Timing of diffusion tensor imaging in the management of a ruptured pediatric arteriovenous malformation: illustrative case.

BACKGROUND: Diffusion tensor imaging (DTI) can characterize eloquent white matter tracts affected by brain arteriovenous malformations (AVMs). However, DTI interpretation can be difficult in ruptured cases due to the presence of blood products. The authors present the case of a ruptured pediatric AVM in the corticospinal tract (CST) and discuss how DTI at different time points informed the treatment. OBSERVATIONS: A 9-year-old female presented with a sudden headache and left hemiparesis. She was found to have a Spetzler-Martin grade III, Supplementary grade I AVM in the right caudate and centrum semiovale, with obliteration and corresponding reduced fractional anisotropy (FA), fiber density (FD), and tract count (TC) of the adjacent CST on DTI. The patient remained stable and was scheduled for elective resection following a 6-week period to facilitate hematoma resorption. After 6 weeks, repeat DTI showed part of the nidus within intact CST fibers with concordant improvement in FA, FD, and TC. Considering the nidus location, CST integrity, and motor function recovery, surgery was deferred in favor of stereotactic radiosurgery. LESSONS: In ruptured AVMs, DTI may initially create an incomplete picture and false assumptions about white matter tract integrity. DTI should be repeated if delayed treatment is appropriate to ensure informed decision-making and prevent avoidable permanent neurological deficits. https://thejns.org/doi/10.3171/CASE24225.

Control of Eating Attributes and Weight Loss Outcomes over One Year After Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) is a commonly performed metabolic-bariatric surgery, but its effectiveness is variable and difficult to predict. Our study aimed to compare control of eating (CoE) attributes pre- and post-SG depending on the achievement of optimal weight loss target at 1 year post-SG. MATERIALS AND METHODS: A prospective longitudinal cohort study using the CoE Questionnaire, pre-SG, and postoperatively at 3, 6, and 12 months was conducted. Total weight loss (TWL) ≥ 25% at 12 months post-SG was set as an optimal weight loss target. RESULTS: Forty-one patients (80.5% females, mean age 41.7 ± 10.6) were included. Sex, age, baseline weight, BMI, and smoking status were all comparable. At 3 months post-SG, "difficulty to control eating" score became significantly different between ≥ 25%TWL and < 25%TWL groups (7 [0-50] vs. 17 [5-63], p = 0.042). At 6 months, it was followed by "feeling of fullness," "frequency of food cravings," and "difficulty to resist cravings" demonstrating significant differences between ≥ 25%TWL and < 25%TWL groups. At 12 months, significant differences between groups were observed in "feeling hungry," "difficulty to resist cravings," "eating in response to cravings," and difficulty to control eating scores. CONCLUSION: Individuals with obesity who achieved a target of ≥ 25%TWL at 1 year post-SG have an early improvement in overall eating control at 3 months that steadily persists at 6 and 12 months. Improvements in other aspects tend to follow later, at 6 and 12 months. These findings may assist in identifying individuals with inadequate response to help attain optimal weight loss targets and developing a prognostic model to identify predictors of successful weight loss.

Neurosurgical Outcomes for Pediatric Central Nervous System Tumors in the United States.

BACKGROUND: Limited data exist on pediatric central nervous system (CNS) tumors, and the results from the National Cancer Database, the largest multicenter national cancer registry, have not previously been comprehensively reported. OBJECTIVE: To capture pediatric neurosurgical outcomes and investigate possible disparities of care. METHODS: The National Cancer Database was queried for pediatric patients who were diagnosed with CNS tumors from 2004 to 2018. Primary outcomes included 30/90 days postoperative mortality (30M/90M), readmission within 30 days of discharge (30R), and length of inpatient stay (LOS). RESULTS: Twenty four thousand nine hundred thirty cases met the inclusion criteria, of which were 4753 (19.1%) juvenile pilocytic astrocytomas, 3262 (13.1%) medulloblastomas, 2200 (8.8%) neuronal/mixed neuronal-glial tumors, and 2135 (8.6%) ependymal tumors. Patients aged 0 to 4 years had significantly poorer outcomes than patients in older age groups (90M: 3.5% vs 0.7%-0.9%; 30R: 6.5% vs 3.6%-4.8%; LOS: 12.0 days vs 6.0-8.9 days). Tumor size was a strong predictor of poor outcomes with each additional cm in diameter conferring a 26%, 7%, and 23% increased risk of 90M, 30R, and prolonged LOS, respectively. Data over the study period demonstrated year over year improvements of 4%, 3%, and 2%, respectively, for 90M, 30R, and prolonged LOS. Facilities with a high volume of pediatric tumor cases had improved 90M (1.1% vs 1.5%, P = .041) and LOS (7.6 vs 8.6 days, P < .001). Patients with private health insurance had better outcomes than patients with government insurance. CONCLUSION: There is substantial variability in surgical morbidity and mortality of pediatric CNS tumors. Additional investigation is warranted to reduce outcome differences that may be based on socioeconomic factors.

Advances and Clinical Trials Update in the Treatment of Diffuse Intrinsic Pontine Gliomas.

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) are high-grade gliomas (HGGs) that occur primarily in children, and represent a leading cause of death in pediatric patients with brain tumors with a median overall survival of only 8-11 months. SUMMARY: While these lesions were previously thought to behave similarly to adult HGG, emerging data have demonstrated that DIPG is a biologically distinct entity from adult HGG frequently driven by mutations in the histone genes H3.3 and H3.1 not found in adult glioma. While biopsy of DIPG was historically felt to confer unacceptable risk of morbidity and mortality, multiple studies have demonstrated that stereotactic biopsy of DIPG is safe, allowing not only for improved understanding of DIPG but also forming the basis for protocols for personalized medicine in DIPG. However, current options for personalized medicine in DIPG are limited by the lack of efficacious targeted therapies for the mutations commonly found in DIPG. Multiple treatment modalities including targeted therapies, immunotherapy, convection-enhanced delivery, and focused ultrasound are in various stages of investigation. KEY MESSAGE: Increasing frequency of biopsy for DIPG has identified distinct driving mutations that may serve as therapeutic targets. Novel treatment modalities are under investigation.

Supervised machine learning algorithms demonstrate proliferation index correlates with long-term recurrence after complete resection of WHO grade I meningioma.

OBJECTIVE: Meningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas. METHODS: The authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence. RESULTS: The cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%-99.9%), 91.0% (95% CI 87.7%-93.6%), 83.6% (95% CI 78.6%-87.6%), and 77.3% (95% CI 69.7%-83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13-1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03-1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors with an MIB-1 index < 8, recurrences were documented up to 8 years after surgery. For tumors with an MIB-1 index ≥ 8, recurrences were documented up to 12 years following surgery. CONCLUSIONS: Long-term imaging follow-up is important even after a complete resection of a meningioma. Higher MIB-1 labeling index is associated with greater risk of recurrence. Imaging screening for at least 8 years in patients with an MIB-1 index < 8 and at least 12 years for those with an MIB-1 index ≥ 8 may be needed to detect long-term recurrences.

Combined retropleural thoracotomy and posterior spinal approach for thoracic dumbbell Schwannoma: Case series and review of the literature.

BACKGROUND: Dumbbell schwannomas of the thoracic spine are challenging to cure surgically. Surgeons are familiar with posterolateral approaches to the spine, however, these may provide inadequate exposure for large tumors extending to ventral extraspinal compartments. Ventrolateral transpleural approaches offer direct access to the ventral thoracic spine and intrathoracic cavity, though are associated with increased morbidity and pulmonary complications, and may necessitate a staged procedure in order to address concomitant dorsal pathology. Herein we describe our experience with single-stage, posterior approach to dumbbell schwannomas with large ventral extraspinal components, and review the literature regarding surgical approaches for these tumors. METHODS: Retrospective review of patients who underwent a single-stage, posterior spinal surgery for thoracic dumbbell schwannomas from 2008 to 2018. Inclusion criteria were age > 18 years and ventral thoracic tumor component. RESULTS: Three patients underwent a simultaneous retropleural thoracotomy and posterior spinal approach, through a single incision, for the resection of dumbbell (intradural and extradural) schwannomas. Mean age was 49.7 years and 2 patients were female. All patients were neurologically intact at baseline. Lesions were 4-8.2 cm in the largest dimension (mean 6.1 cm). GTR was achieved in all patients. One pleural rent occurred intraoperatively; there were no other intraoperative or perioperative complications. At a mean follow-up of 14.1 months all patients remained motor and sensory intact and there was no evidence of recurrence. CONCLUSIONS: The combined retropleural thoracotomy-posterior spinal approach provides safe and sufficient access for resection of large dumbbell schwannomas of the thoracic spine.

The Hybrid Operative Suite with Intraoperative Biplane Rotational Angiography in Pediatric Cerebrovascular Neurosurgery: Utility and Lessons Learned.

INTRODUCTION: The benefits of performing open and endovascular procedures in a hybrid neuroangiography surgical suite include confirmation of treatment results and reduction in number of procedures, leading to improved efficiency of care. Combined procedural suites are infrequently used in pediatric facilities due to technical and logistical limitations. We report the safety, utility, and lessons learned from a single-institution experience using a hybrid suite equipped with biplane rotational digital subtraction angiography and pan-surgical capabilities. METHODS: We conducted a retrospective review of consecutive cases performed at our institution that utilized the hybrid neuroangiography surgical suite from February 2020 to August 2021. Demographics, surgical metrics, and imaging results were collected from the electronic medical record. Outcomes, interventions, and nuances for optimizing preoperative/intraoperative setup and postoperative care were presented. RESULTS: Eighteen procedures were performed in 17 patients (mean age 13.4 years, range 6-19). Cases included 14 arteriovenous malformations (AVM; 85.7% ruptured), one dural arteriovenous fistula, one mycotic aneurysm, and one hemangioblastoma. The average operative time was 416 min (range 321-745). There were no intraoperative or postoperative complications. All patients were alive at follow-up (range 0.1-14.7 months). Five patients had anticipated postoperative deficits arising from their hemorrhage, and 12 returned to baseline neurological status. Four illustrative cases demonstrating specific, unique applications of the hybrid angiography suite are presented. CONCLUSION: The hybrid neuroangiography surgical suite is a safe option for pediatric cerebrovascular pathologies requiring combined surgical and endovascular intervention. Hybrid cases can be completed within the same anesthesia session and reduce the need for return to the operating room for resection or surveillance angiography. High-quality intraoperative angiography enables diagnostic confirmation under a single procedure, mitigating risk of morbidity and accelerating recovery. Effective multidisciplinary planning enables preoperative angiograms to be completed to inform the operative plan immediately prior to definitive resection.

Association of Neurological Impairment on the Relative Benefit of Maximal Extent of Resection in Chemoradiation-Treated Newly Diagnosed Isocitrate Dehydrogenase Wild-Type Glioblastoma.

BACKGROUND: Increases in the extent of resection of both contrast-enhanced (CE) and non-contrast-enhanced (NCE) tissue are associated with substantial survival benefits in patients with isocitrate dehydrogenase wild-type glioblastoma. The fact, however, remains that these lesions exist within the framework of complex neural circuitry subserving cognition, movement, and behavior, all of which affect the ultimate survival outcome. The prognostic significance of the interplay between CE and NCE cytoreduction and neurological morbidity is poorly understood. OBJECTIVE: To identify a clinically homogenous population of 228 patients with newly diagnosed isocitrate dehydrogenase wild-type glioblastoma, all of whom underwent maximal safe resection of CE and NCE tissue and adjuvant chemoradiation. We then set out to delineate the competing interactions between resection of CE and NCE tissue and postoperative neurological impairment with respect to overall survival. METHODS: Nonparametric multivariate models of survival were generated via recursive partitioning to provide a clinically intuitive framework for the prognostication and surgical management of such patients. RESULTS: We demonstrated that the presence of a new postoperative neurological impairment was the key factor in predicting survival outcomes across the entire cohort. Patients older than 60 yr who suffered from at least one new impairment had the worst survival outcome regardless of extent of resection (median of 11.6 mo), whereas those who did not develop a new impairment had the best outcome (median of 28.4 mo) so long as all CE tissue was resected. CONCLUSION: Our data provide novel evidence for management strategies that prioritize safe and complete resection of CE tissue.

A single institution retrospective analysis on survival based on treatment paradigms for patients with anaplastic oligodendroglioma.

INTRODUCTION: Anaplastic oligodendrogliomas are high-grade gliomas defined molecularly by 1p19q co-deletion. There is no curative therapy, and standard of care includes surgical resection followed by radiation and chemotherapy. However, the benefit of up-front radiation with chemotherapy compared to chemotherapy alone has not been demonstrated in a randomized control trial. Given the potential long-term consequences of radiation therapy, such as cognitive impairment, arteriopathy, endocrinopathy, and hearing/visual impairment, there is an effort to balance longevity with radiation toxicity. METHODS: We performed a retrospective single institution analysis of survival of patients with anaplastic oligodendroglioma over 20 years. RESULTS: 159 patients were identified as diagnosed with an anaplastic oligodendroglioma between 1996 and 2016. Of those, 40 patients were found to have AO at original diagnosis and had documented 1p19q co-deletion with a median of 7.1 years of follow-up (range: 0.6-16.7 years). After surgery, 45 % of patients were treated with radiation and chemotherapy at diagnosis, and 50 % were treated with adjuvant chemotherapy alone. The group treated with chemotherapy alone had a trend of receiving more cycles of chemotherapy than patients treated with radiation and chemotherapy upfront (p = 0.051). Median overall survival has not yet been reached. The related risk of progression in the upfront, adjuvant chemotherapy only group was almost 5-fold higher than the patients who received radiation and chemotherapy (hazard ratio = 4.85 (1.74-13.49), p = 0.002). However, there was no significant difference in overall survival in patients treated with upfront chemotherapy compared to patients treated upfront with chemotherapy and radiation (p = 0.8). Univariate analysis of age, KPS, extent of resection, or upfront versus delayed radiation was not associated with improved survival. CONCLUSIONS: Initial treatment with adjuvant chemotherapy alone, rather than radiation and chemotherapy, may be an option for some patients with anaplastic oligodendroglioma, as it is associated with similar overall survival despite shorter progression free survival.

Elderly traumatic central cord syndrome in the USA: a review of management and outcomes.

INTRODUCTION: As the incidence of elderly spinal cord injury rises, improved understanding of risk profiles and outcomes is needed. This review summarizes clinical characteristics, management, and outcomes specific to the elderly (≥65-years) with acute traumatic central cord syndrome in the USA. EVIDENCE AQUISITION: Literature review of the PubMed, Embase, and CINAHL databases (01/2007-03/2020) regarding elderly subjects with acute traumatic central cord syndrome. EVIDENCE SYNTHESIS: Nine studies met inclusion criteria. Acute traumatic central cord syndrome was more common among married (50%), Caucasian (22-71%) males (63-86%) with an annual income <40,999 USA dollars (30%). Mechanisms consisted predominantly of traumatic falls (32-55%) and motor vehicle collisions (15-34%), with admission American Spinal Injury Association Impairment Scale grades D (25-79%) and C (21-51%). Mortality was 2-3%. American Spinal Injury Association Impairment Scale motor score, maximum canal compromise, and extent of parenchymal damage were predictors of one-year recovery. Greater comorbidities (heart failure, weight loss, coagulopathy, diabetes), lower income (<51,000 USA dollars), and age ≥80 were predictors of mortality. A substantial cohort underwent surgery (40-45%). Elderly patients were less likely to receive surgical intervention, and surgery timing had variable effects on recovery. CONCLUSIONS: Elderly patients with acute traumatic central cord syndrome are uniquely at risk due to cumulative comorbidities, protracted recovery times, and unclear effects of surgical timing on outcomes. Prospective research should focus on validating age-specific risk factors, formalizing surgical indications, and delineating the impact of time to surgery on acute and long-term outcomes for this condition.

RETRACTED: A subset of PARP inhibitors induces lethal telomere fusion in ALT-dependent tumor cells.

About 10% of all tumors, including most lower-grade astrocytoma, rely on the alternative lengthening of telomere (ALT) mechanism to resolve telomeric shortening and avoid limitations on their growth. Here, we found that dependence on the ALT mechanism made cells hypersensitive to a subset of poly(ADP-ribose) polymerase inhibitors (PARPi). We found that this hypersensitivity was not associated with PARPi-created genomic DNA damage as in most PARPi-sensitive populations but rather with PARPi-induced telomere fusion. Mechanistically, we determined that PARP1 was recruited to the telomeres of ALT-dependent cells as part of a DNA damage response. By recruiting MRE11 and BRCC3 to stabilize TRF2 at the ends of telomeres, PARP1 blocked chromosomal fusion. Exposure of ALT-dependent tumor cells to a subset of PARPi induced a conformational change in PARP1 that limited binding to MRE11 and BRCC3 and delayed release of the TRF2-mediated block on lethal telomeric fusion. These results therefore provide a basis for PARPi treatment of ALT-dependent tumors, as well as establish chromosome fusion as a biomarker of their activity.

Costs and utility of post-discharge acute inpatient rehabilitation following adult spinal deformity surgery.

PURPOSE: Evaluate costs and functional utility of post-discharge rehabilitation after surgery for adult spinal deformity (ASD). METHODS: Retrospective analysis of ASD patients who underwent operation at a single center and discharged to one rehabilitation facility. Operative details and costs were obtained for index inpatient encounter. Rehabilitation data included: direct costs, length of stay, and patient function, as assessed by Functional Independence Measure (FIM) instrument. RESULTS: Of 937 operations, 391 (41.7%) were discharged to rehabilitation. Ninety-patients (9.6%; 95 care episodes; average age 70.5 ± 10.6 years) were discharged to rehabilitation. Inpatient length of stay was 8.2 ± 2.6 days. Operative details: posterior levels fused 13.6 ± 3.6, PCOs/patient 7 ± 3.7, forty-two 3-column osteotomies, and 11 inter-body fusions. Direct costs were $90,738 ± $24,166 for index hospitalizations and $38,808 ± $14,752 for rehabilitation. Patients spent 11.7 ± 4.0 days in rehabilitation. Direct cost per day in hospital ($11,758 ± $3390) was significantly greater than rehabilitation ($3338 ± $2131) (p < 0.05). Significant improvements in function while in rehabilitation were observed (admit FIM: 66 ± 14 vs. discharge FIM: 94 ± 14). Charlson Comorbidity Index was the only independent predictor of rehabilitation direct costs. Conclusion Post-discharge inpatient rehabilitation following operations for ASD is associated with a direct cost of $38,808 per case. While rehabilitation resulted in significant functional improvements, it came at significant economic expense ($3.7 million) that accounted for 30% of costs for 95 episodes of care. For 100 operatively treated patients (assuming 41% discharge rate to rehab), rehabilitation results in an additional price premium of $1,674,872.

Evaluating the Clinical Utility and Cost of Imaging Strategies in Adults with Newly Diagnosed Primary Intradural Spinal Tumors.

OBJECTIVE: In patients with new primary intradural spinal tumors, the best screening strategy for additional central nervous system (CNS) lesions is unclear. The goal of this study was to document the rate of additional CNS tumors in these patients. METHODS: Adults with primary intradural spinal tumors were retrospectively reviewed. Imaging strategy at diagnosis was classified as focused spine (cervical, thoracic, or lumbar), total spine, or complete neuraxis (brain and total spine). Tumor pathology, genetic syndromes, and presence of additional CNS lesions at diagnosis or follow-up were collected. RESULTS: The study comprised 319 patients with mean age of 51 years and mean follow-up of 41 months. In 151 patients with focused spine imaging, 3 (2.0%) were found to have new lesions with 2 (1.4%) requiring treatment. In 35 patients with total spine imaging, there were no additional lesions. In 133 patients with complete neuraxis imaging, 4 (3.0%) were found to have new lesions with 2 (1.5%) requiring treatment. There was no difference in the identification of new lesions (P = 0.542) or new lesions requiring treatment (P = 0.772) across imaging strategies. Among patients without genetic syndromes, rates of new lesions requiring treatment were 1.4% for focused spine, 0% for total spine, and 2.2% for complete neuraxis (P = 0.683). There were no cases of delayed identification causing risk to life or neurological function. Complete neuraxis imaging carried an increased charge of $4420 per patient. CONCLUSIONS: Among patients without an underlying genetic syndrome, the likelihood of identifying additional CNS lesions requiring treatment is low. In appropriate cases, focused spine imaging may be a more cost-effective strategy.

Falcotentorial meningiomas.

Falcotentorial meningiomas are uncommon tumors that account for 1%-2% of all intracranial meningiomas. They arise at the junction of the falx cerebri and tentorium, from the entry of the vein of Galen posteriorly to the confluence of venous sinuses. Treatment for these tumors depends on patient and tumor factors. Tumor factors include size of the tumor, patency of the straight sinus, and the amount of tumor above and/or below the tentorium. This chapter reviews the clinical presentation, imaging features, treatment options, and results.

Hyperostosing sphenoid wing meningiomas: surgical outcomes and strategy for bone resection and multidisciplinary orbital reconstruction.

OBJECTIVE: Hyperostosing sphenoid wing meningiomas cause bony hyperostosis that may extend into the orbit, resulting in proptosis, restriction of extraocular movements, and/or compressive optic neuropathy. The extent of bony removal necessary and the optimal reconstruction strategy to prevent enophthalmos is debated. Herein, the authors present their surgical outcomes and reconstruction results. METHODS: This is a retrospective review of 54 consecutive patients undergoing resection of sphenoid wing meningiomas associated with bony hyperostosis. The majority of cases were operated on by the senior author. Extent of tumor resection, volumetric bone resection, radiographic exophthalmos index, complications, and recurrence were analyzed. RESULTS: The median age of the cohort was 52.1 years, with women comprising 83% of patients. Proptosis was a presenting symptom in 74%, and 52% had decreased visual acuity. The WHO grade was I (85%) or II (15%). The median follow-up was 2.6 years. On volumetric analysis, a median 86% of hyperostotic bone was resected. Gross-total resection of the intracranial tumor was achieved in 43% and the orbital tumor in 27%, and of all intracranial and orbital components in 20%. Orbital reconstruction was performed in 96% of patients. Postoperative vision was stable or improved in 98% of patients and diplopia improved in 89%. Postoperative complications occurred in 44% of patients, and 26% of patients underwent additional surgery for complication management. The most frequent complications were medical complications and extraocular movement deficits. The median preoperative exophthalmos index was 1.26, which improved to 1.12 immediately postoperatively and to 1.09 at the 6-month follow-up (p < 0.001). Postoperatively, 18 patients (33%) underwent adjuvant radiotherapy after subtotal resection. Tumors recurred/progressed in 12 patients (22%). CONCLUSIONS: Resection of hyperostosing sphenoid wing meningiomas, particularly achieving gross-total resection of hyperostotic bone with a good aesthetic result, is challenging and associated with notable medical and ocular morbidity. Recurrence rates in this series are higher than previously reported. Nevertheless, the authors were able to attain improvement in proptosis and visual symptoms in the majority of patients by using a multidisciplinary approach.

Polytrauma Is Associated with Increased Three- and Six-Month Disability after Traumatic Brain Injury: A TRACK-TBI Pilot Study.

Polytrauma and traumatic brain injury (TBI) frequently co-occur and outcomes are routinely measured by the Glasgow Outcome Scale-Extended (GOSE). Polytrauma may confound GOSE measurement of TBI-specific outcomes. Adult patients with TBI from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study had presented to a Level 1 trauma center after injury, received head computed tomography (CT) within 24 h, and completed the GOSE at 3 months and 6 months post-injury. Polytrauma was defined as an Abbreviated Injury Score (AIS) ≥3 in any extracranial region. Univariate regressions were performed using known GOSE clinical cutoffs. Multi-variable regressions were performed for the 3- and 6-month GOSE, controlling for known demographic and injury predictors. Of 361 subjects (age 44.9 ± 18.9 years, 69.8% male), 69 (19.1%) suffered polytrauma. By Glasgow Coma Scale (GCS) assessment, 80.1% had mild, 5.8% moderate, and 14.1% severe TBI. On univariate logistic regression, polytrauma was associated with increased odds of moderate disability or worse (GOSE ≤6; 3 month odds ratio [OR] = 2.57 [95% confidence interval (CI): 1.50-4.41; 6 month OR = 1.70 [95% CI: 1.01-2.88]) and death/severe disability (GOSE ≤4; 3 month OR = 3.80 [95% CI: 2.03-7.11]; 6 month OR = 3.33 [95% CI: 1.71-6.46]). Compared with patients with isolated TBI, more polytrauma patients experienced a decline in GOSE from 3 to 6 months (37.7 vs. 24.7%), and fewer improved (11.6 vs. 22.6%). Polytrauma was associated with greater univariate ordinal odds for poorer GOSE (3 month OR = 2.79 [95% CI: 1.73-4.49]; 6 month OR = 1.73 [95% CI: 1.07-2.79]), which was conserved on multi-variable ordinal regression (3 month OR = 3.05 [95% CI: 1.76-5.26]; 6 month OR = 2.04 [95% CI: 1.18-3.42]). Patients with TBI with polytrauma are at greater risk for 3- and 6-month disability compared with those with isolated TBI. Methodological improvements in assessing TBI-specific disability, versus disability attributable to all systemic injuries, will generate better TBI outcomes assessment tools.

Applicability of cervical sagittal vertical axis, cervical lordosis, and T1 slope on pain and disability outcomes after anterior cervical discectomy and fusion in patients without deformity.

OBJECTIVE: Understanding what influences pain and disability following anterior cervical discectomy and fusion (ACDF) in patients with degenerative cervical spine disease is critical. This study examines the timing of clinical improvement and identifies factors (including spinal alignment) associated with worse outcomes. METHODS: Consecutive adult patients were enrolled in a prospective outcomes database from two academic centers participating in the Quality Outcomes Database from 2013 to 2016. Demographics, surgical details, radiographic data, arm and neck pain (visual analog scale [VAS] scores), and disability (Neck Disability Index [NDI] and EQ-5D scores) were reviewed. Multivariate analysis was used. RESULTS: A total of 186 patients were included, and 48.4% were male. Their mean age was 55.4 years, and 45.7% had myelopathy. Preoperative cervical sagittal vertical axis (cSVA), cervical lordosis (CL), and T1 slope values were 24.9 mm (range 0-55 mm), 10.4° (range -6.0° to 44°), and 28.3° (range 14.0°-51.0°), respectively. ACDF was performed at 1, 2, and 3 levels in 47.8%, 42.0%, and 10.2% of patients, respectively. Preoperative neck and arm VAS scores were 5.7 and 5.4, respectively. NDI and EQ-5D scores were 22.1 and 0.5, respectively. There was significant improvement in all outcomes at 3 months (p < 0.001) and 12 months (p < 0.001). At 3 months, neck VAS (3.0), arm VAS (2.2), NDI (12.7), and EQ-5D (0.7) scores were improved, and at 12 months, neck VAS (2.8), arm VAS (2.3), NDI (11.7), and EQ-5D (0.8) score improvements were sustained. Improvements occurred within the first 3-month period; there was no significant difference in outcomes between the 3-month and 12-month mark. There was no correlation among cSVA, CL, or T1 slope with any outcome endpoint. The most consistent independent preoperative factors associated with worse outcomes were high neck and arm VAS scores and a severe NDI result (p < 0.001). Similar findings were seen with worse NDI and EQ-5D scores (p < 0.001). A significant linear trend of worse NDI and EQ-5D scores at 3 and 12 months was associated with worse baseline scores. Of the 186 patients, 171 (91.9%) had 3-month follow-up data, and 162 (87.1%) had 12-month follow-up data. CONCLUSIONS: ACDF is effective in improving pain and disability, and improvement occurs within 3 months of surgery. cSVA, CL, and T1 slope do not appear to influence outcomes following ACDF surgery in the population with degenerative cervical disease. Therefore, in patients with relatively normal cervical parameters, augmenting alignment or lordosis is likely unnecessary. Worse preoperative pain and disability were independently associated with worse outcomes.

Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications.

Initial studies on cancer primarily focused on malignant cells themselves. The overarching narrative of cancer revolved around unchecked and rapidly proliferating cells. Special attention was given to the molecular, genetic, and metabolic profiles of isolated cancer cells in hopes of elucidating a critical factor in malignancy. However, the scope of cancer research has broadened over the past few decades to include the local environment around cancer. It has become increasingly apparent that the immune cells, vascular networks, and the extracellular matrix all have a part in cancer progression. The impact of the extracellular matrix is particularly fascinating and key stromal changes have been identified in various cancers. Pioneering work studying laminin and hyaluronate has shown that these molecules have vital roles in cancer progression. More recently, fibronectin has been included as an extracellular driver of malignancy. Fibronectin is thought to play a considerable, albeit poorly understood, role in cancer pathogenesis. In this review, we present fundamental studies that have investigated the impact of fibronectin in cancer. As an abundant component of the extracellular matrix, understanding the effect of this molecule has the potential to elucidate cancer biology.

Systemic therapy for brain metastases.

Metastases from cells outside of the central nervous system are the most common cancer found in the brain and are commonly associated with poor prognosis. Although cancer treatment is improving overall, central nervous system metastases are becoming more prevalent and require finesse to properly treat. Physicians must consider the biology of the primary tumor and the complex neurological environment that the metastasis resides in. This can be further complicated by the fact that the practice of cancer management is constantly evolving and therapy that works outside of the blood-brain barrier may not be effective inside of it. Therefore, this review seeks to update the reader on recent advancements made on the three most common sources of brain metastases: lung cancer, breast cancer, and melanoma. Each of these malignancies has been the subject of intriguing and novel avenues of therapy which are reviewed here.