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.

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.

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.

Fertility treatment is associated with multiple meningiomas and younger age at diagnosis.

PURPOSE: Meningiomas are more common in females and 70-80% express the progesterone receptor, raising the possibility that high-dose exogenous estrogen/progesterone exposure, such as occurs during fertility treatments, may increase the risk of developing a meningioma. The goal of this study was to report the incidence of prior fertility treatment in a consecutive series of female meningioma patients. METHODS: A retrospective review (2015-2018) was performed of female patients with meningioma, and those with prior fertility treatment were compared to those without fertility treatment using standard statistical methods. RESULTS: Of 206 female patients with meningioma, 26 (12.6%) had a history of fertility treatments. Patients underwent various forms of assisted reproductive technology including: in vitro fertilization (50.0%), clomiphene with or without intrauterine insemination (34.6%), and unspecified (19.2%). Median follow up was 1.8 years. Tumors were WHO grade I (78.6%) or grade II (21.4%). Patients who underwent fertility treatments presented at significantly younger mean age compared to those who had not (51.8 vs. 57.3 years, p = 0.0135, 2-tailed T-test), and on multivariate analysis were more likely to have multiple meningiomas (OR 4.97, 95% CI 1.4-18.1, p = 0.0154) and convexity/falx meningiomas (OR 4.45, 95% CI 1.7-11.5, p = 0.0021). CONCLUSIONS: Patients in this cohort with a history of fertility treatment were more likely to present at a younger age and have multiple and convexity/falx meningiomas, emphasizing the importance of taking estrogen/progesterone exposure history when evaluating patients with meningioma. Future clinical studies at other centers in larger populations and laboratory investigations are needed to determine the role of fertility treatment in meningioma development.

Value of aggressive surgical and intensive care unit in elderly patients with traumatic spinal cord injury.

OBJECTIVEThe elderly are a growing subpopulation within traumatic spinal cord injury (SCI) patients. Studies have reported high morbidity and mortality rates in elderly patients who undergo surgery for SCI. In this study, the authors compare the perioperative outcomes of surgically managed elderly SCI patients with those of a younger cohort and those reported in the literature.METHODSData on a consecutive series of adult traumatic SCI patients surgically managed at a single institution in the period from 2007 to 2017 were retrospectively reviewed. The cohort was divided into two groups based on age: younger than 70 years and 70 years or older. Assessed outcomes included complications, in-hospital mortality, intensive care unit (ICU) stay, hospital length of stay (LOS), disposition, and neurological status.RESULTSA total of 106 patients were included in the study: 83 young and 23 elderly. The two groups were similar in terms of imaging features (cord hemorrhage and fracture), operative technique, and American Spinal Injury Association Impairment Scale (AIS) grade. The elderly had a significantly higher proportion of cervical SCIs (95.7% vs 71.1%, p = 0.047). There were no significant differences between the young and the elderly in terms of the ICU stay (13.1 vs 13.3 days, respectively, p = 0.948) and hospital LOS (23.3 vs 21.7 days, p = 0.793). Elderly patients experienced significantly higher complication (73.9% vs 43.4%, p = 0.010) and mortality (13.0% vs 1.2%, p = 0.008) rates; in other words, the elderly patients had 1.7 times and 10.8 times the rate of complications and mortality, respectively, than the younger patients. No elderly patients were discharged home (0.0% vs 18.1%, p = 0.029). Discharge AIS grade and AIS grade change were similar between the groups.CONCLUSIONSElderly patients had higher complication and mortality rates than those in younger patients and were less likely to be discharged home. However, it does seem that mortality rates have improved compared to those in prior historical reports.

The unreimbursed costs of preventing revision surgery in adult spinal deformity: analysis of cost-effectiveness of proximal junctional failure prevention with ligament augmentation.

OBJECTIVE Proximal junctional kyphosis (PJK) is a well-recognized complication of surgery for adult spinal deformity and is characterized by increased kyphosis at the upper instrumented vertebra (UIV). PJK prevention strategies have the potential to decrease morbidity and cost by reducing rates of proximal junctional failure (PJF), which the authors define as radiographic PJK plus clinical sequelae requiring revision surgery. METHODS The authors performed an analysis of 195 consecutive patients with adult spinal deformity. Age, sex, levels fused, upper instrumented vertebra (UIV), use of 3-column osteotomy, pelvic fixation, and mean time to follow-up were collected. The authors also reviewed operative reports to assess for the use of surgical adjuncts targeted toward PJK prevention, including ligament augmentation, hook fixation, and vertebroplasty. The cost of surgery, including direct and total costs, was also assessed at index surgery and revision surgery. Only revision surgery for PJF was included. RESULTS The mean age of the cohort was 64 years (range 25-84 years); 135 (69%) patients were female. The mean number of levels fused was 10 (range 2-18) with the UIV as follows: 2 cervical (1%), 73 upper thoracic (37%), 108 lower thoracic (55%), and 12 lumbar (6%). Ligament augmentation was used in 99 cases (51%), hook fixation in 60 cases (31%), and vertebroplasty in 71 cases (36%). PJF occurred in 18 cases (9%). Univariate analysis found that ligament augmentation and hook fixation were associated with decreased rates of PJF. However, in a multivariate model that also incorporated age, sex, and UIV, only ligament augmentation maintained a significant association with PJF reduction (OR 0.196, 95% CI 0.050-0.774; p = 0.020). Patients with ligament augmentation, compared with those without, had a higher cost of index surgery, but ligament augmentation was overall cost effective and produced significant cost savings. In sensitivity analyses in which we independently varied the reduction in PJF, cost of ligament augmentation, and cost of reoperation by ± 50%, ligament augmentation remained a cost-effective strategy for PJF prevention. CONCLUSIONS Prevention strategies for PJK/PJF are limited, and their cost-effectiveness has yet to be established. The authors present the results of 195 patients with adult spinal deformity and show that ligament augmentation is associated with significant reductions in PJF in both univariate and multivariate analyses, and that this intervention is cost-effective. Future studies will need to determine if these clinical results are reproducible, but for high-risk cases, these data suggest an important role of ligament augmentation for PJF prevention and cost savings.

Disparities in health care determine prognosis in newly diagnosed glioblastoma.

OBJECTIVE Glioblastoma (GBM) is an aggressive brain malignancy with a short overall patient survival, yet there remains significant heterogeneity in outcomes. Although access to health care has previously been linked to impact on prognosis in several malignancies, this question remains incompletely answered in GBM. METHODS This study was a retrospective analysis of 354 newly diagnosed patients with GBM who underwent first resection at the authors' institution (2007-2015). RESULTS Of the 354 patients (median age 61 years, and 37.6% were females), 32 (9.0%) had no insurance, whereas 322 (91.0%) had insurance, of whom 131 (40.7%) had Medicare, 45 (14%) had Medicaid, and 146 (45.3%) had private insurance. On average, insured patients survived almost 2-fold longer (p < 0.0001) than those who were uninsured, whereas differences between specific insurance types did not influence survival. The adjusted hazard ratio (HR) for death was higher in uninsured patients (HR 2.27 [95% CI 1.49-3.33], p = 0.0003). Age, mean household income, tumor size at diagnosis, and extent of resection did not differ between insured and uninsured patients, but there was a disparity in primary care physician (PCP) status-none of the uninsured patients had PCPs, whereas 72% of insured patients had PCPs. Postoperative adjuvant treatment rates with temozolomide (TMZ) and radiation therapy (XRT) were significantly less in uninsured (TMZ in 56.3%, XRT in 56.3%) than in insured (TMZ in 75.2%, XRT in 79.2%; p = 0.02 and p = 0.003) patients. Insured patients receiving both agents had better prognosis than uninsured patients receiving the same treatment (9.1 vs 16.34 months; p = 0.025), suggesting that the survival effect in insured patients could only partly be explained by higher treatment rates. Moreover, having a PCP increased survival among the insured cohort (10.7 vs 16.1 months, HR 1.65 [95% CI 1.27-2.15]; p = 0.0001), which could be explained by significant differences in tumor diameter at initial diagnosis between patients with and without PCPs (4.3 vs 4.8 cm, p = 0.003), and a higher rate of clinical trial enrollment, suggesting a critical role of PCPs for a timelier diagnosis of GBM and proactive cancer care management. CONCLUSIONS Access to health care is a strong determinant of prognosis in newly diagnosed patients with GBM. Any type of insurance coverage and having a PCP improved prognosis in this patient cohort. Higher rates of treatment with TMZ plus XRT, clinical trial enrollment, fewer comorbidities, and early diagnosis may explain survival disparities. Lack of health insurance or a PCP are major challenges within the health care system, which, if improved upon, could favorably impact the prognosis of patients with GBM.

Predictors of Postoperative Complications of Craniosynostosis Repair in the National Inpatient Sample.

INTRODUCTION: Timing of intervention and complication profiles in surgical repair of craniosynostosis have been widely debated. Early intervention is frequently promoted as a means of decreasing morbidity while maintaining favorable outcomes via minimally invasive techniques such as endoscopic strip craniectomy. Immediate postoperative morbidity due to complications of early vs late intervention remains a key element in comparing timing and technique for craniosynostosis repair. In addition, concurrent fronto-orbital advancement with open cranial vault remodeling may increase the risk of postoperative complications. We present an evaluation of surgical timing and the presence of fronto-orbital advancement as independent predictors of in-hospital complications after craniosynostosis repair. METHODS: Retrospective analysis was performed in the National Inpatient Sample database from 1998 to 2009. Patients younger than 3 years having undergone elective surgical repair for craniosynostosis were identified. Comorbidities, demographics, transfusion status, and syndromic diagnosis were included as covariates. A multivariate regression model was used to characterize the association between age at the time of surgery and in-hospital complications. A subgroup analysis using the variable of concurrent fronto-orbital advancement was restricted to patients 8 to 24 months of age to exclude endoscopic craniosynostosis repair, which is traditionally repaired less than 6 months of age. Multivariate logistic regression was used to assess the impact of concurrent fronto-orbital advancement on postoperative complications. RESULTS: A total of 6010 craniosynostosis surgery cases (42.9%, age 0-7 months; 29.5%, age 8-12 months; and 27.6%, age 13-36 months) were included. Patients in the 7-to 12-month age group were more likely to experience complications when compared with the 0- to 6-month age group (odds ratio [OR],1.32; P < 0.05) and 13-to 36-month age group (OR, 1.32; P = 0.056). Syndromic patients (OR, 1.92; P < 0.001) and patients receiving an intraoperative blood transfusion (OR, 1.60; P < 0.05) demonstrated an increased risk for complications. In the subanalysis of 2936 patients aged 8 to 24 months, 15.1% of patients received frontoorbital advancement, which was associated with a significantly increased risk of complications (OR, 1.43; P < 0.05). CONCLUSIONS: Intermediate age (7-12 months) and concurrent fronto-orbital repair were independent risk factors for immediate postoperative complications. These findings may better inform the decision-making process for craniosynostosis repair in terms of timing and need for concurrent fronto-orbital reconstruction.

A Novel Method for Quantifying Intracranial Volume Change by Distraction Osteogenesis for Craniosynostosis.

INTRODUCTION: Methods of reporting quantitative results for distraction osteogenesis (DO) of craniosynostosis have been inconsistent. Therefore, the efficacy of differing techniques and timing in regard to volume change is not well established, with no uniform metric for comparisons. Given that cranial vault remodeling with DO may be completed with different approaches, analysis was made to determine (1) the relative efficiency of different approaches in expanding intracranial volume (ICV) and (2) the impact of adjusting for ICV growth on measured DO efficiency. METHODS: Patients with craniosynostosis were treated with open cranial vault reconstruction combined with internal distraction. Preoperative and postoperative computed tomography scans were used to quantify ICV change. The metric was determined by dividing percent ICV change by total distraction length. The metric was used as a proxy for efficiency to compare posterior and anterior distraction between groups using the Mann-Whitney U test and within a subgroup of patients who underwent 2-stage distraction using the Wilcoxon matched-pairs signed rank test. RESULTS: Twenty patients underwent cranial vault remodeling with DO: 14 unicoronal, 3 bicoronal, 2 multisutural, and 1 lambdoid. Results are reported in medians. Distraction efficiency was 0.99%/mm for primary anterior, unilateral distraction for unicoronal patients (n = 13, aged 9.1 months) and 4.28%/mm for posterior distraction using multiple distractors (n = 4, aged 6.3 months). In terms of the metric, primary posterior distraction was significantly more efficient than primary anterior distraction (P = 0.007). Three patients who had undergone primary posterior distraction later underwent secondary anterior distraction. Again, posterior distraction was shown to be significantly more efficient (5.16 vs 0.62, P = 0.050). For the unicoronal patients who received anterior unilateral distraction, an adjusted metric was calculated to account for normal intracranial growth. This was found to be 0.39%/mm, which was significantly different from the unadjusted metric (P = 0.0001). CONCLUSIONS: Posterior distraction is more efficient for ICV expansion than anterior distraction, which may have implications for the choice of approach for craniosynostosis repair. In addition, this is the first report of a novel standardized metric for analyzing ICV change achieved by DO. This tool allows for adjusting the efficiency metric for expected ICV growth, which significantly impacts its value.

Intracranial Hypotension and Hypertension Associated With Reconstructive Cranioplasty After Decompressive Craniectomy: Report of a Lethal Complication With Recommended Strategies for Future Avoidance.

Reconstructive cranioplasty can be associated with many complications and add to the not insignificant potential risks associated with decompressive craniectomy. In the setting of post-traumatic hydrocephalus, treatment with a ventriculoperitoneal (VP) shunt prior to reconstructive cranioplasty likely increases these risks even further. The authors report a case of a 17-year-old male with a history of a severe closed head injury who initially suffered a life-threatening complication associated with intracranial hypotension after cranioplasty only to succumb to malignant intracranial hypertension following a second cranioplasty attempt. To our knowledge, this is the first description of a single patient developing both these disparate complications after reconstructive cranioplasty and emphasizes the likely synergistic hazards involved with decompressive craniectomy in the setting of a VP shunt in particular and the overall myriad potential complications that may be associated with reconstructive cranioplasty in general.

Incidence of Le Fort Surgery in a Mature Cohort of Patients With Cleft Lip and Palate.

Primary repair of cleft lip and palate occurs early in life, but ideal timing of these interventions remains controversial. Prior research has indicated that a later palate repair may improve patients' midfacial growth long term, whereas optimal timing of lip repair to maximize midfacial growth has not been identified.The purpose of this study is to analyze a large, diverse cohort of patients with cleft lip and palate to determine whether timing of primary palate repair and primary lip repair contributed significantly to subsequent orthognathic surgery. METHODS: Seventy-one nonsyndromic patients with cleft lip and/or palate were followed until age 23 years, and data regarding original diagnosis, surgical procedures, and dates were collected. Within our patient cohort, 12 patients (16.9%) underwent orthognathic surgery. Binary logistic regressions, Fisher exact tests, and Mann-Whitney U tests were used to determine whether timing of primary palate repair and primary lip repair contributed significantly to subsequent orthognathic surgery. RESULTS: In our cohort, the association of early lip repair with later orthognathic surgery trended toward significance (P = 0.080). Timing of primary palate repair was not significantly associated with later orthognathic surgery (P= 0.291). When correcting for sex, race, diagnosis, location of care, incidence of lip adhesions, and incidence of lip revisions, patient age at primary lip procedure was a significant predictor of later orthognathic surgery (P = 0.041). CONCLUSIONS: Inconsistent with prior research, age at primary palate repair in our cohort was not correlated with incidence of orthognathic surgery. Delayed primary lip repair was associated with a significant decrease in the rate of subsequent orthognathic surgery.

Effect of Surgeon Volume and Craniofacial Fellowship Training on Cleft Palate Complication Rates.

BACKGROUND: Both the general and pediatric surgical literature have evidenced an inverse relationship between surgical case volume and complications. This study seeks to ascertain the relationship between case volume and fistula rates in cleft palate patients. We also seek to determine if craniofacial fellowship training impacts fistula rates. METHODS: Charts were reviewed at a multidisciplinary cleft center in San Diego, CA. We performed chart review on 207 nonsyndromic patients with cleft lip and palate who had surgery at our institution from 1988 to 2010. Data were analyzed using independent samples t test, χ test, and stepwise binary logistic regression to assess whether surgeon case volume and craniofacial fellowship training correlated with fistula repair rate. RESULTS: The surgeon with the highest volume had significantly fewer fistula repairs than lower volume surgeons (P = 0.044). Patients operated on by the craniofacial fellowship trained surgeon had significantly fewer fistulas compared with other plastic surgeons who performed cleft palate surgery (P = 0.005). CONCLUSIONS: Based on our retrospective review, it does appear that both high case volume and craniofacial fellowship training are associated with fewer postoperative fistulas.

Qualitative Methods in the Development of a Bilingual and Bicultural Quality of Life Outcomes Measure for Pediatric Patients With Craniofacial Conditions.

INTRODUCTION: Craniofacial surgeons treat patients with diverse craniofacial conditions (CFCs). Yet, little is known about the health-related quality of life (HRQoL) impact of diverse CFCs. Currently, there are no suitable instruments that measure the HRQoL of patients with diverse CFCs from the perspective of children and parents. The objective of this study was to develop the items and support the content validity of a comprehensive patient and parent-reported outcomes measure. METHODS: An iterative process consisting of a systematic literature review, expert opinion and in-depth interviews with patients and parents of patients with diverse CFCs was used. The literature review and expert opinion were used to generate in-depth interview questions. We interviewed 127 subjects: 80 parents of patients ages 0 to 18 years or older and 47 patients ages 7 to 18 years or older. English and Spanish speakers were represented in our sample. The majority of subjects originated from the United States and Mexico (83%). Craniofacial conditions included were cleft lip/palate, craniosynostosis, craniofacial microsomia, microtia, and dermatological conditions. Semistructured interviews were conducted until content saturation was achieved. Line-by-line analysis of interview transcripts identified HRQoL themes. Themes were interpreted and organized into larger domains that represent the conceptual framework of CFC-associated HRQoL. Themes were operationalized into items that represent the HRQoL issues of patients for both parent and patient versions. RESULTS: Six final bilingual and bicultural scales based on the domains derived from the literature review, expert opinion, and in-depth interviews were developed: (1) "Social Impact," (2) "Psychological Function," (3) "Physical Function," (4) "Family Impact," (5) "Appearance," And (6) "Finding Meaning." Some cultural differences were identified: in contrast to children from Mexico and other developing nations, families from the United States did not report public harassment or extremely negative public reactions to patients' CFC. Religion and spirituality were common themes in interviews of Spanish-speaking subjects but less common in interviews of English-speaking subjects. CONCLUSIONS: Qualitative methods involving pediatric patients with diverse CFCs and their parents in the item development process support the content validity for this bilingual and bicultural HRQoL instrument. The items developed in this study will now undergo psychometric testing in national multisite studies for validation.

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.

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.

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.

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.

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.