The effects of bone morphogenetic protein 2 and thrombopoietin treatment on angiogenic properties of endothelial cells derived from the lung and bone marrow of young and aged, male and female mice.

With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.

Safety and efficacy of low-dose rhBMP-2 use for anterior cervical fusion.

OBJECTIVE: The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) in routine anterior cervical fusion (ACF) is controversial. Early reports described high complication rates. A variety of dosing regimens ranging from 0.6 to 2.1 mg per level fused have been reported. The authors hypothesized that the high amounts of rhBMP-2 used in these studies led to the high complication rates observed; therefore, they set out to evaluate the safety and efficacy of low-dose rhBMP-2 for use in ACFs. METHODS: Patient inclusion criteria were 1) age 18 to 70 years; 2) initial stand-alone ACF construct; 3) fusion augmentation with rhBMP-2; and 4) at least 1 year of radiographic follow-up. A successful fusion was defined by either 1) lateral flexion-extension radiographs with less than 1 mm of movement across the fused spinous processes, or 2) bone bridging at least half of the fusion area originally achieved by surgery on fine-cut CT. Patient demographics, perioperative data, and postoperative complications were recorded. RESULTS: A total of 198 patients met the inclusion criteria and were included for analysis. Sixty-two patients (31%) were smokers. The median number of levels fused was 2 (IQR 1.25). The mean dose of rhBMP-2 was 0.50 ± 0.09 mg per level. Twenty-two (11%) patients experienced dysphagia. Eleven (6%) patients experienced cervical swelling. Two (1%) patients returned to the operating room (OR) for postoperative hematoma. One (0.5%) patient returned to the OR for seroma. Two (1%) patients experienced pseudarthrosis requiring a posterior fusion. Three (2%) patients experienced a new postoperative neurological deficit that had recovered by last the follow-up. Overall, 190 (96%) patients experienced solid arthrodesis over an average of 15 months of follow-up. There was no difference in fusion rates between patients who were either smokers or nonsmokers (p = 0.7073). CONCLUSIONS: The use of low-dose rhBMP-2 safely and effectively augmented anterior cervical arthrodesis. The low-dose protocol assessed in this study appeared to significantly reduce complications associated with rhBMP-2 use in ACF compared with the literature. The authors have determined that using low-dose rhBMP-2 in patients who are smokers, those with multilevel ACFs, or others at high risk of developing pseudarthrosis is recommended.

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice.

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20-24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

Ciliochoroidal ganglioneuroma in neurofibromatosis type 1: Report of a case and review of the literature.

Orbitofacial neurofibromatosis (OFNF) is considered a variant of neurofibromatosis type 1 (NF1). OFNF most often affects the eye, orbit and one side of the face. It is characterized by the development of relatively aggressive and disfiguring lesions, including plexiform and diffuse neurofibromas. Ciliochoroidal ganglioneuromas have not been previously reported in patients with this syndrome. We report the case of a 50-year-old man with OFNF, ciliochoroidal ganglioneuroma and a large ipsilateral frontoethmoidal encephalocele.

Incidence of Low Back Pain After Lumbar Discectomy for Herniated Disc and Its Effect on Patient-reported Outcomes.

BACKGROUND: Long-term postdiscectomy degenerative disc disease and low back pain is a well-recognized disorder; however, its patient-centered characterization and quantification are lacking. QUESTIONS/PURPOSES: We performed a systematic literature review and prospective longitudinal study to determine the frequency of recurrent back pain after discectomy and quantify its effect on patient-reported outcomes (PROs). METHODS: A MEDLINE search was performed to identify studies reporting on the frequency of recurrent back pain, same-level recurrent disc herniation, and reoperation after primary lumbar discectomy. After excluding studies that did not report the percentage of patients with persistent back or leg pain more than 6 months after discectomy or did not report the rate of same level recurrent herniation, 90 studies, which in aggregate had evaluated 21,180 patients, were included in the systematic review portion of this study. For the longitudinal study, all patients undergoing primary lumbar discectomy between October 2010 and March 2013 were enrolled into our prospective spine registry. One hundred fifteen patients were more than 12 months out from surgery, 103 (90%) of whom were available for 1-year outcomes assessment. PROs were prospectively assessed at baseline, 3 months, 1 year, and 2 years. The threshold of deterioration used to classify recurrent back pain was the minimum clinically important difference in back pain (Numeric Rating Scale Back Pain [NRS-BP]) or Disability (Oswestry Disability Index [ODI]), which were 2.5 of 10 points and 20 of 100 points, respectively. RESULTS SYSTEMATIC REVIEW: The proportion of patients reporting short-term (6-24 months) and long-term (> 24 months) recurrent back pain ranged from 3% to 34% and 5% to 36%, respectively. The 2-year incidence of recurrent disc herniation ranged from 0% to 23% and the frequency of reoperation ranged from 0% to 13%. PROSPECTIVE STUDY: At 1-year and 2-year followup, 22% and 26% patients reported worsening of low back pain (NRS: 5.3 ± 2.5 versus 2.7 ± 2.8, p < 0.001) or disability (ODI%: 32 ± 18 versus 21 ± 18, p < 0.001) compared with 3 months. CONCLUSIONS: In a systematic literature review and prospective outcomes study, the frequency of same-level disc herniation requiring reoperation was 6%. Two-year recurrent low back pain may occur in 15% to 25% of patients depending on the level of recurrent pain considered clinically important, and this leads to worse PROs at 1 and 2 years postoperatively.

Transforaminal lumbar interbody graft placement using an articulating delivery arm facilitates increased segmental lordosis with superior anterior and midline graft placement.

OBJECTIVE: Transforaminal lumbar interbody fusion (TLIF) is a frequently performed method of lumbar arthrodesis in patients failing medical management of back and leg pain. Accurate placement of the interbody graft and restoration of lordosis has been shown to be crucial when performing lumbar fusion procedures. We performed a single-surgeon, prospective, randomized study to determine whether a novel articulating versus traditional straight graft delivery arm system allows for superior graft placement and increased lordosis for single-level TLIF. METHODS: Thirty consecutive patients undergoing single-level TLIF were included and prospectively randomized to one of the 2 groups (articulated vs. straight delivery arm system). Three radiographic characteristics were evaluated at 6-week follow-up: (1) degree of segmental lumbar lordosis at the fused level; (2) the percent anterior location of the interbody graft in disk space; and (3) the distance (mm) off midline of the interbody graft placement. RESULTS: Randomization yielded 16 patients in the articulated delivery arm cohort and 14 in the straight delivery arm cohort. The articulating delivery arm system yielded an average of 14.7-degree segmental lordosis at fused level, 35% anterior location, and 3.6 mm off midline. The straight delivery arm system yielded an average of 10.7-degree segmental lordosis at fused level, 46% anterior location, and 7.0 mm off midline. All 3 comparisons were statistically significant (P<0.05). CONCLUSIONS: The study suggests that an articulating delivery arm system facilitates superior anterior and midline TLIF graft placement allowing for increased segmental lordosis compared with a traditional straight delivery arm system.

Long-term outcomes after revision neural decompression and fusion for same-level recurrent lumbar stenosis: defining the effectiveness of surgery.

STUDY DESIGN: Single-cohort study of patients undergoing revision neural decompression and fusion for same-level recurrent lumbar stenosis. OBJECTIVE: To assess the long-term outcomes of revision surgery using validated patient-reported outcomes measures. SUMMARY OF BACKGROUND DATA: Recurrent lumbar stenosis may occur after lumbar spine surgery, leading to significant discomfort and radicular pain. Although numerous studies have reported clinical outcomes after primary lumbar surgery, there remains a paucity of data on the outcomes after revision surgery for recurrent same-level stenosis. METHODS: Fifty-three patients undergoing revision neural decompression and instrumented fusion for same-level recurrent stenosis-associated back and leg pain were included in this study. Baseline and 2-year visual analog scale for leg pain (LP-VAS), visual analog scale for low back pain (BP-VAS), Oswestry Disability Index (ODI), Zung self-reported depression score (ZDS), time to narcotic independence, time to return to work, health-state utility [EuroQol (EQ-5D)], and physical and mental quality of life [SF-12 physical and mental component scores (PCS and MCS)] were assessed. RESULTS: Mean±SD duration of time between index surgery and revision surgery was 4.00±4.19 years. A significant improvement from baseline was observed in BP-VAS (9.28±1.01 vs. 5.00±2.94, P=0.001), LP-VAS (9.55±0.93 vs. 3.45±2.95, P=0.001), and ODI (36.02±6.01 vs. 21.75±12.08, P=0.001). Mean±SD SF-12 PCS (7.17±11.22, P=0.001), SF-12 MCS (12.57±13.03, P=0.001), ZDS (12.37±16.80, P=0.001), and EQ-5D (0.42±0.34, P=0.001) were also significantly improved. The mean cumulative 2-year gain in health-utility state was 0.84 QALY. Median (interquartile range) duration of postoperative narcotic use was 6 (1.4-12.2) months and time of missed work was 6 (4.0-10.0) months. CONCLUSIONS: Our study suggests that revision neural decompression and instrumented fusion for recurrent same-level stenosis provides significant improvement in all patient-assessed outcome metrics and should be offered as a viable treatment option.

Minced muscle autografting improves bone healing but not muscle function in a porcine composite injury model.

Composite tissue injuries (CTIs) in extremities include segmental bone defects (SBDs) and volumetric muscle loss. The objective of this study was to determine if skeletal muscle autografting with minced muscle grafts (MMGs) could improve healing in an SBD and improve muscle function in a porcine CTI model that includes an SBD and adjacent volumetric muscle loss injury. Adult Yucatan Minipigs were stratified into three groups including specimens with an isolated SBD, an SBD with volumetric muscle loss (CTI), and an SBD with volumetric muscle loss treated with MMG (CTI + MMG). Bone healing was quantified with serial x-rays and postmortem computed tomography scanning. Muscle function was quantified with a custom in vivo force transducer. Muscle tissue content was determined by biochemical analyses and histology. Anterior cortex-modified Radiographic Union Score for Tibia fractures (mRUSTs) decreased from 2.7 to 1.9 (p = 0.003) in CTI versus SBD animals. MMG improved anterior mRUST scores to 2.5 in CTI + MMG specimens (p = 0.030 compared to CTI specimens) and overall mRUST scores increased from 9.4 in CTI specimens to 11.1 in CTI + MMG specimens (p = 0.049). Residual strength deficits at euthanasia were 42% in SBD (p < 0.001), 44% in CTI (p < 0.001), and 48% in CTI + MMG (p < 0.001) compared to preoperative values. There were no differences in strength deficits between the three groups. Biochemical and histologic analyses demonstrated scattered differences between the three groups compared to contralateral muscle. MMG improved bone healing. However, the primary cause of muscle dysfunction and biochemical changes was the presence of an SBD. Clinical significance: Early mitigation of SBDs may be necessary to prevent muscle damage and weakness in patients sustaining composite extremity trauma.

Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

Type 2 diabetes (T2D) results in physiological and structural changes in bone, contributing to poor fracture healing. T2D compromises microvascular performance, which can negatively impact bone regeneration as angiogenesis is required for new bone formation. We examined the effects of bone morphogenetic protein-2 (BMP-2) administered locally at the time of femoral segmental bone defect (SBD) surgery, and its angiogenic impacts on endothelial cells (ECs) isolated from the ipsilateral or contralateral tibia in T2D mice. Male C57BL/6 mice were fed either a low-fat diet (LFD) or high-fat diet (HFD) starting at 8 weeks. After 12 weeks, the T2D phenotype in HFD mice was confirmed via glucose and insulin tolerance testing and echoMRI, and all mice underwent SBD surgery. Mice were treated with BMP-2 (5 µg) or saline at the time of surgery. Three weeks postsurgery, bone marrow ECs were isolated from ipsilateral and contralateral tibias, and proliferation, angiogenic potential, and gene expression of the cells was analyzed. BMP-2 treatment increased EC proliferation by two fold compared with saline in LFD contralateral tibia ECs, but no changes were seen in surgical tibia EC proliferation. BMP-2 treatment enhanced vessel-like structure formation in HFD mice whereas, the opposite was observed in LFD mice. Still, in BMP-2 treated LFD mice, ipsilateral tibia ECs increased expression of CD31, FLT-1, ANGPT1, and ANGPT2. These data suggest that the modulating effects of T2D and BMP-2 on the microenvironment of bone marrow ECs may differentially influence angiogenic properties at the fractured limb versus the contralateral limb.

Cerebellopontine Angle Primary Choroid Plexus Carcinoma Present in an Adult: Case Report and Literature Review.

Choroid plexus tumors (CPTs) are rare intraventricular neoplasms that primarily occur in children and are rare in adults. Of the CPT subtypes, choroid plexus carcinomas (CPC) are highly aggressive and malignant and of World Health Organization (WHO) Grade III. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. In this case report, we present a 33-year-old female with a past medical history notable for schizophrenia and bipolar disease who suffered from left-sided acute vision loss and hearing loss. Magnetic resonance imaging (MRI) demonstrated multiple enhancing masses found in the left cerebellopontine angle (CPA), right internal auditory canal, the atrium of the left ventricle, and the left foramen of Monroe. After surgical decompression of the CPA tumor, the permanent final pathology was consistent with CPC. To our knowledge, this is the first reported case of a primary CPC occurring within the CPA in an adult. The unique presentation and progression of this rare adult-onset CPC provide insight for the diagnosis and treatment of other rare instances of CPTs.

Endovascular Retreatment of Previously Ruptured Coiled Cerebral Aneurysm Remnants Significantly Reduces Rebleed Rate.

OBJECTIVE: Treatment of ruptured cerebral aneurysms by endovascular coiling is associated with a better neurologic outcome when compared with neurosurgical clipping but has a higher risk for target aneurysm rebleeding after treatment. We hypothesize that aggressive retreatment of coiled aneurysms will lead to fewer recurrent hemorrhages as compared with historical values of 2.3%-3.0%. METHODS: All first-time Guglielmi detachable coil-embolized cerebral aneurysms were retrospectively reviewed at a single institution from 2004 to 2015. Aneurysm retreatment after first-time embolization was recorded as well as time to retreatment. Retreatment at our institution is routinely performed for incomplete coiling with etiologies including incomplete initial coiling, coil compaction, and aneurysmal dilatation. Aneurysm rerupture was treated with additional coiling. Kaplan-Meier survival analysis was performed to evaluate embolization durability. RESULTS: There were 214 aneurysms that met inclusion criteria. Mean (standard deviation) follow-up was 2.74 (2.24) years. Aneurysms that were patent or recanalized were retreated. Mean (standard deviation) time to retreatment was 9 (9) months. Overall, 46 (21.5%) aneurysms required retreatment. Retreatment was performed for coil compaction/remnant growth, recanalization, persistent remnant, and rebleed. Two (0.9%) patients had recurrent aneurysm hemorrhage and both were treated with additional coil embolization. There were no new long-term neurologic deficits caused by aneurysm retreatment. CONCLUSIONS: Aggressive retreatment of previously ruptured, coiled cerebral aneurysms for persistent aneurysm patency reduces the recurrent hemorrhage risk to that historically seen in neurosurgically clipped aneurysms with minimal additional morbidity. This study validates a large body of literature demonstrating the significance of post-treatment aneurysm remnants and their association with recurrent hemorrhage.

Institutional review of the management of type II odontoid fractures: associations and outcomes with fibrous union.

OBJECTIVE: Type II odontoid fractures may be managed operatively or nonoperatively. If managed with bracing, bony union may never occur despite stability. This phenomenon is termed fibrous union. The authors aimed to determine associations with stable fibrous union and compare the morbidity of patients managed operatively and nonoperatively. METHODS: The authors performed a retrospective review of their spine trauma database for adults with type II odontoid fractures between 2015 and 2019. Two-sample t-tests and Fisher's exact tests identified associations with follow-up stability and were used to compare operative and nonoperative outcomes. Sensitivity, specificity, and predictive values were calculated to validate initial stable upright cervical radiographs related to follow-up stability. RESULTS: Among 88 patients, 10% received upfront surgical fixation, and 90% were managed nonoperatively, of whom 22% had fracture instability on follow-up. Associations with instability after nonoperative management include myelopathy (OR 0.04, 95% CI 0.0-0.92), cerebrovascular disease (OR 0.23, 95% CI 0.06-1.0), and dens displacement ≥ 2 mm (OR 0.29, 95% CI 0.07-1.0). Advanced age was not associated with follow-up instability. Initial stability on upright radiographs was associated with stability on follow-up (OR 4.29, 95% CI 1.0-18) with excellent sensitivity and positive predictive value (sensitivity 89%, specificity 35%, positive predictive value 83%, and negative predictive value 46%). The overall complication rate and respiratory failure requiring ventilation on individual complication analysis were more common in operatively managed patients (33% vs 3%, respectively; p = 0.007), even though they were generally younger and healthier than those managed nonoperatively. Operative or nonoperative management conferred no difference in length of hospital or ICU stay, discharge disposition, or mortality. CONCLUSIONS: The authors delineate the validity of upright cervical radiographs on presentation in association with follow-up stability in type II odontoid fractures. In their experience, factors associated with instability included cervical myelopathy, cerebrovascular disease, and fracture displacement but not increased age. Operatively managed patients had higher complication rates than those managed without surgery. Fibrous union, which can occur with nonoperative management, provided adequate stability.

Gene-metabolite networks associated with impediment of bone fracture repair in spaceflight.

Adverse effects of spaceflight on musculoskeletal health increase the risk of bone injury and impairment of fracture healing. Its yet elusive molecular comprehension warrants immediate attention, since space travel is becoming more frequent. Here we examined the effects of spaceflight on bone fracture healing using a 2 mm femoral segmental bone defect (SBD) model. Forty, 9-week-old, male C57BL/6J mice were randomized into 4 groups: 1) Sham surgery on Ground (G-Sham); 2) Sham surgery housed in Spaceflight (FLT-Sham); 3) SBD surgery on Ground (G-Surgery); and 4) SBD surgery housed in Spaceflight (FLT-Surgery). Surgery procedures occurred 4 days prior to launch; post-launch, the spaceflight mice were house in the rodent habitats on the International Space Station (ISS) for approximately 4 weeks before euthanasia. Mice remaining on the Earth were subjected to identical housing and experimental conditions. The right femur from half of the spaceflight and ground groups was investigated by micro-computed tomography (µCT). In the remaining mice, the callus regions from surgery groups and corresponding femoral segments in sham mice were probed by global transcriptomic and metabolomic assays. µCT confirmed escalated bone loss in FLT-Sham compared to G-Sham mice. Comparing to their respective on-ground counterparts, the morbidity gene-network signal was inhibited in sham spaceflight mice but activated in the spaceflight callus. µCT analyses of spaceflight callus revealed increased trabecular spacing and decreased trabecular connectivity. Activated apoptotic signals in spaceflight callus were synchronized with inhibited cell migration signals that potentially hindered the wound site to recruit growth factors. A major pro-apoptotic and anti-migration gene network, namely the RANK-NFκB axis, emerged as the central node in spaceflight callus. Concluding, spaceflight suppressed a unique biomolecular mechanism in callus tissue to facilitate a failed regeneration, which merits a customized intervention strategy.

The effects of high fat diet, bone healing, and BMP-2 treatment on endothelial cell growth and function.

Angiogenesis is a vital process during the regeneration of bone tissue. The aim of this study was to investigate angiogenesis at the fracture site as well as at distal locations from obesity-induced type 2 diabetic mice that were treated with bone morphogenetic protein-2 (BMP-2, local administration at the time of surgery) to heal a femoral critical sized defect (CSD) or saline as a control. Mice were fed a high fat diet (HFD) to induce a type 2 diabetic-like phenotype while low fat diet (LFD) animals served as controls. Endothelial cells (ECs) were isolated from the lungs (LECs) and bone marrow (BMECs) 3 weeks post-surgery, and the fractured femurs were also examined. Our studies demonstrate that local administration of BMP-2 at the fracture site in a CSD model results in complete bone healing within 3 weeks for all HFD mice and 66.7% of LFD mice, whereas those treated with saline remain unhealed. At the fracture site, vessel parameters and adipocyte numbers were significantly increased in BMP-2 treated femurs, irrespective of diet. At distal sites, LEC and BMEC proliferation was not altered by diet or BMP-2 treatment. HFD increased the tube formation ability of both LECs and BMECs. Interestingly, BMP-2 treatment at the time of surgery reduced tube formation in LECs and humeri BMECs. However, migration of BMECs from HFD mice treated with BMP-2 was increased compared to BMECs from HFD mice treated with saline. BMP-2 treatment significantly increased the expression of CD31, FLT-1, and ANGPT2 in LECs and BMECs in LFD mice, but reduced the expression of these same genes in HFD mice. To date, this is the first study that depicts the systemic influence of fracture surgery and local BMP-2 treatment on the proliferation and angiogenic potential of ECs derived from the bone marrow and lungs.

Spinal instrumentation in infants, children, and adolescents: a review.

OBJECTIVEThe evolution of pediatric spinal instrumentation has progressed in the last 70 years since the popularization of the Harrington rod showing the feasibility of placing spinal instrumentation into the pediatric spine. Although lacking in pediatric-specific spinal instrumentation, when possible, adult instrumentation techniques and tools have been adapted for the pediatric spine. A new generation of pediatric neurosurgeons with interest in complex spine disorder has pushed the field forward, while keeping the special nuances of the growing immature spine in mind. The authors sought to review their own experience with various types of spinal instrumentation in the pediatric spine and document the state of the art for pediatric spine surgery.METHODSThe authors retrospectively reviewed patients in their practice who underwent complex spine surgery. Patient demographics, operative data, and perioperative complications were recorded. At the same time, the authors surveyed the literature for spinal instrumentation techniques that have been utilized in the pediatric spine. The authors chronicle the past and present of pediatric spinal instrumentation, and speculate about its future.RESULTSThe medical records of the first 361 patients who underwent 384 procedures involving spinal instrumentation from July 1, 2007, to May 31, 2018, were analyzed. The mean age at surgery was 12 years and 6 months (range 3 months to 21 years and 4 months). The types of spinal instrumentation utilized included occipital screws (94 cases); C1 lateral mass screws (115 cases); C2 pars/translaminar screws (143 cases); subaxial cervical lateral mass screws (95 cases); thoracic and lumbar spine traditional-trajectory and cortical-trajectory pedicle screws (234 cases); thoracic and lumbar sublaminar, subtransverse, and subcostal polyester bands (65 cases); S1 pedicle screws (103 cases); and S2 alar-iliac/iliac screws (56 cases). Complications related to spinal instrumentation included hardware-related skin breakdown (1.8%), infection (1.8%), proximal junctional kyphosis (1.0%), pseudarthroses (1.0%), screw malpositioning (0.5%), CSF leak (0.5%), hardware failure (0.5%), graft migration (0.3%), nerve root injury (0.3%), and vertebral artery injury (0.3%).CONCLUSIONSPediatric neurosurgeons with an interest in complex spine disorders in children should develop a comprehensive armamentarium of safe techniques for placing rigid and nonrigid spinal instrumentation even in the smallest of children, with low complication rates. The authors' review provides some benchmarks and outcomes for comparison, and furnishes a historical perspective of the past and future of pediatric spine surgery.

The Natural History of Coiled Cerebral Aneurysms Stratified by Modified Raymond-Roy Occlusion Classification.

OBJECTIVE: The natural history and long-term durability of Guglielmi detachable coil (GDC) embolization is still unknown. We hypothesize a stepwise decrease in durability of embolized cerebral aneurysms as stratified by the Modified Raymond-Roy Classification (MRRC). METHODS: First-time GDC-embolized cerebral aneurysms were retrospectively reviewed from 2004 to 2015. Loss of durability (LOD) was defined by change in aneurysm size or patency seen on serial radiographic follow-up. Kaplan-Meier survival analysis was performed to evaluate embolization durability. Multivariate Cox regression modeling was used to assess baseline aneurysm and patient characteristics for their effect on LOD. RESULTS: A total of 427 patients with 443 aneurysms met the inclusion criteria. Overall, 89 (21%) aneurysms met LOD criteria. Grade 1 aneurysms had statistically significantly greater durability than did all other MRRC grades. Grade 3b aneurysms had significantly worse durability than did all other aneurysm grades. There was no difference in durability between grade 2 and 3a aneurysms. Of aneurysms with LOD, 26 (29%) experienced worsening of MRRC grade. Thirty-five (24%) initial MRRC grade 2, 72 (45%) initial MRRC grade 3a, and 6 (22%) initial MRRC grade 3b aneurysms progressed to MRRC grade 1 without retreatment. In our multivariate analysis, only initial MRRC grade was statistically significantly associated with treatment durability (P < 0.001). CONCLUSIONS: MRRC grade is independently associated with first-time GDC-embolized cerebral aneurysm durability. Achieving MRRC grade 1 occlusion outcome is significantly associated with greater long-term GDC durability. Although few aneurysms experience further growth and/or recanalization, most incompletely obliterated aneurysms tend to remain stable over time or even progress to occlusion. Grading scales such as the MRRC are useful for characterizing aneurysm occlusion but may lack sensitivity and specificity for characterizing changes in aneurysm morphology over time.

Evaluation of lateral atlantodental interval asymmetry in the pediatric age group: normative values.

OBJECTIVE The revelation of normative radiographic measurements for the developing pediatric spine is incomplete. The purpose of this analysis was to determine the normal range of asymmetry of the lateral atlantodental interval (LADI) and define age- and sex-related differences. METHODS A total of 3072 children aged 0-18 years who underwent CT scanning of the cervical spine were identified at Riley Hospital for Children between 2005 and 2017. Patients were stratified by sex and age (in years) into 36 cohorts. Following this stratification, patients within each group were randomly selected for inclusion until 15 patients in each group had been measured (quota sampling). A total of 540 patients were included for study. Right and left linear measurements were performed in the CT axial plane at the C-1 midlateral mass level. RESULTS The overall mean difference between the right and left LADI was 0.09 ± 1.23 mm (range -6.05 to 4.87 mm). The magnitude of this asymmetry remained statistically insignificant across age groups (p = 0.278) and sex (p = 0.889). The intraclass correlation coefficient was 0.805 (95% CI 0.779-0.829). CONCLUSIONS Asymmetry of the LADI is not unusual in asymptomatic children. There is no appreciable difference in magnitude of this asymmetry across age ranges and sex. Measurement of LADI asymmetry shows "good" reliability and is easy to perform. Pediatric neurosurgeons, emergency department physicians, and radiologists should be aware of normative values of asymmetry when interpreting CT scans of the cervical spine. This may prevent unnecessary further workup with dynamic CT or MRI.

Effect of short-term ε-aminocaproic acid treatment on patients undergoing endovascular coil embolization following aneurysmal subarachnoid hemorrhage.

OBJECTIVE Aneurysmal rebleeding before definitive obliteration of the aneurysm is a cause of mortality and morbidity. There are limited data on the role of short-term antifibrinolytic therapy among patients undergoing endovascular intervention. METHODS All consecutive patients receiving endovascular therapy for their ruptured saccular aneurysm at the authors' institution between 2000 and 2011 were included in this study. These patients underwent endovascular coiling of their aneurysm within 72 hours of admission. In patients receiving ε-aminocaproic acid (EACA), the EACA administration was continued until the time of the endovascular procedure. Complications and clinical outcomes of endovascular treatment after aneurysmal subarachnoid hemorrhage (aSAH) were compared between EACA-treated and untreated patients. RESULTS During the 12-year study period, 341 patients underwent endovascular coiling. Short-term EACA treatment was administered in 146 patients and was withheld in the other 195 patients. EACA treatment did not change the risk of preinterventional rebleeding in this study (OR 0.782, 95% CI 0.176-3.480; p = 0.747). Moreover, EACA treatment did not increase the rate of thromboembolic events. On the other hand, patients who received EACA treatment had a significantly longer duration of hospital stay compared with their counterparts who were not treated with EACA (median 19 days, interquartile range [IQR] 12.5-30 days vs median 14 days, IQR 10-23 days; p < 0.001). EACA treatment was associated with increased odds of shunt requirement (OR 2.047, 95% CI 1.043-4.018; p = 0.037) and decreased odds of developing cardiac complications (OR 0.138, 95% CI 0.031-0.604; p = 0.009) and respiratory insufficiency (OR 0.471, 95% CI 0.239-0.926; p = 0.029). Short-term EACA treatment did not affect the Glasgow Outcome Scale score at discharge, 6 months, or 1 year following discharge. CONCLUSIONS In this study, short-term EACA treatment in patients who suffered from aSAH and received endovascular aneurysm repair did not decrease the risk of preinterventional rebleeding or increase the risk of thrombotic events. EACA did not affect outcome. Randomized clinical trials are required to provide robust clinical recommendation on short-term use of EACA.

Anterior cervical discectomy and fusion in the outpatient ambulatory surgery setting compared with the inpatient hospital setting: analysis of 1000 consecutive cases.

OBJECTIVE In an era of escalating health care costs and pressure to improve efficiency and cost of care, ambulatory surgery centers (ASCs) have emerged as lower-cost options for many surgical therapies. Anterior cervical discectomy and fusion (ACDF) is one of the most prevalent spine surgeries performed, and the frequency of its performance is rapidly increasing as the aging population grows. Although ASCs offer significant cost advantages over hospital-based surgical centers, concern over the safety of outpatient ACDF has slowed its adoption. The authors intended to 1) determine the safety of the first 1000 consecutive ACDF surgeries performed in their outpatient ASC, and 2) compare the safety of these outpatient ACDFs with that of consecutive ACDFs performed during the same time period in the hospital setting. METHODS A total of 1000 consecutive patients who underwent ACDF in an ACS (outpatient ACDF) and 484 consecutive patients who underwent ACDF at Vanderbilt University Hospital (inpatient ACDF) from 2006 to 2013 were included in this retrospective study of patients' medical records. Data were collected on patient demographics, comorbidities, operative details, and perioperative and 90-day morbidity. Perioperative morbidity and hospital readmission were compared between the outpatient and inpatient ACDF groups. RESULTS Of the first 1000 outpatient ACDF cases performed in the authors' ASC, 629 (62.9%) were 1-level and 365 (36.5%) were 2-level ACDFs. Mean patient age was 49.5 ± 8.6, and 484 (48.4%) were males. All patients were observed postoperatively at the ASC postanesthesia care unit (PACU) for 4 hours before being discharged home. Eight patients (0.8%) were transferred from the surgery center to the hospital postoperatively (for pain control [n = 3], chest pain and electrocardiogram changes [n = 2], intraoperative CSF leak [n = 1], postoperative hematoma [n = 1], and profound postoperative weakness and surgical reexploration [n = 1]). No perioperative deaths occurred. The 30-day hospital readmission rate was 2.2%. All 90-day surgical morbidity was similar between outpatient and inpatient cohorts for both 1-level and 2-level ACDFs. CONCLUSIONS An analysis of 1000 consecutive patients who underwent ACDF in an outpatient setting demonstrates that surgical complications occur at a low rate (1%) and can be appropriately diagnosed and managed in a 4-hour ASC PACU window. Comparison with an inpatient ACDF surgery cohort demonstrated similar results, highlighting that ACDF can be safely performed in the outpatient ambulatory surgery setting without compromising surgical safety. In an effort to decrease costs of care, surgeons can safely perform 1- and 2-level ACDFs in an ASC environment.

Accurately measuring the quality and effectiveness of cervical spine surgery in registry efforts: determining the most valid and responsive instruments.

BACKGROUND CONTEXT: There is a growing demand to measure the real-world effectiveness and value of care across all specialties and disease states. Prospective registries have emerged as a feasible way to capture real-world care across large patient populations. However, the proven validity of more robust and cumbersome patient-reported outcome instruments (PROi) must be balanced with what is feasible to apply in large-scale registry efforts. Hence, commercial registry efforts that measure quality and effectiveness of care in an attempt to guide quality improvement, pay for performance, or value-based purchasing should incorporate measures that most accurately represent patient-centered improvement. PURPOSE: We set out to establish the relative validity and responsiveness of common PROi in accurately determining effectiveness of cervical surgery for neck and arm pain in registry efforts. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: Eighty-eight patients undergoing primary anterior cervical discectomy and fusion (ACDF) for neck and arm pain. OUTCOME MEASURES: Patient-reported outcome measures for pain (numeric rating scale for neck pain [NRS-NP] and arm pain [NRS-AP]), disability (neck disability index [NDI]), general health (short-form 12-item survey physical component summary [SF-12 PCS] and mental component summary [SF-12 MCS]), and quality of life (Euro-Qol-5D [EQ-5D]) were assessed. METHODS: Eighty-eight patients undergoing primary ACDF for neck and arm pain were entered into a Web-based prospective registry. Baseline and 12-month patient-reported outcomes (NRS-NP, NRS-AP, NDI, SF-12 PCS, SF-12 MCS, and EQ-5D) were assessed. Patients were also asked whether they experienced a level of improvement after ACDF that met their expectation (meaningful improvement). To assess the validity of NRS-NP, NRS-AP, and NDI (measures of pain and disability) to discriminate between meaningful and nonmeaningful improvement and the validity of SF-12 PCS, SF-12 MCS, and EQ-5D (measures of general health and quality of life) to discriminate between meaningful and nonmeaningful improvement, receiver-operating characteristic curves were generated for each outcome instrument. The greater the area under the curve (AUC), the more valid the discriminator. The difference between standardized response means (SRMs) in patients reporting meaningful improvement versus not was calculated to determine the relative responsiveness of each outcome instrument to changes in pain and QOL after surgery. RESULTS: For pain and disability, both NDI (AUC=0.75) and NRS-AP (AUC=0.74) were valid discriminators of meaningful improvement. Numeric rating scale for neck pain (AUC=0.69) was a poor discriminator. Neck disability index was also most responsive to postoperative improvement (SRM difference 0.78), followed by NRS-AP (SRM difference 0.59) and NRS-NP (SRM difference 0.46). For general health and quality of life, SF-12 PCS (AUC=0.79) was the only valid discriminator of meaningful improvement. Euro-Qol-5D (AUC=0.68) and SF-12 MCS (AUC=0.44) were poor discriminators. Short-form 12 physical component summary (SRM difference 1.08) was also most responsive compared with EQ-5D (SRM difference 0.89) and SF-12 MCS (SRM difference 0.01). CONCLUSIONS: For pain and disability, NDI is the most valid and responsive measure of improvement after surgery for neck and arm pain. Numeric rating scale for neck pain and NRS-AP are poor substitutes for NDI when measuring effectiveness of care in registry efforts. For health-related quality of life, only SF-12 PCS could accurately discriminate meaningful improvement after cervical surgery and was found to be most valid and responsive. Large-scale registry efforts aimed at measuring effectiveness of cervical spine surgery should use NDI and SF-12 to accurately assess improvements in pain, disability, and quality of life.