Extracranial Vertebral Artery Injuries.

Paired vertebral arteries (VAs) travel from the subclavian artery through the cervical spine and into the intracranial space where they contribute to posterior cerebral circulation. Blunt and penetrating injuries to the cervical spine risk injury to the VA. Among the most feared complications of vertebral artery injury (VAI) is posterior circulation stroke. Appropriate screening and treatment of these injuries in the trauma setting remain vitally important to aid in the prevention of devastating neurologic sequelae. A robust knowledge of the VA anatomy is required for spine surgeons to avoid VAI during cervical spine approaches and instrumentation. Both anterior and posterior cervical spine surgeries can place the VA at risk. Careful preoperative assessment with the appropriate advanced imaging studies is necessary to verify the course of the VA in the cervical spine and thus prevent iatrogenic injury because anatomic variations along the course of the artery can prove hazardous if not properly anticipated. Iatrogenic VAI can be treated successfully with tamponade. However, in some cases, ligation, repair, or endovascular procedures may be indicated.

Civilian Ballistic Injuries to the Atlantoaxial Spine: A Single Institution Case Series.

STUDY DESIGN: Retrospective case series. OBJECTIVE: Describe the injury characteristics of ballistic fractures involving the atlantoaxial spine. SUMMARY OF BACKGROUND DATA: Civilian gunshot wounds to the spine are an increasingly common injury in the United States. Civilian studies have focused on ballistic injuries to the entire spine as opposed to a region-specific fashion. Only a single 10-patient case series investigating ballistic fractures to the upper cervical spine (C1 and C2) exists, leaving a large gap in the understanding of this injury complex. METHODS: A retrospective chart review was performed. Extracted data included patient demographics, neurological status on presentation, fracture morphology, assessment of stability, other associated injuries, and surgical procedures performed. Proportional analysis was performed to characterize the fractures and their associated neurological injuries. RESULTS: Thirty-six patients were identified, with 86% being male with an average patient age of 30.0 ± 10.36 years (mean ± SD). Fracture morphology was characterized using proportional analysis. Initial neurological exams were either ASIA A or ASIA E, without any incomplete injuries noted. Patients who sustained a transcanal injury did not show any neurological improvement. The initial in-hospital mortality rate was 5.6%, with a 1-year mortality rate of 8.3%. There is a high incidence of associated vascular injury (66%) and mandible fracture (33%). CONCLUSIONS: Ballistic penetrating trauma to the atlantoaxial spine often results in complex injury patterns necessitating multidisciplinary care with high rates of morbidity and mortality. If neurological deficits are present initially, they are often complete. Two thirds of patients sustained an associated vascular injury, which should be screened for with CT angiography.

Duration and Magnitude of Opioid Use After Minimally Invasive Sacroiliac Joint Fusion.

STUDY DESIGN: Retrospective cohort study performed in a nationwide insurance claims database. OBJECTIVE: To evaluate the duration and magnitude of post-operative opioid prescriptions after minimally invasive surgical sacroiliac joint fusion (MIS SIJF) as compared to other common spine surgeries. SUMMARY OF BACKGROUND DATA: MIS SIJF has been reported to significantly improve quality of life and reduce pain. However, there is a paucity of reported data on post-operative opioid use in patients undergoing MIS SIJF for sacroiliac joint dysfunction. METHODS: A nationwide insurance claims database was queried to identify 4,666 patients who underwent MIS SIJF. Patients were stratified by pre-operative opioid use: Opioid naïve, sporadic use, or chronic use were respectively defined as 0,1, or≥2 opioid prescriptions filled within 6 months prior to surgery. Duration of opioid use was defined by the time between MIS SIJF and last opioid prescription filled while magnitude of opioid use was determined by milligram morphine equivalents filled by 30 days post-operation. This opioid use data was compared to that of other common spine surgeries. RESULTS: Patients undergoing MIS SIJF continued to fill opioid prescriptions 1-year post-operatively at significantly higher proportions than those undergoing other common spine procedures assessed by prior literature within each of the pre-operative opioid use cohorts (chronic: 73% vs. 49-62%; P <0.0001, sporadic: 39% vs. 23-28%; P <0.0001, opioid naïve: 22% vs. 15-18%; P <0.0001). Chronic users filled the highest opiate dosages during the 30-day post-operative period, filling on average 64.75 MME/d compared to 19.75 MME/d and 24.25 MME/d by the opioid naïve and sporadic users, respectively. CONCLUSION: After MIS SIJF, opioid naïve patients use fewer opioids and for a shorter period of time compared to patients with sporadic or chronic pre-operative opioid use. MIS SIJF may result in less effective pain reduction when compared to other common spine surgeries evaluated via identical methodology.

Firearm-Related Injuries-Wound Management, Stabilization, and Associated Injuries: A Critical Analysis Review.

¼: Gun violence-related and firearm-related injuries are a public health crisis with increasing rates, particularly among younger demographics, in the United States despite a decline in incidence worldwide. ¼: There exists limited high-quality evidence to guide the management of firearm-related orthopaedic injuries. ¼: Associated injuries (i.e., neurological and vascular) are common in ballistic injuries to the extremity. ¼: Where indicated, low-energy orthopaedic injuries can be managed successfully with standard fixation and management strategies with similar complications to closed fractures.

Rates of Future Lumbar Fusion in Patients with Cauda Equina Syndrome Treated With Decompression.

INTRODUCTION: The long-term risk of conversion to lumbar fusion is ill-defined for patients with cauda equina syndrome (CES) treated with decompression. This study aimed to identify the rates of fusion in patients with CES and compare those rates with a matched lumbar spinal stenosis (LSS) group. METHODS: Patients with CES who underwent decompression were identified in a national database and matched to control patients with LSS. The rates of conversion to fusion were identified and compared. Multivariate logistic regression analysis identified independently associated risk factors. A subanalysis was conducted after stratifying by timing between CES diagnosis and decompression. RESULTS: The rate of lumbar fusion in the CES cohort was 3.6% after 1 year, 6.7% after 3 years, and 7.8% after 5 years, significantly higher than the LSS control group at all time points (1 year: 1.6%, P = 0.001; 3 years: 3.0%, P < 0.001; 5 years: 3.8%, P < 0.001). CES was independently associated with increased risk of conversion to fusion (odds ratio: 2.13; 95% confidence interval: 1.56 to 2.97; P < 0.001). Surgical timing was not associated with risk of conversion to fusion. CONCLUSIONS: After 5 years, 7.8% of patients with CES underwent fusion, a markedly higher rate compared with patients with LSS. Counseling patients with CES on this increased risk of future surgery is important for patient education and satisfaction.

SATB2: A versatile transcriptional regulator of craniofacial and skeleton development, neurogenesis and tumorigenesis, and its applications in regenerative medicine.

SATB2 (special AT-rich sequence-binding protein 2) is a member of the special AT-rich binding protein family. As a transcription regulator, SATB2 mainly integrates higher-order chromatin organization. SATB2 expression appears to be tissue- and stage-specific, and is governed by several cellular signaling molecules and mediators. Expressed in branchial arches and osteoblast-lineage cells, SATB2 plays a significant role in craniofacial pattern and skeleton development. In addition to regulating osteogenic differentiation, SATB2 also displays versatile functions in neural development and cancer progression. As an osteoinductive factor, SATB2 holds great promise in improving bone regeneration toward bone defect repair. In this review, we have summarized our current understanding of the physiological and pathological functions of SATB2 in craniofacial and skeleton development, neurogenesis, tumorigenesis and regenerative medicine.

Migration of an Anterior Cervical Discectomy and Fusion Screw into the Constrictor Muscle of the Hypopharynx: A Case Report.

CASE: A 53-year-old man developed dysphagia 4 years after anterior cervical discectomy and fusion (ACDF), and radiographs revealed a dislodged screw anterior to the ACDF plate. Intraoperatively, the screw was found to be completely embedded within the pharyngeal constrictor muscle fibers and was removed with assistance from otolaryngology without injury to the pharyngeal mucosa. CONCLUSION: Implant migration after ACDF can variably damage tracheoesophageal and retropharyngeal structures, and a multidisciplinary approach involving otolaryngology or thoracic surgery may be required to diagnose and treat these complications.

Development of a simplified and inexpensive RNA depletion method for plasmid DNA purification using size selection magnetic beads (SSMBs).

Plasmid DNA (pDNA) isolation from bacterial cells is one of the most common and critical steps in molecular cloning and biomedical research. Almost all pDNA purification involves disruption of bacteria, removal of membrane lipids, proteins and genomic DNA, purification of pDNA from bulk lysate, and concentration of pDNA for downstream applications. While many liquid-phase and solid-phase pDNA purification methods are used, the final pDNA preparations are usually contaminated with varied degrees of host RNA, which cannot be completely digested by RNase A. To develop a simple, cost-effective, and yet effective method for RNA depletion, we investigated whether commercially available size selection magnetic beads (SSMBs), such as Mag-Bind® TotalPure NGS Kit (or Mag-Bind), can completely deplete bacterial RNA in pDNA preparations. In this proof-of-principle study, we demonstrated that, compared with RNase A digestion and two commercial plasmid affinity purification kits, the SSMB method was highly efficient in depleting contaminating RNA from pDNA minipreps. Gene transfection and bacterial colony formation assays revealed that pDNA purified from SSMB method had superior quality and integrity to pDNA samples cleaned up by RNase A digestion and/or commercial plasmid purification kits. We further demonstrated that the SSMB method completely depleted contaminating RNA in large-scale pDNA samples. Furthermore, the Mag-bind-based SSMB method costs only 5-10% of most commercial plasmid purification kits on a per sample basis. Thus, the reported SSMB method can be a valuable and inexpensive tool for the removal of bacterial RNA for routine pDNA preparations.

Applications of Biocompatible Scaffold Materials in Stem Cell-Based Cartilage Tissue Engineering.

Cartilage, especially articular cartilage, is a unique connective tissue consisting of chondrocytes and cartilage matrix that covers the surface of joints. It plays a critical role in maintaining joint durability and mobility by providing nearly frictionless articulation for mechanical load transmission between joints. Damage to the articular cartilage frequently results from sport-related injuries, systemic diseases, degeneration, trauma, or tumors. Failure to treat impaired cartilage may lead to osteoarthritis, affecting more than 25% of the adult population globally. Articular cartilage has a very low intrinsic self-repair capacity due to the limited proliferative ability of adult chondrocytes, lack of vascularization and innervation, slow matrix turnover, and low supply of progenitor cells. Furthermore, articular chondrocytes are encapsulated in low-nutrient, low-oxygen environment. While cartilage restoration techniques such as osteochondral transplantation, autologous chondrocyte implantation (ACI), and microfracture have been used to repair certain cartilage defects, the clinical outcomes are often mixed and undesirable. Cartilage tissue engineering (CTE) may hold promise to facilitate cartilage repair. Ideally, the prerequisites for successful CTE should include the use of effective chondrogenic factors, an ample supply of chondrogenic progenitors, and the employment of cell-friendly, biocompatible scaffold materials. Significant progress has been made on the above three fronts in past decade, which has been further facilitated by the advent of 3D bio-printing. In this review, we briefly discuss potential sources of chondrogenic progenitors. We then primarily focus on currently available chondrocyte-friendly scaffold materials, along with 3D bioprinting techniques, for their potential roles in effective CTE. It is hoped that this review will serve as a primer to bring cartilage biologists, synthetic chemists, biomechanical engineers, and 3D-bioprinting technologists together to expedite CTE process for eventual clinical applications.

BMP9-initiated osteogenic/odontogenic differentiation of mouse tooth germ mesenchymal cells (TGMCS) requires Wnt/ß-catenin signalling activity.

Teeth arise from the tooth germ through sequential and reciprocal interactions between immature epithelium and mesenchyme during development. However, the detailed mechanism underlying tooth development from tooth germ mesenchymal cells (TGMCs) remains to be fully understood. Here, we investigate the role of Wnt/ß-catenin signalling in BMP9-induced osteogenic/odontogenic differentiation of TGMCs. We first established the reversibly immortalized TGMCs (iTGMCs) derived from young mouse mandibular molar tooth germs using a retroviral vector expressing SV40 T antigen flanked with the FRT sites. We demonstrated that BMP9 effectively induced expression of osteogenic markers alkaline phosphatase, collagen A1 and osteocalcin in iTGMCs, as well as in vitro matrix mineralization, which could be remarkably blunted by knocking down ß-catenin expression. In vivo implantation assay revealed that while BMP9-stimulated iTGMCs induced robust formation of ectopic bone, knocking down ß-catenin expression in iTGMCs remarkably diminished BMP9-initiated osteogenic/odontogenic differentiation potential of these cells. Taken together, these discoveries strongly demonstrate that reversibly immortalized iTGMCs retained osteogenic/odontogenic ability upon BMP9 stimulation, but this process required the participation of canonical Wnt signalling both in vitro and in vivo. Therefore, BMP9 has a potential to be applied as an efficacious bio-factor in osteo/odontogenic regeneration and tooth engineering. Furthermore, the iTGMCs may serve as an important resource for translational studies in tooth tissue engineering.

Notch signaling: Its essential roles in bone and craniofacial development.

Notch is a cell-cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.

Long-term rates of bladder dysfunction after decompression in patients with cauda equina syndrome.

BACKGROUND CONTEXT: Cauda equina syndrome (CES) occurs due to compression of the lumbar and sacral nerve roots and is considered a surgical emergency. Although the condition is relatively rare, the associated morbidity can be devastating to patients. While substantial research has been conducted on the timing of treatment, the literature regarding long-term rates of bladder dysfunction in CES patients is scarce. PURPOSE: The aim of this study was to identify long-term rates of bladder dysfunction in CES patients and to compare those rates to non-CES patients who underwent similar spinal decompression. STUDY DESIGN/SETTING: Retrospective database study. PATIENT SAMPLE: The CES cohort was comprised of 2,362 patients who underwent decompression surgery following CES diagnosis with a 5-year follow-up. These patients were matched to 9,448 non-CES control patients who underwent spinal decompression without a diagnosis of CES. OUTCOME MEASURES: Diagnosis of bladder dysfunction, surgical procedure to address bladder dysfunction METHODS: Using the national insurance claims database, PearlDiver, CES patients who underwent decompression surgery were identified and 1:4 matched to non-CES patients who underwent similar spinal decompression surgery. The 1-year, 3-year, and 5-year rates of progression to a bladder dysfunction diagnosis and surgical intervention to manage bladder dysfunction were recorded. The CES and non-CES groups were compared with univariate testing, and an analysis of risk factors for bladder dysfunction was performed with multivariate logistic regression analysis. RESULTS: A total of 2,362 CES patients who underwent decompression surgery were identified and matched to 9,448 non-CES control patients. After 5 years, CES patients had a 10%-12% increased absolute risk of continued bladder dysfunction and a 0.7%-0.9% increased absolute risk of undergoing a surgical procedure for bladder dysfunction, as compared to matched non-CES patients. Multivariate analysis controlling for age, sex, obesity, tobacco use, and diabetes, identified CES as independently associated with increased 5-year risk for bladder dysfunction diagnosis (odds ratio [OR]: 1.72; 95% confidence interaval [CI] 1.56-1.89; p<.001) and procedure (OR: 1.40; 95% CI 1.07-1.81; p=.012). CONCLUSIONS: Understanding the long-term risk for bladder dysfunction in CES patients is important for the future care and counseling of patients. Compared to non-CES patients who underwent similar spinal decompression, CES patients were observed to have a significantly higher long-term likelihood for both bladder dysfunction diagnosis and urologic surgical procedure.

The Influence of Selective Serotonin Reuptake Inhibitors on Lumbar Arthrodesis.

STUDY DESIGN: Retrospective analysis using the PearlDiver national insurance claims database. OBJECTIVE: To investigate the relationship between chronic preoperative selective serotonin reuptake inhibitor (SSRI) prescriptions and nonunion following spine fusion surgery. SUMMARY OF BACKGROUND DATA: Contemporary literature has linked SSRIs to decreased bone mineral density and increased rates of future bone fracture. Furthermore, a recent murine model has suggested a potential role in the quality of fracture healing itself. METHODS: All single-level lumbar fusion patients were identified. The rate of nonunion diagnosis between 6 and 24 months following surgery was assessed. A stratified analysis of chronic SSRI use and a number of comorbidities was conducted, followed by a multiple logistic regression analysis of nonunion accounting for qualifying risk factors. Finally, subanalyses of individual procedure codes were carried out. RESULTS: In total, 7905 single-level lumbar fusion patients were included. In the multivariate analysis, chronic SSRI [odds ratio (OR): 1.558, P=0.004] and tobacco use (OR: 1.500, P=0.011) were identified as independent risk factors for nonunion, whereas patient age over 60 years (OR: 0.468, P<0.001) was observed to be negatively associated with nonunion. In the individual procedure subanalyses, SSRIs were significantly associated with nonunion in 2 of 3 univariate analyses and observed to be an independent risk factor for nonunion in 2 of the 3 procedure populations. CONCLUSIONS: These data suggest that patients treated concomitantly for mental health disorders with SSRIs before arthrodesis may be at an increased risk of postoperative nonunion. Closer follow-up may be indicated in this patient population.

Rod fractures and nonunions after long fusion to the sacrum for primary presentation adult spinal deformity: a comparison with and without interbody fusion in the distal lumbar spine.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To investigate the prevalence and incidence rate of rod fractures (RF) in patients undergoing surgery for correction of adult spinal deformity (ASD) with or without the use of interbody fusions in the caudal levels of the fusion construct. BACKGROUND: Data: Pseudarthrosis and rod fracture after long spinal fusion to the sacrum for correction of ASD remain a concern. METHODS: We reviewed clinical records of patients who underwent surgery for correction of ASD between 2004 and 2014. All cases were primary (no prior spine fusion) surgeries with long fusion to the sacrum and bilateral spinopelvic fixation. Patients were dichotomized into one of two groups based on whether an interbody fusion was performed at the caudal levels of the fusion construct. The primary outcome of interest was the prevalence and incidence rate of RFs. RESULTS: A total of 230 patients underwent a long segment fusion for correction of ASD with mean follow-up of 55 months. 117 patients had an interbody fusion (IF) while 113 patients did not (NIF). At last follow-up, there was no significant difference in the prevalence of RFs between the cohort of patients IF vs NIF (IF cohort: n = 20, 17.9% vs NIF cohort: n = 15, 14.2%, p = 0.49). However, the incidence rate for bilateral rod fractures was 1.6%/year for IF group vs 1.0%/year for NIF group (p = 0.02). Location of RF was different between the two groups; RF (unilateral and bilateral) above L4 was the most common location in the IF group (n = 17/20; 85%) compared to L4-S1 in the NIF group (n = 11/15; 73%) (p = 0.02). CONCLUSION: Interbody fusion does not fully protect against rod failure in the lumbar spine in ASD patients with long posterior spinal fusion and may encourage failure at L2-L4, the levels above the interbody fusion. LEVEL OF EVIDENCE: III.

Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine.

Bone is a dynamic organ with high regenerative potential and provides essential biological functions in the body, such as providing body mobility and protection of internal organs, regulating hematopoietic cell homeostasis, and serving as important mineral reservoir. Bone defects, which can be caused by trauma, cancer and bone disorders, pose formidable public health burdens. Even though autologous bone grafts, allografts, or xenografts have been used clinically, repairing large bone defects remains as a significant clinical challenge. Bone tissue engineering (BTE) emerged as a promising solution to overcome the limitations of autografts and allografts. Ideal bone tissue engineering is to induce bone regeneration through the synergistic integration of biomaterial scaffolds, bone progenitor cells, and bone-forming factors. Successful stem cell-based BTE requires a combination of abundant mesenchymal progenitors with osteogenic potential, suitable biofactors to drive osteogenic differentiation, and cell-friendly scaffold biomaterials. Thus, the crux of BTE lies within the use of cell-friendly biomaterials as scaffolds to overcome extensive bone defects. In this review, we focus on the biocompatibility and cell-friendly features of commonly used scaffold materials, including inorganic compound-based ceramics, natural polymers, synthetic polymers, decellularized extracellular matrix, and in many cases, composite scaffolds using the above existing biomaterials. It is conceivable that combinations of bioactive materials, progenitor cells, growth factors, functionalization techniques, and biomimetic scaffold designs, along with 3D bioprinting technology, will unleash a new era of complex BTE scaffolds tailored to patient-specific applications.

FAMSi: A Synthetic Biology Approach to the Fast Assembly of Multiplex siRNAs for Silencing Gene Expression in Mammalian Cells.

RNA interference (RNAi) is mediated by an ∼21-nt double-stranded small interfering RNA (siRNA) and shows great promise in delineating gene functions and in developing therapeutics for human diseases. However, effective gene silencing usually requires the delivery of multiple siRNAs for a given gene, which is often technically challenging and time-consuming. In this study, by exploiting the type IIS restriction endonuclease-based synthetic biology methodology, we developed the fast assembly of multiplex siRNAs (FAMSi) system. In our proof-of-concept experiments, we demonstrated that multiple fragments containing three, four, or five siRNA sites targeting common Smad4 and/or BMPR-specific Smad1, Smad5, and Smad8 required for BMP9 signaling could be assembled efficiently. The constructed multiplex siRNAs effectively knocked down the expression of Smad4 and/or Smad1, Smad5, and Smad8 in mesenchymal stem cells (MSCs), and they inhibited all aspects of BMP9-induced osteogenic differentiation in bone marrow MSCs (BMSCs), including decreased expression of osteogenic regulators/markers, reduced osteogenic marker alkaline phosphatase (ALP) activity, and diminished in vitro matrix mineralization and in vivo ectopic bone formation. Collectively, we demonstrate that the engineered FAMSi system provides a fast-track platform for assembling multiplexed siRNAs in a single vector, and thus it may be a valuable tool to study gene functions or to develop novel siRNA-based therapeutics.

Comprehensive classification system for multirod constructs across three-column osteotomies: a reliability study.

OBJECTIVE: In this study, the authors' goal was to determine the intra- and interobserver reliability of a new classification system that allows the description of all possible constructs used across three-column osteotomies (3COs) in terms of rod configuration and density. METHODS: Thirty-five patients with multirod constructs (MRCs) across a 3CO were classified by two spinal surgery fellows according to the new system, and then were reclassified 2 weeks later. Constructs were classified as follows: the number of rods across the osteotomy site followed by a letter corresponding to the type of rod configuration: "M" is for a main rod configuration, defined as a single rod spanning the osteotomy. "L" is for linked rod configurations, defined as 2 rods directly connected to each other at the osteotomy site. "S" is for satellite rod configurations, which were defined as a short rod independent of the main rod with anchors above and below the 3CO. "A" is for accessory rods, defined as an additional rod across the 3CO attached to main rods but not attached to any anchors across the osteotomy site. "I" is for intercalary rod configurations, defined as a rod connecting 2 separate constructs across the 3CO, without the intercalary rod itself attached to any anchors across the osteotomy site. The intra- and interobserver reliability of this classification system was determined. RESULTS: A sample estimation for validation assuming two readers and 35 subjects results in a two-sided 95% confidence interval with a width of 0.19 and a kappa value of 0.8 (SD 0.3). The Fleiss kappa coefficient (κ) was used to calculate the degree of agreement between interrater and intraobserver reliability. The interrater kappa coefficient was 0.3, and the intrarater kappa coefficient was 0.63 (good reliability). This scenario represents a high degree of agreement despite a low kappa coefficient. Correct observations by both observers were 34 of 35 and 33 of 35 at both time points. Misclassification was related to difficulty in determining connectors versus anchors. CONCLUSIONS: MRCs across 3COs have variable rod configurations. Currently, no classification system or agreement on nomenclature exists to define the configuration of rods across 3COs. The authors present a new, comprehensive MRC classification system with good inter- and intraobserver reliability and a high degree of agreement that allows for a standardized description of MRCs across 3COs.

Preoperative patient expectations and pain improvement after adult spinal deformity surgery.

OBJECTIVE: Patients' expectations for pain relief are associated with patient-reported outcomes after treatment, although this has not been examined in patients with adult spinal deformity (ASD). The aim of this study was to identify associations between patients' preoperative expectations for pain relief after ASD surgery and patient-reported pain at the 2-year follow-up. METHODS: The authors analyzed surgically treated ASD patients at a single institution who completed a survey question about expectations for back pain relief. Five ordinal answer choices to "I expect my back pain to improve" were used to categorize patients as having low or high expectations. Back pain was measured using the 10-point numeric rating scale (NRS) and Scoliosis Research Society-22r (SRS-22r) patient survey. Preoperative and postoperative pain were compared using analysis of covariance. RESULTS: Of 140 ASD patients eligible for 2-year follow-up, 105 patients (77 women) had pre- and postoperative data on patient expectations, 85 of whom had high expectations. The mean patient age was 59 ± 12 years, and 46 patients (44%) had undergone previous spine surgery. The high-expectations and low-expectations groups had similar baseline demographic and clinical characteristics (p > 0.05), except for lower SRS-22r mental health scores in those with low expectations. After controlling for baseline characteristics and mental health, the mean postoperative NRS score was significantly better (lower) in the high-expectations group (3.5 ± 3.5) than in the low-expectations group (5.4 ± 3.7) (p = 0.049). The mean postoperative SRS-22r pain score was significantly better (higher) in the high-expectations group (3.3 ± 1.1) than in the low-expectations group (2.6 ± 0.94) (p = 0.019). CONCLUSIONS: Despite similar baseline characteristics, patients with high preoperative expectations for back pain relief reported less pain 2 years after ASD surgery than patients with low preoperative expectations.

Leptin Potentiates BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells Through the Activation of JAK/STAT Signaling.

Mesenchymal stem cells (MSCs) are multipotent progenitors that have the ability to differentiate into multiple lineages, including bone, cartilage, and fat. We previously demonstrated that the least known bone morphogenetic protein (BMP)9 (also known as growth differentiation factor 2) is one of the potent osteogenic factors that can induce both osteogenic and adipogenic differentiation of MSCs. Nonetheless, the molecular mechanism underlying BMP9 action remains to be fully understood. Leptin is an adipocyte-derived hormone in direct proportion to the amount of body fat, and exerts pleiotropic functions, such as regulating energy metabolism, bone mass, and mineral density. In this study, we investigate the potential effect of leptin signaling on BMP9-induced osteogenic differentiation of MSCs. We found that exogenous leptin potentiated BMP9-induced osteogenic differentiation of MSCs both in vitro and in vivo, while inhibiting BMP9-induced adipogenic differentiation. BMP9 was shown to induce the expression of leptin and leptin receptor in MSCs, while exogenous leptin upregulated BMP9 expression in less differentiated MSCs. Mechanistically, we demonstrated that a blockade of JAK signaling effectively blunted leptin-potentiated osteogenic differentiation induced by BMP9. Taken together, our results strongly suggest that leptin may potentiate BMP9-induced osteogenesis by cross-regulating BMP9 signaling through the JAK/STAT signaling pathway in MSCs. Thus, it is conceivable that a combined use of BMP9 and leptin may be explored as a novel approach to enhancing efficacious bone regeneration and fracture healing.

The Times, They Are A-Changing: Women Entering Academic Orthopedics Today Are Choosing Nonpediatric Fellowships at a Growing Rate.

OBJECTIVE: Pediatrics and hand surgery have historically been the orthopaedic subspecialties with the highest female representations. We sought to identify the gender distribution of orthopedic surgical faculty by subspecialty, geography, and educational background. We hypothesized that the proportion of women entering pediatric orthopaedics has decreased since 1980. DESIGN: The Accreditation Council for Graduate Medical Education was used to generate a list of U.S. orthopedic residencies. Program websites were used to collect data regarding each faculty member's gender, residencies, fellowships, and graduation year. t tests were used to compare quantitative data and Fisher's exact tests to compare categorical data. Significance was defined as p < 0.05. SETTING: Publicly available data from official websites of U.S. orthopedic residencies. PARTICIPANTS: Of 153 residencies, 142 (93%) had accessible faculty lists. RESULTS: Of 3596 orthopedic surgeons, 7.9% were women. Among fellowship-trained faculty, 22% of pediatric orthopedists were women compared with 7.6% of faculty in other orthopedic subspecialties (p < 0.00001). There was a significantly higher percentage of female faculty in the West (13%) than in any other U.S. census region (p < 0.001 vs. Midwest, vs. South, and vs. Northeast). A strong correlation with time was found in number of women completing fellowships other than hand or pediatrics from 1980 to 2014 (R2 = 0.95); a strong inverse correlation with time was found for pediatrics as a percentage of fellowships completed by women during the same period (R2 = 0.94). CONCLUSIONS: Although pediatrics remains the most popular fellowship for female orthopedists, women who enter academic orthopedics are increasingly choosing nonpediatric subspecialties.