GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.

Growth factor receptor-bound protein 2 (GRB2) is a cytoplasmic adapter for tyrosine kinase signaling and a nuclear adapter for homology-directed-DNA repair. Here we find nuclear GRB2 protects DNA at stalled replication forks from MRE11-mediated degradation in the BRCA2 replication fork protection axis. Mechanistically, GRB2 binds and inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks. In GRB2-depleted cells, PARP inhibitor (PARPi) treatment releases DNA fragments from stalled forks into the cytoplasm that activate the cGAS-STING pathway to trigger pro-inflammatory cytokine production. Moreover in a syngeneic mouse metastatic ovarian cancer model, GRB2 depletion in the context of PARPi treatment reduced tumor burden and enabled high survival consistent with immune suppression of cancer growth. Collective findings unveil GRB2 function and mechanism for fork protection in the BRCA2-RAD51-MRE11 axis and suggest GRB2 as a potential therapeutic target and an enabling predictive biomarker for patient selection for PARPi and immunotherapy combination.

Longer Screws Decrease the Risk of Radiographic Pseudarthrosis Following Elective Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: In patients undergoing elective anterior cervical discectomy and fusion (ACDF), we sought to determine the impact of screw length on: (1) radiographic pseudarthrosis, (2) pseudarthrosis requiring reoperation, and (3) patient-reported outcome measures (PROMs). METHODS: A single-institution, retrospective cohort study was undertaken from 2010-21. The primary independent variables were: screw length (mm), screw length divided by the anterior-posterior vertebral body diameter (VB%), and the presence of any screw with VB% < 75% vs all screws with VB% ≥ 75%. Multivariable logistic regression controlled for age, BMI, gender, smoking, American Society of Anesthesiology grade, number of levels fused, and whether a corpectomy was performed. RESULTS: Of 406 patients undergoing ACDF, levels fused were: 1-level (39.4%), 2-level (42.9%), 3-level (16.7%), and 4-level (1.0%). Mean screw length was 14.3 ± 2.3 mm, and mean VB% was 74.4 ± 11.2. A total of 293 (72.1%) had at least one screw with VB% < 75%, 113 (27.8%) had all screws with VB% ≥ 75%, and 141 (34.7%) patients had radiographic pseudarthrosis at 1-year. Patients who had any screw with VB% < 75% had a higher rate of radiographic pseudarthrosis compared to those had all screws with VB% ≥ 75% (39.6% vs 22.1%, P < .001). Multivariable logistic regression revealed that a higher VB% (OR = .97, 95%CI = .95-.99, P = .035) and having all screws with VB% ≥ 75% (OR = .51, 95%CI = .27-.95, P = .037) significantly decreased the odds of pseudarthrosis at 1-year, with no difference in reoperation or PROMs (all P > .05). CONCLUSION: Longer screws taking up ≥75% of the vertebral body protected against radiographic pseudarthrosis at 1-year. Maximizing screw length in ACDF is an easily modifiable factor directly under the surgeon's control that may mitigate the risk of pseudarthrosis.

L1-pelvic angle: a convenient measurement to attain optimal deformity correction.

PURPOSE: (1) Evaluate the associations between L1-pelvic angle (L1PA) and both sagittal vertical axis (SVA) and T1-pelvic angle (T1PA), and (2) assess the clinical impact of L1PA. METHODS: A single-institution retrospective cohort study was undertaken for patients undergoing adult spinal deformity (ASD) surgery from 2013 to 2017. Ideal L1PA was defined as (0.5xPelvic Incidence)-21. Pearson correlation was performed to compare L1PA, SVA, and T1PA. Univariate/multivariate regression was performed to assess the effect of L1PA on mechanical complications, controlling for age, BMI, and postoperative pelvic incidence-lumbar lordosis mismatch (PI/LL). Due to the overlapping nature of patients with pseudarthrosis and rod fracture, these patients were analyzed together. RESULTS: A total of 145 patients were included. Mean preoperative L1PA, SVA, and T1PA were 15.5 ± 8.9°, 90.7 ± 66.8 mm, and 27.1 ± 13.0°, respectively. Mean postoperative L1PA, SVA, and T1PA were 15.0 ± 8.9°, 66.7 ± 52.8 mm, and 22.3 ± 11.1°, respectively. Thirty-six (24.8%) patients achieved ideal L1PA. Though the correlation was modest, preoperative L1PA was linearly correlated with preoperative SVA (r2 = 0.16, r = 0.40, 95%CI = 0.22-0.60, p < 0.001) and T1PA (r2 = 0.41, r = 0.62, 95%CI = 0.46-0.76, p < 0.001). Postoperative L1PA was linearly correlated with postoperative SVA (r2 = 0.12, r = 0.37, 95%CI = 0.18-0.56, p < 0.001) and T1PA (r2 = 0.40, r = 0.62, 95%CI = 0.45-0.74, p < 0.001). Achieving ideal L1PA ± 5° was associated with a decreased risk of rod fracture/pseudarthrosis on univariate and multivariate regression (OR = 0.33, 95%CI = 0.12-0.86, p = 0.024). No association between achieving ideal L1PA and patient-reported outcomes was observed. CONCLUSION: L1PA was modestly correlated with SVA and T1PA, and achieving ideal L1PA was associated with lower rates of rod fracture/pseudarthrosis. Future studies are warranted to better define the clinical implications of achieving a normal L1PA. LEVEL OF EVIDENCE: III.

The importance of Hounsfield units in adult spinal deformity surgery: finding an optimal threshold to minimize the risk of mechanical complications.

Background: Low bone mineral density (BMD) is a well-established risk factor for mechanical complications following adult spinal deformity (ASD) surgery. Hounsfield units (HU) measured on computed tomography (CT) scans are a proxy of BMD. In ASD surgery, we sought to: (I) evaluate the association of HU with mechanical complications and reoperation, and (II) identify optimal HU threshold to predict the occurrence of mechanical complications. Methods: A single-institution retrospective cohort study was undertaken for patients undergoing ASD surgery from 2013-2017. Inclusion criteria were: ≥5-level fusion, sagittal/coronal deformity, and 2-year follow-up. HU were measured on 3 axial slices of one vertebra, either at the upper instrumented vertebra (UIV) itself or UIV ±4 from CT scans. Multivariable regression controlled for age, body mass index (BMI), postoperative sagittal vertical axis (SVA), and postoperative pelvic-incidence lumbar-lordosis mismatch. Results: Of 145 patients undergoing ASD surgery, 121 (83.4%) had a preoperative CT from which HU were measured. Mean age was 64.4±10.7 years, mean total instrumented levels was 9.8±2.6, and mean HU was 153.5±52.8. Mean preoperative SVA and T1PA were 95.5±71.1 mm and 28.8°±12.8°, respectively. Postoperative SVA and T1PA significantly improved to 61.2±61.6 mm (P<0.001) and 23.0°±11.0° (P<0.001). Mechanical complications occurred in 74 (61.2%) patients, including 42 (34.7%) proximal junctional kyphosis (PJK), 3 (2.5%) distal junctional kyphosis (DJK), 9 (7.4%) implant failure, 48 (39.7%) rod fracture/pseudarthrosis, and 61 (52.2%) reoperations within 2 years. Univariate logistic regression showed a significant association between low HU and PJK [odds ratio (OR) =0.99; 95% confidence interval (CI): 0.98-0.99; P=0.023], but not on multivariable analysis. No association was found regarding other mechanical complications, overall reoperations, and reoperations due to PJK. HU below 163 were associated with increased PJK on receiver operating characteristic (ROC) curve analysis [area under the curve (AUC) =0.63; 95% CI: 0.53-0.73; P<0.001]. Conclusions: Though several factors contribute to PJK, it appears that 163 HU may serve as a preliminary threshold when planning ASD surgery to mitigate the risk of PJK.

RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles.

RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog and define separable RAD51C replication stability roles informed by its three-dimensional structure, assembly, and unappreciated polymerization motif. Mapping of cancer patient mutations as a functional guide confirms ATP-binding matching RAD51 recombinase, yet highlights distinct CX3 interfaces. Analyses of CRISPR/Cas9-edited human cells with RAD51C mutations combined with single-molecule, single-cell and biophysics measurements uncover discrete CX3 regions for DNA replication fork protection, restart and reversal, accomplished by separable functions in DNA binding and implied 5' RAD51 filament capping. Collective findings establish CX3 as a cancer-relevant replication stress response complex, show how HDR-proficient variants could contribute to tumor development, and identify regions to aid functional testing and classification of cancer mutations.

Cranially Directed Upper Instrumented Vertebrae Screw Angles Are Associated With Proximal Junctional Kyphosis in Adult Spinal Deformity Surgery.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To evaluate the impact of the upper instrumented vertebral (UIV) screw angle in adult spinal deformity (ASD) surgery on: (1) proximal junctional kyphosis/failure (PJK/F), (2) mechanical complications and radiographic measurements, and (3) patient-reported outcome measures (PROMs). SUMMARY OF BACKGROUND DATA: The effect of UIV screw angle in ASD surgery on patient outcomes remains understudied. MATERIALS AND METHODS: A single-institution, retrospective study was undertaken from 2011 to 2017. UIV screw angle was trichotomized into positive: cranially directed screws relative to the superior endplate (2°≤θ), neutral: parallel to the superior endplate (-2°<θ<2°), and negative: caudally directed screws relative to the superior endplate (-2°≥θ). The primary outcome was PJK/F. Secondary outcomes included remaining mechanical complications, reoperation, and PROMs: Oswestry Disability Index, Numeric Rating Scale (NRS) back/leg, and EuroQol. Regression controlled for age, body mass index, postoperative sagittal vertical axis (SVA), and pelvic incidence lumbar-lordosis mismatch. RESULTS: Among 145 patients undergoing ASD surgery, UIV screw angles were 35 (24.1%) cranially directed, 24 (16.6%) neutral, and 86 (59.3%) caudally directed. PJK occurred in 47(32.4%) patients. Positive screws were independently associated with increased PJK [odds ratio (OR)=4.88; 95% CI, 1.85-13.5, P =0.002] and PJF (OR=3.06; 95% CI, 1.32-12.30, P =0.015). Among 108 (74.5%) patients with lower thoracic UIV, PJK occurred in 38 (35.1%). Cranially directed screws were independently associated with an increased odds of PJK (OR=5.56; 95% CI, 1.86-17.90, P =0.003) with a threshold of 0.2° (area under the curve =0.65; 95% CI, 0.54-0.76, P <0.001), above which the risk of PJK significantly increased. No association was found between positive screw angle and PJF (OR=3.13; 95% CI, 0.91-11.40, P =0.073). Because of the low number of patients with an upper thoracic UIV (N=37, 25.5%), no meaningful conclusions could be drawn from this subgroup. There was no association between UIV screw angle and remaining mechanical complications, reoperations, postoperative SVA and T1-pelvic angle, or PROMs. CONCLUSIONS: Cranially directed UIV screw angles increased the odds of PJK in patients with lower thoracic UIV. Meticulous attention should be paid to the lower thoracic UIV screw angle to mitigate the risk of PJK in ASD.

Oral health and functional outcomes following mechanical thrombectomy for ischemic stroke.

BACKGROUND: An association between poor dentition and the risk of ischemic stroke has previously been reported in the literature. In this study we assessed oral hygiene (OH), including tooth loss and the presence of dental disease, to determine if an association exists with functional outcomes following mechanical thrombectomy (MT) for large-vessel ischemic stroke. METHODS: A retrospective review was conducted of consecutive adult patients at a single comprehensive stroke center who underwent MT from 2012 to 2018. Inclusion criteria included availability of CT imaging to radiographically assess OH. A multivariate analysis was performed, with the primary outcome being 90-day post-thrombectomy modified Rankin Scale (mRS) score >2. RESULTS: A total of 276 patients met the inclusion criteria. The average number of missing teeth was significantly higher in patients with a poor functional outcome (mean (SD) 10 (11) vs 4 (6), p<0.001). The presence of dental disease was associated with poor functional outcome, including cavities (21 (27%) vs 13 (8%), p<0.001), periapical infection (18 (23%) vs 11 (6.7%), p<0.001), and bone loss (27 (35%) vs 11 (6.7%), p<0.001). Unadjusted, missing teeth was a univariate predictor of poor outcome (OR 1.09 (95% CI 1.06 to 1.13), p<0.001). After adjustment for recanalization scores and use of tissue plasminogen activator (tPA), missing teeth remained a predictor of poor outcome (OR 1.07 (95% CI 1.03 to 1.11), p<0.001). CONCLUSION: Missing teeth and the presence of dental disease are inversely correlated with functional independence following MT, independent of thrombectomy success or tPA status.

Imaging score for differentiation of meningioma grade.

PURPOSE: We sought to establish a comprehensive imaging score indicating the likelihood of higher WHO grade meningiomas pre-operatively. METHODS: All surgical intracranial meningioma patients at our institution between 2014 and 2018 underwent retrospective chart review. Preoperative MRI sequences were reviewed, and imaging features were included in the score based on statistical and clinical significance. Point values for each significant feature were assigned based on the beta coefficients obtained from multivariate analysis. The imaging score was calculated by adding up the points, for a total score of 0 to 5. The predictive ability of the score to identify higher-grade meningiomas was evaluated. RESULTS: Ninety patients, 50% of whom had a postoperative diagnosis of WHO grade II meningioma, were included. The mean age for the population was 59.9 years and 70% were female. Tumor volume ≥ 36.0 cc was assigned 2 points, presence of irregular tumor borders was assigned 2 points, and presence of peritumoral edema was assigned 1 point. The probability of having a WHO grade II meningioma was 0% with a score of 0, 25.0% with a score of 1, 38.5% with a score of 2, 65.4% with a score of 3, and 83.3% with a score of 4 or greater. A threshold of ≥ 3 points achieved a recall of 0.80, precision of 0.73, F1-score of 0.77, accuracy of 0.76, and AUC of 0.82. CONCLUSION: The proposed imaging scoring system had good predictive capability for WHO grade II meningiomas with good discrimination and calibration. External validation is needed.

The Effect of a Multidisciplinary Spine Clinic on Time to Care in Patients with Chronic Back and/or Leg Pain: A Propensity Score-Matched Analysis.

Chronic back and leg pain are leading causes of disability worldwide. The purpose of this study was to compare the care in a unidisciplinary (USC) versus multidisciplinary (MSC) spine clinic, where patients are evaluated by different specialists during the same office visit. Adult patients presenting with a chief complaint of back and/or leg pain between June 2018 and July 2019 were assessed for eligibility. The main outcome measures included the first treatment recommendations, the time to treatment order, and the time to treatment occurrence. A 1:1 propensity score-matched analysis was performed on 874 patients (437 in each group). For all patients, the most common recommendation was physical therapy (41.4%), followed by injection (14.6%), and surgery (9.7%). Patients seen in the MSC were more likely to be recommended injection (p < 0.001) and less likely to be recommended surgery as first treatment (p = 0.001). They also had significantly shorter times to the injection order (log-rank test, p = 0.004) and the injection occurrence (log-rank test, p < 0.001). In this study, more efficient care for patients with back and/or leg pain was delivered in the MSC setting, which was evidenced by the shorter times to the injection order and occurrence. The impact of the MSC approach on patient satisfaction and health-related quality-of-life outcome measures warrants further investigation.

Deciphering structural bases of intestinal and hepatic selectivity in targeting pregnane X receptor with indole-based microbial mimics.

Microbial metabolite mimicry is a new concept that promises to deliver compounds that have minimal liabilities and enhanced therapeutic effects in a host. In a previous publication, we have shown that microbial metabolites of L-tryptophan, indoles, when chemically altered, yielded potent anti-inflammatory pregnane X Receptor (PXR)-targeting lead compounds, FKK5 and FKK6, targeting intestinal inflammation. Our aim in this study was to further define structure-activity relationships between indole analogs and PXR, we removed the phenyl-sulfonyl group or replaced the pyridyl residue with imidazolopyridyl of FKK6. Our results showed that while removal of the phenyl-sulfonyl group from FKK6 (now called CVK003) shifts agonist activity away from PXR towards the aryl hydrocarbon receptor (AhR), the imidazolopyridyl addition preserves PXR activity in vitro. However, when these compounds are administered to mice, that unlike the parent molecule, FKK6, they exhibit poor induction of PXR target genes in the intestines and the liver. These data suggest that modifications of FKK6 specifically in the pyridyl moiety can result in compounds with weak PXR activity in vivo. These observations are a significant step forward for understanding the structure-activity relationships (SAR) between indole mimics and receptors, PXR and AhR.

Comparison of 30-Day Outcomes in Patients with Cervical Spine Metastasis Undergoing Corpectomy Versus Posterior Cervical Laminectomy and Fusion: A 2006-2016 ACS-NSQIP Database Study.

BACKGROUND: Patients with metastatic disease to the cervical spine have historically had poor outcomes, with an average survival of 15 months. Every effort should be made to avoid complications of surgical intervention for stabilization and decompression. METHODS: We identified patients who had undergone anterior cervical corpectomy and fusion (ACCF) or posterior cervical laminectomy and fusion (PCLF) for metastatic disease of the cervical spine using the American College of Surgeons National Surgical Quality Improvement Program database from 2006 to 2016. Patients meeting the inclusion criteria were subsequently propensity matched 1:1. We compared the overall complications, intensive care unit level complications, mortality, and return to the operating room between the 2 groups. RESULTS: After identifying the patients who met the inclusion criteria and propensity matching, a cohort of 240 patients was included, with 120 (50%) in the ACCF group and 120 (50%) in the PCLF group. The patients in the ACCF group were more likely to have experienced any complication (odds ratio, 2.1; 95% confidence interval, 1.1-4.1; P = 0.026) but not severe complications or a return to the operating room (P = 0.406 and P = 0.450, respectively). CONCLUSION: In the present study, we found that anterior surgical approaches (ACCF) for metastatic cervical spine disease resulted in a significantly greater rate of overall complications (2.1 times more) compared with PCLF in the first 30 days. Although more studies are required to further elucidate this relationship, the general belief that the anterior approach is better tolerated by patients might not apply to patients with metastatic tumors.

Surgical Outcomes for Upper Lumbar Disc Herniations: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To conduct a literature review on outcomes of discectomy for upper lumbar disc herniations (ULDH), estimate pooled rates of satisfactory outcomes, compare open laminectomy/microdiscectomy (OLM) versus minimally invasive surgical (MIS) techniques, and compare results of disc herniations at L1-3 versus L3-4. METHODS: A systematic review of articles reporting outcomes of nonfusion surgical treatment of L1-2, L2-3, and/or L3-4 disc herniations was performed. The inclusion and exclusion of studies was performed according to the latest version of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of 20 articles were included in the quantitative meta-analysis. Pooled proportion of satisfactory outcome (95% CI) was 0.77 (0.70, 0.83) for MIS and 0.82 (0.78, 0.84) for OLM. There was no significant improvement with MIS techniques compared with standard OLM, odds ratio (OR) = 0.86, 95% CI (0.42, 1.74), P = .66. Separating results by levels revealed a trend of higher satisfaction with L3-4 versus L1-3 with OLM surgery, OR = 0.46, 95% CI (0.19, 1.12), P = .08. CONCLUSION: Our analysis reveals that discectomy for ULDH has an overall success rate of approximately 80% and has not improved with MIS. Discectomy for herniations at L3-4 trends toward better outcomes compared with L1-2 and L2-3, but was not significant.

Risk Factors for 30-Day Non-Neurological Morbidity and Cerebrospinal Fluid Leak in Patients Undergoing Surgery for Vestibular Schwannoma.

Introduction We analyzed perioperative risk factors for morbidity and mortality for the patients undergoing surgical intervention for vestibular schwannoma along with rates of cerebrospinal fluid (CSF) leaks that required surgery. Materials and Methods Patients undergoing surgery vestibular schwannoma were identified in the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016 using current procedural terminology (CPT) codes for posterior fossa surgical approaches and International Classification of Diseases 9th revision (ICD 9) and ICD 10 codes for peripheral nerve sheath tumor. Preoperative laboratories, comorbidities, and operative times were analyzed along with CSF leaks and unplanned returns to the operating room. Results Nine-hundred ninety-three patients fit the inclusion criteria. Average age was 51, 41% were male, and 58% were female. Mortality within 30 days of the operation was very low at 0.4%, complications were 7% with infection being the most common at 2.3%, and unplanned reoperations happened in 7.4% of the cases. Dependent functional status (odds ratio [OR]: 5.7, 95% confidence interval [CI]: 1.9-16.6, p = 0.001), preoperative anemia (OR: 2.4, 95% CI: 1.2-4.5, p = 0.009), and operative time over 8 hours (OR: 1.9, 95% CI: 1.1-3.4, p = 0.017) were the only significant predictors of perioperative complications. CSF leak postoperatively occurred in 37 patients (3.7%). Reoperation for CSF leak was necessary in 56.3% of the cases. Operative time over 8 hours was the only independent significant predictor of postoperative CSF leak (OR: 2.2, 95% CI: 1.1-4.3, p = 0.028). Conclusion Dependent functional status preoperatively, preoperative anemia, and duration of surgery over 8 hours are the greatest predictors of complications in the 30-day postoperative period.

Accuracy of Freehand versus Navigated Thoracolumbar Pedicle Screw Placement in Patients with Metastatic Tumors of the Spine.

OBJECTIVE: To compare the accuracy and breach rates of freehand (FH) versus navigated (NV) pedicle screws in the thoracic and lumbar spine in patients with metastatic spinal tumors. METHODS: A retrospective review of adult patients who underwent pedicle screw fixation in the thoracic or lumbar spine for metastatic spinal tumors between 2012 and 2018 was conducted. Breaches were assessed based on the Gertzbein and Robbins classification and only screws placed >4 mm outside of the pedicle wall (lateral or medial) were considered breached. RESULTS: A total of 62 patients received 547 pedicle screws (average 8 per patient) - 34 patients received 298 pedicle screws in the FH group and 28 patients received 249 screws in the NV group. There were 40/547 breaches, corresponding to a breach and accuracy rate of 7.3% and 92.7%, respectively. The breach rate was 9.7% in the FH group and 4.4% in the NV group (chi-squared test, p=0.017); this corresponded to an accuracy rate of 90.3% and 95.6%, respectively. Only one patient from the overall cohort (in the FH group) required revision surgery due to a medial breach abutting the spinal cord (1.6% of all patients; 2.9% of FH patients); no patient suffered organ, vessel, or neurological injury from screw breaches. CONCLUSION: Navigated pedicle screw placement in patients with metastatic spinal tumors has a significantly higher radiographic accuracy compared to the FH technique. However, the revision surgery was low and no patient suffered from clinically-relevant breach. Navigation also offers the advantage of real-time localization of spinal tumors and aids in targeting and resection of these lesions.

Rates, Risk Factors, and Complications of Red Blood Cell Transfusion in Metastatic Spinal Tumor Surgery: An Analysis of a Prospective Multicenter Surgical Database.

OBJECTIVE: To identify rates, risks, and complications of red blood cell (RBC) transfusion in metastatic spinal tumor surgery. METHODS: The multicenter prospective American College of Surgeons National Quality Improvement Program database was queried for the years 2012-2016. Adult patients with disseminated cancer who underwent metastatic spinal tumor surgery were identified. Transfusion was defined as having received at least 1 intraoperative/postoperative RBC transfusion within the first 72 hours of surgery start time. A stepwise multiple logistic regression model with backward elimination was used. RESULTS: Of 1601 patients identified, 623 patients (38.9%) received a RBC transfusion. Independent predictors of RBC transfusion included higher American Society of Anesthesiologists class (odds ratio [OR] = 1.54), preoperative anemia (OR = 3.10), instrumentation (OR = 1.63), and longer operative time (OR = 1.52). The overall complication rate was significantly higher in patients who received a transfusion compared with patients who did not receive a transfusion (22.3% vs. 15.0%, P < 0.001). Individual complications that were more common in patients who received a transfusion were sepsis (3.5% vs. 1.9%, P = 0.050), deep vein thrombosis (6.1% vs. 3.3%, P = 0.007), and prolonged ventilation (3.9% vs. 1.3%, P = 0.001). RBC transfusion (OR = 1.65), hypoalbuminemia (OR = 1.53), and anterior/anterolateral approaches for corpectomy (OR = 2.11) were independent risk factors for developing a postoperative complication. CONCLUSIONS: RBC transfusion after metastatic spinal tumor surgery may increase the risk of early postoperative complications. Future research into preoperative patient optimization and decreasing intraoperative blood loss is needed.

Failure to extubate and delayed reintubation in elective lumbar fusion: An analysis of 57,677 cases.

OBJECTIVES: There is a scarcity of literature exploring the consequences of Failure To Extubate (FTE) and Delayed Reintubation (DRI) in spine surgery. While it is reasonable to believe that patients who FTE or undergo DRI after Posterior Lumbar Fusion (PLF) and Transforaminal Lumbar Interbody Fusion (TLIF) are at risk for graver outcomes, there is minimal data to explicitly support that. The goal of this study was to investigate the morbidity and mortality associated with FTE and DRI after lumbar spine surgery in a large pool of patients. PATIENTS AND METHODS: We conducted a retrospective multicenter study of patients that underwent elective posterior lumbar fusion (PLF) and transforaminal lumbar interbody fusion (TLIF) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2006 to 2016. We excluded patients with disseminated cancer, metastatic disease to the neural axis, patient with spinal epidural abscess, and patients with ventilator dependency prior to the operation. RESULTS: 57,677 patients from 2006 to 2016 were identified; 55 patients (0.1 %) had FTE and 262 patients (0.46 %) had DRI. The incidence of pneumonia was 27.2-fold greater in the FTE group and septic shock was 63.5-fold greater. All complications listed below are significance to p < 0.001. Deep vein thrombosis, pulmonary embolism, myocardial infarction and cardiac arrest were respectively, 10.4-, 12.2-, 22.8-, and 45.5- fold greater in the FTE group. Overall complication rate differed significantly between the two groups and were 9.8-fold greater in the FTE group. FTE was associated with increased, length of stay and all complications except DVT and pulmonary embolism. FTE was profoundly associated with severe complications (OR 13.0, 95 % CI 7.2-23.5) and mortality (OR = 21.5, CI = 7.5-61.0). The DRI group had a significantly higher morbidity (OR = 71.0, CI = 44.1-114.4), including overall complication (OR = 21.2, CI = 16.0-28.0) and severe complications (OR = 34.4, CI = 26.1-45.3). The DRI group had significantly higher rates of pneumonia (OR = 37.0), DVT (OR = 9.6) and pulmonary embolism (OR = 7.0), septic shock (OR = 60.5), myocardial infarction (OR = 32.1,) and cardiac arrest (OR = 236.4). CONCLUSION: FTE and DRI were highly predictive of morbidity and mortality. Overall, investigations of the effects of FTE and DRI following spine procedures are lacking. This large multi-center national database review is one of the first to provide insight into the consequences of FTE and DRI in lumbar fusion cases. Future investigation into the consequences and predictors of FTE and DRI in spine surgery are required.

Readmission after spinal epidural abscess management in urban populations: a bi-institutional study.

OBJECTIVE: The incidence of spinal epidural abscess (SEA) is rising, yet there are few reports discussing readmission rates or predisposing factors for readmission after treatment. The aims of the present study were to determine the rate of 90-day readmission following medical or surgical treatment of SEA in an urban population, identify patients at increased risk for readmission, and delineate the principal causes of readmission. METHODS: Neurosurgery records from two large urban institutions were reviewed to identify patients who were treated for SEA. Patients who died during admission or were discharged to hospice were excluded. Univariate analysis was performed using chi-square and Student t-tests to identify potential predictors of readmission. A multivariate logistic regression model, controlled for age, body mass index, sex, and institution, was used to determine significant predictors of readmission. RESULTS: Of 103 patients with identified SEA, 97 met the inclusion criteria. Their mean age was 57.1 years, and 56 patients (57.7%) were male. The all-cause 90-day readmission rate was 37.1%. Infection (sepsis, osteomyelitis, persistent abscess, bacteremia) was the most common cause of readmission, accounting for 36.1% of all readmissions. Neither pretreatment neurological deficit (p = 0.16) nor use of surgical versus medical management (p = 0.33) was significantly associated with readmission. Multivariate analysis identified immunocompromised status (p = 0.036; OR 3.5, 95% CI 1.1-11.5) and hepatic disease (chronic hepatitis or alcohol abuse) (p = 0.033; OR 2.9, 95% CI 1.1-7.7) as positive predictors of 90-day readmission. CONCLUSIONS: The most common indication for readmission was persistent infection. Readmission was unrelated to baseline neurological status or management strategy. However, both hepatic disease and baseline immunosuppression significantly increased the odds of 90-day readmission after SEA treatment. Patients with these conditions may require closer follow-up upon discharge to reduce overall morbidity and hospital costs associated with SEA.

Perioperative Complications and Mortality Following Anterior Odontoid Screw Fixation in Elderly Patients: A National Database Analysis.

OBJECTIVE: To identify predictors of short-term mortality and complications after anterior odontoid screw fixation. METHODS: This was a retrospective analysis of a national database. The American College of Surgeons National Quality Improvement Database was queried using Current Procedural Terminology codes to identify patients aged ≥60 years who underwent surgery for anterior fixation of odontoid fracture admitted from 2007 to 2016. Univariate analysis and subsequent multivariate analysis were used to analyze risk factors for postoperative complications and 30-day postoperative mortality. Complications were defined as surgical-site infection, wound breakdown, pneumonia, venous thromboembolism, stroke, myocardial infarction, sepsis, renal progressive renal insufficiency/acute kidney injury, or cardiac arrest. RESULTS: A total of 198 patients were identified. Mean age was 77.7 (±8.7) years and 60.6% were female. Overall mortality rate was 7.6%, and the complication rate was 9.1%. In multivariate analysis, dependent functional status (0.012; odds ratio [OR] 5.2; 95% confidence interval [CI] 1.42-18.72) and preoperative systemic inflammatory response syndrome (P = 0.011; OR 6.2; 95% CI 1.52-25.79) predicted mortality. Emergency case status (P = 0.033; OR 3.4; 95% CI 1.10-10.70) predicted perioperative complications. Age was not significantly associated with either complications or mortality in multivariate analysis. CONCLUSIONS: Functional dependence and preoperative systemic inflammatory response syndrome predict mortality following odontoid screw placement. Although age often is considered a limiting factor in pursuing surgical intervention in patients with odontoid fracture, age did not independently increase odds of either complications or perioperative mortality in this analysis. Further studies are needed to explore these findings.

Multifocal Epidural Neurosarcoidosis Causing Spinal Cord Compression: A Case Report.

We describe a rare case of multifocal extramedullary epidural neurosarcoidosis that presented with myelopathy without motor deficits and perform a literature review for previous cases of epidural neurosarcoidosis. A 46-year-old woman presented with lower back pain, urinary incontinence, gait disturbance, and sensory loss without motor deficits. Spine magnetic resonance imaging (MRI) showed multiple epidural lesions, the largest causing spinal cord compression at the T5 level. A computed tomography (CT)-guided biopsy of the dominant lesion showed noncaseating granulomas consistent with neurosarcoidosis. She was treated with a course of dexamethasone and discharged home after a 10-day hospital course. She was discharged home on oral prednisone taper over a four-month period. At her latest follow-up, she is neurologically intact and gainfully employed. This case demonstrates that certain cases of epidural neurosarcoidosis causing spinal cord compression may be treated with medical therapy alone in the absence of severe neurological deficits.

Postoperative Pulmonary Complications Following Brain Tumor Resection: A National Database Analysis.

OBJECTIVE: There is sparse literature that investigates the adverse effects of postoperative pulmonary complication (PPCs) specifically in postcraniotomy tumor patients. In this study, we describe the rate of PPCs, determine predictive factors, and delineate associations with adverse outcomes. METHODS: The National Surgical Quality Improvement Program (2006-2016) database was queried for patients who underwent craniotomy for brain tumors. A total of 28,700 eligible patients were identified. Univariate tests and/or multivariate logistic regression were used to determine predictors of PPC and associations with adverse outcomes. RESULTS: A total of 19 predictors of PPC across 14 different categories were identified: age 65-79 years (odds ratio [OR] 1.6; P < 0.001), age ≥80 years (OR 2.3; P < 0.001), male sex (OR 1.3; P < 0.001), operative time ≥360 minutes (OR 4.3; P < 0.001), operative time 300-359 minutes (OR 2.5; P < 0.001), operative time 240-299 minutes (OR 1.8; P < 0.001), operative time 180-239 minutes (OR 1.3; P < 0.001), total functional dependence (OR 3.8; P < 0.001), partial functional dependence (OR 1.7; P < 0.001), insulin-dependent diabetes (OR 1.5; P < 0.001), preoperative dyspnea (OR 1.3; P = 0.01), chronic steroid use (OR 1.4; P < 0.001), chronic obstructive pulmonary disease (OR 1.8; P < 0.001), preoperative leukocytosis (OR 1.4; P < 0.001), anemia (OR 1.2; P < 0.001), American Society of Anesthesiologists (ASA) classification ≥3 (OR 2.0; P < 0.001), emergency case status (OR 2.0; P < 0.001), and infratentorial lesions (OR 1.4; P < 0.001). PPCs were significantly associated with higher reoperation, readmission, and mortality rates as well as longer length of stay (univariate). CONCLUSIONS: There are several predictive factors of PPCs in patients that undergo surgical resection of brain tumors, and PPC development is associated with numerous adverse outcomes. It is critically important to understand and, if possible, mitigate controllable circumstances that may reduce morbidity and mortality associated with PPCs.