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.

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.

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.

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.

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.

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.

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.

Traumatic atlantooccipital dislocation: comprehensive assessment of mortality, neurologic improvement, and patient-reported outcomes at a Level 1 trauma center over 15 years.

BACKGROUND CONTEXT: Only Level 3 evidence exists for the diagnosis and treatment of atlantooccipital dislocation (AOD) with few studies examining mortality, neurologic improvement, and patient-reported outcomes (PROs). PURPOSE: First, the aim was to determine: the incidence of AOD, 90-day surgical morbidity and mortality after AOD, patient factors that may be associated with delayed or missed diagnosis, and factors that were associated with mortality and neurologic improvement after AOD. Secondly, the aim was to quantify the pain, disability, and quality of life experienced by patients surviving AOD. STUDY DESIGN/SETTING: This was a retrospective cohort study. PATIENT SAMPLE: A total of 5,337 consecutive spine computed tomography traumagrams from 1997 to 2012 were included. OUTCOME MEASURES: Mortality, neurologic improvement, complications, EuroQol five dimensions (EQ-5D), Neck Disability Index (NDI), Numeric Rating Scale (NRS)-neck, NRS-arm, and return-to-work were the outcome measures. METHODS: Patients were considered to have AOD if they met one of the following radiographic criteria: basion-dens interval greater than 10 mm; basion-axial interval: anterior displacement greater than 12 mm or posterior displacement greater than 4 mm between the basion and posterior C2 line; and condyle to C1 interval greater than 1.4 mm. Linear regression analysis was performed to identify factors associated with 90-day mortality, neurologic improvement, and missed diagnosis. Patient-reported outcomes were assessed via phone interview. RESULTS: Thirty-one patients met radiographic criteria for AOD; an incidence of 0.6% over 15 years. Twenty-one (68%) patients were treated with occipital cervical fusion. At 90 days postoperatively, there were no new neurologic deficits or reoperations. Eight (26%) patients died within 90 days. All patients who died had no documented AOD diagnosis and were not treated surgically. Missed AOD diagnosis was the strongest predictor of mortality. Younger age, lower Glasgow Coma Score, lower Injury Severity Score (ISS) score, and worse initial American Spinal Injury Association (ASIA) score were significantly associated with greater neurologic improvement. Higher ISS score and better ASIA score were significantly associated with missed AOD diagnosis. The average PROs metrics at time of telephone follow-up were as follows: EQ-5D=0.73±0.19, NDI=30.89±18.57, NRS-neck=2.33±2.21, NRS-arm=2.00±2.54. Of the patients with follow-up data, four were employed full-time, and five were receiving disability. CONCLUSIONS: Our work suggests that failure to diagnose AOD is a powerful predictor of mortality. Higher ISS scores and better neurologic presentation were significantly associated with missed diagnosis. Craniocervical arthrodesis preserved neurologic function with low complication rate and unexpectedly high PROs and return-to-work. These results must be carefully interpreted because it is unclear whether missed AOD diagnosis accompanies another death-causing injury (eg, traumatic brain injury) or if failure to treat AOD contributes to mortality in a multifactorial manner.

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.

Cost-effectiveness of cell saver in short-segment lumbar laminectomy and fusion (≤3 levels).

STUDY DESIGN: Mixed retrospective-prospective cohort study. OBJECTIVE: To characterize practice patterns for the use of Cell Saver at our institution, investigate its cost-effectiveness, and propose a new tool for patient selection. SUMMARY OF BACKGROUND DATA: Blood loss is an exceedingly common complication of spine surgery, and Cell Saver intraoperative cell salvage has been used to decrease reliance on allogeneic blood transfusions for blood volume replacement. The cost-effectiveness of Cell Saver has not been established for lumbar spinal surgery, and no universal guidelines exist for clinicians to decide when to utilize this tool. Other authors have proposed cutoffs for anticipated blood loss volumes which indicate that Cell Saver should be used. METHODS: Five hundred and eight patients undergoing lumbar laminectomy in 3 or fewer levels were reviewed from our prospective spinal outcomes registry. Cost information for Cell Saver and allogeneic transfusions was collected from our institution's billing and collections department. Logistic regression was used to identify patient characteristics associated with use of Cell Saver. An incremental cost effectiveness ratio was calculated based on transfusion and cost data. A clinical prediction score was derived using logistic regression. RESULTS: Use of Cell Saver correlated with increased age, higher body mass index, diabetes, greater American Society of Anesthesiologists classification, and greater number of previous spine surgeries. Outcomes for patients who did and did not have Cell Saver set up intraoperatively were equivocal. Cell Saver was not cost effective based on current usage patterns, but may become cost effective if used for patients with high expected blood loss. A simple clinical prediction rule is proposed which may aid in selection of patients to have Cell Saver present intraoperatively. CONCLUSION: Cell Saver is not a cost-effective intervention but may become cost effective if a threshold of expected intraoperative blood loss is used to select patients more judiciously. LEVEL OF EVIDENCE: 3.

Extent of preoperative depression is associated with return to work after lumbar fusion for spondylolisthesis.

BACKGROUND: The ability to understand factors associated with an increased duration of missed work postoperatively could be used to more effectively select patients with the greatest opportunity for a successful outcome. We set out to determine the effect of preoperative depression on postoperative return to work in patients undergoing transforaminal lumbar interbody fusion (TLIF) for degenerative spondylolisthesis. METHODS: Fifty-eight patients undergoing TLIF for symptomatic grade I degenerative lumbar spondylolisthesis were included in this analysis. Patient demographics, clinical presentation, indications for surgery, radiologic studies, and operative variables were assessed for each case. Patient-assessed outcome measures were obtained prospectively at baseline and 2 years postoperatively. To understand the factors associated with prolonged return to work, univariate linear regression analysis and stepwise multivariate Cox proportional hazards model was used. RESULTS: All patient-reported outcomes assessed were significantly improved 2 years after TLIF (P < 0.001). Of the 32 patients working preoperatively, 26 (81%) returned to work postoperatively. Median time to return to work was 56 days (range, 10-150 days). Independent of patient age; preoperative pain, disability, and quality of life; and extent of postoperative improvement, increased preoperative Zung depression score remained associated with prolonged return to work (P = 0.02). CONCLUSIONS: Independent of postoperative improvement in pain, disability, and quality of life, the extent of preoperative depression was an independent predictor of time to return to work in patients undergoing TLIF for spondylolisthesis, suggesting that regardless of how successful TLIF surgery may be at improving a patient's pain, disability, or quality of life, greater depression will delay or prohibit their ability to return to work postoperatively.

C2 nerve root transection during C1 lateral mass screw fixation: does it affect functionality and quality of life?

BACKGROUND: Sectioning of the C2 nerve root allows for direct visualization of the C1-2 joint and may facilitate arthrodesis. OBJECTIVE: To determine the clinical and functional consequences of C2 nerve root sectioning during placement of C1 lateral mass screws. METHODS: All patients undergoing C1 lateral mass screw fixation were included in this prospective study. A standard questionnaire was used to determine the severity of occipital numbness/pain and its effect on quality of life (QOL). Domains of the neck disability index were used to assess the disability related to C2 symptoms. RESULTS: A total of 28 patients were included (C2 transection, 8; C2 preservation, 20). A trend of decreased blood loss and length of surgery was observed in the C2 transection cohort. Occipital numbness was reported by 4 (50.0%) patients after C2 transection. Occipital neuralgia was reported by 7 (35.0%) patients with C2 preservation. None of the patients with numbness after C2 transection reported being "bothered" by it. All patients with occipital neuralgia after C2 sparing reported being "bothered" by it, and 57.1% reported a moderate to severe effect on QOL. The use of medication was reported by 5 (71.4%) patients with neuralgia vs none with numbness. Mean disability was significantly higher with neuralgia vs numbness (P = .016). CONCLUSION: C2 nerve root transection is associated with increased occipital numbness but this has no effect on patient-reported outcomes and QOL. C2 nerve root preservation can be associated with occipital neuralgia, which has a negative impact on patient disability and QOL. C2 nerve root transection has no negative consequences during C1-2 stabilization.

Minimally invasive versus open transforaminal lumbar interbody fusion for degenerative spondylolisthesis: comparative effectiveness and cost-utility analysis.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) for lumbar spondylolisthesis allows for the surgical treatment of back/leg pain while minimizing tissue injury and accelerating the patient's recovery. Although previous results have shown shorter hospital stays and decreased intraoperative blood loss for MIS versus open TLIF, short- and long-term outcomes have been similar. Therefore, we performed comparative effectiveness and cost-utility analysis for MIS versus open TLIF. METHODS: A total of 100 patients (50 MIS, 50 open) undergoing TLIF for lumbar spondylolisthesis were prospectively studied. Back-related medical resource use, missed work, and quality-adjusted life years were assessed. Cost of in-patient care, direct cost (2-year resource use × unit costs based on Medicare national allowable payment amounts), and indirect cost (work-day losses × self-reported gross-of-tax wage rate) were recorded, and the incremental cost-effectiveness ratio was calculated. RESULTS: Length of hospitalization and time to return to work were less for MIS versus open TLIF (P = 0.006 and P = 0.03, respectively). MIS versus open TLIF demonstrated similar improvement in patient-reported outcomes assessed. MIS versus open TLIF was associated with a reduction in mean hospital cost of $1758, indirect cost of $8474, and total 2-year societal cost of $9295 (P = 0.03) but similar 2-year direct health care cost and quality-adjusted life years gained. CONCLUSIONS: MIS TLIF resulted in reduced operative blood loss, hospital stay and 2-year cost, and accelerated return to work. Surgical morbidity, hospital readmission, and short- and long-term clinical effectiveness were similar between MIS and open TLIF. MIS TLIF may represent a valuable and cost-saving advancement from a societal and hospital perspective.