Annalise N. Larson

Avascular necrosis most common indication for hip arthroplasty in patients with slipped capital femoral epiphysis

Background Recently, much attention has been focused on the prevention of arthritis after slipped capital femoral epiphysis (SCFE). Little, however, is published on which subset of SCFE patients eventually require hip replacement, how soon arthroplasty is required, and the long-term outcomes after arthroplasty. Methods A hip registry database at a tertiary referral center was searched for all primary hip arthroplasties in patients with a confirmed childhood diagnosis of SCFE. Results From 1954-2007, 38 hips in 33 patients underwent arthroplasty, including total hip arthroplasty (28), hip resurfacing (8), and hemiarthroplasty (2) for the diagnosis of SCFE. During this time period, over 33,000 primary total hip arthroplasties were carried out at our center. Underlying diagnoses included avascular necrosis or chondrolysis in 25 hips and degenerative changes and/or impingement in 13 hips. The slip severity in 20 cases was severe, 4 moderate, 7 mild, and 7 hips had unknown slip severity. Half of the slips (7/14) in the degenerative group were mild or moderate. Fourteen (70%) of the 20 severe slips and 10 (71%) of the 14 acute or acute-on-chronic slips presented for arthroplasty with the diagnosis of avascular necrosis. Avascular necrosis was associated with a severe slip (P=0.03) and an acute or acute-on-chronic presentation (P=0.008). With the exception of 2 mild slips treated nonoperatively, all slips underwent either pin fixation (27) or primary osteotomy (9). Mean time from slip to arthroplasty was 7.4 years in patients with AVN or chondrolysis, compared with 23.6 years in patients with degenerative change (P<0.0002). Mean age at arthroplasty was 20 years in the AVN or chondrolysis group compared with 38 years in the degenerative group (P<0.0001). Sixteen hips required revision arthroplasty at a mean of 11.6 years postoperatively, most commonly for component loosening and/or polyethylene wear. Kaplan Meier 5-year survival free from revision for all causes was 87% overall and 95% in the total hip arthroplasty subset. Conclusions The majority of hip arthroplasties in patients with slipped capital femoral epiphysis were carried out for the indication of avascular necrosis rather than degenerative changes related to femoroacetabular impingement. We found a moderately high revision rate in SCFE patients undergoing total hip arthroplasty or other joint replacement. Level of Evidence IV, case series.

Iatrogenic thoracic outlet syndrome secondary to vertical expandable prosthetic titanium rib expansion thoracoplasty: pathogenesis and strategies for prevention/treatment.

Background: An innovative treatment for thoracic insufficiency syndrome involves a vertical expansion of the chest wall through a horizontal chest wall osteotomy maintained by a distraction device (vertical expandable prosthetic titanium rib or VEPTR). Upper-extremity neurovascular dysfunction has been reported after expansion. The purposes of this study are to identify potential etiologies for compression of the brachial plexus after expansion thoracoplasty and to suggest strategies to reduce the incidence of this complication. Methods: A simulated VEPTR procedure was performed on 8 fresh cadaveric specimens. Manometric measurements were taken in the 3 anatomic regions of the thoracic outlet after thoracotomy and rib distraction were performed. Confirmation of the location of compression was performed by placing barium-impregnated putty along the course of the brachial plexus and evaluating the effect of expansion using video fluoroscopy. A midclavicular osteotomy was then performed and video fluoroscopy repeated. Results: A 20% increase in pressure was seen in the costoclavicular region of the thoracic outlet after expansion. Constriction of the midclavicular region of the thoracic outlet between the first rib and clavicle was confirmed using the putty model. Midclavicular osteotomy alleviated this region of compression. Conclusions: Expansion thoracoplasty with the VEPTR procedure causes increased pressure in the costoclavicular region of the thoracic outlet. A midclavicular osteotomy may be one method to alleviate thoracic outlet narrowing after VEPTR procedure, although the short- and long-term effects of this is procedure is not known. Clinical Relevance: Our model supports an iatrogenic thoracic outlet syndrome caused by expansion thoracoplasty. Based on our data as well as a review of the literature, we recommend intraoperative neurologic monitoring of the ipsilateral upper extremity during the VEPTR procedure.

Risk Factors for 30-Day Unplanned Readmission and Major Perioperative Complications After Spine Fusion Surgery in Adults: A Review of the National Surgical Quality Improvement Program Database.

Study Design. Retrospective review of a prospective cohort. Objective. The aim of the study was to determine the patient characteristics and surgical procedure factors related to increased rates of 30-day unplanned readmission and major perioperative complications after spinal fusion surgery, and the association between unplanned readmission and major complications. Summary of Background Data. Reducing unplanned readmissions can reduce the cost of healthcare. Payers are implementing penalties for 30-day readmissions after discharge. There is limited data regarding the current rates and risk factors for unplanned readmission and major complications related to spinal fusion surgery. Methods. Spine fusion patients were identified using the 2012 and 2013 American College of Surgeons National Surgical Quality Improvement Program Participant User File. Rates of readmissions within 30 days after spine fusion surgery were calculated using the person-years method. Cox proportional hazards models were used to assess the independent associations of spine surgical procedure types, diagnoses, patient profiles, and major perioperative complications with unplanned related readmissions. Independent risk factors for major complications were assessed by multivariable logistic regression. Results. Of the 18,602 identified patients, there was a 5.2% overall major perioperative complication rate. There was a rate of 4.4% per 30 person-days for unplanned readmissions related to index surgery. Independent risk factors for both readmissions and major perioperative complications included combined anterior and posterior surgery, diagnosis of solitary tumor, older age, and higher American Society of Anesthesiologists class. Patients with deep/organ surgical site infection carried higher risk of having unplanned readmission, followed by pulmonary embolism, acute renal failure, and stroke/cerebral vascular accident with neurological deficit. Conclusion. This study provides benchmark rates of 30-day readmission based on diagnosis and procedure codes from a high-quality database for adult spinal fusion patients and showed increased rates of 30-day unplanned readmission and major perioperative complications for patients with specific risk factors. Targeted preoperative planning on modifiable risk factors with proportional reimbursement may promote higher-quality healthcare. Level of Evidence: 3

RNA-seq analysis of clinical-grade osteochondral allografts reveals activation of early response genes

Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA‐seq) and real‐time reverse transcription quantitative polymerase chain reaction (RT‐qPCR) to assess genome‐wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM‐related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation.

Surgical Hip Dislocation is Safe and Effective Following Acute Traumatic Hip Instability in the Adolescent.

Background: A traumatic hip dislocation in the pediatric patient is a rare but potentially catastrophic injury. The purpose of this study was to review our early clinical results and radiographic morphology of hips treated with a surgical hip dislocation (SHD) approach for intra-articular hip pathology resulting from traumatic instability in pediatric and adolescent patients. Methods: This is a retrospective analysis of a consecutive series of patients presenting with nonconcentric reduction after traumatic hip instability. All patients were treated with a transtrochanteric SHD with concomitant procedures based on intra-articular findings. Radiographic evaluations and Harris Hip Scores were completed at final follow-up. Results: Eleven male patients, mean age of 12.3 years (range, 9.3 to 16.1 y) and mean body mass index 19.6 kg/m2 (range, 15.4 to 28.0 kg/m2). Intraoperative findings included: labral tear (8), femoral cartilage injury (5), acetabular rim fracture (4), acetabular cartilage delamination (3), loose body (2), and femoral head osteochondral fracture (1). Postoperatively, 1 patient developed a transient peroneal nerve palsy. At a mean 24.5 months (range, 12.0 to 48.1 mo) postoperatively, no hips have radiographic evidence of osteonecrosis. The mean lateral center edge angle was 20 degrees (range, 9 to 38 degrees) with 6 hips of <20 degrees; mean acetabular index 9 degrees (range, −2 to 23 degrees) with 5 hips of >10 degrees; mean &agr;-angle 56 degrees (range, 48 to 62 degrees) with 6 hips of >55 degrees; mean acetabular version 12 degrees (range, 8 to 16 degrees) with 8 hips of <15 degrees. At 1-year follow-up, the mean Harris Hip Score was 95.8 (range, 84.7 to 100). Conclusions: Early results suggest that SHD is a safe approach to treat an incomplete reduction following posterior hip instability and is effective for identification and treatment of acute intra-articular pathology. Acetabular dysplasia, relative acetabular retroversion, and/or decreased femoral offset may be risk factors for posterior hip instability in adolescents. Level of Evidence: Level IV.

A critical appraisal of the first-year experience of 5 pediatric orthopaedic surgeons.

Background: The transition into practice following a fellowship in pediatric orthopaedics is challenging. This study seeks to describe the first-year experiences of 5 pediatric orthopaedists. Methods: An Institutional Review Board-approved retrospective review was conducted of 5 pediatric orthopaedic surgeons’ first year in practice. All were fellowship trained and practiced at private or academic subspecialty groups. Clinical volume, payor mix, surgical cases, as well as complications were evaluated. Results: A total of 1172 surgical procedures were available for review. Surgeons performed an average of 234 cases with a mean case load of 19.5 procedures per month. Fracture care and surgical management of infection represented the largest number of procedures. 42.3% of patients were covered by government insurance or were uninsured. Surgeons saw an average of 30.5 new patients per week in clinic. Of these, 10.7% of patients were scheduled for an elective surgical case. A sample of clinical practice revealed that 41.3% of patients were covered by government or no insurance. 17.8% of surgical patients sustained a complication with the majority being minor or expected. 18.8% of complications were major and required repeat operation. Complications peaked in the fourth month of practice. Conclusions: Although clinical and surgical volumes can vary during the first year of practice, fracture care and surgical management of infection represent the majority of operative cases. A large portion of surgical volume results from emergent care, whereas elective cases are more elusive with only 1 in 10 elective patients resulting in surgical treatment. Despite a significant number of untoward events related to surgery, major surgical complications are uncommon in the first year of practice. Clinical Relevance: The majority of surgical cases in the first year of practice are due to trauma and infection. A high volume of patients must be seen to establish a practice, particularly given the high rate of Medicaid patients. These figures provide benchmarks to guide training programs and to establish realistic expectations for new pediatric orthopaedic surgeons and their partners.

Hypoxia‐related microRNA‐210 is a diagnostic marker for discriminating osteoblastoma and osteosarcoma

Osteoblastoma is a benign bone tumor that can often be difficult to distinguish from malignant osteosarcoma. Because misdiagnosis can result in unfavorable clinical outcomes, we have investigated microRNAs as potential diagnostic biomarkers for distinguishing between these two tumor types. Next generation RNA sequencing was used as an expression screen to evaluate >2,000 microRNAs present in tissue derived from rare formalin fixed paraffin embedded (FFPE) archival tumor specimens. MicroRNAs displaying the greatest ability to discriminate between these two tumors were validated on an independent tumor set, using qPCR assays. Initial screening by RNA‐seq identified four microRNA biomarker candidates. Expression of three miRNAs (miR‐451a, miR‐144‐3p, miR‐486‐5p) was higher in osteoblastoma, while the miR‐210 was elevated in osteosarcoma. Validation of these microRNAs on an independent data set of 22 tumor specimens by qPCR revealed that miR‐210 is the most discriminating marker. This microRNA displays low levels of expression across all of the osteoblastoma specimens and robust expression in the majority of the osteosarcoma specimens. Application of these biomarkers to a clinical test case showed that these microRNA biomarkers permit re‐classification of a misdiagnosed FFPE tumor sample from osteoblastoma to osteosarcoma. Our findings establish that the hypoxia‐related miR‐210 is a discriminatory marker that distinguishes between osteoblastoma and osteosarcoma. This discovery provides a complementary molecular approach to support pathological classification of two diagnostically challenging musculoskeletal tumors. Because miR‐210 is linked to the cellular hypoxia response, its detection may be linked to well‐established pro‐angiogenic and metastatic roles of hypoxia in osteosarcomas and other tumor cell types.

RNA sequencing identifies gene regulatory networks controlling extracellular matrix synthesis in intervertebral disk tissues: RNA-SEQ CHARACTERIZATION OF INTERVERTEBRAL DISK

Degenerative disk disease of the spine is a major cause of back pain and disability. Optimization of regenerative medical therapies for degenerative disk disease requires a deep mechanistic understanding of the factors controlling the structural integrity of spinal tissues. In this investigation, we sought to identify candidate regulatory genes controlling extracellular matrix synthesis in spinal tissues. To achieve this goal we performed high throughput next generation RNA sequencing on 39 annulus fibrosus and 21 nucleus pulposus human tissue samples. Specimens were collected from patients undergoing surgical discectomy for the treatment of degenerative disk disease. Our studies identified associations between extracellular matrix genes, growth factors, and other important regulatory molecules. The fibrous matrix characteristic of annulus fibrosus was associated with expression of the growth factors platelet derived growth factor beta (PDGFB), vascular endothelial growth factor C (VEGFC), and fibroblast growth factor 9 (FGF9). Additionally we observed high expression of multiple signaling proteins involved in the NOTCH and WNT signaling cascades. Nucleus pulposus extracellular matrix related genes were associated with the expression of numerous diffusible growth factors largely associated with the transforming growth signaling cascade, including transforming factor alpha (TGFA), inhibin alpha (INHA), inhibin beta A (INHBA), bone morphogenetic proteins (BMP2, BMP6), and others. Clinical significance: this investigation provides important data on extracellular matrix gene regulatory networks in disk tissues. This information can be used to optimize pharmacologic, stem cell, and tissue engineering strategies for regeneration of the intervertebral disk and the treatment of back pain.

Pediatric orthopaedic trauma and associated injuries of snowmobile, ATV, and dirtbike accidents: a 19-year experience at a Level 1 pediatric trauma center

Objectives: The purpose of this study was to evaluate the type and severity of orthopaedic and associated injuries for snowmobile, All-terrain vehicles (ATV) and motorized dirtbike accidents in a pediatric patient population. Methods: A total of 758 patients who presented following either snowmobile (n=87), ATV-related (n=308) or dirtbike (n=363)-related trauma at our institution between 1996 and 2015 were retrospectively reviewed. Results: A total of 441 axial and appendicular fractures occurred requiring 533 procedures. Snowmobile and dirtbike accidents were associated with a higher rate of fractures (63%, 64%) than the ATV group (50%) (P=0.0008). Snowmobile injuries had the highest rate of spinal (23%) and lower extremity fractures (53%) (P=0.0004). Snowmobile and dirtbike cohorts had higher rate of femur fractures (22%, 17%, P=0.001) whereas the ATV cohort had higher rates of upper extremity (18%), hand (11%), scapula (4.6%), and open fractures (28.6%) (P<0.01). Head trauma was the most commonly associated injury in 275 patients with the highest rate in the ATV group (44%) who also had the highest rate of no helmet use (76%). Snowmobile and ATV patients had higher Injury Severity Score (11.3, 9.6) than dirtbike patients (7.8) (P=0.001). ATV patients were found to be younger (11.8 y) compared with snowmobile (13.2 y) and dirtbike (13.5 y) (P<0.01). Conclusions: Pediatric snowmobile, ATV and dirtbike accidents result in severe orthopaedic and associated injuries with each vehicle demonstrating significantly different injury patterns. Injury prevention should focus on improved safety mechanisms, protective gear, safe areas for off-road vehicle use and strict laws with minimum age requirements Level of Evidence: Level IV.

High-energy Pediatric Scapula Fractures and Their Associated Injuries

Objectives: The purpose of this study was to evaluate pediatric scapula fractures occurring in high-energy motorized vehicle accidents and their associated injury patterns in a pediatric patient population. Methods: One thousand nine hundred sixty-eight pediatric patients who presented after either on-road or off-road motorized vehicle accidents between 1996 and 2015 were retrospectively reviewed. Thirty-eight patients were found to have scapula fractures and the remaining 1930 were identified as controls. Results: A total of 39 scapula fractures occurred in 38 patients. The most common pattern was the AO/OTA 14-A3 (n=32), followed by 14-A2 (n=5), 14-B1 (n=1), and 14-C2 (n=1). Scapula fracture patients experienced higher rate of spine fractures (42% vs. 18%, P=0.001), skull fractures (26% vs. 12%, P=0.02), rib fractures (40% vs. 7.6%, P<0.0001), clavicle fractures (34% vs. 6%, P<0.0001), and upper extremity fractures (58% vs. 21%, P<0.0001) compared with controls. Scapula fracture patients had higher Injury Severity Scores (22.1 vs. 10.8, P<0.0001), thoracic injury (79% vs. 31%, P<0.0001), intracranial hemorrhage (32% vs. 15%, P=0.012), pneumothorax (55% vs. 8%, P<0.0001), and lung contusion (63% vs. 12%, P<0.0001). No difference in mortality was observed for scapula and control patients (5% vs. 2%, P=0.302). Conclusions: Pediatric scapula fractures were not associated with higher mortality rates in this series but were associated with significant morbidity as demonstrated by high rates of associated intracranial hemorrhage, skull fractures, thoracic injury, upper extremity fractures, and spine fractures compared with control patients. Surgeons who care for pediatric trauma patients should view scapula fractures as an indicator for more significant injuries. Level of Evidence: Level III.