Live-cell imaging reveals single-cell and population-level infection strategies of Listeria monocytogenes in macrophages.

Pathogens have developed intricate strategies to overcome the host's innate immune responses. In this paper we use live-cell microscopy with a single bacterium resolution to follow in real time interactions between the food-borne pathogen L. monocytogenes and host macrophages, a key event controlling the infection in vivo. We demonstrate that infection results in heterogeneous outcomes, with only a subset of bacteria able to establish a replicative invasion of macrophages. The fate of individual bacteria in the same host cell was independent from the host cell and non-cooperative, being independent from co-infecting bacteria. A higher multiplicity of infection resulted in a reduced probability of replication of the overall bacterial population. By use of internalisation assays and conditional probabilities to mathematically describe the two-stage invasion process, we demonstrate that the higher MOI compromises the ability of macrophages to phagocytose bacteria. We found that the rate of phagocytosis is mediated via the secreted Listeriolysin toxin (LLO), while the probability of replication of intracellular bacteria remained constant. Using strains expressing fluorescent reporters to follow transcription of either the LLO-encoding hly or actA genes, we show that replicative bacteria exhibited higher PrfA regulon expression in comparison to those bacteria that did not replicate, however elevated PrfA expression per se was not sufficient to increase the probability of replication. Overall, this demonstrates a new role for the population-level, but not single cell, PrfA-mediated activity to regulate outcomes of host pathogen interactions.

Trends in Racial, Ethnic, and Gender Diversity in Orthopedic Surgery Spine Fellowships From 2007 to 2021.

STUDY DESIGN: Descriptive. OBJECTIVE: The objective of this study is to analyze trends in racial, ethnic, and gender diversity in orthopedic spine surgery fellowship trainees. SUMMARY OF BACKGROUND DATA: Orthopedic surgery has consistently been labeled as one of the least diverse fields in Medicine. Although some effort has been made to combat this in recent years at the residency level, it is uncertain whether spine fellowships have had any changes in fellow demographics. MATERIALS AND METHODS: Fellowship demographic data were collected through the Accreditation Council for Graduate Medical Education. Data collected included gender (male, female, and not reported) and race (White, Asian, Black, Hispanic, Native Hawaiians, American Indian or Alaskan Native, other, and unknown). Percentage equivalents were calculated for each group from 2007 to 2008 to 2020 to 2021. A χ 2 test for trend (Cochran-Armitage test) was done to determine whether there was a significant change in percentages of each race and gender during the study period. The results were considered statistically significant at P <0.05. RESULTS: White, Non-Hispanic males represent the largest proportion of orthopedic spine fellowship positions each year. From 2007 to 2021, there were no significant changes in the representation of any race or gender of orthopedic spine fellows. Males ranged from 81% to 95%, Whites from 28% to 66%, Asians from 9% to 28%, Blacks from 3% to 16%, and Hispanics from 0% to 10%. Native Hawaiians and American Indians remained at 0% for all years included in the study. Females and all races, excluding Whites, continue to be under-represented in orthopedic spine fellowship. CONCLUSIONS: Orthopedic spine surgery fellowship programs have not made substantial progress in diversifying its population. More attention is needed to increase diversity in residency programs through pipeline programs, increased mentorship and sponsorship, and early exposure to the field. LEVEL OF EVIDENCE: 1.

Development and External Validation of a Risk Calculator for Prediction of Major Complications and Readmission After Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: A retrospective, case-control study. OBJECTIVE: We aim to build a risk calculator predicting major perioperative complications after anterior cervical fusion. In addition, we aim to externally validate this calculator with an institutional cohort of patients who underwent anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: The average age and proportion of patients with at least one comorbidity undergoing ACDF have increased in recent years. Given the increased morbidity and cost associated with perioperative complications and unplanned readmission, accurate risk stratification of patients undergoing ACDF is of great clinical utility. METHODS: This is a retrospective cohort study of adults who underwent anterior cervical fusion at any nonfederal California hospital between 2015 and 2017. The primary outcome was major perioperative complication or 30-day readmission. We built standard and ensemble machine learning models for risk prediction, assessing discrimination, and calibration. The best-performing model was validated on an external cohort comprised of consecutive adult patients who underwent ACDF at our institution between 2013 and 2020. RESULTS: A total of 23,184 patients were included in this study; there were 1886 cases of major complication or readmissions. The ensemble model was well calibrated and demonstrated an area under the receiver operating characteristic curve of 0.728. The variables most important for the ensemble model include male sex, medical comorbidities, history of complications, and teaching hospital status. The ensemble model was evaluated on the validation cohort (n=260) with an area under the receiver operating characteristic curve of 0.802. The ensemble algorithm was used to build a web-based risk calculator. CONCLUSION: We report derivation and external validation of an ensemble algorithm for prediction of major perioperative complications and 30-day readmission after anterior cervical fusion. This model has excellent discrimination and is well calibrated when tested on a contemporaneous external cohort of ACDF cases.

The Impact of Global Alignment and Proportion Score and Bracing on Proximal Junctional Kyphosis in Adult Spinal Deformity.

STUDY DESIGN: Retrospective chart review. OBJECTIVE: The goal of this study is to examine the relationship between global alignment and proportion (GAP) score and postoperative orthoses with likelihood of developing proximal junctional kyphosis (PJK). METHODS: Patients who underwent thoracic or lumbar fusions of ≥4 levels for adult spinal deformity (ASD) with 1-year post-operative alignment x-rays were included. Chart review was conducted to determine spinopelvic alignment parameters, PJK, and reoperation. RESULTS: A total of 81 patients were included; baseline and 1-year postoperative alignment did not differ between patients with and without PJK. There was no PJK in 53.1%, 29.6% had PJK from 10-20°, and 17.3% had severe PJK over 20° (sPJK). At baseline, 80% of patients had severely disproportioned GAP, 13.75% moderate, 6.25% proportioned. GAP improved across the population, but improved GAP was not associated with sPJK. Greater correction of the upper instrumented vertebra to pelvic angle (UIV-PA) was associated with a larger PJK angle (PJKA) change (R = -0.28) as was the 1 year T1-upper instrumented vertebra (T1-UIV) angle (R = 0.30), both P < .05. GAP change was not correlated with PJKA change. Postoperative orthoses were used in 46% of patients and did not impact sPJK. CONCLUSIONS: There was no correlation between PJK and GAP or change in GAP. Greater correction of UIV-PA and larger postop T1-UIV was associated with greater PJKA change; suggesting that the greater alignment correction led to greater likelihood of failure. Postoperative orthoses had no impact on PJK.

The Impact of Global Spinal Alignment on Standing Spinopelvic Alignment Change After Total Hip Arthroplasty.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The interactions between hip osteoarthritis (OA) and spinal malalignment are poorly understood. The purpose of this study was to assess the influence of total hip arthroplasty (THA) on standing spinopelvic alignment. METHODS: In this retrospective cohort study, patients undergoing THA for OA with pre-and postoperative full-body radiographs were included. Standing spinopelvic parameters were measured. Contralateral hip was graded on the Kellgren-Lawrence scale. Pre-and postoperative alignment parameters were compared by paired t-test. The severity of preoperative thoracolumbar deformity was measured using TPA. Linear regression was performed to assess the impact of preoperative TPA and changes in spinal alignment. Patients were separated into low and high TPA (<20 or >/=20 deg) and change in parameters were compared between groups by t-test. Similarly, the influence of K-L grade, age, and PI were also tested. RESULTS: 95 patients were included (mean age 58.6 yrs, BMI 28.7 kg/m2, 48.2% F). Follow-up radiographs were performed at mean 220 days. Overall, the following significant changes were found from pre-to postoperative: SPT (14.2 vs. 16.1, P = 0.021), CL (-8.9 vs. -5.3, P = .001), TS-CL (18.2 vs. 20.5, P = .037) and SVA (42.6 vs. 32.1, P = .004). Preoperative TPA was significantly associated with the change in PI-LL, SVA, and TPA. High TPA patients significantly decreased SVA more than low TPA patients. There was no significant impact of contralateral hip OA, PI, or age on change in alignment parameters. CONCLUSION: Spinopelvic alignment changes after THA, evident by a reduction in SVA. Preoperative spinal sagittal deformity impacts this change. Level of evidence: III.

Biologics in Spine Fusion.

Achieving fusion in spine surgery can be challenging because of patient factors such as smoking and diabetes. The consequences of pseudarthrosis can be severe, including pain, instability, and additional surgery. Autologous iliac crest bone graft is the historical standard for augmenting spine fusion, providing high rates of fusion throughout the cervical, thoracic, and lumbar spine. Harvest of autologous iliac crest bone can be associated with comorbidities and this has led to development of alternative biologic materials to enhance spine fusion. Substitutes include various forms of allograft products including decellularized allograft; demineralized bone matrix; synthetic materials including bioactive glass; and autologous and allograft mesenchymal stem cells. Bone morphogenetic proteins can be efficacious for fusion but have significant risks and are not suitable for all spine procedures. There is a wide variety of utilization of biologics for spine fusion that are influenced by spinal region, surgeon preference, surgical training, health system formulary, and cost.

National trends in the utilization of lumbar disc replacement for lumbar degenerative disc disease over a 10-year period, 2010 to 2019.

Background: Lumbar fusion (LF) is commonly performed to manage lumbar degenerative disc disease (LDDD) that has failed conservative measures. However, lumbar disc replacement (LDR) procedures are increasingly prevalent and designed to preserve motion in carefully selected patients. Methods: A retrospective cohort study was performed using the National Inpatient Sample (NIS), queried from 2010 to 2019 to identify patients undergoing single and double-level LF or LDR with a diagnosis of LDDD using International Classification of Diseases (ICD) 9th (ICD-9) and 10th (ICD-10) revision diagnostic and procedure codes. Propensity score matching (PSM) with a ratio of 2:1 was performed. All cost estimates reflect reported hospital costs adjusted to December 2019 United States Dollars. Results: A total of 1,129,121 LF cases (99.3%) and 8,049 LDR cases (0.7%) were identified, with 364,637 (32.3%) and 712 (8.8%) comprising two-level surgeries, respectively. 1,712 LDRs were performed in 2010 (1.27% of all), decreasing to 565 in 2013 (0.52%), and increased slightly to 870 in 2019 (0.74%). LDR patients were significantly more likely to be younger (mean age 41.2 vs. 57.1, P<0.001) and healthier (mean ECI 0.88 vs. 1.80, P<0.001). On matched analysis, LDR hospital costs were $4,529 less (P<0.001) and length of stay was 0.65 days shorter (P<0.001) than LF patients. LDR patients had lower rates of any complication (7.0% vs. 13.2%, P<0.001), neurologic complication (3.0% vs. 4.2%, P=0.006), and blood transfusion (3.1% vs. 8.1%, P<0.001) compared to LF patients. Conclusions: The prevalence of LDR procedures decreased from 2010-2017 but began to increase again in 2018 and 2019. Single-level LDR was associated with reduced costs and length of stay (LOS), and lower rates of blood transfusion compared to LF in patients with LDDD.

A Risk Calculator for the Prediction of C5 Nerve Root Palsy After Instrumented Cervical Fusion.

BACKGROUND: C5 palsy is a common postoperative complication after cervical fusion and is associated with increased health care costs and diminished quality of life. Accurate prediction of C5 palsy may allow for appropriate preoperative counseling and risk stratification. We primarily aim to develop an algorithm for the prediction of C5 palsy after instrumented cervical fusion and identify novel features for risk prediction. Additionally, we aim to build a risk calculator to provide the risk of C5 palsy. METHODS: We identified adult patients who underwent instrumented cervical fusion at a tertiary care medical center between 2013 and 2020. The primary outcome was postoperative C5 palsy. We developed ensemble machine learning, standard machine learning, and logistic regression models predicting the risk of C5 palsy-assessing discrimination and calibration. Additionally, a web-based risk calculator was built with the best-performing model. RESULTS: A total of 1024 patients were included, with 52 cases of C5 palsy. The ensemble model was well-calibrated and demonstrated excellent discrimination with an area under the receiver-operating characteristic curve of 0.773. The following features were the most important for ensemble model performance: diabetes mellitus, bipolar disorder, C5 or C4 level, surgical approach, preoperative non-motor neurologic symptoms, degenerative disease, number of fused levels, and age. CONCLUSIONS: We report a risk calculator that generates patient-specific C5 palsy risk after instrumented cervical fusion. Individualized risk prediction for patients may facilitate improved preoperative patient counseling and risk stratification as well as potential intraoperative mitigating measures. This tool may also aid in addressing potentially modifiable risk factors such as diabetes and obesity.

Retrospective evaluation of cervical fusion with DTRAX (R) cervical cage.

Background: Cervical radiculopathy is a relatively common problem that often affects individuals in their 5th decade. Most cases resolve with conservative treatment, but when unsuccessful, many opt for surgical intervention. Anterior cervical discectomy and fusion is currently considered the gold standard for the surgical management of cervical radiculopathy. One promising alternative, the DTRAX facet system is minimally invasive and may significantly reduce or eliminate cervical radicular symptoms. This case series and literature review looks to investigate the safety and efficacy of the DTRAX facet system in treating cervical radiculopathy. Methods: This retrospective analysis was performed by chart review of patients who underwent posterior cervical fusion and received the DTRAX spinal implant at University of California, Los Angeles within the last 8 years. Patient charts were located using the surgical cases report function of Epic electronic medical record, and patients were included in the study if they received a DTRAX implant during the stated time period. Data were compiled and analyzed using Microsoft Excel. Results: A total of 14 patient charts were reviewed. Of the 14, there were no immediate postoperative complications. One international patient was subsequently lost to follow-up, and of the remaining 13, mean follow-up duration was 273 days, with a range of 15-660 days. All but one reported improvement of symptoms postoperatively, there were no device failures, and no reoperations were required. There were similar outcomes in patients who received single versus multilevel operations. Conclusion: The findings of this retrospective study of 14 patients who received the DTRAX facet system over the last 8 years support the conclusions of previous studies that DTRAX is safe and effective. In addition, this is the first study to look for differences in outcomes between single and multi-level DTRAX operations, of which there were none. Further investigation with larger cohorts should be conducted as DTRAX becomes more widely adopted in order to verify its safety and efficacy in various clinical scenarios.

Machine learning-driven identification of novel patient factors for prediction of major complications after posterior cervical spinal fusion.

PURPOSE: Posterior cervical fusion is associated with increased rates of complications and readmission when compared to anterior fusion. Machine learning (ML) models for risk stratification of patients undergoing posterior cervical fusion remain limited. We aim to develop a novel ensemble ML algorithm for prediction of major perioperative complications and readmission after posterior cervical fusion and identify factors important to model performance. METHODS: This is a retrospective cohort study of adults who underwent posterior cervical fusion at non-federal California hospitals between 2015 and 2017. The primary outcome was readmission or major complication. We developed an ensemble model predicting complication risk using an automated ML framework. We compared performance with standard ML models and logistic regression (LR), ranking contribution of included variables to model performance. RESULTS: Of the included 6822 patients, 18.8% suffered a major complication or readmission. The ensemble model demonstrated slightly superior predictive performance compared to LR and standard ML models. The most important features to performance include sex, malignancy, pneumonia, stroke, and teaching hospital status. Seven of the ten most important features for the ensemble model were markedly less important for LR. CONCLUSION: We report an ensemble ML model for prediction of major complications and readmission after posterior cervical fusion with a modest risk prediction advantage compared to LR and benchmark ML models. Notably, the features most important to the ensemble are markedly different from those for LR, suggesting that advanced ML methods may identify novel prognostic factors for adverse outcomes after posterior cervical fusion.

Acute Colonic Pseudo-Obstruction (Ogilvie Syndrome) After Primary Spinal Fusion: An Analysis of Outcomes and Risk Factors from 2005 to 2014.

BACKGROUND: Ogilvie syndrome (OS) is a rare but serious condition seen in the postoperative period. This was an epidemiologic study using data from the National Inpatient Sample from 2005 to 2014 to look at incidence, risk factors, and outcomes associated with OS after primary spine fusion. METHODS: International Classification of Diseases, Ninth Revision codes were used to identify patients who underwent spine fusion surgery. Patients were separated into 2 cohorts based on the diagnosis of OS. Outcome measures and risk factors for cohorts were analyzed using multivariate logistic regression and compared. RESULTS: Over the 10-year study period, 3,884,395 patients underwent primary spine fusion surgery. Among these, 0.04% developed OS during the index hospitalization. The greatest incidence seen in primary fusion involved the thoracic spine (0.15%). OS was more common after spine fusion for spine deformity (P < 0.001). Patients with OS were more likely to be men (P < 0.001), older (P < 0.0001), and have more comorbidities (P < 0.0001). Patients with OS were more likely to require postoperative blood transfusions (odds ratio [OR], 3.39; 95% confidence interval [CI], 2.51-4.59; P < 0.001) and sustain any complication (OR, 4.20; 95% CI, 3.17-5.57; P < 0.001). Patients with OS had a longer length of stay (15.7 vs. 3.9 days; P < 0.001) and increased average hospitalization cost ($63,037.03 vs. $26,792.19; P < 0.001). The development of OS was associated with fluid electrolyte disorder (OR, 4.06; 95% CI, 2.99-5.51; P < 0.001). CONCLUSIONS: OS is a rare but serious complication of primary spine fusion surgery. Identifying the specific risk factors, symptoms, and potential complications related to OS is critical to aid in decreasing the significant morbidity associated with its development.

Prediction of Major Complications and Readmission After Lumbar Spinal Fusion: A Machine Learning-Driven Approach.

BACKGROUND: Given the significant cost and morbidity of patients undergoing lumbar fusion, accurate preoperative risk-stratification would be of great utility. We aim to develop a machine learning model for prediction of major complications and readmission after lumbar fusion. We also aim to identify the factors most important to performance of each tested model. METHODS: We identified 38,788 adult patients who underwent lumbar fusion at any California hospital between 2015 and 2017. The primary outcome was major perioperative complication or readmission within 30 days. We build logistic regression and advanced machine learning models: XGBoost, AdaBoost, Gradient Boosting, and Random Forest. Discrimination and calibration were assessed using area under the receiver operating characteristic curve and Brier score, respectively. RESULTS: There were 4470 major complications (11.5%). The XGBoost algorithm demonstrates the highest discrimination of the machine learning models, outperforming regression. The variables most important to XGBoost performance include angina pectoris, metastatic cancer, teaching hospital status, history of concussion, comorbidity burden, and workers' compensation insurance. Teaching hospital status and concussion history were not found to be important for regression. CONCLUSIONS: We report a machine learning algorithm for prediction of major complications and readmission after lumbar fusion that outperforms logistic regression. Notably, the predictors most important for XGBoost differed from those for regression. The superior performance of XGBoost may be due to the ability of advanced machine learning methods to capture relationships between variables that regression is unable to detect. This tool may identify and address potentially modifiable risk factors, helping risk-stratify patients and decrease complication rates.

Utilization trends and outcomes of computer-assisted navigation in spine fusion in the United States.

BACKGROUND CONTEXT: Computer-assisted navigation (CAN) has emerged in spine surgery as an approach to improve patient outcomes. While there is substantial evidence demonstrating improved pedicle screw accuracy in CAN as compared to conventional spinal fusion (CONV), there is limited data regarding clinical outcomes and utilization trends in the United States. PURPOSE: The purpose of this study was to determine the utilization rates of CAN in the United States, identify patient and hospital trends associated with both techniques, and to compare their results. STUDY DESIGN: Retrospective review of national database. PATIENT SAMPLE: Nationwide Inpatient Sample (NIS), United States national database. OUTCOME MEASURES: CAN utilization, mortality, medical complications, neurologic complications, discharge destination, length of hospital stay, cost of hospital stay. METHODS: The NIS database was queried to identify patients undergoing spinal fusion with CAN or CONV. CAN and CONV utilization were tracked by year and anatomic location (cervical, thoracic, lumbar/lumbosacral). Patient demographics, hospital characteristics, index length of stay (LOS), and cost of stay (COS) were compared between the cohorts. After multivariate adjustment, index hospitalization clinical outcomes were compared. RESULTS: A total of 4,275,413 patients underwent spinal fusion surgery during the study period (2004 to 2014). CONV was performed in 98.4% (4,208,068) of cases and CAN was performed in 1.6% (67,345) of cases. The utilization rate of CAN increased from 0.04% in 2004 to 3.3% in 2014. Overall, CAN was performed most commonly in the lumbar/lumbosacral region (70.4%) compared to the cervical (20.4%) or thoracic (9.2%) regions. When normalized to region-specific rates of fusion with any technique, the proportional utilization of CAN was highest in the thoracic spine (2.7%), followed by the lumbar/lumbosacral (2.2%) and cervical (0.9%) regions. CAN utilization was positively correlated with patient factors including increasing age and number of medical comorbidities. Multivariate adjusted clinical outcomes demonstrated that compared to CONV, CAN was associated with a statistically significant decreased risk of mortality (0.28% vs 0.31%, OR=0.67, 95% CI: 0.46-0.97, p=.035) and increased risk of blood transfusions (9.1% vs 6.7%, OR=1.19, 95% CI: 1.02-1.39, p=.032). However, there was no difference in risk of neurologic complications. CAN patients had an increased average LOS (4.44 days vs. 3.97 days, p<.0001) and average COS ($34,669.49 vs $26,784.62, p<.0001) compared to CONV patients. CONCLUSIONS: CAN utilization increased in the United States from 2004-2014. Use of CAN was proportionately higher in the thoracic and lumbar/lumbosacral regions and in older patients with more comorbidities. Given the continued trend towards increased CAN utilization, large-scale studies are needed to determine the impact of this technology on long-term clinical outcomes.

Surgical treatment of metastatic spine disease: an update on national trends and clinical outcomes from 2010 to 2014.

BACKGROUND CONTEXT: Metastatic spine disease (MSD) is becoming more prevalent as medical treatment for cancers advance and extend survival. More MSD patients are treated surgically to maintain neurological function, ambulation, and quality of life. PURPOSE: The purpose of this study was to use a large, nationally representative database to examine the trends, patient outcomes, and health-care resource utilization associated with surgical treatment of MSD. DESIGN: This was an epidemiologic study using national administrative data from the Nationwide Readmissions Database (NRD). PATIENT SAMPLE: All patients in the NRD from 2010 to 2014 who underwent spinal surgery were included in the study. OUTCOME MEASURES: Mortality, blood transfusion, complications, length of stay, cost, and discharge location during index hospitalization as well as hospital readmission and revision surgery within 90-days of surgery were analyzed. METHODS: International Classification of Diseases, Ninth Revision, (ICD-9) codes was used to identify patients of interest within the NRD from 2010 to 2014. Patients were separated into two cohorts - those with MSD and those without. Trends for surgical treatment of MSD were assessed and outcomes measures for both cohorts were analyzed and compared. RESULTS: The number of surgical treatments for MSD increased from 6,007 in 2010 to 7,032 in 2014 (p-trend<.0001) which represented a 17.1% increase. During index hospitalization, MSD patients had an increased risk of mortality (odds ratio [OR]=3.22, 95% confidence interval [CI]: 2.85-3.63, p<.0001), blood transfusion (OR=2.93, 95% CI: 2.66-3.23, p<.0001), any complication (OR=1.24, 95% CI: 1.18-1.31, p<.0001), and discharge to skilled nursing facility (OR=1.51, 95% CI:1.41-1.61, p<.0001). MSD patients had longer average length of stay (13.05 vs. 4.56 days, p<.0001) and cost ($49,421.75 vs. $26,190.37, p<.0001) during index hospitalization. Furthermore, MSD patients had an increased risk of hospital readmission (OR=2.82, 95% CI: 2.68-2.96, p<.0001), readmission for surgical site infection (OR=2.38, 95% CI: 2.20-2.58, p<.0001), and readmission with neurologic deficits (OR=1.62, 95% CI: 1.27-2.06, p<.0001) despite a decreased risk of revision fusion (OR=0.71, 95% CI: 0.53-0.96, p=.026). CONCLUSIONS: The number of MSD patients who undergo surgical treatments is increasing. Not only do these patients have worse outcomes during index hospitalization, but they are also at an increased risk of hospital readmission for surgical site infection and neurologic complications. These findings stress the need for multidisciplinary perioperative treatment plans that mitigate risks and facilitate quick, effective recovery in these unique, at-risk patients.

Implications of sagittal alignment and complication profile with stand-alone anterior lumbar interbody fusion versus anterior posterior lumbar fusion.

BACKGROUND: Anterior lumbar interbody fusion (ALIF) is commonly utilized in lumbar degenerative pathologies. Standalone ALIF (ST-ALIF) systems were developed to avoid added morbidity, surgical time, and cost of anterior and posterior fusion (APF). Controversy exists in the literature about which of these two techniques yields superior clinical and radiographic outcomes, and few studies have directly compared them. This study seeks to compare ST-ALIF and APF in terms of sagittal correction and surgical complications. METHODS: Ninty-two consecutive ALIF cases performed from 2013-2018 were retrospectively reviewed and separated into 2 groups. Radiographic measurements were performed on pre- and post-operative radiographs, including segmental lordosis (SL), lumbar lordosis (LL), and pelvic incidence-lumbar lordosis mismatch (PI-LL). Surgical complications were determined. Statistical analysis was performed using chi-square test of homogeneity, Fisher's exact test, and independent sample t-test. Comparisons between groups were deemed statistically significant at the P<0.05 threshold. RESULTS: Fifty-seven ST-ALIF, 35 APF were identified. There were no differences in age, gender, BMI, Charlson Comorbidity Index (CCI), preoperative diagnosis, or surgical level between the 2 cohorts. Bone Morphogenetic Protein (BMP) was utilized in 24.6% of ST-ALIF versus none of APF (P=0.001). No differences were detected in SL, LL, and PI-LL mismatch. ST-ALIF cohort had significantly greater risk of subsidence and revision surgery versus APF (12.3% vs. 0%, RD 95% CI: 3.8-20.8%, P=0.042). Recurrent spondylolisthesis occurred in 5 ST-ALIF cases, 3 cases with implant failure, and 2 nonunions versus none in the APF group. CONCLUSIONS: ST-ALIF was associated with significantly greater subsidence and revision surgery versus APF. Careful patient selection is paramount when considering ST-ALIF. The potential for revision surgery may offset the potential benefit in avoiding posterior fusion. Despite the greater risk of subsidence, sagittal alignment was not significantly affected.

Initial Single-Institution Experience With a Novel Robotic-Navigation System for Thoracolumbar Pedicle Screw and Pelvic Screw Placement With 643 Screws.

BACKGROUND: Robotic-guided navigation systems for pedicle screw placement has gained recent interest to ensure accuracy and safety and diminish radiation exposure. There have been no published studies using a new combined robotics and navigation system (Globus ExcelsiusGPS system). The purpose of this study was to demonstrate safety with this system. METHODS: This is a case series of consecutive patients at a single institution from February 1, 2018, to August 31, 2018. All patients who had planned placement of thoracic and lumbar pedicle screws using the combined robotics-navigation system were included. Chart review was performed for operative details. A subgroup analysis was performed on patients with postoperative computed tomography (CT) scans to assess screw placement accuracy using the Gertzbein and Robbins system. Acceptable pedicle screw position was defined as grade A or B. RESULTS: One hundred six patients were included, with 636 pedicle screws, 6 iliac screws, and 1 S2AI screw. Five cases were aborted for technical issues. In the remaining 101 patients, 88 patients had screws placed using preoperative CT planning and 13 patients using intraoperative fluoroscopy planning. All screws except for 5 pedicle screws in 2 patients were placed successfully using the robot (99%). These 5 pedicle screws were placed by converting to a fluoro-guided technique without robotic assistance. Eighty-six patients had screws placed using a percutaneous technique, and 15 patients had screws placed using an open technique. Ninety-eight patients underwent interbody placement: 28 anterior lumbar interbody fusions (ALIFs), 12 lateral lumbar interbody fusions (LLIFs), and 58 transforaminal lumbar interbody fusions (TLIFs). All ALIFs and LLIFs were performed prior to placement of the screws. Four LIF patients had screws placed in the lateral position. No patients had screw-related complications intraoperatively or postoperatively, and no patients returned to the operating room for screw revision. Thirteen patients underwent postoperative CT for various reasons. Of the 66 pedicle screws that were examined with postoperative CT, all screws (100%) had acceptable position. CONCLUSION: This study demonstrates that the combined robotics and navigation system is a novel technology that can be utilized to place pedicle screws and pelvic screws safely and has the potential to reduce screw-related complications. LEVEL OF EVIDENCE: 4 (case series).

Demographic Trends in the Use of Intraoperative Neuromonitoring for Scoliosis Surgery in the United States.

BACKGROUND: Intraoperative neuromonitoring (ION), such as motor-evoked potential (MEP), somatosensory evoked potentials (SSEP), and electromyography (EMG), is used to detect impending neurological injuries during spinal surgery. To date, little is known about the trends in the use of ION for scoliosis surgery in the United States. METHODS: A retrospective review was performed using the PearlDiver Database to identify patients that had scoliosis surgery with and without ION from years 2005 to 2011. Demographic information (such as age, gender, region within the United States) and clinical information (such as type of ION and rates of neurological injury) were assessed. RESULTS: There were 3618 patients who had scoliosis surgery during the study period. Intraoperative neuromonitoring was used in 1361 (37.6%) of these cases. The number of cases in which ION was used increased from 27% in 2005 to 46.9% in 2011 (P < .0001). Multimodal ION was used more commonly than unimodal ION (64.6% versus 35.4%). The most commonly used modality was combined SSEP and EMG, while the least used modality was MEP only. Neurological injuries occurred in 1.8 and 2.0% of patients that had surgery with and without ION, respectively (P = .561). Intraoperative neuromonitoring was used most commonly in patients <65 years of age and in the Northeastern part of the United States (age P = .006, region P < .0001). CONCLUSIONS: The use of ION for scoliosis surgery gradually increased annually from 2005 to 2011. Age and regional differences were noted with neuromonitoring being most commonly used for scoliosis surgery in nonelderly patients and in the Northeastern part of the United States. No differences were noted in the risk of neurological injury in patients that had surgery with and without ION. Although the findings from this study may seem to suggest that ION may not influence the risk of neurologic injury, this result must be interpreted with caution as inherently riskier surgeries may utilize ION more, leading to an actual reduction in injuries more dramatic than observed in this study.

Functional analysis of the Helicobacter pullorum N-linked protein glycosylation system.

N-linked protein glycosylation systems operate in species from all three domains of life. The model bacterial N-linked glycosylation system from Campylobacter jejuni is encoded by pgl genes present at a single chromosomal locus. This gene cluster includes the pglB oligosaccharyltransferase responsible for transfer of glycan from lipid carrier to protein. Although all genomes from species of the Campylobacter genus contain a pgl locus, among the related Helicobacter genus only three evolutionarily related species (H. pullorum, H. canadensis and H. winghamensis) potentially encode N-linked protein glycosylation systems. Helicobacter putative pgl genes are scattered in five chromosomal loci and include two putative oligosaccharyltransferase-encoding pglB genes per genome. We have previously demonstrated the in vitro N-linked glycosylation activity of H. pullorum resulting in transfer of a pentasaccharide to a peptide at asparagine within the sequon (D/E)XNXS/T. In this study, we identified the first H. pullorum N-linked glycoprotein, termed HgpA. Production of histidine-tagged HgpA in the background of insertional knockout mutants of H. pullorum pgl/wbp genes followed by analysis of HgpA glycan structures demonstrated the role of individual gene products in the PglB1-dependent N-linked protein glycosylation pathway. Glycopeptide purification by zwitterionic-hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry identified six glycosites from five H. pullorum proteins, which was consistent with proteins reactive with a polyclonal antiserum generated against glycosylated HgpA. This study demonstrates functioning of a H. pullorum N-linked general protein glycosylation system.

The Effects of Systemic Therapy of PEGylated NEL-Like Protein 1 (NELL-1) on Fracture Healing in Mice.

Fractures are common, with an incidence of 13.7 per 1000 adults annually. Systemic agents have been widely used for enhancing bone regeneration; however, the efficacy of these therapeutics for the management and prevention of fracture remains unclear. NEL-like protein 1 (NELL-1) is a potent pro-osteogenic cytokine that has been modified with polyethylene glycol (PEG)ylation [PEGylated NELL-1 (NELL-PEG)] to enhance its pharmacokinetics for systemic therapy. Our aim was to investigate the effects of systemic administration of NELL-PEG on fracture healing in mice and on overall bone properties in uninjured bones. Ten-week-old CD-1 mice were subjected to an open osteotomy of bilateral radii and treated with weekly injections of NELL-PEG or PEG phosphate-buffered saline as control. Systemic injection of NELL-PEG resulted in improved bone mineral density of the fracture site and accelerated callus union. After 4 weeks of treatment, mice treated with NELL-PEG exhibited substantially enhanced callus volume, callus mineralization, and biomechanical properties. NELL-PEG injection significantly augmented bone regeneration, as confirmed by high expression of bone turnover rate, bone formation rate, and mineral apposition rate. Consistently, the immunohistochemistry results also confirmed a high bone remodeling activity in the NELL-PEG-treated group. Our findings suggest that weekly injection of NELL-PEG may have the clinical potential to accelerate fracture union and enhance overall bone properties, which may help prevent subsequent fractures.