lead to respiratory compromise secondary to lung compression. Surgical goals aim to increase lung aeration through decreasing the size of the meningocele through shunting, excision or repair of the meningocele, and varying degrees of dural tube reconstruction. There is no agreement on the best approach for large, symptomatic meningoceles. Here, we discuss the case of a 41-year-old woman with NF1 who presented with dyspnea and enlargement of a large, 19 cm thoracic meningocele. A multidisciplinary team of thoracic, plastic, and neurological surgery participated in the operation to excise the meningocele and reconstruct the dural tube without the need for subsequent shunting of spinal fluid. We also systematically review the literature on thoracic meningoceles in NF1 to understand the optimal treatment of this pathology.

Fenestrated pedicle screws for thoracolumbar instrumentation in patients with poor bone quality: Case series and systematic review of the literature.

OBJECTIVE: To describe the results of a single-surgeon series and systematically review the literature on cement-augmented instrumented fusion with fenestrated pedicle screws. METHODS: All patients treated by the senior surgeon using fenestrated screws between 2017 and 2019 with a minimum of 6-months of clinical and radiographic follow-up were included. For the systematic review, we used PRISMA guidelines to identify all prior descriptions of cement-augmented instrumented fusion with fenestrated pedicle screws in the English literature. Endpoints of interest included hardware loosening, cement leakage, and pulmonary cement embolism (PCE). RESULTS: Our series included 38 patients (mean follow-up 14.8 months) who underwent cement-augmented instrumentation for tumor (47.3%), deformity/degenerative disease (39.5%), or osteoporotic fracture (13.2%). Asymptomatic screw lucency was seen in 2.6%, cement leakage in 445, and pulmonary cement embolism (PCE) in 5.2%. Our literature review identified 23 studies (n = 1526 patients), with low reported rates of hardware loosening (0.2%) and symptomatic PCE (1.0%). Cement leakage, while common (55.6%), produced symptoms in fewer than 1% of patients. Indications for cement-augmentation in this cohort included: spine metastasis with or without pathologic fracture (n = 18; 47.3%), degenerative spine disease or fixed deformity with poor underlying bone quality (n = 15; 39.5%), and osteoporotic fracture (n = 5; 13.2%). CONCLUSION: Cement-augmented fusion with fenestrated screws appears to be a safe, effective means of treating patients with poor underlying bone quality secondary to tumor or osteoporosis. High-quality evidence with direct comparisons to non-augmented patients is needed.

Utility of prediction model score: a proposed tool to standardize the performance and generalizability of clinical predictive models based on systematic review.

OBJECTIVE: The objective of this study was to evaluate the characteristics and performance of current prediction models in the fields of spine metastasis and degenerative spine disease to create a scoring system that allows direct comparison of the prediction models. METHODS: A systematic search of PubMed and Embase was performed to identify relevant studies that included either the proposal of a prediction model or an external validation of a previously proposed prediction model with 1-year outcomes. Characteristics of the original study and discriminative performance of external validations were then assigned points based on thresholds from the overall cohort. RESULTS: Nine prediction models were included in the spine metastasis category, while 6 prediction models were included in the degenerative spine category. After assigning the proposed utility of prediction model score to the spine metastasis prediction models, only 1 reached the grade of excellent, while 2 were graded as good, 3 as fair, and 3 as poor. Of the 6 included degenerative spine models, 1 reached the excellent grade, while 3 studies were graded as good, 1 as fair, and 1 as poor. CONCLUSIONS: As interest in utilizing predictive analytics in spine surgery increases, there is a concomitant increase in the number of published prediction models that differ in methodology and performance. Prior to applying these models to patient care, these models must be evaluated. To begin addressing this issue, the authors proposed a grading system that compares these models based on various metrics related to their original design as well as internal and external validation. Ultimately, this may hopefully aid clinicians in determining the relative validity and usability of a given model.

Clinical utility of enhanced recovery after surgery pathways in pediatric spinal deformity surgery: systematic review of the literature.

OBJECTIVES: More than 7500 children undergo surgery for scoliosis each year, at an estimated annual cost to the health system of $1.1 billion. There is significant interest among patients, parents, providers, and payors in identifying methods for delivering quality outcomes at lower costs. Enhanced recovery after surgery (ERAS) protocols have been suggested as one possible solution. Here the authors conducted a systematic review of the literature describing the clinical and economic benefits of ERAS protocols in pediatric spinal deformity surgery. METHODS: The authors identified all English-language articles on ERAS protocol use in pediatric spinal deformity surgery by using the following databases: PubMed/MEDLINE, Web of Science, Cochrane Reviews, EMBASE, CINAHL, and OVID MEDLINE. Quantitative analyses of comparative articles using random effects were performed for the following clinical outcomes: 1) length of stay (LOS); 2) complication rate; 3) wound infection rate; 4) 30-day readmission rate; 5) reoperation rate; and 6) postoperative pain scores. RESULTS: Of 950 articles reviewed, 7 were included in the qualitative analysis and 6 were included in the quantitative analysis. The most frequently cited benefits of ERAS protocols were shorter LOS, earlier urinary catheter removal, and earlier discontinuation of patient-controlled analgesia pumps. Quantitative analyses showed ERAS protocols to be associated with shorter LOS (mean difference -1.12 days; 95% CI -1.51, -0.74; p < 0.001), fewer postoperative complications (OR 0.37; 95% CI 0.20, 0.68; p = 0.001), and lower pain scores on postoperative day (POD) 0 (mean -0.92; 95% CI -1.29, -0.56; p < 0.001) and POD 2 (-0.61; 95% CI -0.75, -0.47; p < 0.001). There were no differences in reoperation rate or POD 1 pain scores. ERAS-treated patients had a trend toward higher 30-day readmission rates and earlier discontinuation of patient-controlled analgesia (both p = 0.06). Insufficient data existed to reach a conclusion about cost differences. CONCLUSIONS: The results of this systematic review suggest that ERAS protocols may shorten hospitalizations, reduce postoperative complication rates, and reduce postoperative pain scores in children undergoing scoliosis surgery. Publication biases exist, and therefore larger, prospective, multicenter data are needed to validate these results.

To operate, or not to operate? Narrative review of the role of survival predictors in patient selection for operative management of patients with metastatic spine disease.

Accurate prediction of patient survival is an essential component of the preoperative evaluation of patients with spinal metastases. Over the past quarter of a century, a number of predictors have been developed, although none have been accurate enough to be instituted as a staple of clinical practice. However, recently more comprehensive survival calculators have been published that make use of larger data sets and machine learning to predict postoperative survival among patients with spine metastases. Given the glut of calculators that have been published, the authors sought to perform a narrative review of the current literature, highlighting existing calculators along with the strengths and weaknesses of each. In doing so, they identify two "generations" of scoring systems-a first generation based on a priori factor weighting and a second generation comprising predictive tools that are developed using advanced statistical modeling and are focused on clinical deployment. In spite of recent advances, the authors found that most predictors have only a moderate ability to explain variation in patient survival. Second-generation models have a greater prognostic accuracy relative to first-generation scoring systems, but most still require external validation. Given this, it seems that there are two outstanding goals for these survival predictors, foremost being external validation of current calculators in multicenter prospective cohorts, as the majority have been developed from, and internally validated within, the same single-institution data sets. Lastly, current predictors should be modified to incorporate advances in targeted systemic therapy and radiotherapy, which have been heretofore largely ignored.

Skull Base 3D Modeling of Rigid Buttress for Gasket-Seal Closure Using Operative Endoscopic Imaging: Cadaveric Feasibility.

Surgical defect closure following endonasal transsphenoidal tumor resection is a critical component of procedural success. Three-dimensional (3D) modeling of relevant skull base anatomy during resection can potentially facilitate design of a custom rigid buttress for gasket-seal closure; however, access to conventional cross-sectional imaging intraoperatively is limited and cumbersome. Endoscopic imaging, by contrast, is always available. This work demonstrates the feasibility of 3D modeling of the visible skull base through structure-from-motion photogrammetric postprocessing techniques, providing a suitable template to design a gasket-seal buttress. Additionally, endoscopic 3D reconstruction of skull base surface anatomy may represent a more robust depiction of the surgical defect than is available by conventional 3D modeling with computed tomography, which suboptimally recapitulates very thin bones and mucosal surfaces typical of this regional anatomy.

The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.

RATIONALE: Synthetic cathinones continue to emerge in recreational drug markets worldwide. 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone) and 1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone) are derivatives of the cathinone compound, 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (methylone), that are being detected in drug products and human casework. OBJECTIVES: The purpose of the present study was to examine the neuropharmacology of butylone and pentylone using in vitro and in vivo methods. METHODS: In vitro uptake and release assays were carried out in rat brain synaptosomes and in cells expressing human dopamine transporters (DAT) and 5-HT transporters (SERT). In vivo microdialysis was performed in the nucleus accumbens of conscious rats to assess drug-induced changes in neurochemistry. RESULTS: Butylone and pentylone were efficacious uptake blockers at DAT and SERT, though pentylone was more DAT-selective. Both drugs acted as transporter substrates that evoked release of [3H]5-HT at SERT, while neither evoked release at DAT. Consistent with the release data, butylone and pentylone induced substrate-associated inward currents at SERT but not DAT. Administration of butylone or pentylone to rats (1 and 3 mg/kg, i.v.) increased extracellular monoamines and motor activity, but pentylone had weaker effects on 5-HT and stronger effects on motor stimulation. CONCLUSIONS: Our data demonstrate that increasing the α-carbon chain length of methylone creates "hybrid" transporter compounds which act as DAT blockers but SERT substrates. Nevertheless, butylone and pentylone elevate extracellular dopamine and stimulate motor activity, suggesting both drugs possess significant risk for abuse.