Faculty Bibliography

BACKGROUND:Whiplash is a common traumatic cervical injury which is most often a consequence of rear-end motor vehicle accidents. It has been estimated that up to 50% of the whiplash patients suffer from chronic symptoms, resulting in extensive individual and societal burden. Several measurement instruments are used for initial assessment of whiplash and evaluation of response to treatment. However, a comprehensive assessment of the performance of these measures is lacking. Furthermore, there is no consensus on the most relevant outcome domains and their corresponding measurement instruments of choice. This systematic review aims to identify, describe, and critically appraise the performance properties of health-related measurement instruments in whiplash population. METHODS:The following literature databases will be searched from their date of establishment: PubMed, Embase®, MEDLINE, CINAHL Complete, PsycINFO, and HAPI. All original articles evaluating the reliability, validity, responsiveness, and feasibility of health-related measurement instruments in whiplash will be included, without additional restriction on their intended use, source of data, and structure. Risk of bias will be assessed using the COSMIN Risk of Bias checklist. Findings of the studies will be judged against the criteria for good measurement properties, and results from all studies will be qualitatively summarized to generate an overall quality of findings. Overall quality of evidence will be determined using a modified GRADE approach, which will be used in conjunction with the overall quality of results for generation of recommendations. Two reviewers will perform all steps of the review independently. Discrepancies will be discussed between the reviewers, and in case of remaining disagreement, the senior reviewer will make the final decision. DISCUSSION:This systematic review will summarize the body of literature on health-related measurement instruments in whiplash, aiming to facilitate the selection of high-quality measurement instrument for researchers and physicians. Findings of this study will guide the ongoing efforts for development of a core outcome set. SYSTEMATIC REVIEW REGISTRATION:PROSPERO reference number CRD42018070901.

The aim of this study was to evaluate disc degeneration and kinematic changes in translation and angular motion of the thoracic spine using kinematic MRI (kMRI). 105 thoracic spine kMRI were analyzed from T4-5 to T11-12 using MRAnalyzer3. Translational and angular motion were evaluated in neutral, flexion, and extension positions. Thoracic disc height and disc degeneration grading were measured in the neutral position. Intraclass Correlation Coefficients were used to analyze agreement among three observers. The Friedman's test was used to analyze the difference in disc height, disc degeneration, translational motion, and angular motion. The Wilcoxon-signed rank test was used for post-hoc analysis with a Bonferroni correction. A p-value of 0.00625 was used to establish a statistically significant difference. Analysis using the Friedman's test revealed that translational motion, disc height, and disc degeneration were significantly different from T4-5 to T11-12 (p < 0.001). The T4-5 level showed the least translational motion, while the T10-11 showed the most translational motion. The lower thoracic level (T8-12) showed significantly more translational motion, more advanced disc degeneration, and greater disc height than the upper thoracic level (T4-8, p < 0.001). T11-12 showed the most advanced disc degeneration. There was a significant negative correlation between disc degeneration and translational motion at the upper thoracic level (p = 0.013). The lower thoracic region (below T8) had significantly more translational motion, more advanced disc degeneration, and greater disc height. This information is crucial in further understanding thoracic spinal kinematics and may contribute to determining the stopping level in fusion surgeries involving the thoracic spine.

The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/β-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while β-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3α and p-GSK-3β were also significantly upregulated indicating that the Wnt/β-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/β-catenin signaling pathway. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1638-1648, 2019.

OBJECTIVES/OBJECTIVE:To evaluate the effect of pre-existing mental health (MH) conditions on 90-day complication, 90-day readmission, and all-time revision surgical intervention rates following femoral, tibial, and pilon fractures. DESIGN/METHODS:Data were collected using a commercially available database software for which Current Procedural Terminology codes were used to identify patients who underwent surgical treatment of tibial, femoral, or pilon fractures. These patients were then subdivided into those with and without pre-existing MH condition using International Classification of Disease, Ninth Edition codes. Ninety-day postoperative complications, revision surgery, and 90-day readmission rates were then compared between those with and without MH conditions. SETTING/METHODS:National databases of 70 million combined patients from 2007 to 2015. PATIENTS/PARTICIPANTS/METHODS:Humana and Medicare insured patients. INTERVENTION/METHODS:Surgical treatment of tibial, femoral, and pilon fractures. MAIN OUTCOME MEASUREMENTS/METHODS:Ninety-day readmission, 90-day complications, and all-time revision surgical intervention. RESULTS:The total number of patients for femoral, tibial, and pilon treatment, respectively, included 6207, 6253, and 5940 without MH conditions and 4879, 5247, and 2911 with MH conditions. Femoral, tibial, and pilon readmission rates, revision rates, and complication rates were significantly higher among patients with MH disorders in matched cohorts after controlling for medical comorbidities (P ≤ 0.05 for all). CONCLUSIONS:Comorbid MH conditions are associated with higher postoperative complication, readmission, and revision surgery rates for treated femoral, tibial, and pilon fractures. LEVEL OF EVIDENCE/METHODS:Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Study Design/UNASSIGNED:Retrospective, database study. Objectives/UNASSIGNED:The aim of this study was to investigate incidence and risk factors associated with venous thromboembolic events (VTEs) after lumbar spine surgery. Methods/UNASSIGNED:Patients who underwent lumbar surgery between 2007 and 2014 were identified using the Humana within PearlDiver database. ICD-9 (International Classification of Diseases Ninth Revision) diagnosis codes were used to search for the incidence of VTEs among surgery types, patient demographics and comorbidities. Complications including DVT and PE were queried each day from the day of surgery to postoperative day 7 and for periods 0 to 1 week, 0 to 1 month, 0 to 2 months, and 0 to 3 months postoperatively. Results/UNASSIGNED:< .001). Risk factors associated with the highest VTE incidence and odds ratios (ORs) were primary coagulation disorder (10.01%, OR 4.33), extremity paralysis (7.49%, OR 2.96), central venous line (6.70%, OR 2.87), and varicose veins (6.51%, OR 2.58). Conclusions/UNASSIGNED:This study identified several patient comorbidities that were independent predictors of postoperative VTE occurrence after lumbar surgery. Clinical VTE risk assessment may improve with increased focus toward patient comorbidities rather than surgery type or patient demographics.

Study Design/UNASSIGNED:Retrospective cohort study. Objective/UNASSIGNED:To determine the rates of perioperative complications in patients undergoing anterior cervical discectomy and fusion (ACDF) with allograft versus synthetic cage. Methods/UNASSIGNED:test. Complications within 90 days were identified via ICD-9 codes and compared between the 2 cohorts. Revision rates within 2 years were noted. Results/UNASSIGNED:= .03). Conclusions/UNASSIGNED:This data suggests that synthetic cages are associated with a marginally higher overall rate of complications with similar revision rates.

Study Design/UNASSIGNED:Systematic review. Objective/UNASSIGNED:To review, critically appraise, and synthesize evidence on use of cell therapy for intervertebral disc repair. Methods/UNASSIGNED:A systematic search of PubMed/MEDLINE was conducted for literature published through October 31, 2018 and EMBASE and ClinicalTrials.gov databases through April 13, 2018 comparing allogenic or autologous cell therapy for intervertebral disc (IVD) repair in the lumbar or cervical spine. In the absence of comparative studies, case series of ≥10 patients were considered. Results/UNASSIGNED:From 1039 potentially relevant citations, 8 studies across 10 publications on IVD cell therapies in the lumbar spine met the inclusion criteria. All studies were small and primarily case series. For allogenic cell sources, no difference in function or pain between mesenchymal cell treatment and sham were reported in 1 small randomized controlled trial; 1 small case series reported improved function and pain relative to baseline but it was unclear if the change was clinically significant. Similarly for autologous cell sources, limited data across case series suggest pain and function may be improved relative to baseline; whether the changes were clinically significant was not clear. Safety data was sparse and poorly reported. The need for subsequent surgery was reported in 3 case-series studies ranging from 6% to 80%. Conclusions/UNASSIGNED:The overall strength of evidence for efficacy and safety of cell therapy for lumbar IVD repair was very low primarily due to substantial risk of bias, small sample sizes and lack of a comparator intervention. Methodologically sound studies comparing cell therapies to other treatments are needed.

Study Design/UNASSIGNED:Systematic review. Objectives/UNASSIGNED:To review, critically appraise, and synthesize evidence on the use of allogenic stem cell products for spine fusion compared with other bone graft materials. Methods/UNASSIGNED:Systematic searches of PubMed/MEDLINE, through October 31, 2018 and of EMBASE and ClinicalTrials.gov through April 13, 2018 were conducted for literature comparing allogenic stem cell sources for fusion in the lumbar or cervical spine with other fusion methods. In the absence of comparative studies, case series of ≥10 patients were considered. Results/UNASSIGNED:From 382 potentially relevant citations identified, 6 publications on lumbar fusion and 5 on cervical fusion met the inclusion criteria. For lumbar arthrodesis, mean Oswestry Disability Index (ODI), visual analogue scale (VAS) pain score, and fusion rates were similar for anterior lumbar interbody fusion (ALIF) using allogenic multipotent adult progenitor cells (Map3) versus recombinant human bone morphogenetic protein-2 (rhBMP-2) in the one comparative lumbar study (90% vs 92%). Across case series of allogenic stem cell products, function and pain were improved relative to baseline and fusion occurred in ≥90% of patients at ≥12 months. For cervical arthrodesis across case series, stem cell products improved function and pain compared with baseline at various time frames. In a retrospective cohort study fusion rates were not statistically different for Osteocel compared with Vertigraft allograft (88% vs 95%). Fusion rates varied across time frames and intervention products in case series. Conclusions/UNASSIGNED:The overall quality (strength) of evidence of effectiveness and safety of allogenic stem cells products for lumbar and cervical arthrodesis was very low, meaning that we have very little confidence that the effects seen are reflective of the true effects.

OBJECTIVE:To compare the rates of deep venous thrombosis (DVT), rates of pulmonary embolus (PE), and complication profiles of warfarin and low-molecular-weight heparin (LMWH) in patients undergoing operative fixation of hip fractures. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Insurance-based database of more than 22 million patient records. PATIENTS/METHODS:Adult hip fracture patients who were treated operatively and received chemoprophylaxis from 2007 to 2016. A total of 7594 patients met inclusion criteria and were available for final analysis. INTERVENTION/METHODS:Pharmacological anticoagulation with warfarin or LMWH to prevent postoperative venous thromboembolism after hip fracture surgery. MAIN OUTCOME MEASURES/METHODS:Development of DVT or PE within 30 and 90 days of surgery. RESULTS:Patients prescribed warfarin had higher rates of DVT and PE compared with those prescribed LMWH. Patients on warfarin were more likely to develop a postoperative hematoma and to be readmitted within 30 and 90 days compared with those on LMWH. Patients in both groups had similar rates of total complications. CONCLUSIONS:Patients prescribed warfarin after hip fractures had higher rates of DVT and PE compared with those prescribed LMWH, although both agents had similar complication profiles. LEVEL OF EVIDENCE/METHODS:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.