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Objective: Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD., Methods: Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures., Results: The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events., Conclusions: This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.Reprinted from Am J Psychiatry 2021; 178:193-202 , with permission from American Psychiatric Association Publishing. Copyright © 2021., (Copyright © 2023 by the American Psychiatric Association.)

Background: Given the physical and economic burden of complications in spine surgery, reducing the prevalence of perioperative adverse events is a primary concern of both patients and health care professionals. This study aims to identify specific perioperative factors predictive of developing varying grades of postoperative complications in adult spinal deformity (ASD) patients, as assessed by the Clavien-Dindo complication classification (Cc) system., Methods: Surgical ASD patients ≥18 years were identified in the American College of Surgeons' National Surgical Quality Improvement Program from 2005 to 2015. Postoperative complications were stratified by Cc grade severity: minor (I, II, and III) and severe (IV and V). Stepwise regression models generated dataset-specific predictive models for Cc groups. Model internal validation was achieved by bootstrapping and calculating the area under the curve (AUC) of the model. Significance was set at P < 0.05., Results: Included were 3936 patients (59 ± 16 years, 63% women, 29 ± 7 kg/m 2 ) undergoing surgery for ASD (4.4 ± 4.7 levels, 71% posterior approach, 11% anterior, and 18% combined). Overall, 1% of cases were revisions, 39% of procedures involved decompression, 27% osteotomy, and 15% iliac fixation. Additionally, 66% of patients experienced at least 1 complication, 0% of which were Cc grade I, 51% II, 5% III, 43% IV, and 1% V. The final model predicting severe Cc (IV-V) complications yielded an AUC of 75.6% and included male sex, diabetes, increased operative time, central nervous system tumor, osteotomy, cigarette pack-years, anterior decompression, and anterior lumbar interbody fusion. Final models predicting specific Cc grades were created., Conclusions: Specific predictors of adverse events following ASD-corrective surgery varied for complications of different severities. Multivariate modeling showed smoking rate, osteotomy, diabetes, anterior lumbar interbody fusion, and higher operative time, among other factors, as predictive of severe complications, as classified by the Clavien-Dindo Cc system. These factors can help in the identification of high-risk patients and, consequently, improve preoperative patient counseling., Clinical Relevance: The findings of this study provide a foundation for identifying ASD patients at high risk of postoperative complications ., Competing Interests: Declaration of Conflicting Interests: The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Objective: To assess whether surgical cervical deformity (CD) patients meet spinopelvic age-adjusted alignment targets, reciprocal, and lower limb compensation changes., Study Design: Retrospective review., Methods: CD was defined as C2-C7 lordosis >10°, cervical sagittal vertical angle (cSVA) >4 cm, or T1 slope minus cervical lordosis (TS-CL) >20°. Inclusion criteria were age >18 years and undergoing surgical correction with complete baseline and postoperative imaging. Published formulas were used to create age-adjusted alignment target for pelvic tilt (PT), pelvic incidence and lumbar lordosis (PI-LL), sagittal vertical angle (SVA), and lumbar lordosis and thoracic kyphosis (LL-TK). Actual alignment was compared with age-adjusted ideal values. Patients who matched ±10-year thresholds for age-adjusted targets were compared with unmatched cases (under- or overcorrected)., Results: A total of 120 CD patients were included (mean age, 55.1 years; 48.4% women; body mass index, 28.8 kg/m 2 ). For PT, only 24.4% of patients matched age-adjusted alignment, 51.1% overcorrected for PT, and 24.4% undercorrected. For PI-LL, only 27.6% of CD patients matched age-adjusted targets, with 49.4% overcorrected and 23% undercorrected postoperatively. Forty percent of patients matched age-adjusted target for SVA, 41.3% overcorrected, and 18.8% undercorrected. CD patients who had worsened in TS-CL or cSVA postoperatively displayed increased TK (-41.1° to -45.3°, P = 1.06). With lower extremity compensation, CD patients decreased in ankle flexion angle postoperatively (6.1°-5.5°, P = 0.036) and trended toward smaller sacrofemoral angle (199.6-195.6 mm, P = 0.286) and knee flexion (2.6° to -1.1°, P = 0.269)., Conclusions: In response to worsening CD postoperatively, patients increased in TK and recruited less lower limb compensation. Almost 75% of CD patients did not meet previously established spinopelvic alignment goals, of whom a subset of patients were actually made worse off in these parameters following surgery. This finding raises the question of whether we should be looking at the entire spine when treating CD., Competing Interests: Declaration of Conflicting Interests: The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2022 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Most breast cancer patients die of non-cancer causes. The risk of death from heart disease, a leading cause of death, is unknown. The aim of this study is to characterize the long-term risk of fatal heart disease in breast cancer patients., Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database. Standard mortality ratios (SMR) were calculated for breast cancer patients diagnosed from 1992 to 2014. Patients were stratified by receipt of radiotherapy and/or chemotherapy, disease laterality, and diagnosis era. Hazard ratios (HRs) and odds ratios (ORs) were calculated to compare the risk of death from heart disease among other breast cancer patients., Results: There were 1,059,048 patients diagnosed with breast cancer from 1992 to 2014, of which 47,872 (4.6%) died from heart disease. The SMR for death from heart disease at 10+ years for patients who received only radiotherapy was 2.92 (95% CI 2.81-3.04, p < 0.001) and in patients who received only chemotherapy was 5.05 (95% CI 4.57-5.55, p < 0.001). There was no statistically significant difference in SMR for death from heart disease for left-sided vs. right-sided disease. At 10+ years, heart disease made up 28% of deaths from non-primary cancer. HRs and ORs showed that the risk of death from heart disease was highest in patients older than 70 years of age and with longer follow-up., Conclusion: The risk of fatal heart disease was highest in older breast cancer patients with longer follow-up (i.e., >5-10 years) and who received chemotherapy. These patients should be referred to cardio-oncology clinics to mitigate this risk., Competing Interests: AL received honoraria from AstraZeneca for advisory board and speaker’s fees, unrelated to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Agha, Wang, Wang, Lehrer, Horn, Rosenberg, Trifiletti, Diaz, Louie and Zaorsky.)

Background: More sophisticated surgical techniques for correcting adult spinal deformity (ASD) have increased operative times, adding to physiologic stress on patients and increased complication incidence. This study aims to determine factors associated with operative time using a statistical learning algorithm., Methods: Retrospective review of a prospective multicenter database containing 837 patients undergoing long spinal fusions for ASD. Conditional inference decision trees identified factors associated with skin-to-skin operative time and cutoff points at which factors have a global effect. A conditional variable-importance table was constructed based on a nonreplacement sampling set of 2000 conditional inference trees. Means comparison for the top 15 variables at their respective significant cutoffs indicated effect sizes., Results: Included: 544 surgical ASD patients (mean age: 58.0 years; fusion length 11.3 levels; operative time: 378 minutes). The strongest predictor for operative time was institution/surgeon. Center/surgeons, grouped by decision tree hierarchy, a and b were, on average, 2 hours faster than center/surgeons c-f, who were 43 minutes faster than centers g-j, all P < 0.001. The next most important predictors were, in order, approach (combined vs posterior increases time by 139 minutes, P < 0.001), levels fused (<4 vs 5-9 increased time by 68 minutes, P < 0.050; 5-9 vs < 10 increased time by 47 minutes, P < 0.001), age (age <50 years increases time by 57 minutes, P < 0.001), and patient frailty (score <1.54 increases time by 65 minutes, P < 0.001). Surgical techniques, such as three-column osteotomies (35 minutes), interbody device (45 minutes), and decompression (48 minutes), also increased operative time. Both minor and major complications correlated with < 66 minutes of increased operative time. Increased operative time also correlated with increased hospital length of stay (LOS), increased estimated intraoperative blood loss (EBL), and inferior 2-year Oswestry Disability Index (ODI) scores., Conclusions: Procedure location and specific surgeon are the most important factors determining operative time, accounting for operative time increases <2 hours. Surgical approach and number of levels fused were also associated with longer operative times, respectively. Extended operative time correlated with longer LOS, higher EBL, and inferior 2-y ODI outcomes., Clinical Relevance: We further identified the poor outcomes associated with extended operative time during surgical correction of ASD, and attributed the useful predictors of time spent in the operating room, including site, surgeon, surgical approach, and the number of levels fused., Competing Interests: Declaration of Conflicting Interests: The International Spine Study Group (ISSG) is funded through research grants from DePuy Synthes, and supported the current work. Portions of this work were accepted for podium presentation at the North American Spine Society Conference, Orlando, Florida, United States, October 27, 2017., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2022 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N = 21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala). Improvements in PTSD severity were associated with increased functional connectivity between the ventromedial prefrontal cortex (vmPFC) and amygdala during emotional face-viewing (change score retained in model with minimum predictive error in left-out subjects, standardized regression coefficient [β] = 2.90). This effect was stronger in participants who received ketamine compared to midazolam (interaction β = 0.86), and persisted following inclusion of concomitant change in depressive symptoms in the analysis model (β = 0.69). Improvement following ketamine was also predicted by decreased dorsal anterior cingulate activity during emotional conflict regulation, and increased task-free connectivity between the vmPFC and anterior insula (βs = -2.82, 0.60). Exploratory follow-up analysis via dynamic causal modelling revealed that whilst improvement in PTSD symptoms following either drug was associated with decreased excitatory modulation of amygdala→vmPFC connectivity during emotional face-viewing, increased top-down inhibition of the amygdala by the vmPFC was only observed in participants who improved under ketamine. Individuals with low prefrontal inhibition of amygdala responses to faces at baseline also showed greater improvements following ketamine treatment. These preliminary findings suggest that, specifically under ketamine, improvements in PTSD symptoms are accompanied by normalization of hypofrontal control over amygdala responses to social signals of threat., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Introduction: Lung metastasis is usually associated with poor outcomes in cancer patients. This study was performed to characterize and analyze the population of patients with de novo (synchronous) lung metastases using the Surveillance, Epidemiology and End Results (SEER) database. Materials and Methods: Baseline characteristics of lung metastasis patients were obtained from SEER case listings. Incidence rates and counts of synchronous lung metastasis were also obtained using the SEER * Stat software. Survival outcomes were analyzed using univariate and multivariable Cox regressions, controlling for confounders. An alpha threshold of 0.05 was used for statistical significance and p -values were subject to correction for multiple comparisons. Results: The age-adjusted incidence rate of synchronous lung metastasis was 17.92 per 100,000 between 2010 and 2015. Synchronous lung metastases most commonly arose from primary lung cancers, colorectal cancers, kidney cancers, pancreatic cancers and breast cancers. During this time period, 4% of all cancer cases presented with synchronous lung metastasis. The percentage of patients presenting with synchronous lung metastasis ranged from 0.5% of all prostate cancers to 13% of all primary lung cancers. The percentage of all cancer cases presenting with synchronous lung metastasis increased over time. De novo metastatic patients with lung metastases had worse overall survival [hazard ratio = 1.22 (1.21-1.23), p < 0.001] compared to those with only extrapulmonary metastases, controlling for potential confounders. Conclusions: Synchronous lung metastasis occurs frequently and is an independent predictors of poor patient outcomes. As treatment for lung metastases becomes more complicated, patients with synchronous lung metastasis represent a high-risk population., Competing Interests: NZ received personal fees from Springer Nature Inc. and Weatherby Healthcare, unrelated to the submitted work. DT reports clinical trial research support from Novocure, and publishing fees from Springer Nature Inc. for projects unrelated to the submitted work. AL has received honoraria from Varian Medical Systems Inc. and AstraZeneca, unrelated to the current work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Stoltzfus, Lehrer, Horn, Siva, Trifiletti, Meng, Verma, Louie and Zaorsky.)

Background: Although stress is a risk factor for mental and physical health problems, it can be difficult to assess, especially on a continual, non-invasive basis. Mobile sensing data, which are continuously collected from naturalistic smartphone use, may estimate exposure to acute and chronic stressors that have health-damaging effects. This initial validation study validated a mobile-sensing collection tool against assessments of perceived and lifetime stress, mental health, sleep duration, and inflammation., Methods: Participants were 25 well-characterized healthy young adults ( M age  = 20.64 years, SD = 2.74; 13 men, 12 women). We collected affective text language use with a custom smartphone keyboard. We assessed participants' perceived and lifetime stress, depression and anxiety levels, sleep duration, and basal inflammatory activity (i.e. salivary C-reactive protein and interleukin-1β)., Results: Three measures of affective language (i.e. total positive words, total negative words, and total affective words) were strongly associated with lifetime stress exposure, and total negative words typed was related to fewer hours slept (all large effect sizes: r  = 0.50 - 0.78). Total positive words, total negative words, and total affective words typed were also associated with higher perceived stress and lower salivary C-reactive protein levels (medium effect sizes; r  = 0.22 - 0.32)., Conclusions: Data from this initial longitudinal validation study suggest that total and affective text use may be useful mobile sensing measures insofar as they are associated with several other stress, mental health, behavioral, and biological outcomes. This tool may thus help identify individuals at increased risk for stress-related health problems., Competing Interests: Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Using mobile sensing data to assess stress: Associations with perceived and lifetime stress, mental health, sleep, and inflammation. Nicholas Allen and Michelle Byrne both hold equity interests in Ksana Health Inc., a company that has the sole commercial license for certain versions of the Effortless Assessment of Risk States (EARS) mobile phone application and some related EARS tools. The other authors have nothing else to disclose., (© The Author(s) 2021.)

Introduction: Osteotomies are commonly performed to correct sagittal malalignment in cervical deformity (CD). However, the risks and benefits of performing a major osteotomy for cervical deformity correction have been understudied. The objective of this retrospective cohort study was to investigate the risks and benefits of performing a major osteotomy for CD correction., Methods: Patients stratified based on major osteotomy (MAJ) or minor (MIN). Independent t -tests and Chi-squared tests were used to assess differences between MAJ and MIN. A sub-analysis compared patients with flexible versus rigid CL., Results: 137 CD patients were included (62 years, 65% F). 19.0% CD patients underwent a MAJ osteotomy. After propensity score matching for cSVA, 52 patients were included. About 19.0% CD patients underwent a MAJ osteotomy. MAJ patients had more minor complications ( P = 0.045), despite similar surgical outcomes as MIN. At 3M, MAJ and MIN patients had similar NDI, mJOA, and EQ5D scores, however by 1 year, MAJ patients reached MCID for NDI less than MIN patients ( P = 0.003). MAJ patients with rigid deformities had higher rates of complications (79% vs. 29%, P = 0.056) and were less likely to show improvement in NDI at 1 year (0.95 vs. 0.54, P = 0.027). Both groups had similar sagittal realignment at 1 year (all P > 0.05)., Conclusions: Cervical deformity patients who underwent a major osteotomy had similar clinical outcomes at 3-months but worse outcomes at 1-year as compared to minor osteotomies, likely due to differences in baseline deformity. Patients with rigid deformities who underwent a major osteotomy had higher complication rates and worse clinical improvement despite similar realignment at 1 year., Competing Interests: The International Spine Study Group (ISSG) is funded through research grants from DePuy Synthes and individual donations, and supported the current work., (Copyright: © 2021 Journal of Craniovertebral Junction and Spine.)

Background: For cervical deformity (CD) surgery, goals include realignment, improved patient quality of life, and improved clinical outcomes. There is limited research identifying patients most likely to achieve all three., Objective: The objective is to create a model predicting good 1-year postoperative realignment, quality of life, and clinical outcomes following CD surgery using baseline demographic, clinical, and radiographic factors., Methods: Retrospective review of a multicenter CD database. CD patients were defined as having one of the following radiographic criteria: Cervical sagittal vertical axis (cSVA) >4 cm, cervical kyphosis/scoliosis >10°° or chin-brow vertical angle >25°. The outcome assessed was whether a patient achieved both a good radiographic and clinical outcome. The primary analysis was stepwise regression models which generated a dataset-specific prediction model for achieving a good radiographic and clinical outcome. Model internal validation was achieved by bootstrapping and calculating the area under the curve (AUC) of the final model with 95% confidence intervals., Results: Seventy-three CD patients were included (61.8 years, 58.9% F). The final model predicting the achievement of a good overall outcome (radiographic and clinical) yielded an AUC of 73.5% and included the following baseline demographic, clinical, and radiographic factors: mild-moderate myelopathy (Modified Japanese Orthopedic Association >12), no pedicle subtraction osteotomy, no prior cervical spine surgery, posterior lowest instrumented vertebra (LIV) at T1 or above, thoracic kyphosis >33°°, T1 slope <16 and cSVA <20 mm., Conclusions: Achievement of a positive outcome in radiographic and clinical outcomes following surgical correction of CD can be predicted with high accuracy using a combination of demographic, clinical, radiographic, and surgical factors, with the top factors being baseline cSVA <20 mm, no prior cervical surgery, and posterior LIV at T1 or above., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Craniovertebral Junction and Spine.)

Background: Age-adjusted alignment targets in the context of distal junctional kyphosis (DJK) development have yet to be investigated. Our aim was to assess age-adjusted alignment targets, reciprocal changes, and role of lowest instrumented level orientation in DJK development in cervical deformity (CD) patients., Methods: CD patients were evaluated based on lowest fused level: cervical (C7 or above), upper thoracic (UT: T1-T6), and lower thoracic (LT: T7-T12). Age-adjusted alignment targets were calculated using published formulas for sagittal vertical axis (SVA), pelvic incidence-lumbar lordosis (PI-LL), pelvic tilt (PT), T1 pelvic angle (TPA), and LL-thoracic kyphosis (TK). Outcome measures were cervical and global alignment parameters: Cervical SVA (cSVA), cervical lordosis, C2 slope, C2-T3 angle, C2-T3 SVA, TS-CL, PI-LL, PT, and SVA. Subanalysis matched baseline PI to assess age-adjusted alignment between DJK and non-DJK., Results: Seventy-six CD patients included. By 1Y, 20 patients developed DJK. Non-DJK patients had 27% cervical lowest instrumented vertebra (LIV), 68% UT, and 5% LT. DJK patients had 25% cervical, 50% UT, and 25% LT. There were no baseline or 1Y differences for PI, PI-LL, SVA, TPA, or PT for actual and age-adjusted targets. DJK patients had worse baseline cSVA and more severe 1Y cSVA, C2-T3 SVA, and C2 slope ( P < 0.05). The distribution of over/under corrected patients and the offset between actual and ideal alignment for SVA, PT, TPA, PI-LL, and LL-TK were similar between DJK and non-DJK patients. DJK patients requiring reoperation had worse postoperative changes in all cervical parameters and trended toward larger offsets for global parameters., Conclusion: CD patients with severe baseline malalignment went on to develop postoperative DJK. Age-adjusted alignment targets did not capture differences in these populations, suggesting the need for cervical-specific goals., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Craniovertebral Junction and Spine.)

Study Design: Retrospective cohort study of prospective patients undergoing minimally invasive lumbar fusion at a single academic institution., Objective: To assess differences in perioperative outcomes between primary and revision MIS (minimally invasive surgical) lumbar interbody fusion patients and compare with those undergoing corresponding open procedures., Methods: Patients ≥18 years old undergoing lumbar interbody fusion were grouped by surgical technique: MIS or open. Patients within each group were propensity score matched for comorbidities and levels fused. Patient demographics, surgical factors, and perioperative complication incidences were compared between primary and revision cases using means comparison tests, as appropriate., Results: Of the 214 lumbar interbody fusion patients included after propensity score matching, 44 (21%) cases were MIS, and 170 (79%) were open. For MIS patients, there were no significant differences between primary and revision cases in estimated blood loss (EBL; 344 vs 299 cm 3 , P = .682); however, primary cases had longer operative times (301 vs 246 minutes, P = .029). There were no differences in length of stay (LOS), intensive care unit LOS, readmission, and intraoperative or postoperative complications (all P > .05). For open patients, there were no differences between primary and revision cases in EBL ( P > .05), although revisions had longer operative times (331 vs 278 minutes, P = .018) and more postoperative complications (61.7% vs 23.8%, P < .001). MIS revision procedures were shorter than open revisions (182 vs 213 minutes, P = .197) with significantly less EBL (294 vs 965 cm 3 , P < .001), shorter inpatient and intensive care unit LOS, and fewer postoperative complications (all P < .05)., Conclusions: Clinical outcomes of revision MIS lumbar interbody fusion were similar to those of primary surgery. Additionally, MIS techniques were associated with less EBL, shorter LOS, and fewer perioperative complications than corresponding open revisions.

Study Design: Retrospective review of single institution., Objective: To assess the relationship between Patient-Reported Outcomes Measurement Information System (PROMIS) and Oswestry Disability Index (ODI) scores in thoracolumbar patients., Methods: Included: Patients ≥18 years with a thoracolumbar spine condition (spinal stenosis, disc herniation, low back pain, disc degeneration, spondylolysis). Bivariate correlations assessed the linear relationships between ODI and PROMIS (Physical Function, Pain Intensity, and Pain Interference). Correlation cutoffs assessed patients with high and low correlation between ODI and PROMIS. Linear regression predicted the relationship of ODI to PROMIS., Results: A total of 206 patients (age 53.7 ± 16.6 years, 49.5% female) were included. ODI correlated with PROMIS Physical Function ( r = -0.763, P < .001), Pain Interference ( r = 0.800, P < .001), and Pain Intensity ( r = 0.706, P < .001). ODI strongly predicted PROMIS for Physical Function ( R 2 = 0.58, P < .001), Pain Intensity ( R 2 = 0.50, P < .001), and Pain Interference ( R 2 = 0.64, P < .001); however, there is variability in PROMIS that ODI cannot account for. ODI questions about sitting and sleeping were weakly correlated across the 3 PROMIS domains. Linear regression showed overall ODI score as accounting for 58.3% ( R 2 = 0.583) of the variance in PROMIS Physical Function, 63.9% ( R 2 = 0.639) of the variance in Pain Interference score, and 49.9% ( R 2 = 0.499) of the variance in Pain Intensity score., Conclusions: There is a large amount of variability with PROMIS that cannot be accounted for with ODI. ODI questions regarding walking, social life, and lifting ability correlate strongly with PROMIS while sitting, standing, and sleeping do not. These results reinforce the utility of PROMIS as a valid assessment for low back disability, while indicating the need for further evaluation of the factors responsible for variation between PROMIS and ODI., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter G. Passias consults for Medicrea and SpineWave; is on the Scientific Advisory Board of Allosource; receives teaching/speaking from Zimmer Biomet and Globus; receives grant from CSRS; does a research study for Aesculap., (© The Author(s) 2019.)

Background: A small number of high-need patients account for a disproportionate amount of Medicaid spending, yet typically engage little in outpatient care and have poor outcomes., Objective: To address this issue, we developed ECHO (Extension for Community Health Outcomes) Care™, a complex care intervention in which outpatient intensivist teams (OITs) provided care to high-need high-cost (HNHC) Medicaid patients. Teams were supported using the ECHO model™, a continuing medical education approach that connects specialists with primary care providers for case-based mentoring to treat complex diseases., Design: Using an interrupted time series analysis of Medicaid claims data, we measured healthcare utilization and expenditures before and after ECHO Care., Participants: ECHO Care served 770 patients in New Mexico between September 2013 and June 2016. Nearly all had a chronic mental illness, and over three-quarters had a chronic substance use disorder., Intervention: ECHO Care patients received care from an OIT, which typically included a nurse practitioner or physician assistant, a registered nurse, a licensed mental health provider, and at least one community health worker. Teams focused on addressing patients' physical, behavioral, and social issues., Main Measures: We assessed the effect of ECHO Care on Medicaid costs and utilization (inpatient admissions, emergency department (ED) visits, other outpatient visits, and dispensed prescriptions., Key Results: ECHO Care was associated with significant changes in patients' use of the healthcare system. At 12 months post-enrollment, the odds of a patient having an inpatient admission and an ED visit were each reduced by approximately 50%, while outpatient visits and prescriptions increased by 23% and 8%, respectively. We found no significant change in overall Medicaid costs associated with ECHO Care., Conclusions: ECHO Care shifts healthcare utilization from inpatient to outpatient settings, which suggests decreased patient suffering and greater access to care, including more effective prevention and early intervention for chronic conditions.

Background: The objectives of this study were to characterize (1) epidemiology of brain metastases at the time of primary cancer diagnosis, (2) incidence and trends of synchronous brain metastases from 2010 to 2015, and (3) overall survival (OS) of patients with synchronous brain metastases., Methods: A total of 42 047 patients with synchronous brain metastases from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results database. Descriptive analysis was utilized to analyze demographics and incidence. The Kaplan-Meier method and a Cox proportional hazards model were utilized to evaluate potential prognostic factors for OS., Results: The majority of patients were diagnosed from age older than 50 (91.9%). Common primary sites included lung (80%), melanoma (3.8%), breast (3.7%), and kidney/renal pelvis (3.0%). Among pediatric patients, common primaries included kidney/renal pelvis and melanomas. The incidence was roughly 7.3 persons/100 000. Synchronous brain metastases were associated with significantly poorer OS compared to extracranial metastases alone (hazard ratio [HR] =1.56; 95% CI: 1.54-1.58; P < .001). Among patients with brain metastases, male gender (HR = 1.60 vs 1.52), age older than 65 years (HR = 1.60 vs 1.46), synchronous liver, bone, or lung metastases (HR = 1.61 vs 1.49), and earlier year of diagnosis (HR = 0.98 for each year following 2010) were associated with significantly poorer OS., Conclusions: The vast majority of brain metastases are from lung primaries. Synchronous brain metastases are associated with poorer OS compared to extracranial metastases alone., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Programs for high-need, high-cost (HNHC) patients can improve care and reduce costs. However, it may be challenging to implement these programs in rural and underserved areas, in part due to limited access to specialty consultation., Aim: Evaluate the feasibility of using the Extension for Community Health Outcomes (ECHO) model to provide specialist input to outpatient intensivist teams (OITs) dedicated to caring for HNHC patients., Setting: Weekly group videoconferencing sessions that connect multidisciplinary specialists with OITs., Participants: Six OITs across New Mexico, typically consisting of a nurse practitioner or physician assistant, a registered nurse, a counselor or social worker, and at least one community health worker., Program Description: OITs and specialists participated in weekly teleECHO sessions focused on providing the OITs with case-based mentoring and support., Program Evaluation: OITs and specialists discussed 427 highly complex patient cases, many of which had social or behavioral health components to address. In 70% of presented cases, the teams changed their care plan for the patient, and 87% reported that they applied what they learned in hearing case presentations to other HNHC patients., Discussion: Pairing the ECHO model with intensive outpatient care is a feasible strategy to support OITs to provide high-quality care for HNHC patients.

Study Design: Retrospective review of a prospectively collected database., Objective: To predict the occurrence of hospital-acquired conditions (HACs) 30-days postoperatively and to compare predictors of HACs for spine surgery with other common elective surgeries., Methods: Patients ≥18 years undergoing elective spine surgery were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2013. Outcome measures included any HACs: superficial or deep surgical site infection (SSI), venous thromboembolism (VTE), urinary tract infection (UTI). Spine surgery patients were compared with those undergoing other common procedures. Random forest followed by multivariable regression analysis was used to determine risk factors for the occurrence of HACs., Results: A total of 90 551 elective spine surgery patients, of whom 3021 (3.3%) developed at least 1 HAC, 1.4% SSI, 1.3% UTI, and 0.8% VTE. The occurrence of HACs for spine patients was predicted with high accuracy (area under the curve [AUC] 77.7%) with the following variables: female sex, baseline functional status, hypertension, history of transient ischemic attack (TIA), quadriplegia, steroid use, preoperative bleeding disorders, American Society of Anesthesiologists (ASA) class, operating room duration, operative time, and level of residency supervision. Functional status and hypertension were HAC predictors for total knee arthroplasty (TKA), bariatric, and cardiothoracic patients. ASA class and operative time were predictors for most surgery cohorts. History of TIA, preoperative bleeding disorders, and steroid use were less predictive for most other common surgical cohorts., Conclusions: Occurrence of HACs after spine surgery can be predicted with demographic, clinical, and surgical factors. Predictors for HACs in surgical spine patients, also common across other surgical groups, include functional status, hypertension, and operative time. Understanding the baseline patient risks for HACs will allow surgeons to become more effective in their patient selection for surgery., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter G. Passias, MD, reports personal consulting fees for Spinewave, Zimmer Biomet, and Medicrea outside the submitted work. Virginie Lafage, PhD, is paid for lectures by Depuy Synthes, Nuvasive, K2M, and Medtronic and is a Nemaris Board member and shareholder.

Background: Regional and segmental changes of the lumbar spine have previously been described as patients transition from standing to sitting; however, alignment changes in the cervical and thoracic spine have yet to be investigated. So, the aim of this study was to assess cervical and thoracic regional and segmental changes in patients with thoracolumbar deformity versus a nondeformed thoracolumbar spine population., Methods: This study was a retrospective cohort study of a single center's database of full-body stereoradiographic imaging and clinical data. Patients were ≥ 18 years old with nondeformed spines (nondegenerative, nondeformity spinal pathologies) or thoracolumbar deformity (ASD: PI-LL > 10°). Patients were propensity-score matched for age and maximum hip osteoarthritis grade and were stratified by Scoliosis Research Society (SRS)-Schwab classification by PI-LL, SVA, and PT. Patients with lumbar transitional anatomy or fusions were excluded. Outcome measures included changes between standing and sitting in global alignment parameters: sagittal vertical axis (SVA), pelvic incidence minus lumbar lordosis (PI-LL), pelivc tilt (PT), thoracic kyphosis, cervical alignment, cervical SVA, C2-C7 lordosis (CL), T1 slop minus CL (TS-CL), and segmental alignment from C2 to T12. Another analysis was performed using patients with cervical and thoracic segmental measurements., Results: A total of 338 patients were included (202 nondeformity, 136 ASD). After propensity-score matching, 162 patients were included (81 nondeformity, 81 ASD). When categorized by SRS-Schwab classification, all nondeformity patients were nonpathologically grouped for PI-LL, SVA, and PT, whereas ASD patients had mix of moderately and markedly deformed modifiers. There were significant differences in pelvic and global spinal alignment changes from standing to sitting between nondeformity and ASD patients, particularly for SVA (nondeformed: 49.5 mm versus ASD: 27.4 mm; P &thinsp ; < .001) and PI-LL (20.12° versus 13.01°, P  < .001). With application of the Schwab classification system upon the cohort, PI-LL ( P  = .040) and SVA ( P  = .007) for severely classified deformity patients had significantly less positional alignment change. In an additional analysis of patients with segmental measurements from C2 to T12, nondeformity patients showed significant mobility of T2-T3 (-0.99° to -0.54°, P  = .023), T6-T7 (-3.39° to -2.89°, P  = .032), T7-T8 (-2.68° to -2.23°, P  = .048), and T10-T11 (0.31° to 0.097°, P  = .006) segments from standing to sitting. ASD patients showed mobility of the C6-C7 (1.76° to 3.45°, P  < .001) and T11-T12 (0.98° to 0.54°, P  = 0.014) from standing to sitting. The degree of mobility between nondeformity and ASD patients was significantly different in C6-C7 (-0.18° versus 1.69°, P  = .003), T2-T3 (0.45° versus -0.27°, P  = .034), and T10-T11 (0.45° versus -0.30°, P  = .001) segments. With application of the Schwab modifier system upon the cohort, mobility was significant in the C6-C7 (nondeformed: 0.18° versus moderately deformed: 2.12° versus markedly deformed: 0.92°, P  = .039), T2-T3 (0.45° versus -0.08° versus -0.63°, P  = .020), T6-T7 (0.48° versus 0.36° versus -1.85°, P  = .007), and T10-T11 (0.45° versus -0.21° versus -0.23°, P  = .009) segments., Conclusions: Nondeformity patients and ASD patients have significant differences in mobility of global spinopelvic parameters as well as segmental regions in the cervical and thoracic spine between sitting and standing. This study aids in our understanding of flexibility and compensatory mechanisms in deformity patients, as well as the possible impact on unfused segments when considering deformity corrective surgery., Competing Interests: Disclosures and COI: No funding was received in relation to the creation of this work. Each institution obtained approval from their local Institutional Review Board to enroll patients in the prospective database and informed consent was obtained from each patient. Peter G. Passias, MD, reports personal consulting fees for Spinewave, Zimmer Biomet, and Medicrea outside the submitted work. Virginie Lafage, PhD, reports Depuy Synthes paid lectures, Nuvasive paid lectures, K2M paid lectures, Medtronic paid lectures, and Nemaris board member and shareholder.

Background: Klippel-Feil syndrome (KFS) includes craniocervical anomalies, low posterior hairline, and brevicollis, with limited cervical range of motion; however, there remains no consensus on inheritance pattern. This study defines incidence, characterizes concurrent diagnoses, and examines trends in the presentation and management of KFS., Methods: This was a retrospective review of the Kid's Inpatient Database (KID) for KFSpatients aged 0-20 years from 2003 to 2012. Incidence was established using KID-supplied year and hospital-trend weights. Demographics and secondary diagnoses associated with KFS were evaluated. Comorbidities, anomalies, and procedure type trends from 2003 to 2012 were assessed for likelihood to increase among the years studied using ANOVA tests., Results: Eight hundred and fifty-eight KFS diagnoses (age: 9.49 years; 51.1% females) and 475 patients with congenital fusion (CF) (age: 8.33 years; 50.3% females) were analyzed. We identified an incidence rate of 1/21,587 discharges. Only 6.36% of KFS patients were diagnosed with Sprengel's deformity; 1.44% with congenital fusion. About 19.1% of KFS patients presented with another spinal abnormality and 34.0% presented with another neuromuscular anomaly. About 36.51% of KFS patients were diagnosed with a nonspinal or nonmusculoskeletal anomaly, with the most prevalent anomalies being of cardiac origin (12.95%). About 7.34% of KFS patients underwent anterior fusions, whereas 6.64% of KFS patients underwent posterior fusions. The average number of levels operated on was 4.99 with 8.28% receiving decompressions. Interbody devices were used in 2.45% of cases. The rate of fusions with <3 levels (7.46%) was comparable to that of 3 levels or greater (7.81%)., Conclusions: KFS patients were more likely to have other spinal abnormalities (19.1%) and nonnervous system abnormalities (13.63%). Compared to congenital fusions, KFS patients were more likely to have congenital abnormalities such as Sprengel's deformity. KFS patients are increasingly being treated with spinal fusion., Level of Evidence: III., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Craniovertebral Junction and Spine.)

Introduction: Correction of cervical deformity (CD) often involves different types of osteotomies to address sagittal malalignment. This study assessed the relationship between osteotomy grade and vertebral level on alignment and clinical outcomes., Methods: Retrospective review of a multi-center prospectively collected CD database. CD was defined as at least one of the following: C2-C7 Cobb >10°, cervical lordosis (CL) >10°, C2-C7 sagittal vertical axis (cSVA) >4 cm, and chin-brow vertical angle > 25°. Patients were evaluated for level and type of cervical osteotomy., Results: 86 CD patients were included (61.4 ± 10.6 years, 66.3% female, body mass index 29.1 kg/m 2 ). 141 osteotomies were in the cervical spine and 79 were in the thoracic spine. There were 19 major osteotomies performed, with 47% at T1. Patients with an osteotomy in the cervical spine improved in T1 slope minus CL (TS - CL), CL, and C2 slope (all P < 0.05). Patients with upper thoracic osteotomies improved in TS - CL, cSVA, C2-T3, C2-T3 sagittal vertical axis (SVA), and C2 slope (all P < 0.05). Minor osteotomies in the upper thoracic spine showed improvement in cSVA (63 mm to 49 mm, P = 0.022), C2-T3 ( P = 0.007), and SVA (-16 mm to 27 mm, P < 0.001). The greatest amount of C2-T3 angular change occurred for patients with a major osteotomy at T2 (39.1° change), then T3 (15.7°), C7 (16.9°°), and T1 (13.5°°). Patients with a major osteotomy in the upper thoracic spine showed similar radiographic changes from pre- to post-operative as patients with three or more minor osteotomies, although C2-T3 SVA trended toward greater improvement with a major osteotomy (-22.5 mm vs. +5.9 mm, P = 0.058) due to lever arm effect., Conclusions: CD patients undergoing osteotomies in the cervical and upper thoracic spine experienced improvement in TS--CL and C2 slope. In the upper thoracic spine, multiple minor osteotomies achieved similar alignment changes to major osteotomies at a single level, while a major osteotomy focused at T2 had the greatest overall impact in cervicothoracic and global alignment in CD patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Craniovertebral Junction and Spine.)

Background: Given the paucity of literature regarding compensatory mechanisms used by obese patients with sagittal malalignment, it is necessary to gain a better understanding of the effects of obesity on compensation after comparing the degree of malalignment to age-adjusted ideals. This study aims to compare baseline alignment of obese and nonobese patients using age-adjusted spino-pelvic alignment parameters, describing associated spinal changes., Methods: Patients ≥ 18 years with full-body stereoradiographs were propensity-score matched for sex, baseline pelvic incidence (PI), and categorized as nonobese (body mass index < 30kg/m 2 ) or obese (body mass index ≥ 30). Age-adjusted ideals were calculated for sagittal vertical axis, spino-pelvic mismatch (PI-LL), pelvic tilt, and T1 pelvic angle using established formulas. Patients were stratified as meeting alignment ideals, being above ideal, or being below. Spinal alignment parameters included C0-C2, C2-C7, C2-T3, cervical thoracic pelvic angle, cervical sagittal vertical axis SVA, thoracic kyphosis, T1 pelvic angle, T1 slope, sagittal vertical axis, lumbar lordosis (LL), PI, PI-LL, pelvic tilt. Lower-extremity parameters included sacrofemoral angle, knee flexion (KA), ankle flexion (AA), pelvic shift (PS), and global sagittal angle (GSA). Independent t tests compared parameters between cohorts., Results: Included: 800 obese, 800 nonobese patients. Both groups recruited lower-extremity compensation: sacrofemoral angle ( P  = .004), KA, AA, PS, GSA (all P  < .001). Obese patients meeting age-adjusted PI-LL had greater lower-extremity compensation than nonobese patients: lower sacrofemoral angle ( P  = .002), higher KA ( P  = .008), PS ( P  = .002), and GSA ( P  = .02). Obese patients with PI-LL mismatch higher than age-adjusted ideal recruited greater lower-extremity compensation than nonobese patients: higher KA, AA, PS, GSA (all P  < .001). Obese patients showed compensation through the cervical spine: increased C0-C2, C2-C7, C2-T3, and cervical sagittal vertical axis (all P  < .001), high T1 pelvic angle ( P  < .001), cervical thoracic pelvic angle ( P  = .03), and T1 slope ( P  < .001), with increased thoracic kyphosis ( P  = .015) and decreased LL ( P  < .001) compared to nonobese patients with PI-LL larger than age-adjusted ideal., Conclusions: Regardless of malalignment severity, obese patients recruited lower-limb compensation more than nonobese patients. Obese patients with PI-LL mismatch larger than age-adjusted ideal also develop upper-cervical and cervicothoracic compensation for malalignment., Level of Evidence: III., Clinical Relevance: Clinical evaluation should extend to the cervical spine in obese patients not meeting age-adjusted sagittal alignment ideals., Competing Interests: Disclosures and COI: The authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper. Ethics Review Committee Statement: Institutional Review Board approval was obtained for this study, prior to patient enrollment.

Study Design: Retrospective cohort study., Purpose: The aim of this study was to identify features associated with increased mortality risk in traumatic C2 fractures in the elderly, including measures of comorbidity and frailty., Overview of Literature: C2 fractures in the elderly are of increasing relevance in the setting of an aging global population and have a high mortality rate. Previous analyzes of risk factors for mortality have not included the measures of comorbidity and/or frailty, and no local data have been reported to date., Methods: This study comprises a retrospective review of 70 patients of age >65 years at Waikato Hospital, New Zealand with traumatic C2 fractures identified on computed tomography between 2010 and 2016. Demographic details, medical history, laboratory results on admission, mechanism of injury, and neurological status on presentation were recorded. Medical comorbidities were also detailed allowing calculation of the Charlson Comorbidity Index (CCI) and the modified Frailty Index (mFI)., Results: The most common mechanism of injury was a fall from standing height (n=52, 74.3%). Mortality rates were 14.3% (n=10) at day 30, and 35.7% (n=25) at 1 year. Bivariate analysis showed that both CCI and mFI correlated with 1-year mortality rates. Reduced albumin and hemoglobin levels were also associated with 30-day and 1-year mortality rates. Forward stepwise logistic regression models determined CCI and low hemoglobin as predictors of mortality within 30 days, whereas CCI, low albumin, increased age, and female gender predicted mortality at 1 year., Conclusions: The CCI was a useful tool for predicting mortality at 1 year in the patient cohort. Other variables, including common laboratory markers, can also be used for risk stratification, to initiate timely multidisciplinary management, and prognostic counseling for patients and family members.

Background: Full-body stereographs for adult spinal deformity (ASD) have enhanced global deformity and lower-limb compensation associations. The advent of age-adjusted goals for classic ASD parameters (sagittal vertical axis, pelvic tilt, spino-pelvic mismatch [PI-LL]) has enabled individualized evaluation of successful versus failed realignment, though these remain to be radiographically assessed postoperatively. This study analyzes pre- and postoperative sagittal alignment to quantify patient-specific correction against age-adjusted goals, and presents differences in compensation in patients whose postoperative profile deviates from targets., Methods: Single-center retrospective review of ASD patients ≥ 18 years with biplanar full-body stereographic x-rays. Inclusion: ≥ 4 levels fused, complete baseline and early (≤ 6-month) follow-up imaging. Correction groups generated at postoperative visit for actual alignment compared to age-adjusted ideal values for pelvic tilt, PI-LL, and sagittal vertical axis derived from clinically relevant formulas. Patients that matched exact ± 10-year threshold for age-adjusted targets were compared to unmatched cases (undercorrected or overcorrected). Comparison of spinal alignment and compensatory mechanisms (thoracic kyphosis, hip extension, knee flexion, ankle flexion, pelvic shift) across correction groups were performed with ANOVA and paired t tests., Results: The sagittal vertical axis, pelvic tilt, and PI-LL of 122 patients improved at early postoperative visits ( P  < .001). Of lower-extremity parameters, knee flexion and pelvic shift improved ( P  < .001), but hip extension and ankle flexion were similar ( P  > .170); global sagittal angle decreased overall, reflecting global postoperative correction (8.3° versus 4.4°, P  < .001). Rates of undercorrection to age-adjusted targets for each spino-pelvic parameter were 30.3% (sagittal vertical axis), 41.0% (pelvic tilt), and 43.6% (PI-LL). Compared to matched/overcorrections, undercorrections recruited increased posterior pelvic shift to compensate ( P  < .001); knee flexion was recruited in undercorrections for sagittal vertical axis and pelvic tilt; thoracic hypokyphosis was observed in PI-LL undercorrections. All undercorrected groups displayed consequentially larger global sagittal angle ( P  < .001)., Conclusions: Global alignment cohort improvements were observed, and when comparing actual to age-adjusted alignment, undercorrections recruited pelvic and lower-limb flexion to compensate., Level of Evidence: 3., Competing Interests: Disclosures and COI: The authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper. Institutional Review broad approval was obtained prior to study.

Childhood adversity is a potent risk factor for mental health conditions via disruptions to stress response systems. Dysregulations in oxidative stress systems have been associated with both childhood adversity and several psychological disorders (e.g., major depressive disorder) in adult populations. However, few studies have examined associations between childhood adversity, oxidative stress, and mental health in pediatric populations. Childhood adversity (Adverse Childhood Events [ACE]), oxidative stress [F2t-isoprostanes (IsoPs)], and mental health pathology were assessed in 50 adolescent females recruited primarily through the Department of Youth Services. Standard ordinary least squares regression models were run co-varying for age, race/ethnicity, adolescent nicotine use, study condition, and parent history of ACEs. Adolescents who reported experiencing four or more ACEs had significantly elevated IsoP levels. Further, internalizing symptom scores across diagnoses were significantly associated with elevated IsoPs, whereas no externalizing symptoms scores, except Attention Deficit Hyperactivity Disorder, were related to altered oxidative stress. Results indicate that IsoPs may be a global marker of childhood adversity and mental health symptomatology, particularly within internalizing symptom domains. A limitation is that body mass index was not collected for this sample. Future studies are needed to replicate and extend these findings in larger, more diverse samples., Competing Interests: The authors have declared that no competing interests exist.

Background: The study aimed to characterize trends in incidence, etiology, fracture types, surgical procedures, complications, and concurrent injuries associated with traumatic pediatric cervical fracture using a nationwide database., Methods: The Kids' Inpatient Database (KID) was queried. Trauma cases from 2003 to 2012 were identified, and cervical fracture patients were isolated. Demographics, etiologies, fracture levels, procedures, complications, and concurrent injuries were assessed. The t -tests elucidated significance for continuous variables, and χ 2 for categoric values. Logistic regressions identified predictors of spinal cord injury (SCI), surgery, any complication, and mortality. Level of significance was P < .05., Results: A total of 11 196 fracture patients were isolated (age, 16.63 years; male, 65.7%; white, 65.4%; adolescent, 55.4%). Incidence significantly increased since 2003 (2003 vs 2012, 2.39% vs 3.12%, respectively), as did Charlson Comorbidity Index (CCI; 2003 vs 2012, 0.2012 vs 0.4408, respectively). Most common etiology was motor vehicle accidents (50.5%). Infants and children frequently fractured at C2 (closed: 43.1%, 32.9%); adolescents and young adults frequently fractured at C7 (closed: 23.9%, 26.5%). Upper cervical SCI was less common (5.8%) than lower cervical SCI (10.9%). Lower cervical unspecified-SCI, anterior cord syndrome, and other specified SCIs significantly decreased since 2003. Complications were common (acute respiratory distress syndrome, 7.8%; anemia, 6.7%; shock, 3.0%; and mortality, 4.2%), with bowel complications, cauda equina, anemia, and shock rates significantly increasing since 2003. Concurrent injuries were common (15.2% ribs; 14.4% skull; 7.1% pelvis) and have significantly increased since 2003. Predictors of SCI included sports injury and CCI. Predictors of surgery included falls, sports injuries, CCI, length of stay, and SCI. CCI, SCIs, and concurrent injuries were predictors of any complication and mortality, all ( P < .001)., Conclusions: Since 2003, incidence, complications, concurrent injuries, and fusions have increased. CCI, SCI, falls, and sports injuries were significant predictors of surgical intervention. Decreased mortality and SCI rates may indicate improving emergency medical services and management guidelines., Level of Evidence: III., Clinical Relevance: Clinicians should be aware of increased case complexity in the onset of added perioperative complications and concurrent injuries. Cervical fractures resultant of sports injuries should be scrutinized for concurrent SCIs., Competing Interests: Disclosures and COI: Dr Gerling received personal consulting fees for Paradigm Spine and speaking/teaching fees for Stryker Spine. Dr Passias received personal consulting fees for Spinewave and Medicrea. The other authors received no funding for this study and report no conflicts of interest.

Background: The recommended timing of surgical intervention for vertebral osteomyelitis (VO) is controversial; however, most studies are not sufficiently powered. Our goal was to investigate the associated effects of delaying surgery in VO patients on in-hospital complications, neurologic deficits, and mortality., Methods: Retrospective review of the National Inpatient Sample. Patients who underwent surgery for VO from 1998 to 2013 were identified using codes from the International Classification of Disease, Ninth Revision, Clinical Modification. Patients were stratified into groups based on incremental delay of surgery: 0-day delay (same-day surgery), 1-day delay, 2-day delay, 3- to 6-day delay, 7- to 14-day delay, and 14- to 30-day delay. Univariate analysis compared demographics and outcomes between groups. Multivariate logistic regression models calculated independent predictors of any complication, mortality, and neurologic deficits. A 0-day delay was the reference group., Results: A total of 34 465 patients were identified. Delayed groups were older (same day: 53.5 vs. 7-14-day delay: 61.1) and had a higher Deyo-Charlson score (same day: 0.4901 vs. 14-30-day delay: 1.66), length of stay (same day: 4.2 vs. 14-30-day delay: 34.04 days), and total charges (same day: $63,390.78 vs. 14-30-day delay: $245,752.4), all P  < .001. Delayed groups had higher surgical combined-approach rates (same day: 9.1% vs. 14-30-day delay: 31.5%) and lower anterior-approach rates (same day: 42.4% vs. 14-30-day delay: 24.2%). Delayed groups had increased mortality and complication rates. Regressions showed delayed groups as the strongest independent indicators of any complication (14-30-day delay: odds ratio [OR] 3.384), mortality (14-30-day delay: OR 10.658), and neurologic deficits (14-30-day delay: OR 3.464), all P  < .001., Conclusion: VO patients who operate within 24 hours of admission are more likely to have desirable outcomes. Patients with delayed surgery had a significantly increased risk of developing any complication, mortality, and discharging with neurologic deficits., Level of Evidence: III., Clinical Relevance: Medically fit patients may benefit from earlier surgical management in order to reduce risk of postoperative complications, improve outcomes, and reduce overall hospital costs., Competing Interests: Disclosures and COI: The seventh author received personal consulting fees for Spinewave and Medicrea. The eighth author received personal consulting fees for DePuy Synthes. The first through sixth authors and the ninth author report no conflicts of interest. Each institution obtained approval from its local institutional review board, in which this study was deemed exempt due to the deidentified nature of the data. No sources of funding.

Purpose: Evaluate the presence of new-onset cervical deformity (CD) in nonoperative adult spinal deformity (ASD) patients with extended follow-up, with consideration for predictors, prevalence, and impact on patient-reported outcomes., Methods: Retrospective review of a prospective nonoperative ASD cohort. New onset CD patients at 1- (CD-1Y) and 2-year (CD-2Y) follow-up were defined as displaying baseline cervical alignment. Univariate analyses determined differences in radiographic parameters and outcome scores of CD and maintained-cervical-alignment patients. Multivariate binary logistic regression models determined new-onset CD predictors., Results: A total of 143 patients were included (mean age 54 years, mean body mass index 25.6 kg/m 2 , 86% female). Cervical deformity rate was 38.5% at baseline. New-onset CD incidence at 1- and 2-year follow-up was 30.0% and 41.7%, respectively. Global sagittal profile comparison of CD-1Y/CD-2Y versus maintained cervical alignment cases revealed no differences ( P  > .05) at any interval. Baseline C2-C7 sagittal vertical axis (SVA) was associated with increased new-onset CD risk at 1 (odds ratio [OR] 1.14, P  = .025) and 2 years (OR 1.04, P  = .032); prior spine surgical history was associated with CD risk at 1-year follow-up (OR 6.75, P  = .047); baseline C2 slope was associated with increased CD risk at 2-year follow-up (OR 1.12, P  = .041). CD development did not significantly impact health-related quality of life ( P  > .05)., Conclusions: Cervical deformity can manifest in nonoperative ASD patients: 30.0% at 1-year follow-up, and 41.7% at 2-year follow-up. Progressive CD manifested independently of thoracolumbar profile changes. Increased baseline C2-C7 SVA, C2 slope, and prior surgical history increased new-onset CD odds at 1 and 2 years., Competing Interests: Disclosures and COI: All authors are a part of the International Spine Study Group Foundation, which receives funding from a company through which this study was conducted. Funding for the International Spine Study Group Foundation is from research grants from DePuy Spine and individual donations.

Introduction: This study assessed the incidence and risk factors for pseudarthrosis among primary spine fusion patients., Methods: Retrospective review of ACS-NSQIP (2005-2013). Differences in comorbidities between spine fusion patients with and without pseudarthrosis (Pseud, N-Pseud) were assessed using chi-squared tests and Independent Samples t -tests. Binary logistic regression assessed patient-related and procedure-related predictors for pseudarthrosis., Results: 52,402 patients (57yrs, 53%F, 0.4% w/pseudarthrosis). Alcohol consumption (OR:2.6[1.2-5.7]) and prior history of surgical revision (OR:1.6[1.4-1.8]) were risk factors for pseudarthrosis operation. Pseud patients at higher risk for deep incisional SSI (at 30-days:OR:6.6[2.0-21.8]). Pseud patients had more perioperative complications (avg:0.24 ± 0.43v0.18 ± 0.39, p =0.026)., Conclusions: Alcoholism and surgical revision are major risk factors for pseudarthrosis in patients undergoing spine fusion.

Background: Cervical deformity (CD) surgery has become increasingly more common and complex, which has also led to reoperations for complications such as distal junctional kyphosis (DJK). Cost-utility analysis has yet to be used to analyze CD revision surgery in relation to the cost-utility of primary CD surgeries. The aim of this study was to determine the cost-utility of revision surgery for CD correction., Methods: Retrospective review of a multicenter prospective CD database. CD was defined as at least one of the following: C2-C7 Cobb >10°, cervical lordosis (CL) >10°, cervical sagittal vertical axis (cSVA) >4 cm, chin-brow vertical angle (CBVA) >25°. Quality-adjusted life year (QALY) were calculated by EuroQol Five-Dimensions questionnaire (EQ-5D) and Neck Disability Index (NDI) mapped to SF-6D index and utilized a 3% discount rate to account for residual decline to life expectancy (men: 76.9 years, women: 81.6 years). Medicare reimbursement at 30 days assigned costs for index procedures (9+ level posterior fusion, 4-8 level posterior fusion with anterior fusion, 2-3 level posterior fusion with anterior fusion, 4-8 level anterior fusion) and revision fusions (2-3 level, 4-8 level, or 9+ level posterior refusion). Cost per QALY gained was calculated., Results: Eighty-nine CD patients were included (61.6 years, 65.2% female). CD correction for these patients involved a mean 7.7±3.7 levels fused, with 34% combined approach surgeries, 49% posterior-only and 17% anterior-only, 19.1% three-column osteotomy. Costs for index surgeries ranged from $20,001-55,205, with the average cost for this cohort of $44,318 and cost per QALY of $27,267. Eleven revision surgeries (mean levels fused 10.3) occurred up to 1-year, with an average cost of $41,510. Indications for revisions were DJK (5/11), neurologic impairment [4], infection [1], prominent/painful instrumentation [1]. Average QALYs gained was 1.62 per revision patient. Cost was $28,138 per QALY for reoperations., Conclusions: CD revisions had a cost of $28,138 per QALY, in addition to the $27,267 per QALY for primary CD surgeries. For primary CD patients, CD surgery has the potential to be cost effective, with the caveats that a patient livelihood extends long enough to have the benefits and durability of the surgery is maintained. Efforts in research and surgical technique development should emphasize minimization of reoperation causes just as DJK that significantly affect cost utility of these surgeries to bring cost-utility to an acceptable range., Competing Interests: Conflicts of Interest: The International Spine Study Group (ISSG) is funded through research grants from DePuy Synthes, and supported the current work. The other authors have no conflicts of interest to declare.

Background: The study is a retrospective review of a multi-institutional database, aiming to determine predictors of non-depressed, satisfied adult spinal deformity (ASD) patients with good self-image at 2-year follow-up (2Y). ASD significantly impacts a patients' psychological status. Following treatment, little is known about predictors of satisfied patients with high self-image and mental status., Methods: Inclusion: primary ASD pts >18 y/o with complete 2Y follow-up. Non-depressed [Short Form 36-mental component score (SF36-MCS) >42], satisfied patients (SRS22-satisfaction >3) with good self-image (SR22-self-image >3) at 2Y were isolated (happy). Happy and control patients were propensity-matched by baseline and 2Y leg pain, Charlson, frailty, and radiographic measures for the operative (OP) and non-operative cohorts (NOP). Health related quality of life (HRQL), surgical and radiographic metrics were compared. Regression models identified predictors of happy patients. Thresholds were calculated using area under the curve (AUC) and 95%CI., Results: Of 480 patients, 94 OP (happy: 47 vs. control: 47) and 92 NOP (46 each) reached inclusion. At baseline, groups had similar age, gender, Oswestry disability index (ODI) (OP: 39.13 vs. 37.49, NOP: 17.70 vs. 19.74) and SF36-physical component score (PCS) (OP: 33.51 vs. 35.04, NOP: 47.93 vs. 44.72). Despite similar (P>0.05) surgeries, length of stay (LOS), and radiographic outcomes between OP happy and control groups, happy had less peri-operative complications (31.9% vs. 57.4%, P=0.13), better 2Y ODI (17.77 vs. 29.98), SRS22 component, total, and SF36 scores (P<0.05). NOP happy patients also exhibited better 2Y ODI (13.24 vs. 22.09), SRS22 component, total, and SF36 scores (P<0.05). Baseline SRS-mental (OR: 2.199, AUC: 0.617, cutoff: 2.5) and ODI improvement (OR: 1.055, AUC: 0.717, cutoff: >12) predicted happy OP patients, while baseline SRS-self-image (OR: 5.195, AUC: 0.740, cutoff: 3.5) and ODI improvement (OR: 1.087, AUC: 0.683, cutoff: >9) predicted happy NOP patients., Conclusions: Baseline mental-status, self-image and ODI improvement significantly impact long-term happiness in ASD patients. Despite equivalent management and alignment outcomes, operative and non-operative happy patients had better 2Y disability scores. Management strategies aimed at improving baseline mental-status, perception-of-deformity, and maximizing ODI may optimize treatment outcomes., Competing Interests: Conflicts of Interest: E Klineberg (DePuy Synthes—consulting, Stryker—consulting, Springer—consulting, Trevana—consulting, AOSpine—honoraria, fellowship support, K2M—honoraria); V Lange (Nemaris—stock ownership, DePuy Synthes—teaching/speaking, Nuvasive—teaching/speaking, K2M—teaching/speaking, Medtronic—teaching/speaking, Nemaris—board of directors); F Schwab (Zimmer Biomet—speaking/teaching, consulting, royalties/patents, NuVasive—speaking/teaching, consulting, royalties/patents, K2M—speaking/teaching, consulting, royalties/patents, MSD—speaking/teaching, consulting, royalties/patents, Medicrea—speaking/teaching, consulting, Nemaris—board of directors, shareholder); PG Passias (Medicrea—consulting, SpineWave—consulting, Allosource—Scientific Advisory Board, Zimmer Biomet—teaching/speaking, Globus—teaching/speaking, CSRS—grant, Aesculap—research study). The other authors have no conflicts of interest to declare.

Background: Informed patient selection and counseling is key in improving surgical outcomes. Understanding the impact that certain baseline variables can have on postoperative outcomes is essential in optimizing treatment for certain symptoms, such as radiculopathy from cervical spine pathologies. The aim was to identify baseline characteristics that were related to improved or worsened postoperative outcomes for patients undergoing surgery for cervical spine radiculopathic pain., Methods: Retrospective review of prospectively collected data. Patient Sample: Surgical cervical spine patients with a diagnosis classification of "degenerative." Diagnoses included in the "degenerative" category were those that caused radiculopathy: cervical disc herniation, cervical stenosis, and cervical spondylosis without myelopathy. Baseline variables considered as predictors were: (1) age, (2) body mass index (BMI), (3) gender, (4) history of cervical spine surgery, (5) baseline Neck Disability Index (NDI) score, (6) baseline SF-36 Physical Component Summary (PCS) scores, (7) baseline SF-36 Mental Component Summary (MCS) scores, (8) Visual Analog Scale (VAS) Arm score, and (9) VAS Neck. Outcome Measures: Improvement in NDI (≥50%), VAS Arm/Neck (≥50%), SF-36 PCS/MCS (≥10%) scores at 2-years postoperative. An arm-to-neck ratio (ANR) was also generated from baseline VAS scores. Univariate and multivariate analyses evaluated predictors for 2-year postoperative outcome improvements, controlling for surgical complications and technique., Results: Three hundred ninety-eight patients were included. Patients with ANR ≤ 1 (n = 214) were less likely to reach improvements in 2-year NDI (30.0% vs 39.2%, P = .050) and SF-36 PCS (42.4% vs 53.5%, P = .025). Multivariate analysis for neck disability revealed higher baseline SF-36 PCS (odds ratio [OR] 1.053) and MCS (OR 1.028) were associated with over 50% improvements. Higher baseline NDI were reduced odds of postoperative neck pain improvement (OR 0.958). Arm pain greater than neck pain at baseline was associated with both increased odds of postoperative arm pain improvement (OR 1.707) and SF36 PCS improvement (OR 1.495)., Conclusions: This study identified specific symptom locations and health-related quality of life (HRQL) scores, which were associated with postoperative pain and disability improvement. In particular, baseline arm pain greater than neck pain was determined to have the greatest impact on whether patients met at least 50% improvement in their upper body pain score. These findings are important for clinicians to optimize patient outcomes through effective preoperative counseling., Competing Interests: Disclosures and COI: Dr. Passias reports consultancy for Medicrea and SpineWave, speaking/teaching arrangements from Zimmer-Biomet, and grant from CSRS, all outside the submitted work. All other authors have no conflicts of interest to report. Institutional Review Board (IRB) approval was obtained from each contributing center prior to study initiation.

Background: The rate of mortality in surgical procedures involving the lumbar spine has historically been low, and as a result, there has been difficulty providing accurate quantitative mortality rates to patients in the preoperative planning phase. Awareness of these mortality rates is essential in reducing postoperative complications and improving outcomes. Additionally, mortality rates can be influenced by procedure type and patient profile, including demographics and comorbidities. The purpose of this study is to assess rates and risk factors associated with mortality in surgical procedures involving the lumbar spine using a large national database., Methods: The Nationwide Inpatient Sample database was reviewed from 2003 to 2012. A total of 803,949 patients age 18 years or older were identified by ICD-9CM procedure codes for spinal fusion or decompression of the lumbar spine. Mortality was stratified based on type of procedure (simple or complex fusion, decompression), patient demographics and comorbidities, and in-hospital complications. Binary logistic regression was used to identify the risk of death while controlling for comorbidities, race, sex, and procedure performed. Significance was defined as P < .05 differences relative to the overall cohort., Results: Mortality for all patients requiring surgery of the lumbar spine was 0.13%. Mortality based on procedure type was 0.105% for simple fusions, 0.321% for complex fusions, and 0.081% for decompression only. Increased mortality was observed demographically in patients who were male (odds ratio [OR]: 1.75; 95% confidence interval [CI]: 1.51-2.03), black (OR: 1.40; CI: 1.10-1.79), ages 65-74 (OR: 1.46; CI: 1.25-1.70), and age 75+ (OR: 2.70; CI: 2.30-3.17). Comorbidities associated with the greatest increase in mortality were mild (OR: 10.04; CI: 7.76-13.01) and severe (OR: 26.47; CI: 16.03-43.70) liver disease and congestive heart failure (OR: 4.57; CI: 3.77-5.53). The complications with the highest mortality rates were shock (OR: 20.67; CI: 13.89-30.56) and pulmonary embolism (OR: 20.15; CI: 14.01-29.00)., Conclusions: From 2003 to 2012, the overall mortality rate in 803,949 lumbar spine surgery patients was 0.13%. Risk factors that were significantly associated with increased mortality rates were male gender, black race, and ages 65-74 and 75+. Comorbidities associated with an increased mortality rate were mild and severe liver disease and congestive heart failure. Inpatient complications with the highest mortality rates were shock and pulmonary embolism. These findings can be helpful to surgeons providing preoperative counseling for patients considering elective lumbar procedures and for allocating resources to treat and prevent perioperative complications leading to mortality., Level of Evidence: 3., Competing Interests: Disclosures and COI: Gregory Wyatt Poorman, John Y. Moon, Charles Wang, Samantha R. Horn, Bryan M. Beaubrun, Olivia J. Bono, Anne-Marie Francis, and Cyrus M. Jalai all report no conflict of interest. Peter G. Passias reports consulting with Medicrea and Zimmer, unrelated to and outside of the current work. All other authors report no conflicts of interest. Given the deidentified nature of the data reported from this study, it is exempt from IRB approval.

Early life adversity is a documented risk factor for substance abuse and addiction. The pre- and perinatal period (i.e., from implantation, through pregnancy, to 6 months of age) is a critical period marked by high biological plasticity and vulnerability, making perinatal stress a particularly robust form of adversity. The neuroendocrine and immune systems are key mechanisms implicated in the transmission of addiction risk. We review animal and human studies that provide preliminary evidence for links between perinatal stress, neuroendocrine and immune dysregulation, and risk for substance abuse and addiction. A translational neuroscience perspective is employed to elucidate pre- and perinatally-induced biological mechanisms linked to addiction and discuss implications for prevention and intervention efforts. Significant evidence supports associations between pre- and perinatal stress and dysregulation of the hypothalamic-pituitary-adrenal axis and immune systems as well as links between neuroendocrine/immune functioning and addiction risk. More work is needed to explicitly examine the interplay between pre- and perinatal stress and neuroendocrine/immune disruptions that together heighten substance abuse risk. Future work is needed to fully understand how pre- and perinatal stress induces biological alterations to predispose individuals to higher risk for addiction. Such knowledge will strengthen theoretically-driven and empirically-supported prevention efforts for substance abuse and addiction.

Introduction: Early Onset and Adolescent Idiopathic Scoliosis, relatively common diagnoses (∼3% general population), have been associated with developmental dysplasia of the hip (DDH); a more rare spectrum of anomalies related to the abnormal development of acetabulum, proximal femur, and hip joint. To the best of our knowledge, no high powered investigations have been performed in an attempt to assess incidence and associated risks of DDH in scoliosis patients., Methods: The KID database was queried for ICD-9 codes from 2003 to 2012 pertaining to EOS (Congenital and Idiopathic <10y/o) and AIS patients. Descriptive analysis assessed patient demographics and yearly trends in hip dysplasia rates. EOS and AIS patients with hip dysplasia were isolated, and incidence of hospital admissions for associated anomalies (osteonecrosis, osteoarthritis, recurrent hip dislocation, hip ankylosis) and hip arthroplasty (total + partial) were investigated. Univariate analysis of hip pathology determined significant predictors of hip arthroplasty. Binary logistic regression analysis was used to determine the relationship between these predictors., Results: 111,827 scoliosis patients (EOS: 25,747; AIS: 77,183) were included. AIS patients were older (15.2 vs 4.3), more female (64.2% vs 52.1%), had a higher CCI (0.84 vs 0.64), and less racially diverse (all p < 0.001). The incidence of hip dysplasia was 1.4% for AIS patients and 3.9% for EOS patients (p < 0.001). Of the AIS (n = 1073) and EOS (n = 1005) patients with hip dysplasia, 0.3% (p > 0.05 between groups) developed hip osteonecrosis, 0% of patients were coded as having a hip labral tear, hip ankylosis, and 0.6% (EOS: 0.2%; AIS: 0.9%, p = 0.025) developed hip osteoarthritis. AIS patients were more likely to have recurrent hip dislocations (35.4% vs 17.0%, p < 0.001), and both groups had similar primary hip arthroplasty rates (6.7% vs 5.4%, p = 0.118) and revision hip arthroplasty rates (0% vs 0.4%, p = 0.053). Hip osteoarthritis (OR: 13.43[5.21-34.66], p=<0.001) and older age (OR: 1.039[1.007-1.073], p = 0.017) were the only significant predictors of hip arthroplasty (p=<.001)., Conclusions: The incidence of hip dysplasia in EOS and AIS populations is higher than that of the general population. The rate of DDH was 3.9% and 1.8% for EOS and AIS, respectively. While the incidence of DDH is higher, associated anomalies of osteoarthritis, osteonecrosis, labral tears, and ankylosis appear to be a minimal risk for AIS and EOS patients with Hip Dysplasia.

Background: Risk of death is important in counseling patients and improving quality of care. Incidence of death in cervical surgery is not firmly established due to its rarity and limited sample sizes, particularly in the context of different surgeries, demographics, and risk factors. Particularly, different patient risk profiles may have varying degrees of risk in terms of surgeries, comorbidities, and demographics. This study aims to use a large patient cohort available on a national database to study the prevalence of death associated with cervical spine surgery., Methods: This study was a retrospective review of the Nationwide Inpatient Sample (NIS) years 2003-2012. A total of 342 477 patients were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes undergoing spinal fusion or decompression for disc degeneration, stenosis, spondylosis, myelopathy, postlaminectomy syndrome, scoliosis, or neck pain associated with the cervical region. Patients with malignancy were excluded from analysis. Incidence of mortality was assessed by χ 2 tests across different patient demographics and comorbidities, procedures performed, and concurrent in-hospital complications. Binary logistic regression identified significant increases or decreases in risk of death while controlling for comorbidities, race, sex, and Mirza invasiveness. Significance was defined as P < .05 differences relative to overall cohort., Results: The study analyzed 342 477 patients with an overall mortality rate of 0.32%. A total of 231 977 simple fusions (single approach and <3 levels) experienced a mortality rate of 0.256%; 49 594 complex fusions (combined approach or ≥3 levels) had a mortality rate of 0.534%; and 61 285 decompression-only procedures reported a 0.424% mortality rate, all P < .001 from overall rate. In reporting rates across different demographics, male patients experienced a significantly higher risk for mortality (odds ratio [OR], 2.16; 95% CI, 1.87-4.49), as did black patients (OR, 1.58; CI, 1.32-1.90) and patients over age 75 (OR, 7.55; 95% CI, 6.58-8.65), all P < .001. Patients with liver disease reported 6.40% mortality. Similarly, patients with congestive heart failure (3.91%), cerebrovascular disease (3.41%), and paraplegia (3.79%) experienced high mortality rates, all in cohorts of over 2000 patients, all P < .001. Concurrent in-hospital complications with the highest risk of mortality were shock (OR, 51.41; 95% CI, 24.08-109.76), pulmonary embolism (OR, 25.01; 95% CI, 14.70-42.56), and adult respiratory distress disorder (OR, 14.94; 95% CI, 12.75-17.52), all P < .001., Conclusion: In 342 477 cervical spine surgery patients an overall mortality rate of 0.32% was reported. The rate was 3.91% in a cohort of 5933 patients with congestive heart failure and 3.79% in a cohort of 6947 patients with paraplegia. These findings are consistent with previous estimates and may help counsel patients and improve in-hospital safety., Level of Evidence: 3., Competing Interests: Disclosures and COI: Gregory Wyatt Poorman, John Y. Moon, Samantha R. Horn, Cyrus Jalai, Peter L. Zhou, and Olivia Bono all report no conflict of interest. Peter G. Passias, the corresponding author, reports consulting with Medicrea and Zimmer, unrelated to and outside of the current work. Given the deidentified nature of the data reported from this study, it is exempt from IRB approval.

Background: Effects of nonoperative treatments on surgical outcomes for patients who failed conservative management for cervical spine pathologies remain unknown. The objective is to describe conservative modality use in patients indicated for surgery for degenerative cervical spine conditions and its impact on perioperative outcomes., Methods: The current study comprises a retrospective review of a prospective multicenter database. A total of 1522 patients with 1- to 2-level degenerative cervical pathology who were undergoing surgical intervention were included. Outcome measures used were health-related quality-of-life scores, length of hospitalization, estimated blood loss, length of surgery, and return-to-work status at 2 weeks, 6 months, 1 year, and 2 years postoperatively. Patients were grouped by diagnosis (radiculopathy vs. myelopathy), then divided based on epidural injection(s), physical therapy (PT), or opioid use prior to enrollment. Univariate t -tests and χ 2 tests were performed to determine differences between groups and impact on outcomes., Results: Among 1319 radiculopathy patients, 25.7% received preoperative epidural injections, 35.3% received PT, and 35.5% received opioids. Radiculopathy patients who received epidurals and PT had higher 1-year postoperative return-to-work rates ( P  < .05). Radiculopathy patients without preoperative PT had longer hospitalization times, whereas those who received PT had higher 36-Item Short Form Health Survey (SF-36) physical functioning and physical component scores, lower 2-year visual analog scale (VAS) neck/arm pain scores, and higher 2-year return-to-work incidence ( P  < .05). Of myelopathy patients (n = 203), 14.8% received epidural injections, 25.1% received opioids, and 41.5% received PT. Myelopathy patients with preoperative PT had worse VAS arm pain scores 2 years postoperatively ( P  < .05). Patients receiving opioids were younger and had greater baseline-2-year Neck Disability Index improvement ( P  < .05)., Conclusions: Radiculopathy patients receiving epidurals returned to work after 1 year more frequently. PT was associated with shorter hospitalizations, greater SF-36 bodily pain norm and physical component score improvements, and increased return-to-work rates after 1 and 2 years. No statistically significant nonoperative treatment was associated with return-to-work rate in myelopathy patients., Clinical Relevance: These findings suggest certain preoperative conservative treatment modalities are associated with improved outcomes in radiculopathy patients., Competing Interests: Disclosures and COI: M.C.G. reports a past history of personal fees from Paradigm Spine and Stryker Spine, outside the submitted work. K.R. reports personal fees from Globus Medical, 4 Web Medical, Medtronic Advanced Energy, DePuy, Globus, LDR, Orthopedic Sciences Inc., NuVasive, and NEXXT Spine, and grants from Pacira Pharmaceuticals, outside the submitted work; nonfinancial disclosure includes serving on the board of directors at Association for Collaborative Spinal Research and the scientific advisory board of 4 Web Medical, outside the submitted work. R.I. reports grants and personal fees from NuVasive Inc., and personal fees from the Association for Collaborative Spine Research, and serves as a scientific advisor for Providence Medical Technology, outside the submitted work. P.M.A. reports personal fees and nonfinancial support from Evoke Medical and Z-Plasty; personal fees from Medtronic Sofamor Danek, Stryker Spine, and Fzio Med; and travel reimbursement from AOSpine North America, outside the submitted work. A.R.V. reports personal fees from Medtronic, Striker Spine, Biomet Spine, Globus, Aesculap, Thieme, Jaypee, Elsevier, Taylor Francis, DePuy, Medtronic, Gerson Lehrman Group, Guidepoint Global, Medacorp, Innovative Surgical Design, and Orthobullets; expert testimony for Ellipse and Vertex; and stock ownership in Replication Medica, Paradigm Spine, Stout Medical, Progressive Spinal Technologies Advanced Spinal Intellectual Properties, Spine Medica, Computational Biodynamics, Spinology, Small Bone Innovations, Cross Current, In Vivo, Flagship Surgical, Cytonics, Bonovo Orthopaedics, Electrocore, Gamma Spine, Location Based Intelligence, FlowPharma, R.S.I, Rothman Institute and Related Properties, Innovative Surgical Design, and Avaz Surgical, outside the submitted work; and nonfinancial disclosure includes serving on the scientific advisory board for AOSpine, Innovative Surgical Design, and the Association for Collaborative Spine Research, outside the submitted work. P.G.P. reports nonfinancial support from Medicrea and personal fees from Zimmer Biomet, outside the submitted work.

Background: Current health-related quality of life (HRQL) metrics used to assess patient outcomes following surgical correction of cervical deformity (CD) are not deformity-specific and thus cannot capture all aspects of a patient's deformity and outcomes. The purpose of this study is to evaluate the sensitivity of different HRQL outcome measures in assessing CD patients' outcomes 1-year post-operatively., Methods: Retrospective review of prospective multi-center database. Inclusion criteria: CD patients ≥18 yrs with pre- and 1-year post-operative radiographs and HRQLs [modified Japanese Orthopaedic Association (mJOA), EuroQol five-dimensions (EQ-5D), neck disability index (NDI)]. Associations between changes in EQ5D and NDI with improvement at 1-year in mJOA scores were assessed by whether or not the patient met the minimum clinically important difference (MCID) as well as whether or not they improved by one or more categories (i.e., change from moderate to mild). Odds ratios reported with 95% confidence intervals., Results: Sixty-three CD patients were included (mean 62 y, 55.6% F). Average baseline NDI scores were 46.75, mJOA was 13.68, and EQ-5D 0.74. Overall baseline myelopathy breakdown: none-9.5%, mild-30.2%, moderate-42.9%, high-17.5%. At 1-year, 46% of patients improved in mJOA, 71.4% NDI, and 65.1% EQ-5D. 19% of patients met mJOA MCID, 44.4% NDI MCID, 19% EQ-5D MCID. One-point improvement in NDI increased the odds of mJOA improvement and reaching mJOA MCID (improvement: OR, 1.06, CI: 1.01-1.10, P=0.01; MCID: OR, 1.06, CI: 1.02-1.11, P=0.006). Improvement in EQ-5D by 0.1 increased the odds of improving in mJOA and reaching mJOA MCID at 1-year (improvement: OR, 3.85, CI: 1.51-9.76, P=0.005; MCID: OR, 3.88, CI: 1.52-9.88, P=0.005). While correlations exist between outcome measures, when modeling these outcomes while controlling for confounders including cSVA change, surgical invasiveness, age and CCI, these HRQLs were not strongly correlated., Conclusions: Improvements in functional outcomes, as defined by mJOA score, were correlated with changes in neck based disability and general health state, defined by NDI and EQ-5D respectively. In an adjusted model, however, these direct relationships were not maintained. A CD-specific HRQL might be more useful for surgeons in assessing patient outcomes using a single metric., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Study Design: Retrospective cohort study., Objectives: The purpose of this study was to report incidence of cardiopulmonary complications in elective spine surgery, demographic and surgical predictors, and outcomes. Understanding the risks and predictors of these sentinel events is important for risk evaluation, allocation of hospital resources, and counseling patients., Methods: A retrospective review of the National Surgical Quality Improvement Program (NSQIP) was performed on 60 964 patients undergoing elective spine surgery (any region; laminectomy, arthrodesis, discectomy, or laminoplasty) between 2011 and 2013. Incidence of myocardial infarction, cardiac arrest, unplanned reintubation, on ventilator >48 hours, perioperative pneumonia, and pulmonary embolism was measured. Demographic and surgical predictors of cardiopulmonary complications and associated outcomes (length of stay, discharge disposition, and mortality) were measured using binary logistic regression controlling for confounders., Results: Incidence rates per 1000 elective spine patients were 2.1 myocardial infarctions, 1.3 cardiac arrests, 4.3 unplanned intubations, 3.5 on ventilator >48 hours, 6.1 perioperative pneumonia, and 3.7 pulmonary embolisms. In analysis of procedure, diagnosis, and approach risk factors, thoracic cavity (odds ratio = 2.47; confidence interval = 1.95-3.12), scoliosis diagnosis, and combined approach (odds ratio = 1.51; confidence interval = 1.15-1.96) independently added the most risk for cardiopulmonary complication. Cardiac arrest had the highest mortality rate (34.57%). Being on ventilator greater than 48 hours resulted in the greatest increase to length of stay (17.58 days)., Conclusions: Expected risk factors seen in the Revised Cardiac Risk Index were applicable in the context of spine surgery. Surgical planning should take into account patients who are at higher risk for cardiopulmonary complications and the implications they have on patient outcome., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chiari malformations type 1 (CM-1), a developmental anomaly of the posterior fossa, usually presents in adolescence or early adulthood. There are few studies on the national incidence of CM-1, taking into account outcomes based on concurrent diagnoses. To quantify trends in treatment and associated diagnoses, as retrospective review of the Kid's Inpatient Database (KID) from 2003-2012 was conducted., Methods: Patients aged 0-20 with primary diagnosis of CM-1 in the KID database were identified. Demographics and concurrent diagnoses were analyzed using chi-squared and t -tests for categorical and numerical variables, respectively. Trends in diagnosis, treatments, and outcomes were analyzed using analysis of variance (ANOVA)., Results: Five thousand four hundred and thirty-eight patients were identified in the KID database with a primary diagnosis of CM-1 (10.5 years, 55% female). CM-1 primary diagnoses have increased over time (45 to 96 per 100,000). CM-1 patients had the following concurrent diagnoses: 23.8% syringomyelia/syringobulbia, 11.5% scoliosis, 5.9% hydrocephalus, 2.2% tethered cord syndrome. Eighty-three point four percent of CM-1 patients underwent surgical treatment, and rate of surgical treatment for CM-1 increased from 2003-2012 (66% to 72%, P<0.001) though complication rate decreased (7% to 3%, P<0.001) and mortality rates remained constant. Seventy percent of surgeries involved decompression-only, which increased neurologic complications compared to fusions (P=0.039). Cranial decompressions decreased from 2003-2012 (42.2-30.5%) while spinal decompressions increased (73.1-77.4%). Fusion rates have increased over time (0.45% to 1.8%) and are associated with higher complications than decompression-only (11.9% vs. 4.7%). Seven point four percent of patients experienced at least one peri-operative complication (nervous system, dysphagia, respiratory most common). Patients with concurrent hydrocephalus had increased; nervous system, respiratory and urinary complications (P<0.006) and syringomyelia increased the rate of respiratory complications (P=0.037)., Conclusions: CM-1 diagnoses have increased in the last decade. Despite the decrease in overall complication rates, fusions are becoming more common and are associated with higher peri-operative complication rates. Commonly associated diagnoses including syringomyelia and hydrocephalus, can dramatically increase complication rates., Competing Interests: Conflicts of Interest: Dr. PG Passias reports personal consulting fees for Spinewave, Zimmer Biomet, and Medicrea, grants to the institution from the Cervical Spine Research Society. The other authors have no conflicts of interest to declare.

Background: Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder., Methods: Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes., Results: Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score., Conclusions: Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519)., (© The Author(s) 2017. Published by Oxford University Press on behalf of CINP.)

OBJECTIVE Depression and anxiety have been demonstrated to have negative impacts on outcomes after spine surgery. In patients with cervical deformity (CD), the psychological and physiological burdens of the disease may overlap without clear boundaries. While surgery has a proven record of bringing about significant pain relief and decreased disability, the impact of depression and anxiety on recovery from cervical deformity corrective surgery has not been previously reported on in the literature. The purpose of the present study was to determine the effect of depression and anxiety on patients' recovery from and improvement after CD surgery. METHODS The authors conducted a retrospective review of a prospective, multicenter CD database. Patients with a history of clinical depression, in addition to those with current self-reported anxiety or depression, were defined as depressed (D group). The D group was compared with nondepressed patients (ND group) with a similar baseline deformity determined by propensity score matching of the cervical sagittal vertical axis (cSVA). Baseline demographic, comorbidity, clinical, and radiographic data were compared among patients using t-tests. Improvement of symptoms was recorded at 3 months, 6 months, and 1 year postoperatively. All health-related quality of life (HRQOL) scores collected at these follow-up time points were compared using t-tests. RESULTS Sixty-six patients were matched for baseline radiographic parameters: 33 with a history of depression and/or current depression, and 33 without. Depressed patients had similar age, sex, race, and radiographic alignment: cSVA, T-1 slope minus C2-7 lordosis, SVA, and T-1 pelvic angle (p > 0.05). Compared with nondepressed individuals, depressed patients had a higher incidence of osteoporosis (21.2% vs 3.2%, p = 0.028), rheumatoid arthritis (18.2% vs 3.2%, p = 0.012), and connective tissue disorders (18.2% vs 3.2%, p = 0.012). At baseline, the D group had greater neck pain (7.9 of 10 vs 6.6 on a Numeric Rating Scale [NRS], p = 0.015), lower mean EQ-5D scores (68.9 vs 74.7, p < 0.001), but similar Neck Disability Index (NDI) scores (57.5 vs 49.9, p = 0.063) and myelopathy scores (13.4 vs 13.9, p = 0.546). Surgeries performed in either group were similar in terms of number of levels fused, osteotomies performed, and correction achieved (baseline to 3-month measurements) (p < 0.05). At 3 months, EQ-5D scores remained lower in the D group (74.0 vs 78.2, p = 0.044), and NDI scores were similar (48.5 vs 39.0, p = 0.053). However, neck pain improved in the D group (NRS score of 5.0 vs 4.3, p = 0.331), and modified Japanese Orthopaedic Association (mJOA) scores remained similar (14.2 vs 15.0, p = 0.211). At 6 months and 1 year, all HRQOL scores were similar between the 2 cohorts. One-year measurements were as follows: NDI 39.7 vs 40.7 (p = 0.878), NRS neck pain score of 4.1 vs 5.0 (p = 0.326), EQ-5D score of 77.1 vs 78.2 (p = 0.646), and mJOA score of 14.0 vs 14.2 (p = 0.835). Anxiety/depression levels reported on the EQ-5D scale were significantly higher in the depressed cohort at baseline, 3 months, and 6 months (all p < 0.05), but were similar between groups at 1 year postoperatively (1.72 vs 1.53, p = 0.416). CONCLUSIONS Clinical depression was observed in many of the study patients with CD. After matching for baseline deformity, depression symptomology resulted in worse baseline EQ-5D and pain scores. Despite these baseline differences, both cohorts achieved similar results in all HRQOL assessments 6 months and 1 year postoperatively, demonstrating no clinical impact of depression on recovery up until 1 year after CD surgery. Thus, a history of depression does not appear to have an impact on recovery from CD surgery.

Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating life cycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral life cycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2' O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index. All subjects provided baseline blood samples, and TRD subjects had additional blood draw at 4 and 24 h following intravenous infusion of ketamine (0.5 mg kg -1 ). Samples underwent multiplex analysis of 41 cytokines, chemokines and growth factors using quantitative immunoassay technology. Our a priori hypothesis was that TRD patients would show elevations in canonical pro-inflammatory cytokines; analyses demonstrated significant elevation of the pro-inflammatory cytokine interleukin-6. Further exploratory analyses revealed significant regulation of four additional soluble factors in patients with TRD. Several cytokines showed transient changes in level after ketamine, but none correlated with treatment response. Low pretreatment levels of fibroblast growth factor 2 were associated with ketamine treatment response. In sum, we found that patients with TRD demonstrate a unique pattern of increased inflammatory mediators, chemokines and colony-stimulating factors, providing support for the immune hypothesis of TRD. These patterns suggest novel treatment targets for the subset of patients with TRD who evidence dysregulated immune functioning.

IFN-α/β was first described as a potent inhibitor of viral replication, but it is now appreciated that IFN signaling plays a pleiotropic role in regulating peripheral T cell functions. Recently, IFN-α/β was shown to block human Th2 development by suppressing the transcription factor GATA3. This effect is consistent with the role for IFN-α/β in suppressing allergic inflammatory processes by blocking granulocyte activation and IL-4-mediated B cell isotype switching to IgE. With the consideration of recent studies demonstrating a defect in IFN-α/β secretion in DCs and epithelial cells from individuals with severe atopic diseases, there is an apparent reciprocal negative regulatory loop in atopic individuals, whereby the lack of IFN-α/β secretion by innate cells contributes to the development of allergic Th2 cells. Is it possible to overcome these events by treating with IFN-α/β or by inducing its secretion in vivo? In support of this approach, case studies have documented the therapeutic potential of IFN-α/β in treating steroid-resistant allergic asthma and other atopic diseases. Additionally, individuals with asthma who are infected with HCV and respond to IFN therapy showed a reduction in symptoms and severity of asthma attacks. These findings support a model, whereby allergic and antiviral responses are able to cross-regulate each other, as IgER cross-linking of pDCs prevents IFN-α/β production in response to viral infection. The clinical importance of upper-respiratory viruses in the context of allergic asthma supports the need to understand how these pathways intersect and to identify potential therapeutic targets., (© Society for Leukocyte Biology.)