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BACKGROUND CONTEXT Renal cell carcinoma (RCC) is one of the most commonly diagnosed malignancies, with an estimated 74,000 new cases in 2019. Approximately 40% of bony metastasis occurs in the spine. Prognostic scoring systems predict the survival time of patients with spinal metastatic disease and guide spine surgeons with decision-making about the best treatment modality. PURPOSE This study aims to assess the performance of previously validated prediction models for spine metastatic disease to predict the survival of RCC patients. STUDY DESIGN/SETTING A multi-centric retrospective study PATIENT SAMPLE Included n=86 patients with spinal metastatic RCC. OUTCOME MEASURES Preoperative scores were calculated using: (1 Tomita, (2 original Tokuhashi, (3 revised Tokuhashi, (4 original Bauer, (5 modified Bauer, (6 Katagiri, (7 Van Der Linden, (8 SORG classic algorithm, (9 SORG nomogram, (10 New England spinal metastasis score (NESMS). METHODS Univariate Cox proportional hazard models were calculated to assess the association of patient variables with 1-year survival. The time-dependent ROC was performed for each model. Cutoffs for (AUC) are as follows: excellent (AUC ≥ 0.90), good (AUC ≥ 0.80 and ˂ 0.90), fair (AUC ≥ 0.70 and ˂ 0.80), and poor performance (AUC ˂ 0.70). RESULTS N=86 patients (60.90±11.36 years, 73.25% male) undergoing spine surgery for spinal metastatic RCC. Univariate analysis showed that patient and tumor factors were strongly associated with 1-year survival: (1 Poor KPS (HR:6.78 [95% CI:1.96–23.48]), (2 ECOG grade 3-4 (HR:3.52 [1.57-7.91]), (3 Frankel grade A-D (HR:2.54 [1.01-6.46]), (4 albumin CONCLUSIONS Most validated prognostic scores have a poor or fair performance in predicting the survival of RCC surgical patients with spinal metastatic disease. Tumor-specific factors and newer treatment modalities affect the survival of RCC patients and should be evaluated in future prognostic studies. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Interbody spacers have been successfully used in spinal fusion procedures with the aim to restore disc height, provide stability and promote the bone fusion. PURPOSE The authors aimed to evaluate the efficacy of structural body allograft vs polyetheretherketone (PEEK) implants in patients undergoing spinal fusion surgery. STUDY DESIGN/SETTING We conducted a systematic review of the electronic databases using different MeSH terms from January 1970 to August 2019. PATIENT SAMPLE A total of 6,640 patients (structural allograft: 64% and PEEK cage: 36%) from 7 comparative studies were included in our analysis. OUTCOME MEASURES Outcome parameters included subsidence rate, mean change in lordotic angle, pseudarthrosis, reoperation, fusion rates and patient reported outcome measures. METHODS Pooled and sub-group analysis were performed using the random and fixed effect model based upon the I2 heterogeneity. RESULTS There was no statistically significant difference in terms of age (p=0.27), gender (p=0.31), body mass index (p=0.82) and smoking status (p=0.27) between the two groups. Overall, the mean follow-up was 12.9 ±1.5 months. Pooled meta-analysis revealed that patients with structural allograft had a 2.59-fold higher likelihood of fusion rates compared to patients with PEEK cages (OR: 2.59, 95% CI:1.02-6.57, p=0.05) at the last follow-up evaluation. Furthermore, patients with structural allograft had 61% less likelihood of pseudarthroses (OR: 0.39, 95%CI: 0.15-0.98, p=0.05) and 74% lower incidence of reoperation compared to patients with PEEK implants (OR:0.26, 95% CI:0.09-0.79, p=0.02). Although our results suggest that patients with structural allografts had a higher subsidence rate compared to PEEK implants, but it was statistically insignificant (OR:1.07, 95% CI: 0.45-2.53, p=0.89). CONCLUSIONS Our results corroborate that structural allografts are highly effective in promoting bony fusion compared to PEEK implants in patients undergoing spinal fusion surgery. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Metabolic syndrome (MetS) is a global epidemic disorder, especially in the Western capitalistic economic development model. PURPOSE To elucidate the predictive ability of the Adult Treatment Panel (ATP)-III for survival and complications in patients who underwent decompressive surgery (DS) for metastatic spinal cord compression (MSCC). STUDY DESIGN/SETTING Patients with MSCC presented at an academic tertiary care hospital from 2011 to 2018 were identified through retrospective chart review. PATIENT SAMPLE Statistical analysis included 119 patients (median age: 67 years; 63% males), with a median survival of 14 months (95%CI: 1-28.2 months, p=0.01). OUTCOME MEASURES Survival and complications following surgery for MSCC. METHODS Patients were categorized into MetS-ATP III (42.9%, n=51) if they met 3 or more of the following criterion: waist circumference (men >102 cm and women >88 cm), triglycerides (≥150 mg/dl), high density cholesterol (men RESULTS All-cause mortality and complications were 62.2% (n=74) and 22.7% (n=27) in our cohort respectively. Patients with MetS-ATP III had a 1.74-fold higher risk of mortality at last follow-up evaluation (HR: 1.74, 95%CI: 1.07-2.81, p=0.02), after adjusting for age, sex, tumor histology and spine instability neoplastic score (SINS). Overall complication rates were significantly higher among patients with MetS (HR: 4.06, 95% CI: 1.68-9.82, p=0.002). Furthermore, the patients with MetS had a higher probability of impaired wound healing (HR: 3.85, 95% CI: 1.57-9.40, p=0.003) and thrombotic disorders (HR: 5.56, 95%CI: 1.63-19.0, p=0.006), adjusted for age, sex, tumor histology and SINS. CONCLUSIONS MetS-ATP III analysis in patients with MSCC who underwent DS was effective in identifying patients at higher risk for shorter survival and more complications. However, further prospective studies are needed to validate our results. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

This study evaluated the safety and performance of the Guardian™ continuous glucose monitoring (CGM) system in children and adolescents with type 1 diabetes (T1D).Subjects 2-18 years of age (mean ± standard deviation [SD] 13.1 ± 3.9 years) with T1D and duration of diagnosis ≥1 year were enrolled at 11 sites in the United States and wore two Guardian Sensor 3 sensors in the abdomen and/or buttock. Sensors were connected to a transmitter paired with either a Guardian Connect system (i.e., mobile device with software application allowing display of sensor glucose [SG] values) or a Guardian Link 3 transmitter used as a Glucose Sensor Recorder (GSR). There were 145 participants who underwent a 6-h in-clinic frequent sample testing (FST) on day 1 (n = 54), day 3 (n = 48), or day 7 (n = 43) postsensor insertion. During FST, SG values were compared with a Yellow Springs Instrument (YSI) plasma reference every 5-15 min (n = 124, 7-18 years of age; n = 2, 2-6 years of age), or to a self-monitoring of blood glucose (SMBG) reference every 5-30 min (n = 19, 2-6 years of age).The overall mean absolute relative difference (ARD ± SD) between SG and reference values (YSI or SMBG) when calibrating approximately every 12 h, was 10.9% ± 10.7% (3102 paired points) for sensors communicating with the Guardian Connect system and 11.1% ± 10.6% (2624 paired points) for sensors connected to the GSR. The overall percentage of SG values within ±20% of reference values80 mg/dL or within 20 mg/dL of reference values ≤80 mg/dL was 87.8% for the Guardian Connect system and 86.7% for the GSR, respectively. There was one device-related adverse event of contact dermatitis, but no serious device-related adverse events.The Guardian CGM system demonstrated good accuracy in children and adolescents. These findings support its use in sensor-integrated insulin pump platforms, as well as a standalone technology, for managing diabetes in pediatric populations.

In-home use of the MiniMed™ 670G system with SmartGuard™ technology for 3 months improved A1C, 24-hour, and overnight (10PM-7AM) glycemia in T1D patients ≥14 years.1 Recently, the system was shown to improve A1C and time in target range (TIR) (>70-180mg/dL, 3.9-10mmol/L) during 24-h and overnight periods in T1D children aged 7-13 years. Effect of the system on insulin delivery and early morning glycemia was also examined. During a 2 week run-in phase in Manual Mode and a 3-month study phase using HCL Auto Mode; 24-hour, 10PM-7AM, and 3AM-7AM insulin delivery (programmed hourly basal rates during Manual Mode, variable basal from 0 units to an individualized daily maximum every 5min during Auto Mode); time in sensor glucose (SG) ranges; and SG SD were examined in 1T1D children (mean±SD age 10.8±1.8 years). The table shows Auto Mode use across periods. Total insulin delivered increased from baseline run-in (1990 patient-days) through study phase (10,602 patient-days); SG, TIR, and SG SD improved. During the study phase, there was no severe hypoglycemia, DKA, or serious device-related AEs. The ability of the MiniMed™ 670G system to automate basal insulin delivery and safely improve 24-hour and overnight glycemic control in children was comparable to that observed in patients 14-75 years, over 3 months. Improved early morning glycemia further indicates that patients ≥7 years can benefit from this HCL therapy. Disclosure G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc.. Research Support; Self; Medtronic, Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Novo Nordisk Inc., Bigfoot Biomedical. D.I. Shulman: Other Relationship; Self; Novo Nordisk Inc.. Research Support; Self; Medtronic MiniMed, Inc.. Board Member; Self; Pediatric Endocrine Society. Research Support; Self; Versartis, Inc. M.A. Wood: Research Support; Self; Medtronic MiniMed, Inc. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. S. Huang: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic. S.W. Lee: Employee; Self; Medtronic. T.L. Cordero: Employee; Self; Medtronic. F.R. Kaufman: Employee; Self; Medtronic.

Activation of “suspend before low” in the Medtronic PLGM algorithm stops insulin delivery when sensor glucose (SG) is predicted to reach or fall below a preset low glucose limit in 30min. Basal insulin delivery automatically resumes once the algorithm detects an increasing SG trend. We evaluated the “suspend before low” feature of the MiniMed™ 670G with SmartGuard™ technology in children with T1D. Participants (N=105, aged 7-13 years) underwent an overnight in-clinic evaluation. Hypoglycemia was defined as 2 or more consecutive events of YSI or fingerstick blood glucose reference values ≤65 mg/dL (≤3.6 mmol/L). Children had exercise in the afternoon, no increase in basal insulin delivery, and were not in Auto Mode. Of the 1experiments, there were 79 with PLGM activation. Hypoglycemia was prevented 79.7% of the time (63/79). Mean duration of a suspension was 85.6±32.4min. The Table shows mean reference glucose values with respect to the start of automated insulin suspension and resumption, as well as 2 and 4 hours after insulin resumption. Rates of change (ROC) at insulin suspension and resumption start are also shown. All were evaluated by TDD and duration of diabetes, and stratified in quartiles. The “suspend before low” feature of the MiniMed™ 670G system reduced hypoglycemia events without rebound hyperglycemia in children with T1D regardless of TDD or duration of diabetes. Disclosure D.I. Shulman: Other Relationship; Self; Novo Nordisk Inc.. Research Support; Self; Medtronic MiniMed, Inc.. Board Member; Self; Pediatric Endocrine Society. Research Support; Self; Versartis, Inc. M.A. Wood: Research Support; Self; Medtronic MiniMed, Inc. G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc.. Research Support; Self; Medtronic, Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Novo Nordisk Inc., Bigfoot Biomedical. B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. T.L. Cordero: Employee; Self; Medtronic. B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. X. Chen: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic.

Glucocorticoids (GCs) are excellent anti-inflammatory drugs but are dose-limited by on-target toxicity. We sought to solve this problem by delivering GCs to immune cells with antibody-drug conjugates (ADCs) using antibodies containing site-specific incorporation of a non-natural amino acid, novel linker chemistry for in vitro and in vivo stability, and existing and novel glucocorticoid receptor (GR) agonists as payloads. We directed fluticasone propionate to human antigen-presenting immune cells to afford GR activation that was dependent on the targeted antigen. However, mechanism of action studies pointed to accumulation of free payload in the tissue culture supernatant as the dominant driver of activity and indeed administration of the ADC to human CD74 transgenic mice failed to activate GR target genes in splenic B cells. Suspecting dissipation of released payload, we designed an ADC bearing a novel GR agonist payload with reduced permeability which afforded cell-intrinsic activity in human B cells. Our work shows that antibody-targeting offers significant potential for rescuing existing and new dose-limited drugs outside the field of oncology.

Fasting C-peptide levels are used to differentiate type 1 from type 2 diabetes (T2D), thereby determining eligibility for coverage of continuous subcutaneous insulin infusion (CSII) for patients with T2D.A total of 168 patients (74 female/94 male, aged 55.5 ± 9.7 years) were randomized to CSII, and 163 patients (77 female/86 male, aged 56.4 ± 9.5 years) were randomized to multiple daily injections (MDI) of insulin and grouped by baseline C-peptide level: group A (≤183 pmol/L [≤0.55 ng/mL]); group B (183 pmol/L [0.55 ng/mL]). At 6 months, the MDI group crossed over to CSII. Within- and between-group comparisons were recorded at 6 and 12 months in the entire group and separately for those patients aged ≥65 years.CSII reduced hemoglobin A1c (A1c) equally in groups A ( P = .0006, P = .0022) and B ( P.0001, P.0001) at 6 and 12 months, respectively. There was an increase in weight in group A versus group B at 6 months but not 12 months ( P.03). CSII therapy reduced total daily dose (TDD) of insulin and improved treatment satisfaction similarly in groups A and B. The results for patients aged ≥65 years displayed a similar trend as the entire group.A1c, TDD of insulin, and treatment satisfaction improved for T2D patients using CSII versus MDI therapy, irrespective of baseline C-peptide level. A subgroup of patients aged ≥65 years displayed a similar trend. These results support abandoning C-peptide as a criterion for reimbursing CSII therapy in patients with diabetes.A1c = hemoglobin A1c; CMS = Centers for Medicare and Medicaid Services; CSII = continuous subcutaneous insulin infusion; DTSQ = Diabetes Treatment Satisfaction Questionnaire; MDI = multiple daily injections; RCT = randomized controlled trials; T1D = type 1 diabetes; T2D = type 2 diabetes; TDD = total daily dose.

STUDY DESIGN A retrospective cohort study. OBJECTIVE We performed a retrospective study of patients treated at our institution over the last 7 years to ascertain whether gene expression signatures in patients with advanced metastatic disease are associated with survival, when the disease has progressed to the spine. SUMMARY OF BACKGROUND DATA Spinal metastases are a major cause of morbidity in patients with cancer. Molecular profiling strategies to characterize lung cancer have identified several genetic biomarkers that may lead to more effective prognostication. METHODS We queried our institutional database for patients with metastatic lung cancer who underwent treatment for spinal metastases between 2011 and 2017. Genetic mutations in ALK, MET, ROS1, EGFR, and KRAS were chosen a priori for study based on availability by standard SNaPshot Lung Tumor Genotyping Analysis. Survival time was the duration between treatment for spinal metastases and death. Kaplan-Meier methods and the log-rank test were applied to characterize survival data. RESULTS Twenty-six patients met criteria for inclusion. Median survival after surgery was 0.67 years. Median overall survival (OS) after diagnosis was 2.7 years. The presence of molecular abnormalities in patients with spinal metastases was significantly associated with increased OS (HR 0.38, 95% CI 0.12-1.22, P = 0.03). CONCLUSION Molecular phenotyping may provide prognostic insight in patients undergoing surgery for spinal metastases. This is the first study to demonstrate an association between genetic mutational data and OS in this patient population. It also represents the largest published series of such patients (n = 26) for which genetic mutational data are reported. Future models estimating survival for patients with spinal metastases may be enhanced by incorporation of molecular criteria. LEVEL OF EVIDENCE 4.

OBJECTIVEThe purpose of this study was to investigate the spectrum of current treatment protocols for managing newly diagnosed chordoma of the mobile spine and sacrum.METHODSA survey on the treatment of spinal chordoma was distributed electronically to members of the AOSpine Knowledge Forum Tumor, including neurosurgeons, orthopedic surgeons, and radiation oncologists from North America, South America, Europe, Asia, and Australia. Survey participants were pre-identified clinicians from centers with expertise in the treatment of spinal tumors. The suvey responses were analyzed using descriptive statistics.RESULTSThirty-nine of 43 (91%) participants completed the survey. Most (80%) indicated that they favor en bloc resection without preoperative neoadjuvant radiation therapy (RT) when en bloc resection is feasible with acceptable morbidity. The main area of disagreement was with the role of postoperative RT, where 41% preferred giving RT only if positive margins were achieved and 38% preferred giving RT irrespective of margin status. When en bloc resection would result in significant morbidity, 33% preferred planned intralesional resection followed by RT, and 33% preferred giving neoadjuvant RT prior to surgery. In total, 8 treatment protocols were identified: 3 in which en bloc resection is feasible with acceptable morbidity and 5 in which en bloc resection would result in significant morbidity.CONCLUSIONSThe results confirm that there is treatment variability across centers worldwide for managing newly diagnosed chordoma of the mobile spine and sacrum. This information will be used to design an international prospective cohort study to determine the most appropriate treatment strategy for patients with spinal chordoma.

Traditionally, surgical skills are meant to be acquired through years of experience in the operating room (OR) on live patients. This chapter introduces the use of cadaveric models in spine surgery, how such laboratories are organized worldwide. Spine surgery is associated with increased morbidity due to the complexity of these surgical procedures, so the increasing need for improvement of postoperative results forces the physicians on enchasing the effectiveness of their surgical standards. Spine surgery’s high exacting nature is common ground due to the complex anatomy as well as the dangers surgeons can face intra- and postoperatively. Cadaveric training programs offer the infrastructure and the personnel to face this need through a combination of theoretical and practical training through up-to-date teaching, make a truly very meaningful advance to improve patient care, and improve the quality of spine surgery. Included in this chapter are the advantages and disadvantages of cadaveric spine surgery, as well as the methods through which spine surgeons are introduced to recognize the anatomical landmarks of each part of the spine and learn how to perform certain surgical procedures of the cervical, thoracic, and lumbar spine. Additionally, the new role of minimally invasive surgery is being presented and how training using cadavers can potentially expand our therapeutic options. Despite some limitations in this type of training, cadaver-based surgical skill learning courses are worldwide recognized as the gold standard in surgical training. New doctors, as well as medical professionals, are encouraged to practice spine surgery on cadaveric models, which gives them the best way to effectively improve their skills and make significant progress in achieving their treatment goals effectively.

BACKGROUND CONTEXT Several surgical techniques for atlantoaxial fixation and arthrodesis have been proposed over the years to treat patients with atlantoaxial instability with the goal of achieving C1-2 fusion. PURPOSE We report a novel C1-2 fixation technique for treating patients with atlantoaxial instability using a loop-suture technique without the use of cables or wires. We propose a safer alternative to securing structural bone graft between C1-2. STUDY DESIGN/SETTING A retrospective review of a prospective database was performed using this technique from 2013-2018 for patients with atlantoaxial instability related to trauma, degeneration, and inflammatory arthropathy. Primary bone and metastatic cancer were excluded. The technique entails anchoring a structural iliac crest autograft or allograft between C1 and C2 for interlaminar arthrodesis in addition to C1 lateral mass and C2 pars/pedicle screw placement. The bone graft is secured using a 0-Prolene suture which is looped under the C1 lamina with the blunt end of the needle first. The needle is then passed through the graft, through the C2-3 interspinous ligaments, and then tied over the graft. We report the utility, safety, durability, and effectiveness of this approach in 32 consecutive patients METHODS A retrospective review of a prospective database was performed using this technique from 2013-2018 for patients with atlantoaxial instability related to trauma, degeneration, and inflammatory arthropathy. Primary bone and metastatic cancer were excluded. The technique entails anchoring a structural iliac crest autograft or allograft between C1 and C2 for interlaminar arthrodesis in addition to C1 lateral mass and C2 pars/pedicle screw placement. The bone graft is secured using a 0-Prolene suture which is looped under the C1 lamina with the blunt end of the needle first. The needle is then passed through the graft, through the C2-3 interspinous ligaments, and then tied over the graft. We report the utility, safety, durability, and effectiveness of this approach in 32 consecutive patients. RESULTS A total of 32 patients were identified who met criteria for atlantoaxial instability due to traumatic dislocation or ligamentous injury (60.0%), cervical spine degeneration (34.5%), deformity (5.25%) or combination of trauma and degeneration (5.25%). The follow-up period ranged from 6 to 24 months (mean 7.8 months). All patients had improvement in their pain by VAS and NDI (85% and 60% improvement respectively, p CONCLUSIONS We demonstrate a novel approach for C1-2 arthrodesis that utilizes a safe technique for securing bone graft without the use of wires or cables, allowing for less sublaminar dissection and potential dural and neurologic injury as well as improved clinical outcomes. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Spinal injuries are a major cause of morbidity and mortality resulting from either destabilization of the bony spine or neurological injury to the spinal cord or spinal nerves. Prompt medical and surgical treatment is essential to minimize chronic functional disability. Major non-operative issues are immobilization and management of hypoxia and hypotension to reduce secondary neurological damage to the spinal cord. Accurate diagnosis of the injury requires careful neurological examination and imaging. Optimal surgical decisions depend upon the need for decompression, reduction of any induced deformity, and maintenance and/or restoration of spinal stability. This report reviews the commonly used criteria, guidelines, and approaches for operative management of spinal injury.

Background The purpose of this study was to evaluate the extension of delamination and the cuff integrity after arthroscopic repair of delaminated rotator cuff tears. Methods Sixty-five patients with delaminated rotator cuff tears were retrospectively reviewed. The delaminated tears were divided into full-thickness delaminated tears and partial-thickness delaminated tears. To evaluate the medial extension, we calculated the coronal size of the delaminated portion. To evaluate the posterior extension, we checked the tendon involved. Cuff integrity was evaluated by computed tomography arthrography. Results The mean medial extension in the full-thickness and partial-thickness delaminated tears was 18.1 ± 6.0 mm and 22.7 ± 6.3 mm, respectively ( P = .0084). The posterior extension into the supraspinatus and the infraspinatus was 36.9% and 32.3%, respectively, in the full-thickness delaminated tears, and it was 27.7% and 3.1%, respectively, in the partial-thickness delaminated tears ( P = .0043). With regard to cuff integrity, 35 cases of anatomic healing, 10 cases of partial healing defects, and 17 cases of retear were detected. Among the patients with retear and partial healing of the defect, all the partially healed defects showed delamination. Three retear patients showed delamination, and 14 retear patients did not show delamination; the difference was statistically significant ( P = .0001). Conclusion The full-thickness delaminated tears showed less medial extension and more posterior extension than the partial-thickness delaminated tears. Delamination did not develop in retear patients, but delamination was common in the patients with partially healed defects.

Purpose To evaluate plan quality and delivery efficiency gains of volumetric modulated arc therapy (VMAT) versus a multicriteria optimization-based intensity modulated radiation therapy (MCO-IMRT) for stereotactic radiosurgery of spinal metastases. Methods and materials MCO-IMRT plans (RayStation V2.5; RaySearch Laboratories, Stockholm, Sweden) of 10 spinal radiosurgery cases using 7-9 beams were developed for clinical delivery, and patients were replanned using VMAT with partial arcs. The prescribed dose was 18 Gy, and target coverage was maximized such that the maximum dose to the planning organ-at-risk volume (PRV) of the spinal cord was 10 or 12 Gy. Dose-volume histogram (DVH) constraints from the clinically acceptable MCO-IMRT plans were utilized for VMAT optimization. Plan quality and delivery efficiency with and without collimator rotation for MCO-IMRT and VMAT were compared and analyzed based upon DVH, planning target volume coverage, homogeneity index, conformity number, cord PRV sparing, total monitor units (MU), and delivery time. Results The VMAT plans were capable of matching most DVH constraints from the MCO-IMRT plans. The ranges of MU were 4808-7193 for MCO-IMRT without collimator rotation, 3509-5907 for MCO-IMRT with collimator rotation, 4444-7309 for VMAT without collimator rotation, and 3277-5643 for VMAT with collimator of 90 degrees. The MU for the VMAT plans were similar to their corresponding MCO-IMRT plans, depending upon the complexity of the target and PRV geometries, but had a larger range. The delivery times of the MCO-IMRT and VMAT plans, both with collimator rotation, were 18.3 ± 2.5 minutes and 14.2 ± 2.0 minutes, respectively ( P Conclusions The MCO-IMRT and VMAT can create clinically acceptable plans for spinal radiosurgery. The MU for MCO-IMRT and VMAT can be reduced significantly by utilizing a collimator rotation following the orientation of the spinal cord. Plan quality for VMAT is similar to MCO-IMRT, with similar MU for both modalities. Delivery times can be reduced by nominally 25% with VMAT.

This study evaluated the accuracy and performance of a fourth-generation subcutaneous glucose sensor (GuardianEighty-eight subjects (14-75 years of age, mean ± standard deviation [SD] of 42.0 ± 19.1 years) with type 1 or type 2 diabetes participated in the study. Subjects wore two sensors in the abdomen that were paired with either a MiniMedThe overall mean absolute relative difference (MARD ± SD) between abdomen sensor glucose (SG) and YSI reference values was 9.6% ± 9.0% and 9.4% ± 9.8% for the MiniMed 640G insulin pump and Guardian Connect system, respectively; and 8.7% ± 8.0% between arm SG and YSI reference values. The percentage of SG values within 20% agreement of the YSI reference value (for YSI80 mg/dL) was 90.7% with the MiniMed 640G insulin pump, 91.8% with the Guardian Connect system, and 93.1% for GSR-connected arm sensors. Mean functional sensor life, when calibrating 3-4 times/day, was 145.9 ± 39.3 h for sensors paired with the MiniMed 640G insulin pump, 146.1 ± 41.6 h for sensors paired with the Guardian Connect system, and 147.6 ± 40.4 h for sensors connected to the GSR. Responses to survey questions regarding sensor comfort and ease of use were favorable.The Guardian Sensor 3 glucose sensor, whether located in abdomen or the arm, provided accurate glucose readings when compared with the YSI reference and demonstrated functional life commensurate with the intended 7-day use. ClinicalTrials.gov : NCT02246582.

OBJECTIVEPrimary osteosarcoma of the spine is a rare osseous neoplasm. While previously reported retrospective studies have demonstrated that overall patient survival is impacted mostly by en bloc resection and chemotherapy, the continued management of residual disease remains to be elucidated. This systematic review was designed to address the role of revision surgery and multimodal adjuvant therapy in cases in which en bloc excision is not initially achieved.METHODSA systematic literature search spanning the years 1966 to 2015 was performed on PubMed, Medline, EMBASE, and Web of Science to identify reports describing outcomes of patients who underwent biopsy alone, neurological decompression, or intralesional resection for osteosarcoma of the spine. Studies were reviewed qualitatively, and the clinical course of individual patients was aggregated for quantitative meta-analysis.RESULTSA total of 16 studies were identified for inclusion in the systematic review, of which 8 case reports were summarized qualitatively. These studies strongly support the role of chemotherapy for overall survival and moderately support adjuvant radiation therapy for local control. The meta-analysis revealed a statistically significant benefit in overall survival for performing revision tumor debulking (p = 0.01) and also for chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated with longer survival, although this did not reach statistical significance (p = 0.06).CONCLUSIONSWhile the initial therapeutic goal in the management of osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc marginal resection, this objective is not always achievable given anatomical constraints and other limitations at the time of initial clinical presentation. This systematic review supports the continued aggressive use of revision surgery and multimodal adjuvant therapy when possible to improve outcomes in patients who initially undergo subtotal debulking of osteosarcoma. A limitation of this systematic review is that lesions amenable to subsequent resection or tumors inherently more sensitive to adjuvants would exaggerate a therapeutic effect of these interventions when studied in a retrospective fashion.

This study sought to report mechanisms of ventricular tachycardia (VT) and outcomes of VT ablation in patients with a left ventricular assist device (LVAD) as destination therapy.Continuous flow LVAD implantation plays a growing role in the management of end-stage heart failure, and VT is common. There are limited reports of VT ablation in patients with a destination LVAD.Patients with a continuous-flow LVAD referred for VT ablation from 2010 to 2016 were analyzed retrospectively. Baseline patient characteristics, procedural data, and clinical follow-up were evaluated. Arrhythmia-free survival was assessed.Twenty-one patients (90% male, 62 ± 10 years) underwent catheter ablation of VT at a median of 191 days (interquartile range: 55 to 403 days) after LVAD implantation (15 HeartMate II, 6 HeartWare HVAD). Five patients (24%) had termination (n = 4) or slowing (n = 1) of VT with ablation near the apical inflow cannula, and 3 (14%) had bundle-branch re-entry. Freedom from recurrent VT among surviving patients was 64% at 1 year, with overall survival 67% at 1 year for patients without arrhythmia recurrence and 29% for patients with recurrence (p = 0.049). One patient had suspected pump thrombosis within 30 days of the ablation procedure, with no other major acute complications.In this relatively large, single-center experience of VT ablation in destination LVAD, freedom from recurrent VT and implantable cardioverter-defibrillator shocks was associated with improved 1-year survival. Bundle branch re-entry was more prevalent than anticipated, and cannula-adjacent VT was less common. This challenging population remains at risk for late pump thrombosis and mortality.

Background: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated. Methods: Adolescents (n = 30, ages 14–21 years) and adults (n = 94, ages 22–75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase. Results: Adolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%–88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%–92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P

OBJECTIVE Vascular malformations of the spine represent rare clinical entities with profound neurological implications. Previously reported studies on management strategies for spinal dural arteriovenous fistulas (sDAVFs) appeared before the advent of modern liquid embolic agents. Authors of the present study review their institutional experience with endovascularly and surgically treated sDAVFs. METHODS The authors performed a retrospective, observational, single-center case series on sDAVFs treated with endovascular embolization, microsurgical occlusion, or both between 2004 and 2013. The mode, efficacy, and clinical effect of treatment were evaluated. RESULTS Forty-seven patients with spinal arteriovenous malformations were evaluated using spinal angiography, which demonstrated 34 Type I sDAVFs (thoracic 20, lumbar 12, and cervical 2). Twenty-nine of the patients (85%) were male, and the median patient age was 63.3 years. Twenty patients underwent primary endovascular embolization (16 Onyx, 4 N-butyl cyanoacrylate [NBCA]), and 14 underwent primary surgical clipping. At a mean follow-up of 36 weeks, according to angiography or MR angiography, 5 patients treated with endovascular embolization demonstrated persistent arteriovenous shunting, whereas none of the surgically treated patients showed lesion persistence (p = 0.0237). Thirty patients (88%) experienced some resolution of their presenting symptoms (embolization 17 [85%], surgery 13 [93%], p = 1.00). CONCLUSIONS Microsurgical occlusion remains the most definitive treatment modality for sDAVFs, though modern endovascular techniques remain a viable option for the initial treatment of anatomically amenable lesions. Treatment of these lesions usually results in some clinical improvement.

Assessing quality of life, functional outcome, and pain has become important in assessing the effectiveness of treatment for metastatic spine disease. Many questionnaires are able to measure these outcomes; few are validated in patients with metastatic spine disease. As a result, there is no consensus on the ideal questionnaire to use in these patients. Our study aim was to assess whether certain questionnaires measuring quality of life, functional outcome, and pain (1) correlated with each other, (2) measured the construct they claim to measure, (3) had good coverage-floor and ceiling effects, (4) were reliable, and (5) whether there were differences in completion time between them. This is a prospective cross-sectional survey study from three outpatient clinics (two orthopedic oncology clinics and one neurosurgery clinic) from two affiliated tertiary hospital care centers. We included 100 consecutive patients with metastatic spine disease between July 2014 and February 2016. We excluded non-English-speaking patients. The following questionnaires were given in random order: Oswestry Disability Index (ODI) or Neck Disability Index (NDI), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, PROMIS Pain Intensity, EuroQol-5 Dimensions (EQ-5D), and the Spine Oncology Study Group Outcome Questionnaire (SOSG-OQ). We used exploratory factor analysis-correlating questionnaires with an underlying mathematically derived trait-to assess if questionnaires measured the same concept. Coverage was assessed by floor and ceiling effects, and reliability was assessed by standard error of measurement as a function of ability. Differences in completion times were tested using the Friedman test. Questionnaires measured the construct they were developed for, as demonstrated with high correlations (>0.7) with the underlying trait. A floor effect was present in the PROMIS Pain Intensity (7.0%), ODI or NDI (4.0%), and the PROMIS Physical Function (1.0%) questionnaires. A ceiling effect was present in the EQ-5D questionnaire (6.0%). The SOSG-OQ had no floor or ceiling effect. The PROMIS Physical Function and PROMIS Pain Intensity proved to be the most reliable, whereas the EQ-5D was the least reliable. Completion time differed among questionnaires (p

The ASPIRE in-clinic study established that automatic suspension of insulin with the threshold suspend (TS) feature reduces the duration of induced hypoglycemia. The study's crossover design allowed the effects of antecedent hypoglycemia to be studied.The study enrolled 50 subjects who exercised until plasma glucose (YSI glucose and lactate analyzer; YSI, Inc., Yellow Springs, OH) reached ≤85 mg/dL. Hypoglycemia was evaluated after the YSI value reached70 mg/dL. In TS experiments, insulin was stopped for 2 h once a sensor glucose (SG) value of ≤70 mg/dL was detected; in control experiments, basal insulin delivery continued. Subjects were randomly assigned to Group A (TS in Period 1; control in Period 2) or Group B (control in Period 1; TS in Period 2). Experiments were separated by 3-10 days.Hypoglycemia was 63.7 min shorter in Period 1 TS experiments (no preceding control experiment) than in Period 2 TS experiments (one or more preceding control experiment(s)) (P0.01). The number of experiments prior to a successful TS experiment was lower for Period 1 than for Period 2 (0.36 ± 0.64 vs. 1.57 ± 0.84; P0.001), as was the cumulative duration of antecedent hypoglycemia (16.6 min vs. 204.6 min; P0.001). The between-groups difference in hypoglycemia duration was not attributable to differences in SG rates of change, the duration of exercise, or area under the curve of70 mg/dL × min in the 2 days before the successful experiment (all P0.3).The TS feature's ability to mitigate hypoglycemia was decreased by an episode or episodes of prolonged antecedent hypoglycemia, suggesting hypoglycemia begets hypoglycemia. The effect of antecedent hypoglycemia should be taken into consideration in the design of future experiments assessing strategies to reduce hypoglycemia.

Study design A retrospective cohort study. Objective We performed a retrospective study of patients treated at our institution over the last 3 years to assess predictive value of immunotherapy exposure on overall survival (OS) of patients with metastatic melanoma to the spine in an effort to better inform surgical decision making. Summary of background data Modern management of metastatic melanoma includes adjuvant targeted therapies and immunomodulators that have shown to significantly improve OS. Methods Baseline characteristics were recorded for patients, including performance scores, use of adjuvant therapies, progression-free survival (PFS), and OS. Pre-procedural imaging was reviewed to assign Spinal Instability Neoplastic Score (SINS) and epidural spinal cord compression (ESCC) classification. Kaplan-Meier survival analysis was performed. Results We identified 18 patients with metastatic melanoma to the spine treated between 2012 and 2015. Instrumented fixation was performed for median SINS 12. Eleven patients undergoing surgery were noted to have ESCC classification of at least 2. Median OS for the entire group was 117 days. Univariate analysis revealed that prior immunotherapy treatment was associated with significantly shorter survival following surgery (median survival 98 vs. 315 days for patients previously on immunotherapies compared to those who were not). Meanwhile, neither BRAF mutation status nor treatments targeting these pathways were associated with this prognostic effect. Conclusion Progressive metastatic spine disease following immunotherapy may herald a particularly aggressive time point and recognizing this natural history is critical for appropriate multimodal planning. Level of evidence 4.

Study design Systematic review. Objective To determine evidence-based guidelines for the management of locally recurrent spinal chordoma. Summary of background data Chordoma of the spine is a low-grade malignant tumor with a strong propensity for local recurrence. Salvage therapy is challenging due to its relentless nature and refractoriness to adjuvant therapies. There are currently no guidelines regarding the best management of recurrent chordoma. Methods We combined the results of a systematic review with expert opinion to address the following research questions: (1) For locally recurrent chordoma of the spine without systemic disease, if surgery is planned, should en bloc resection be attempted if technically feasible with acceptable morbidity? (2) For locally recurrent chordoma without systemic disease, in which wide en bloc excision is not possible, what is the treatment of choice? (2) Should adjuvant or neoadjuvant radiation therapy be used in the treatment of locally recurrent chordoma? Results A total of nine surgical and seven radiation therapy articles met study criteria. Evidence quality was low or very low. Recurrent disease is associated with predominantly poor outcome, regardless of treatment modality. As for primary chordoma, resection with wide margins appears to confer an advantage with respect to local control, although this effect is attenuated in the setting of relapse. Postoperative radiation therapy likely reduces the rate of further relapse. Conclusion (1) For locally recurrent chordoma of the spine without systemic disease, when surgery is planned, wide en bloc resection should be performed if technically feasible with acceptable morbidity. Strong recommendation, Low Quality of Evidence. (2) For locally recurrent chordoma without systemic disease, in which wide en bloc excision is not possible, partial resection is the treatment of choice. Weak recommendation, Very Low Quality of Evidence. (3) For the treatment of locally recurrent chordoma, high-dose conformal radiation therapy should be administered postoperatively to reduce the risk of further recurrence, and may be considered as a primary therapy. Strong recommendation, Very Low Quality of Evidence. Level of evidence 2.

Study design Systematic review. Objective To identify risk factors and preventive methods for wound complications and instrumentation failure after metastatic spine surgery. Summary of background data We focused on two postoperative complications of metastatic spine tumor surgery: wound complications and instrumentation failure and preventive measures. Methods We performed a systematic review of the literature from 1980 to 2015. The articles were analyzed for the presence of documented infection and/or wound complications and instrumentation failure. Results Forty articles met our inclusion criteria for wound complications and prevention. There is very low level of evidence that preoperative radiation, preoperative neurological deficit, revision procedures, and posterior approaches can contribute to wound complications (infections, wound dehiscence). There is very low level of evidence that plastic surgery soft tissue reconstruction, intrawound vancomycin powder, and percutaneous pedicle screws may prevent postoperative wound complications. Fourteen articles met our inclusion criteria for instrumentation failure. There is very low level of evidence that constructs greater than six levels, positive sagittal balance, preoperative radiation, and history of chest wall resection can contribute to implant failures. Conclusion • For patients undergoing revision metastatic spine tumor surgery, plastic surgery should perform the soft tissue reconstruction (strong recommendation/very low quality of evidence).• For patients undergoing metastatic spine tumor surgery, plastic surgery may perform immediate soft tissue reconstruction (weak recommendation/very low quality of evidence).• For patients undergoing metastatic spine tumor surgery, intrawound vancomycin can be applied to decrease the risk of postoperative wound infections (weak recommendation/very low quality of evidence).• For patients undergoing metastatic spine tumor surgery, percutaneous pedicle screws can be placed to decrease the risk of postoperative wound complications (weak recommendation/very low quality of evidence).• Instrumentation failure risk factors include constructs greater than six levels, positive sagittal balance, preoperative radiation, and history of chest wall resections (weak recommendation/very low quality of evidence). Level of evidence N/A.

BACKGROUND CONTEXT Increasing prevalence of metastatic disease has been accompanied by increasing rates of surgical intervention. Current tools have poor to fair predictive performance for intermediate (90-day) and long-term (one-year) mortality. PURPOSE The purpose of this study was to develop predictive algorithms for spinal metastatic disease at these time points and to provide patient-specific explanations of the predictions generated by these algorithms. STUDY DESIGN/SETTING Retrospective review was conducted at two large academic medical centers. PATIENT SAMPLE Patients undergoing initial operative management for spinal metastatic disease between January 2000 and December 2016. OUTCOME MEASURES Ninety-day and one-year overall survival. METHODS Five models (penalized logistic regression, random forest, stochastic gradient boosting, neural network, and support vector machine) were developed to predict ninety-day and one-year mortality. RESULTS Overall, 732 patients were identified with ninety-day and one-year mortality rates of 181 (25.1%) and 385 (54.3%), respectively. The stochastic gradient boosting algorithm had the best performance for 90-day mortality and one-year mortality. On global variable importance assessment, albumin, primary tumor histology, and performance status were the three most important predictors of 90-day mortality. The final models were incorporated into an open access web application able to provide predictions as well as patient-specific explanations of the results generated by the algorithms. The application can be found at: https://sorg-apps.shinyapps.io/spinemetssurvival/ CONCLUSIONS Preoperative estimation of 90-day and one-year mortality was achieved with assessment of more flexible modeling techniques such as machine learning. Integration of these models into applications and patient-centered explanations of predictions represent opportunities for incorporation into health care systems as decision tools in the future. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Immune checkpoint blockade (ICB) has revolutionized the treatment of metastatic melanoma, however, cases of resistance have now begun to emerge. We report here a case of acquired resistance by melanoma phenotypic transformation in a patient treated on a Phase 1b/2 clinical trial (NCT02437136) with anti-PD1 (Pembrolizumab) and a histone deacetylase (HDAC) inhibitor (Entinostat). The patient presented to MGH with metastatic melanoma confirmed by core-needle biopsy of a liver lesion. A PET/CT scan one month after starting the trial revealed interval regression of liver and bone lesions, however, four months later the patient presented with disease progression. A tumor debulked from the L2 vertebral body at that time revealed the presence of a pleomorphic rhabdomyosarcoma. The patient was started on anti-CTLA4 (Ipilumimab) with further disease progression, and surgical specimens thereafter revealed either melanoma or rhabdomyosarcoma. Tumor tissue was evaluated for markers by immunohistochemistry. All tumors (5 specimens in total) were subjected to whole exosome sequencing (WES), RNA-sequencing (RNAseq) and epigenomic sequencing (ATACseq). WES revealed 844 mutations were shared between all tumors, suggesting a common ancestor including driver mutations in NRAS (G13D), NF1 (E1121* and W1314*) and the TERT2 promoter, among others. The pre-treatment melanoma biopsy had positive staining for S100 and MART-1, nuclear staining patterns for SOX10 and MITF, and were BRAF V600E negative. Importantly, 80% of the tumor cells had strong staining for PD-L1 expression and CD8 CTL infiltration was associated with 25% of the tumor. The post-treatment rhabdomyosarcoma biopsy was notable for diffusely positive staining for Desmin and MyoD1, and multifocal positivity for myogenin. The tumor stained negative for S100 and SOX10, and there was no PD-L1 staining and less than 5% tumor CD8 CTL infiltration. Gene expression analysis revealed distinct expression patterns between melanoma and rhabdomyosarcoma samples, with 150 differentially expressed genes implicated in processes such as antigen presentation, T cell activation, cell death and protein metabolism. In addition, each tumor was found to have a unique immune cell composition and T-cell receptor repertoire, suggesting an interplay between phenotypic transformation and immune response. Results from epigenomic sequencing are pending, but may shed light on the mechanisms of transformation leading to resistance. These data therefore elucidate a previously undescribed mechanism of acquired resistance to ICB through melanoma phenotypic transformation to a rhabdomyosarcoma. Whereas these tumors were genetically similar, they expressed distinct gene expression patterns suggestive of underlying epigenomic differences in the setting of an HDAC inhibitor. Citation Format: Arnav Mehta, David Liu, Alvin Shi, Dennie T. Frederick, Li-Lun Ho, Ana B. Larque, Benchun Miao, Rumya S. Raghavan, Tatyana Sharova, John H. Shin, Nicola Rinaldi, Ivan A. Chebib, Manolis Kellis, Eliezer Van Allen, Nir Hacohen, Keith T. Flaherty, Genevieve M. Boland, Ryan J. Sullivan. Acquired resistance to immune checkpoint inhibition by melanoma phenotypic transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3013.

Spleen tyrosine kinase (SYK) is a key activator of signaling pathways downstream of multiple surface receptors implicated in asthma. SYK function has been extensively studied in mast cells downstream of the high-affinity IgE receptor, FcεR1. Preclinical studies have demonstrated a role for SYK in models of allergic inflammation, but a role in airway constriction has not been demonstrated. Here, we have used a potent and selective pharmacological inhibitor of SYK to determine the role of SYK in allergen-mediated inflammation and airway constriction in preclinical models. Attenuation of allergic airway responses was evaluated in a rat passive anaphylaxis model and rat and sheep inhaled allergen challenge models, as well as an ex vivo model of allergen-mediated airway constriction in rats and cynomolgus monkeys. Pharmacological inhibition of SYK dose-dependently blocked IgE-mediated tracheal plasma extravasation in rats. In a rat ovalbumin-sensitized airway challenge model, oral dosing with an SYK inhibitor led to a dose-dependent reduction in lung inflammatory cells. Ex vivo analysis of allergen-induced airway constriction in ovalbumin-sensitized brown Norway rats showed a complete attenuation with treatment of a SYK inhibitor, as well as a complete block of allergen-induced serotonin release. Similarly, allergen-mediated airway constriction was attenuated in ex vivo studies from nonhuman primate lungs. Intravenous administration of an SYK inhibitor attenuated both early- and late-phase allergen-induced increases in airway resistance in an Ascaris-sensitive sheep allergen challenge model. These data support a key role for SYK signaling in mediating allergic airway responses.

The effect of defibrillation threshold (DFT) testing with induction of ventricular fibrillation (VF) on renal function is currently unknown. This study examined the acute effect of DFT testing on renal function in patients undergoing implantable cardioverter defibrillator (ICD) implantation. We performed a prospective cohort study of 148 consecutive patients who underwent ICD implantation from January 1, 2007 to May 30, 2008. Patients were assigned to one of two cohorts: a DFT group who underwent DFT testing at device implantation and a no-DFT group that was not tested. Baseline and 24-h postprocedure renal function were assessed with measurements of serum creatinine and estimated glomerular filtration rate (GFR) by the Modified Diet in Renal Disease equation. Changes in serum creatinine and estimated GFR were compared between cohorts. Ninety-eight patients (66 %) underwent DFT testing (average VF induction count, 1.5 ± 0.9; mean VF duration, 10 ± 4 s). Fifty patients (34 %) were not tested. Patients in the no-DFT group had lower mean left ventricular ejection fraction, higher New York Heart Association class, higher atrial fibrillation incidence, and greater intravenous contrast utilization at device implant. Baseline and postprocedure serum creatinine values were similar between groups (baseline, 1.25 ± 0.45 mg/dL; post-ICD, 1.26 ± 0.5 mg/dL). Baseline GFR was lower in the DFT cohort (55.2 ± 18.8 mL/min/BSA vs 63.7 ± 22.7 mL/min/BSA, p = 0.023). No significant differences between groups were observed in the mean change in serum creatinine or estimated GFR. DFT testing at the time of ICD implantation is not associated with acute adverse effects on renal function.

Study Design Retrospective clinical study. Objectives Recent biomechanical studies have shown no differences in stiffness or range of motion following minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) between unilateral pedicle and contralateral facet screw (UPFS) and bilateral pedicle screw (BPS) constructs. No studies have compared these two constructs based upon clinical outcomes. Methods Twenty-six consecutive patients who had single-level MIS TLIF were retrospectively reviewed. Outcome measures collected for patients with BPS were compared with those with UPFS. Results No associations were found between construct and length of stay ( p = 0.5), operative time ( p = 0.2), or Odom's criteria ( p = 0.7); 79% of patients in the UPFS group as compared with 71.5% in the BPS group had good or excellent outcomes. Mean follow-up was 17.7 months for the UPFS group and 20.2 months for the BPS group. There was one complication in each group, including a seroma in the BPS group and a revision operation in the UPFS group. Implant costs for the BPS group were 35% greater than the UPFS group. Conclusions The present study is the first to demonstrate that patients undergoing MIS TLIF with BPS as compared with UPFS for single-level degenerative lumbar disease had similar clinical outcomes.

Study design A retrospective analysis. Objective The aim of this study was to identify whether age is a risk factor for postoperative complications after adult deformity surgery (ADS). Summary of background data Spinal deformity is a prevalent cause of morbidity in the elderly population, occurring in as many as 68% of patients older than 60 years. Given the increasing prevalence of adult spinal deformities and an aging population, understanding the safety of ADS in elderly patients is becoming increasingly important. Methods A retrospective cohort analysis was performed on the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database from 2010 to 2014. Patients (≥18 years of age) from the NSQIP database undergoing ADS were separated into age-based cohorts (≤52, 53-61, 62-69, and ≥70 years of age). Age groups were determined by interquartile analysis. Chi-squared, t tests, and multivariate logistic regression models were used to identify independent risk factors. Results A total of 5805 patients met the inclusion criteria. Age groups 1, 2, 3, and 4 contained 1518 (26.1%), 1478 (25.4%), 1451 (25.0%), and 1358 (23.4%) patients, respectively. Multivariate logistic regression analysis revealed increasing age (relative to age group 1) to be an independent risk factor for prolonged length of stay [odds ratio (OR) 1.39, confidence interval (CI) 1.12-1.69], all complications (OR 1.64, CI 1.35-2.00), renal complications (OR 3.45, CI 1.43-8.33), urinary tract infection (OR 2.70, CI 1.49-4.76), postoperative transfusion (OR 1.47, CI 1.20-1.82), and unplanned readmission (OR 1.64, CI 1.18-2.23). Gradations in ORs existed between the different cohorts, such that the deleterious effect of age was less pronounced in cohort 3 compared with cohort 4, and even more less so between cohort 2 and cohort 4. Conclusion Age has been shown to be an independent risk factor for increased length of stay, all complications, renal complications, urinary tract infection, transfusion, and unplanned readmission. Level of evidence 3.

Background Hepatocellular carcinoma (HCC) frequently metastasizes to the spine. The impact of medical and/or surgical intervention on overall survival has been examined in a limited number of clinical studies, and herein we systematically review these data. Methods We performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles that reported survival, clinical outcomes, and/or prognostic factors associated with patients diagnosed with spinal metastases. The methodologic quality of each review was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses tool. Results There were 26 articles (152 patients) that met the inclusion criteria and were treated with either surgery, radiotherapy, chemotherapy, and/or observation. There were 3 retrospective cohort studies, 17 case reports, 5 case series, and 1 longitudinal observational study. Of the patients with known overall survival after diagnosis of spinal metastasis, survival at 3 months, 6 months, 1 year, 2 years, and 5 years was 95.2%, 83.0%, 28.6%, 2.0%, and 1.4%, respectively. The median survival after diagnosis of the metastasis was 0.7 months in the patients who received no treatment, 7 months in the patients treated with surgical intervention alone, 6 months for patients who received chemotherapy and/or radiation, and 13.5 months in the patients treated with a combination of surgery and medical management. All other clinical or prognostic parameters were of low or insufficient strength. Conclusions Patients diagnosed with HCC spinal metastasis have a 10.6-month overall survival. Further analysis of patients in prospective controlled trials will be essential to the development of treatment algorithms for these patients in the future.

Given the rising incidence of revision total joint arthroplasty (RJR), bundled payments will likely be applied to RJR in the near future. This study aimed to compare postdischarge adverse events by discharge destination, identify risk factors for discharge placement, and stratify RJR patients based on these risk factors to identify the most appropriate discharge destination.Patients that underwent revision total hip or knee arthroplasty from 2011 to 2013 were identified in the American College of Surgeon's National Surgical Quality Improvement Program database. Analysis of risk factors was assessed using preoperative and intraoperative variables.A total of 9973 RJR patients from 2011 to 2013 were included for analysis. The most common discharge destination included home (66%), skilled nursing facility (SNF; 23%), and inpatient rehabilitation facility (IRF; 11%). Bivariate analysis revealed higher rate of postdischarge 30-day severe adverse events (6.1% vs 4.1%, P.001) and unplanned readmissions (9.3% vs 6.1%, P.001) in nonhome vs home patients. In multivariate analysis, SNF and IRF patients were 1.30 and 1.51 times more likely to suffer an unplanned 30-day readmission relative to home patients (P ≤ .01), respectively. After stratifying patients by number of significant risk factors and discharge destination, IRF patients consistently had significantly higher rates of unplanned 30-day readmission than home patients (P ≤ .05).RJR patients who are discharged to SNF or IRF have significantly increased risk for unplanned readmissions as compared with patients discharged home. Across risk levels, home discharge destination (when feasible) is the optimal strategy compared with IRF, although the distinction between SNF and home is less clear.

Accounting for less than 0.2% of all glioblastomas, high grade gliomas of the spinal cord are very rare. Here, we discuss our approach to managing patients with high grade spinal cord glioma and review the literature on the subject. Six patients with high grade spinal cord gliomas who presented to our institution between 1990 and 2015 were reviewed. Each patient underwent subtotal surgical resection, with a subset receiving adjuvant chemotherapy and radiation. Our primary outcomes of interest were pre-operative and post-operative functional status. One year survival rate was 100%. All patients had stable or improved American Spine Injury Association score immediately after surgery, which was maintained at 3months in 83.3% of patients. Karnofsky Performance Status (KPS) was stable at 3month follow up in 50% of patients, but all had decreased KPS 1year after surgery. A subset of patients received post-operative radiation and chemotherapy with 0% tumor recurrence rate at 3months. We assessed the molecular profiles of tumors from two patients in our series and found that each had mutations in TP53, but had wildtype BRAF, IDH-1, and MGMT. Taken together, our data show that patients with high grade spinal cord gliomas have an excellent survival at 1year, but with some decline in functional status within this period. Further studies are needed to elucidate the natural history of the disease and to explore the role of adjuvant targeted molecular therapies.

ional athletes vanced degenaradigm shift tion experts. only an all-orso result from al detrimental nto the media veteran footer of the ball were heavier, after a 5-year tensive degenCTE were disted as cause of y” was docuA concussive episode refers to inertially induced duced traumatic alteration of function of the cere associated imaging abnormalities. Appreciation f of gravity linear acceleration, angular velocity, and eration during dynamic motion of the head a emerged recently in the neurosurgical community literature details potential detrimental effects of r cussive episodes in contact sports such as boxin American football (4, 8, 13-15, 25, 32, 35-37), rug 42), hockey (9, 49, 50), and soccer (18, 23, 24, repeat concussive episode before resolution of init symptoms has been associated with fatal cerebral hypothesized “second impact syndrome” (5, 6, 27 prevention efforts in sports have focused on minim lete’s concussive episode risk, and although the e tive subconcussive trauma in contact sports ha creased attention recently, it has yet to be fully add The term dementia pugilistica (22) describes a syndro sive neurodegeneration, first described in retired box repetitive subconcussive head impacts, that shares logic features with Alzheimer disease (1, 2, 11, 31, 3 term replacing dementia pugilistica, chronic traumati pact-inwithout ad center lar accelrain has luminous itive con, 17, 26), 9, 20, 29, 46-48). A ncussion a via the ain injury g an athof repetieived ined. f progresxposed to icopatho. The new phalopathy which is recognized to result from a variety of minor CTE is associated with personality changes, memor parkinsonism, and speech and gait abnormalities. P marks include gross cerebral andmedial temporal lo extensive tau-immunoreactive neurofibrillary tangle 30, 45). Spurred by highly publicized cases of profess who died at a young age and were found to have ad erative brain changes at autopsy, there has been a p among sports medicine and head injury preven An increasing realization is that brain injury is not nothing phenomenon (eg, concussion) but may al accumulated subconcussive impacts. The potenti effect of repetitive heading in soccer was thrust i limelight in 2002 following the death of English baller Jeffrey Astle. Astle had been a prolific head during an era in which the leather balls employed especially in wet conditions. Astle died at age 59 history of rapidly deterioratingmental capacity. Ex erative brain disease and taupathy consistent with covered at autopsy;minor repetitive traumawas sta death, and a verdict of “death by industrial injur ic entity, mented (28). This ruling of cause of death was especially striking

BACKGROUND CONTEXT The decision for surgical intervention of metastatic lesions of the spine integrates the etiology of pain and neurologic deficits, oncologic history, mechanical instability and systemic disease status. For instance, given the lack of sensitivity to radiation therapy, patients with symptomatic metastatic renal cell cancer (RCC) to the spine are treated with surgical decompression, radiosurgery and medical adjuvant therapies. Modern medical management of metastatic RCC includes therapies targeting growth pathways (PDGFR, mTOR), angiogenesis, and immunotherapy. PURPOSE We hypothesized that patients with spinal RCC metastases would continue to benefit from postoperative initiation of these therapeutics despite presenting with advanced stages of disease. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE We included patients with metastatic renal cell carcinoma involving the spine treated with surgery between 2010 and 2017. The study was approved by the IRB at Massachusetts General Hospital. OUTCOME MEASURES Baseline characteristics were recorded for patients, including ASIA and performance scores, Fuhrman grade, adjuvant therapies, progression free (PFS) and overall survival (OS) following the respective procedures. Preprocedural imaging was reviewed to assign spinal instability neoplastic score (SINS) and epidural spinal cord compression (ESCC) classification. METHODS Kaplan-Meier survival analysis was performed using R statistical software. RESULTS We identified 32 patients with metastatic RCC to the spine treated at MGH between 2010 and 2017 by surgical resection with 72% also receiving postoperative radiosurgery. Instrumented stabilization was performed in 81% of patients for ESCC 2-3 and median preoperative SINS 12. Preoperative embolization was performed in 62% of patients with lower intraoperative blood loss (500±310cc vs. 1000±510cc). Increased progression free (160±91 days vs. 112±50days) and overall survival (913±317 days vs. 466±255 days) following surgery was noted in patients who received postoperative targeted therapies, including inhibitors of PDGFR (100%), VEGF (50%), mTOR (33%) and PD-L1 (11%) initiated at a median of 63 days (28-1254 days) postoperatively. All patients noted postoperative improvement in pain and neurologic function. Postoperative complications included one wound infection and one pulmonary embolus requiring anticoagulation. CONCLUSIONS Postoperative outcomes for metastatic RCC without targeted therapies in this cohort are similar to those reported in earlier series prior to the adoption of these adjuvants. However, we observe a significant increase in survival when modern targeted therapies are administered postoperatively. This has implications on optimizing postoperative multimodal management and also the preoperative evaluation of patients with systemic disease who may have previously been deemed poor surgical candidates. Future analyses of the molecular alterations in metastatic RCC of the spine may further resolve the natural history and predicted treatment response. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Spinal metastases are a major cause of morbidity in patients with cancer. Molecular profiling strategies to characterize lung cancer have identified several genetic biomarkers that may lead to more effective prognostication. PURPOSE The aim of this study was to ascertain whether gene expression signatures in patients with advanced metastatic disease are associated with survival, when the disease has progressed to the spine. PATIENT SAMPLE We identified every consecutive patient at our institution with metastatic lung cancer who underwent surgery for spinal metastases from 2011 to 2017. Inclusion criteria were the availability of genetic mutational data through chart review, and the existence of any known metastatic lesion in the body and spine at the time of presentation. OUTCOME MEASURES Median overall survival (OS) was recorded following both diagnosis and surgical treatment. METHODS Genetic mutations in ALK, MET, ROS1, EGFR, and KRAS were chosen a priori for study based on availability by standard SNaPshot Lung Tumor Genotyping Analysis. Survival time was the duration between treatment for spinal metastases and death. Kaplan-Meier methods and the log-rank test were applied to characterize survival data. RESULTS Twenty-six patients met criteria for inclusion. Median survival following surgery was 0.67 years. Median overall survival (OS) following diagnosis was 2.7 years. The presence of molecular abnormalities in patients with spinal metastases was significantly associated with increased OS(HR 0.38, 95% CI 0.12-1.22, P=.03). CONCLUSIONS Molecular phenotyping may provide prognostic insight in patients undergoing surgery for spinal metastases. This is the first study to demonstrate an association between genetic mutational data and OS in this patient population. It also represents the largest published series of such patients (n=26) for which genetic mutational data are reported. Future models estimating survival for patients with spinal metastases may be enhanced by incorporation of molecular criteria. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Treatment strategies for spinal chordomas are heterogeneous and are mainly driven by institutional biases and local protocols. Surgery plays a central role in their management but the extent of surgery and the role of adjuvant therapy, particularly radiation therapy, is not standard across centers. PURPOSE The aims of this international collaborative effort are to identify the main management options for newly diagnosed chordoma of the spine, understand the variations in treatment protocols among experienced centers, and to consequently design a multicenter prospective cohort study to help determine the best multimodal treatment for this patient population. STUDY DESIGN/SETTING A survey was distributed to 39 spinal oncology specialists in neurosurgery, orthopedic surgery, and radiation oncology from 29 centers. METHODS Two clinical scenarios were presented and the preferred management strategy was queried among the respondents: (1) a newly diagnosed chordoma of the spine when en bloc resection is feasible with acceptable morbidity, and (2) when en bloc resection is not feasible as it would result in significant morbidity. Based on the results of this survey, a prospective cohort study combining centers with similar treatment strategies for newly diagnosed chordoma of the spine is proposed. RESULTS When en bloc resection is feasible with acceptable morbidity, most participants (79.5%) favored an en bloc resection without preoperative neo-adjuvant radiation treatment (RT). The main disagreement is with the role of postoperative radiation with 41% giving RT only if positive margins and 38% giving adjuvant RT to everyone irrespective of marginal status. When en bloc resection would result in significant morbidity, results were more evenly distributed and 33% of respondents preferred to do a deliberate intralesional resection followed by RT, and 33% chose to give neo-adjuvant RT prior to surgery. By combining centers with similar philosophies, three distinct treatment cohorts were identified for tumors for which en bloc resection is feasible with acceptable morbidity and 5 treatment groups for tumors in which en bloc resection would result in significant morbidity. These will constitute the distinct treatment cohorts of a prospective international cohort study. CONCLUSIONS The results of this survey allowed the design of an international collaborative prospective cohort study to uncover the best treatment strategy for patient with spinal chordomas. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Pedicle screw fixation can be a major challenge in patients with spinal metastases. The osteopenic nature of the vertebrae along with factors like previous radiation, immunosuppression, and marrow replacement by cancer affect the bone quality for fixation. Complications related to cement augmentation are known. We share our initial experience with the fenestrated screws. PURPOSE To demonstrate the efficacy and safety of this new screw technology in challenged fixation environements, specifically vertebral column metastases. STUDY DESIGN/SETTING Retropsective analysis from a prospective spine oncology database at a major cancer center. PATIENT SAMPLE We identified 38 consecutive patients who underwent posterior thoracic, lumbar, or sacral decompression and stabilization for pathologic fracture or cord compression (T1-sacrum) related to metastatic cancer over a 1 year period. OUTCOME MEASURES Preoperative SINS (spine instability neoplastic score), ASIA grade, cancer histology, radiation history, ECOG, and patient demographics were recorded and analyzed in a multivariable regression analysis. Postoperative CT was performed in all cases. CT was reviewed and cement extravasation was recorded at each level of pedicle screw placement in (1) the epidural space, (2) neural foramen, (3) paravertebral space, (4) lung, and (5) nearby vasculature including the segmental vessels and aorta. Complications and instrumentation or implant failure were recorded. Patient reported outcomes measures were recorded prospectively including EQ-5D, PROMIS-pain, PROMIS-disability, PROMIS-depression, Spine Oncology Study Group Questionnaire. METHODS IRB approval was obtained and a retrospective analysis was performed on a prospective spine oncology outcomes database. Fenestrated screws became available at our institution in November 2016. We identified 38 consecutive patients who underwent posterior thoracic, lumbar, or sacral decompression and stabilization for pathologic fracture or cord compression (T1-sacrum). In each case, postoperative CT imaging was performed within 24 hours of surgery. The investigators independently reviewed the studies evaluating for the extent of cement fill and extravasation. Chart review was performed for analysis of implant or construct failure and complications. RESULTS Thirty eight patients were identified and a total of 292 fenestrated screws were placed with an mean 7.21 screws implanted percase. The most common construct was two levels above and two levels below the site of worst vertebral fracture or cord compression. Cement extravasated into the (1) epidural space at six levels (2.97%), (2) neural foramen at three levels (1.49%), (3) paravertebral space at 37 levels (18.3%), (4) lung – 0, (5) nearby vasculature at 15 levels (7.42%). There was no cement spread to the aorta or vena cava. No patients developed a symptomatic radiculopathy from foraminal extent. No patient required reexploration, cement removal, or hardware revision. Follow-up ranged from 1 month to 15 months with no significant change invertebral body height at the instrumented levels by CT and x-ray. CONCLUSIONS Fenestrated screws with cement provide a safe and effective method for stabilization in the cancer patient.

The Antibody-Coupled T-cell Receptor (ACTR) platform is an autologous engineered T-cell therapy developed to combine with tumor-targeting antibodies to exert potent antitumor immune responses and tumor cell killing. The ACTR construct is composed of the extracellular domain of CD16 (FCGR3A; high-affinity V158 variant) linked to CD3ζ signaling and costimulatory domains. ACTR-expressing T cells are universal, and can be flexibly paired with desired therapeutic antibodies to target tumor antigens. Unum’s most advanced clinical candidate, ACTR087, is currently in clinical testing in combination with rituximab for the treatment of CD20+ B cell lymphoma (NCT02776813). To expand upon the ACTR platform, over 90 different domain-modified variant ACTRs were generated and evaluated through rigorous in vitro and in vivo testing in combination with a broad range of tumor-targeting antibodies for use in hematologic and solid tumor indications. ACTR T-cell cytotoxicity, cytokine release and proliferation assays, combined with performance in an in vitro repeated stimulation “stress test,” led to the identification of several lead ACTR candidates. The final ACTR candidate was identified on the ability to mediate tumor regressions of aggressive CD20+ lymphomas and HER2+ solid tumors in vivo when combined with rituximab or trastuzumab, respectively. These efforts identified ACTR707, an ACTR construct containing a CD28 costimulatory domain with additional molecular elements. Here we present nonclinical data supporting an ongoing first-in-human phase 1 clinical trial of ACTR707 in combination with rituximab. When combined with rituximab, ACTR707 T cells had potent activation, proliferation, cytokine production, and tumor-directed cytotoxicity in the presence of CD20+ lymphoma cell lines. ACTR707 T-cell in vitro activity was dependent on rituximab and was dose-titratable. ACTR707 T cells had potent antitumor efficacy in vivo in an aggressive Raji lymphoma xenograft model in NSG mice; ACTR707 T cell antitumor activity was ACTR T cell and rituximab dose-dependent, with higher T-cell numbers and antibody concentrations mediating improved responses. Further, ACTR707 in combination with rituximab outperformed a CD19 targeted CAR-T against aggressive Raji tumors in vivo. Taken together, these nonclinical data demonstrate the specificity and versatility of the ACTR707 T-cell therapeutic approach to target diverse cancer antigens and directly supports clinical testing in combination with rituximab. The phase I study, ATTCK-20-03 (NCT03189836), in subjects with relapsed or refractory CD20+ B cell lymphoma is a multicenter, single-arm, open-label dose escalation study evaluating the safety and antilymphoma efficacy of ACTR707 T cells in combination with rituximab. Subjects who meet eligibility requirements with histologically confirmed relapsed or refractory CD20+ B cell lymphoma of one of the following histologic subtypes are eligible: DLBCL, MCL, PMBCL, Gr3b-FL, TH-FL. The study’s primary objective is to assess the safety of the combination and define dose recommendations for further study. Additional study objectives include the assessment of antilymphoma activity, ACTR707 persistence, ACTR707 product characterization, inflammatory laboratory assessments, and rituximab pharmacokinetics. Enrollment is ongoing. Citation Format: Greg Motz, Kathleen Whiteman, John Shin, Tapasya Pai, Casey Judge, Anthony Barnitz, James Hemphill, James Kim, Ann Ranger, Heather Huet, Kathleen McGinness, Birgit Schultes, Geoffrey Hodge, Michael Vasconcelles, Seth Ettenberg. ACTR707: a novel T-cell therapy for the treatment of relapsed or refractory CD20+ B cell lymphoma in combination with rituximab [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B105.

Object Eagle syndrome is characterized by unilateral pain in the oropharynx, face, and earlobe, and is caused by an elongated styloid process or ossification of the stylohyoid ligament with associated compression of the glossopharyngeal nerve. The pain syndrome may be successfully treated with surgical intervention that involves resection of the styloid process. Although nerve decompression is routinely considered a neurosurgical intervention, Eagle syndrome and its treatment are not sufficiently examined in the neurosurgical literature. Methods A review was performed of cases of Eagle syndrome treated in the Department of Neurosurgery at the University of Illinois at Chicago Medical Center over the last 7 years. The clinical characteristics, radiographic imaging, operative indications, procedural details, surgical morbidity, and clinical outcomes were collected and analyzed. Results Of the many patients with facial pain treated between 2001 and 2007, 7 were diagnosed with Eagle syndrome, and 5 of these patients underwent resection of the elongated styloid process. There were 4 women and 1 man, ranging in age from 20 to 68 years (mean 43 years). The average duration of disease was 11 years. In all patients, a preoperative workup revealed unilateral or bilateral elongation of the styloid process. All patients underwent resection of the styloid process on the symptomatic side using a lateral transcutaneous approach. There were no surgical complications. All patients experienced pain relief immediately after the operation. At the latest follow-up (average 46 months, range 7 months to 7.5 years) all but 1 patient maintained complete pain relief. In 1 patient, the pain recurred 12 months postoperatively and additional interventions were required. Conclusions Eagle syndrome may be considered an entrapment syndrome of the glossopharyngeal nerve. It is a distinct clinical entity that should be considered when evaluating patients referred for glossopharyngeal neuralgia. The authors' experience indicates that patients with Eagle syndrome may be successfully treated using open resection of the elongated styloid process, which appears to be both safe and effective in terms of long-lasting pain relief.