Potential endpoints for assessment of bone health in persons with neurofibromatosis type 1.

Neurofibromatosis type 1 is a genetic syndrome characterized by a wide variety of tumor and non-tumor manifestations. Bone-related issues, such as scoliosis, tibial dysplasia, and low bone mineral density, are a significant source of morbidity for this population with limited treatment options. Some of the challenges to developing such treatments include the lack of consensus regarding the optimal methods to assess bone health in neurofibromatosis type 1 and limited data regarding the natural history of these manifestations. In this review, the Functional Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration: (1) presents the available techniques for measuring overall bone health and metabolism in persons with neurofibromatosis type 1, (2) reviews data for use of each of these measures in the neurofibromatosis type 1 population, and (3) describes the strengths and limitations for each method as they might be used in clinical trials targeting neurofibromatosis type 1 bone manifestations. The Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration supports the development of a prospective, longitudinal natural history study focusing on the bone-related manifestations and relevant biomarkers of neurofibromatosis type 1. In addition, we suggest that the neurofibromatosis type 1 research community consider adding the less burdensome measurements of bone health as exploratory endpoints in ongoing or planned clinical trials for other neurofibromatosis type 1 manifestations to expand knowledge in the field.

Guided Growth to Treat Anterolateral Tibial Bowing Associated with Congenital Pseudarthrosis of the Tibia.

BACKGROUND: Anterolateral tibial bowing associated with congenital tibial pseudarthrosis occurs often in patients with neurofibromatosis type 1 and results from the inability of the fractured bone to unite, leading to persistent nonunion, abnormal bone growth, and further bowing of the tibia. Current surgical and nonsurgical approaches demonstrate persistent nonunion or refracture, often resulting in amputation. METHODS: This report describes the management of 3 patients with anterolateral tibial bowing and NF1 who underwent distal tibia-guided growth. RESULTS: The patients had an average age of 1.6 years at initial operation, with a total of 3 to 4 surgeries over an average of 2.1 years. The latest follow-up on all patients is included, at a mean of 5.1 years after the initial operation. All 3 patients experienced substantial functional improvement and improved alignment of the mechanical axis of the tibia. One patient has experienced refracture. CONCLUSIONS: Our study indicates that guided growth can serve as an additional surgical option to improve ALTB and potentially reduce the risk of fracture and pseudarthrosis by restoring normal mechanical alignment. LEVEL OF EVIDENCE: Level-IV, Case Series.

Preliminary Study of Motion Preservation Following Posterior Dynamic Distraction Device in Adolescent Idiopathic Scoliosis Patients.

BACKGROUND: Motion-sparing scoliosis surgeries such as the posterior dynamic distraction device (PDDD) are slowly increasing in use. However, there is limited clinical data documenting postoperative motion across the PDDD construct. With this cohort study, we aim to measure sagittal and coronal motion following PDDD. We hypothesize coronal and sagittal spinal motion will be partially preserved across the construct. METHODS: Retrospective review of prospectively collected data. Preoperative and minimum 1-year postoperative coronal range of motion across the instrumented levels was compared. Available flexion/extension radiographs were evaluated postoperatively to assess sagittal arc of motion. Radiographs from latest follow-up were used. RESULTS: At a mean of 1.9 years (1 to 5 y), flexibility radiographs were available on 29 patients treated with PDDD (17 thoracic, 12 lumbar). Mean age at surgery was 16 years (12 to 25). Postoperative coronal arc of motion in PDDD patients was 11 degrees (3 to 19 degrees) in the thoracic spine and 10 degrees (0 to 28 degrees) in the lumbar spine. Compared with preoperative motion, the thoracic arc of motion was maintained by 33% (35 to 11 degrees) and lumbar motion was maintained by 30% (34 to 10 degrees). Flexion-extension radiographs were available on 7 patients. Sagittal arc for the upper instrumented vertebral end plate to the lower instrumented vertebral endplate of the cohort was 10 degrees in the thoracic spine (6 to 18) and 14 degrees in the lumbar spine (5 to 21). Sagittal measurements for the changes in the arc of the upper and lower screws on the construct were 4 degrees in the thoracic group (2 to 8) and 9 degrees in the lumbar group (2 to 17). By latest follow-up 11 patients (38%) underwent reoperation, with most cases due to implant breakage (N=4, 14%), extender misalignment (N=2, 7%), and screw misplacement (N=2, 7%). CONCLUSION: At mean 1.9 years postoperatively, PDDD preserves measurable spinal motion over the construct both in the coronal and the sagittal plane without evidence for autofusion. Coronal arc of motion averages 10 to 12 degrees and sagittal arc of motion ranged from 4 to 14 degrees, although this varies by patient. This study confirms that PDDD for pediatric scoliosis preserves a measurable degree of postoperative flexibility both in the sagittal and coronal planes. LEVEL OF EVIDENCE: Level II-therapeutic study.

Institutional Variability in Anesthesia Time for Mehta Casting in Early-Onset Scoliosis (EOS).

PURPOSE: Mehta casting is a potentially curative intervention for early-onset scoliosis (EOS) that typically requires multiple anesthetics. The Food and Drug Administration (FDA) reported that >3 hours of anesthesia under the age of 3 years old may alter brain development; however, no standard exists for the duration of anesthesia during casting. The purpose of this study is to quantify the variability in anesthesia during Mehta casting. We hypothesize that significant institutional variability exists and may be attributed to modifiable factors. METHODS: An EOS registry was used to identify patients who underwent at least one Mehta casting procedure. Anesthesia exposure was quantified, and site variability was assessed by patient characteristics, cast placement, procedure type, and equipment used. RESULTS: Our cohort consisted of 208 patients from 5 institutions (age 2.6±1.4 y). There were 1097 Mehta casting procedures, with 5.4±3.6 castings per patient. Of these patients, 106 (51%) were female, with an average age of 2.11±1.29 years old at the time casting was initiated. Patient etiologies included 154 idiopathic (74.0%), 22 syndromic (10.6%), 18 congenital (8.7%), 11 neuromuscular (5.3%), and 3 unknown (1.4%). Anesthesia time was 69±31 minutes and varied significantly between sites (59±14 to 117±46 min; P <0.001). Cumulative anesthesia time for patients under 3 years was 320±197 minutes with 120/161 (74.5%) patients exceeding 3 hours. Anesthesia time was lower after the FDA warning in 2016 compared with pre-2016 (71±30 vs. 66±32, P =0.008). CONCLUSIONS: Patients undergoing Mehta casting are at significant risk of exceeding 3 hours of anesthesia, which the FDA has stated may be harmful for children <3 years. Significant site variability indicates that standardization protocols should be developed to encourage best practices and minimize anesthetic times. LEVEL OF EVIDENCE: Prognostic Level II.

Artificial intelligence-based three-dimensional templating for total joint arthroplasty planning: a scoping review.

PURPOSE: The purpose of this review is to evaluate the current status of research on the application of artificial intelligence (AI)-based three-dimensional (3D) templating in preoperative planning of total joint arthroplasty. METHODS: This scoping review followed the PRISMA, PRISMA-ScR guidelines, and five stage methodological framework for scoping reviews. Studies of patients undergoing primary or revision joint arthroplasty surgery that utilised AI-based 3D templating for surgical planning were included. Outcome measures included dataset and model development characteristics, AI performance metrics, and time performance. After AI-based 3D planning, the accuracy of component size and placement estimation and postoperative outcome data were collected. RESULTS: Nine studies satisfied inclusion criteria including a focus on computed tomography (CT) or magnetic resonance imaging (MRI)-based AI templating for use in hip or knee arthroplasty. AI-based 3D templating systems reduced surgical planning time and improved implant size/position and imaging feature estimation compared to conventional radiographic templating. Several components of data processing and model development and testing were insufficiently covered in the studies included in this scoping review. CONCLUSIONS: AI-based 3D templating systems have the potential to improve preoperative planning for joint arthroplasty surgery. This technology offers more accurate and personalized preoperative planning, which has potential to improve functional outcomes for patients. However, deficiencies in several key areas, including data handling, model development, and testing, can potentially hinder the reproducibility and reliability of the methods proposed. As such, further research is needed to definitively evaluate the efficacy and feasibility of these systems.

Operative differences for posterior spinal fusion after vertebral body tethering: Are we fusing more levels in the end?

PURPOSE: Little is known about the perioperative characteristics associated with a posterior spinal fusion (PSF) in adolescent idiopathic scoliosis patients previously treated with vertebral body tethering (VBT). We aimed to determine if operative time, estimated blood loss, postoperative length of stay, instrumentation type, and implant density differed in patients that received a PSF (i.e., PSF-Only) or a PSF following a failed VBT (i.e., PSF-VBT). METHODS: We retrospectively assessed matched cohort data (PSF-VBT = 22; PSF-Only = 22) from two multi-center registries. We obtained: (1) operative time, (2) estimated blood loss, (3) postoperative length of stay, (4) instrumentation type, and (5) implant density. Theoretical fusion levels prior to the index procedure were obtained for PSF-VBT and compared to the actual levels fused. RESULTS: We observed no difference in operative time, estimated blood loss, or postoperative length of stay. Instrumentation type was all-screw in PSF-Only and varied in PSF-VBT with nearly 25% of patients exhibiting a hybrid construct. There was no added benefit to removing anterior instrumentation prior to fusion; however, implant density was higher in PSF-Only (1.9 ± 0.2) than when compared to PSF-VBT (1.7 ± 0.3). An additional two levels were fused in 50% of PSF-VBT patients, most of which were added to the distal end of the construct. CONCLUSIONS: We found that operative time, estimated blood loss, and postoperative length of stay were similar in both cohorts; however, the length of the fusion construct in PSF-VBT is likely to be two levels longer when a failed VBT is converted to a PSF.

Minimum 5-Year Results of Elongation Derotation Flexion Casting for Early Onset Scoliosis: The Story Is Not Over Until Skeletal Maturity.

BACKGROUND: Early conservative treatment for patients with idiopathic infantile scoliosis (IIS) with elongation derotation flexion (EDF) casting and subsequent serial bracing has become widely utilized. However, the long-term outcomes of patients treated with EDF casting are limited. METHODS: We performed a retrospective chart review of all patients who had undergone serial elongation derotation flexion casting and subsequent bracing for scoliosis presenting at a single large tertiary center. All patients were followed for a minimum of 5 years or until surgical intervention. RESULTS: Our study included 21 patients diagnosed with IIS and treated with EDF casting. At a mean 7-year follow-up, 13 of the 21 patients were considered successfully treated with a mean final major coronal curvature of 9 degrees compared to a pretreatment coronal curve of 36 degrees. These patients, on average, began casting at 1.3 years old and spent 1 year in a cast. Patients that did not have substantial improvement began casting at mean 4 years old and remained in a cast for 0.8 years. Three patients initially had substantial improvement with the correction to <20 degrees at a mean age of 7; however, their curves worsened in adolescence with poor brace compliance. All 3 patients will require surgical intervention. Of the patients not successfully treated with casting, 7 required surgery at a mean 8.2 years of age, 4.3 years after initiation of casting. A significant predictor of treatment failure was older age of cast initiation ( P <0.001). CONCLUSIONS: EDF casting can be an effective cure for IIS patients if initiated at a young age with 15 of 21 patients successfully treated (76%). However, 3 patients had a recurrence in adolescence resulting in an overall success rate of only 62%. Casting should be initiated early to maximize the likelihood of treatment success and periodic monitoring should be continued through skeletal maturity as recurrence during adolescence can occur.

Does Shorter Time to Treatment of Pediatric Supracondylar Humerus Fractures Impact Clinical Outcomes?

BACKGROUND: Treatment of supracondylar humerus (SCH) fractures within 18 hours of presentation is a tracked quality metric for ranking of pediatric hospitals. This is in contrast with literature that shows time to treatment does not impact outcomes in SCH fractures. We aim to determine whether an 18-hour cutoff for pediatric supracondylar humerus fracture treatment is clinically significant by comparing the complication risks ofpatients on either side of this timepoint. Our hypothesis is that there will be no statistically significant differences based on time to treatment. METHODS: A retrospective review of clinical outcomes was performed for 472 pediatric patients who underwent surgical management of isolated supracondylar humerus fractures between 1997 and 2022 at a single level I pediatric trauma hospital. The cohort was split based on time to surgery (within or ≥18 h from Emergency Department admission). RESULTS: Surgical treatment occurred within 18 hours of arrival in 435 (92.2%) patients and after 18 hours in 37 (7.8%) patients. Mean age was 5.6±2.2 years and 51.5% of patients were female. Gartland fracture classification was type II [n=152 (32.3%)], type III [n=284 (60.3%)], type IV [n=13 (2.8%)], or flexion-type [n=18 (3.8%)]. There were no differences in demographic characteristics or fracture classification between cohorts. Fractures in the ≥18-hour cohort were treated more commonly with 2 pins (62.2% vs. 38.5%, P =0.04). There were no statistically significant differences in open versus closed reduction, utilization of medial pins, or postoperative immobilization between cohorts. We were unable to detect any differences in postoperative complications, including non-union, delayed union, stiffness, malunion, loss of reduction, iatrogenic nerve injury, or infection. This remained true when type II fractures were excluded. CONCLUSIONS: Using an arbitrary time cutoff of <18 hours does not influence clinical outcomes in the surgical treatment of SCH fractures. This held true when type II fractures were excluded. For this reason, we recommend modification to the USNWR guidelines to decrease emphasis on time-to-treatment of SCH fractures. LEVEL OF EVIDENCE: Level III.

Creating High Fidelity Synthetic Pelvis Radiographs Using Generative Adversarial Networks: Unlocking the Potential of Deep Learning Models Without Patient Privacy Concerns.

BACKGROUND: In this work, we applied and validated an artificial intelligence technique known as generative adversarial networks (GANs) to create large volumes of high-fidelity synthetic anteroposterior (AP) pelvis radiographs that can enable deep learning (DL)-based image analyses, while ensuring patient privacy. METHODS: AP pelvis radiographs with native hips were gathered from an institutional registry between 1998 and 2018. The data was used to train a model to create 512 × 512 pixel synthetic AP pelvis images. The network was trained on 25 million images produced through augmentation. A set of 100 random images (50/50 real/synthetic) was evaluated by 3 orthopaedic surgeons and 2 radiologists to discern real versus synthetic images. Two models (joint localization and segmentation) were trained using synthetic images and tested on real images. RESULTS: The final model was trained on 37,640 real radiographs (16,782 patients). In a computer assessment of image fidelity, the final model achieved an "excellent" rating. In a blinded review of paired images (1 real, 1 synthetic), orthopaedic surgeon reviewers were unable to correctly identify which image was synthetic (accuracy = 55%, Kappa = 0.11), highlighting synthetic image fidelity. The synthetic and real images showed equivalent performance when they were assessed by established DL models. CONCLUSION: This work shows the ability to use a DL technique to generate a large volume of high-fidelity synthetic pelvis images not discernible from real imaging by computers or experts. These images can be used for cross-institutional sharing and model pretraining, further advancing the performance of DL models without risk to patient data safety. LEVEL OF EVIDENCE: Level III.

Consensus-Based Best Practice Guidelines for the Management of Spinal Deformity and Associated Tumors in Pediatric Neurofibromatosis Type 1: Screening and Surveillance, Surgical Intervention, and Medical Therapy.

BACKGROUND: Spinal conditions, such as scoliosis and spinal tumors, are prevalent in neurofibromatosis type 1 (NF1). Despite the recognized importance of their early detection and treatment, there remain knowledge gaps in how to approach these manifestations. The purpose of this study was to utilize the experience of a multidisciplinary committee of experts to establish consensus-based best practice guidelines (BPGs) for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric patients with NF1. METHODS: Using the results of a prior systematic review, 10 key questions that required further assessment were first identified. A committee of 20 experts across medical specialties was then chosen based on their clinical experience with spinal deformity and tumors in NF1. These were 9 orthopaedic surgeons, 4 neuro-oncologists/oncologists, 3 neurosurgeons, 2 neurologists, 1 pulmonologist, and 1 clinical geneticist. An initial online survey on current practices and opinions was conducted, followed by 2 additional surveys via a formal consensus-based modified Delphi method. The final survey involved voting on agreement or disagreement with 35 recommendations. Items reaching consensus (≥70% agreement or disagreement) were included in the final BPGs. RESULTS: Consensus was reached for 30 total recommendations on the management of spinal deformity and tumors in NF1. These were 11 recommendations on screening and surveillance, 16 on surgical intervention, and 3 on medical therapy. Five recommendations did not achieve consensus and were excluded from the BPGs. CONCLUSION: We present a set of consensus-based BPGs comprised of 30 recommendations for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric NF1.

Navigation Options for Spinal Surgeons: State of the Art 2021.

The use of navigation in spinal surgery has been increasing over the past decade. There are three primary types of navigation in spinal surgery: three-dimensional image-based computer-assisted navigation, robot-assisted navigation, and three-dimensional printed patient-specific drill guides for navigation. All three have demonstrated increased accuracy in placement of spinal instrumentation versus freehand or fluoroscopic-assisted techniques. Each has unique preoperative and intraoperative technical considerations. All three typically rely on three-dimensional imaging and will have varied radiation exposure to the patient and surgical staff based on specific imaging settings used. Navigation options are continually improving and are expected to broaden efficiency, accuracy, and indications in the future.

Innovation With Ethics in Pediatric Orthopaedics.

Surgeons should thoughtfully consider whether to introduce a new procedure into their practice. Considerations include the severity of the condition, potential risk of harm, treatment alternatives, patient population, ability to appropriately consent patient/families, and available clinical and institutional resources as well as published evidence and regulatory status. Whenever possible, new procedures should be standardized, studied, and reported upon so that the greater community can learn from experience and refine the indications to minimize risks for future patients. Small scale innovation can readily be introduced into practice. Surgeons should always strive to systemically study new procedures so as to be able to assess benefits and effects.

Measurable Lumbar Motion Remains 1 Year After Vertebral Body Tethering.

INTRODUCTION: Vertebral body tethering (VBT) is growing in popularity for skeletally immature patients with scoliosis because of presumed preservation of spinal motion. Although results have shown preserved thoracic motion, there is minimal data to support motion over the lumbar instrumented segments after VBT. The purpose of this study was to analyze the range of motion of the thoracolumbar and lumbar spine after lumbar VBT. METHODS: Retrospective review of patients treated with lumbar VBT underwent low-dose biplanar flexion-extension and lateral bending radiographs at 1 year after surgery to assess motion. Coronal motion at 1 year was compared with preoperative side-bending radiographs. The angle subtended by the screws at the upper instrumented vertebra and lower instrumented vertebra was measured on left-bending and right-bending radiographs to evaluate the coronal arc of motion and was compared with preoperative values over the same levels measured from the end plates. At 1 year postoperatively, the sagittal angle was measured over the instrumented levels on flexion and extension radiographs. RESULTS: Of the 71 scoliosis patients who underwent VBT at our center eligible for 1-year follow-up, 20 had lumbar instrumentation, all of whom had lumbar bending films available at 1 year after surgery. Seven patients had both thoracic and lumbar VBT on the same day and 13 had lumbar or thoracolumbar tether only. Mean age was 13.5±1.9 years. Mean preoperative major coronal curve measured 52+8 degrees (range: 42 to 70) and mean 27 degrees (range: 13 to 40) at latest follow-up. Mean levels instrumented was 8 (range: 5 to 12), with the lowest instrumented level typically L3 (N=14). The mean preoperative coronal arc of motion over the instrumented segments was 38±13 degrees (range: 19 to 73 degrees) and decreased after surgery to a mean arc of 17±7 degrees (range: 7 to 31 degrees). However, 19 of the 20 (95%) had at least a 10-degree coronal arc of motion. Patients maintained on average 46% (range: 22% to 100%) of their preoperative coronal arc of lumbar motion over the instrumented lumbar segments. On flexion-extension lateral radiographs taken at 1 year postoperatively, there was a mean postoperative arc of motion of 30±13 degrees. CONCLUSIONS: Lumbar VBT resulted in preserved flexion and extension motion at 1 year postoperatively. We also noted some preserved coronal plane motion, but this was decreased compared with preoperative values by ~50%. These findings provide proof of concept that some spinal motion is preserved after lumbar VBT in contrast to lumbar fusion where no motion is retained over the instrumented segments.

Intervertebral Disk Health Following Vertebral Body Tethering for Adolescent Idiopathic Scoliosis: A Preliminary Study.

BACKGROUND: Interest in vertebral body tethering (VBT) as an alternative to posterior spinal fusion for adolescent idiopathic scoliosis (AIS) continues to grow. The purpose of this study was to prospectively assess intervertebral disk health on magnetic resonance imaging (MRI) at 1 year following VBT in AIS patients. METHODS: AIS patients were enrolled in a prospective surgeon-sponsored Food and Drug Administration (FDA) Investigational Device Exemption (IDE) Study and underwent MRI at 1-year following VBT. All spanned disks and the untethered disks immediately adjacent to the upper instrumented vertebra and lowest instrumented vertebra levels were evaluated according to Pfirrmann grading criteria. Associations between patient factors and preoperative and postoperative disk health and patient-reported outcomes were evaluated. RESULTS: Twenty-two patients were enrolled with a postoperative MRI (25 curves, 188 disks), and 7 patients (7 curves) had both preoperative and postoperative MRIs (67 disks). The mean age was 12.7 years. Most were Risser 0 (65%) and either Sanders Skeletal Maturity Score 3 (35%) or 4 (53%). In the 7 patients with preoperative and postoperative MRI, the mean Pfirrmann grade of the disks spanned by the tether was 1.88 preoperatively and 2.31 postoperatively ( P =0.0075). No statistically significant differences in preoperative versus postoperative Pfirrmann grade were identified in the disks adjacent to the upper or lower instrumented vertebrae. No association was found between patient-reported outcomes and Pfirrmann grade. CONCLUSION: At 1 year postoperatively, increased degenerative changes in disks spanned by the tether was identifiable on MRI without evidence of adjacent segment disk disease. These changes were not associated with patient-reported outcomes. LEVEL OF EVIDENCE: Level III.

Connective Tissue Disease Patients Maintain Greater Distraction During Growth Friendly Surgery.

STUDY DESIGN: Multicenter retrospective study. BACKGROUND: Recent studies have demonstrated diminishing returns in patients with early onset scoliosis (EOS) undergoing repeated lengthening of growing rods. Little is known about whether this same phenomenon occurs in patients with lax connective tissue disease (CTD). The primary purpose of this study is to investigate whether EOS patients with connective tissue laxity disorders have diminishing returns during growth friendly surgery. METHODS: CTD EOS patients below 10 years old, underwent growth friendly spine surgery with distal anchors and at least 1 proximal spine anchor, and had minimum follow-up of 5 years were included in this study. Coronal T1-S1 height at preindex surgery, postindex, and every available lengthening was assessed. Mean coronal height change during early set distractions and late set distractions were calculated for the cohort. To account for varying distraction intervals, we normalized the distractions by the time interval. The outcome parameter was T1-S1 height gain, mm/year. RESULTS: Twenty-one CTD patients were included in this study. Total coronal height (T1-S1) was 26.7MHCcm before index, 32.2 cm at D1-D3, 34.7 cm at D4-D6, and 36.7 cm at D7-L10. There were no significant differences in coronal height gains between early and late distractions (P=0.70). Moreover, when normalized for time, there was no significant difference in net gain per year at different lengthening time points for the CTD group, P=0.59. CONCLUSION: There is no evidence of diminishing returns in coronal T1-S1 height gain in patients with EOS in the setting of CTD. LEVEL OF EVIDENCE: Level III.

Noninvasive Hemoglobin Monitoring for Postoperative Pediatric Orthopaedic Patients: A Preliminary Study.

BACKGROUND: Hemoglobin (Hgb) levels are frequently checked through venipuncture [invasive hemoglobin (iHgb)] in pediatric orthopaedic patients after high blood loss procedures. This needlestick may causes further anxiety and fear in hospitalized children. Noninvasive hemoglobin (nHgb) monitoring has been effectively utilized in the adult intensive care and postoperative total joint arthroplasty setting. nHgb monitoring has not yet been validated in children for routine postoperative Hgb assessment in pediatric orthopaedics. METHODS: In this prospective study, 46 pediatric orthopaedic patients were enrolled who were undergoing surgery and postoperative standard of care iHgb testing. On postoperative day 1, Hgb levels were obtained through venipuncture and nHgb monitor (Pronto-7; Masimo) within a 2-hour period. Patient preferences, iHgb and nHgb values, time to result, and provider preferences were recorded. Cost data were estimated based on the standard Medicare payment rates for lab services versus the cost of nHgb probe. RESULTS: nHgb results were obtained after 1 attempt in 38 patients (83%), after multiple attempts in 7 patients (15%), and could not be obtained in 1 patient. The mean time to obtain nHgb value was significantly shorter than that to obtain iHgb results (1.3±1.5 vs. 40±18.1 min; P <0.0001). The mean nHgb value was significantly higher than the mean iHgb value (11.7±1.5 vs. 10.6±1.1 g/dL, P <0.0001). nHgb exceeded iHgb by 2 g/dL or more in 12 (26%) patients (2.64±0.9 vs. 0.54±0.84 g/dL; P <0.0001). The concordance correlation coefficient between the 2 Hgb methods was 0.59, indicating moderate agreement. Forty-three (93%) of our patients and 34 (74%) of the care providers preferred nHgb over iHgb if results were equivalent. At our institution, the cost per iHgb monitoring is approximately $28 per blood draw as compared with $5 for nHgb monitoring. Interestingly, no patients required postoperative transfusion during the study period, as asymptomatic patients with no cardiac disease are typically observed unless the Hgb is <6. CONCLUSIONS: nHgb monitoring in postoperative pediatric patients overestimated Hgb levels compared with the standard of care methods; however, nHgb had high patient and provider satisfaction and had moderate agreement with iHgb. As no patients required transfusion, postoperative Hgb checks could likely be discontinued in some portion of our population. LEVEL OF EVIDENCE: Level Ib-Diagnostic study.

Are Serum Ion Levels Elevated in Pediatric Patients With Metal Implants?

BACKGROUND: Previous studies report elevated serum titanium (Ti) levels in children with spinal implants. To provide additional data on this topic, we sought to assess serum ion levels at multiple timepoints in pediatric patients with growing spine devices, spinal fusion instrumentation, and extremity implants placed for fracture treatment. We hypothesized that serum Ti, cobalt (Co), and chromium (Cr) levels would be elevated in pediatric patients with growing spine devices compared with patients with extremity implants. METHODS: Pediatric patients undergoing any primary spine implant placement, those with spine implant revision or removal surgery and patients with other appendicular implant removal had serum Ti, Co, and Cr ion levels drawn at the time of surgery. Fifty-one patients (12 growing spine devices, 13 fusions, and 26 extremity implants) had one set of labs, 31 of whom had labs drawn both preoperatively and postoperatively. Biopsies obtained from tissue specimens at the time of implant revision were analyzed histologically for the presence of metal debris and macrophage activity. RESULTS: Patients with growing spine implants had elevated serum Ti (3.3 vs. 1.9 ng/mL, P=0.01) and Cr levels (1.2 vs. 0.27 ng/mL, P=0.01) in comparison to patients with fusion rods or extremity implants. With respect to patients with extremity implants, patients with growing spine devices had elevated serum Ti (3.3 vs. 0.98 ng/mL, P=0.013), Co (0.63 vs. 0.26 ng/mL, P=0.017), and Cr levels (1.18 vs. 0.26 ng/mL, P=0.005). On matched pairs analysis, patients who had labs drawn before and after spine implantation had significant increase in serum Ti levels (0.57 vs. 3.3 ng/mL, P=0.02). Histology of tissue biopsies adjacent to growing spine implants showed presence of metal debris and increased macrophage activity compared with patients with extremity implants. CONCLUSION: Serum Ti, Co, and Cr levels are elevated in children with spinal implants compared with those with extremity implants, particularly in those with growing spine devices. However, the clinical significance of these findings remains to be determined. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Tiered Guidelines in a Pediatric Orthopaedic Practice Reduce Opioids Prescribed at Discharge.

BACKGROUND: Data regarding opioid prescribing patterns following pediatric orthopaedic procedures is limited. The aim of this work was to evaluate the effects of tiered guidelines for discharge opioid prescriptions following common pediatric orthopaedic procedures. METHODS: Quality improvement project conducted at a single academic institution. Guidelines for discharge opioid prescriptions were implemented January 2018 and established 4 tiers of increasing invasiveness for 28 common pediatric orthopaedic procedures. Patients who underwent these procedures in 2017 comprised the preguideline cohort (N=258), while patients treated in 2019 comprised the postguideline cohort (N=212). Opioid prescriptions were reported as oral morphine equivalents (OMEs). Univariate tests were performed to assess statistically significant differences before and after implementation of the guidelines. RESULTS: There was a significant decrease in OME prescribed between preguideline and postguideline cohorts (median OME 97.5 vs. 37.5). When analyzed according to procedure tiers, tiers 1, 2, and 4 showed significant decreases in OME prescribed between 2017 and 2019. The rate of no opioids prescribed at discharge increased from 13% to 23% between preguideline and postguideline cohorts. The 30-day refill rate did not significantly change. After implementation of guidelines, 91% of all prescriptions were within the guideline parameters, and there was a significant reduction in prescription variability. In tier 4 procedures, median OME prescribed decreased from 375 preguideline to 188 postguideline, but was associated with greater opioid refills within 30 days of discharge (10.2% preguideline vs. 28.8% postguideline). CONCLUSIONS: Tiered guidelines for discharge opioid prescriptions following pediatric orthopaedic procedures can significantly decrease the quantity of opioids prescribed. Furthermore, we noted excellent adherence and no overall increase in the rates of narcotic refills. Such guidelines may improve pediatric orthopaedists' ability to responsibly treat postoperative pain while limiting the distribution of unneeded opioids. LEVEL OF EVIDENCE: Level IV-quality improvement project.

Best Practice Guidelines for Surgical Site Infection in High-risk Pediatric Spine Surgery: Definition, Prevention, Diagnosis, and Treatment.

BACKGROUND: Prior "best practice guidelines" (BPG) have identified strategies to reduce the risk of acute deep surgical site infection (SSI), but there still exists large variability in practice. Further, there is still no consensus on which patients are "high risk" for SSI and how SSI should be diagnosed or treated in pediatric spine surgery. We sought to develop an updated, consensus-based BPG informed by available literature and expert opinion on defining high-SSI risk in pediatric spine surgery and on prevention, diagnosis, and treatment of SSI in this high-risk population. MATERIALS AND METHODS: After a systematic review of the literature, an expert panel of 21 pediatric spine surgeons was selected from the Harms Study Group based on extensive experience in the field of pediatric spine surgery. Using the Delphi process and iterative survey rounds, the expert panel was surveyed for current practices, presented with the systematic review, given the opportunity to voice opinions through a live discussion session and asked to vote regarding preferences privately. Two survey rounds were conducted electronically, after which a live conference was held to present and discuss results. A final electronic survey was then conducted for final voting. Agreement ≥70% was considered consensus. Items near consensus were revised if feasible to achieve consensus in subsequent surveys. RESULTS: Consensus was reached for 17 items for defining high-SSI risk, 17 items for preventing, 6 for diagnosing, and 9 for treating SSI in this high-risk population. After final voting, all 21 experts agreed to the publication and implementation of these items in their practice. CONCLUSIONS: We present a set of updated consensus-based BPGs for defining high-risk and preventing, diagnosing, and treating SSI in high-risk pediatric spine surgery. We believe that this BPG can limit variability in practice and decrease the incidence of SSI in pediatric spine surgery. LEVEL OF EVIDENCE: Not applicable.

Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2.

Bone-stimulatory therapeutics include bone morphogenetic proteins (e.g. BMP2), parathyroid hormone, and antibody-based suppression of WNT antagonists. Inhibition of the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is both bone anabolic and osteoprotective. EZH2 inhibition stimulates key components of bone-stimulatory signaling pathways, including the BMP2 signaling cascade. Because of high costs and adverse effects associated with BMP2 use, here we investigated whether BMP2 dosing can be reduced by co-treatment with EZH2 inhibitors. Co-administration of BMP2 with the EZH2 inhibitor GSK126 enhanced differentiation of murine (MC3T3) osteoblasts, reflected by increased alkaline phosphatase activity, Alizarin Red staining, and expression of bone-related marker genes (e.g. Bglap and Phospho1). Strikingly, co-treatment with BMP2 (10 ng/ml) and GSK126 (5 µm) was synergistic and was as effective as 50 ng/ml BMP2 at inducing MC3T3 osteoblastogenesis. Similarly, the BMP2-GSK126 co-treatment stimulated osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells, reflected by induction of key osteogenic markers (e.g. Osterix/SP7 and IBSP). A combination of BMP2 (300 ng local) and GSK126 (5 µg local and 5 days of 50 mg/kg systemic) yielded more consistent bone healing than single treatments with either compound in a mouse calvarial critical-sized defect model according to results from µCT, histomorphometry, and surgical grading of qualitative X-rays. We conclude that EZH2 inhibition facilitates BMP2-mediated induction of osteogenic differentiation of progenitor cells and maturation of committed osteoblasts. We propose that epigenetic priming, coupled with bone anabolic agents, enhances osteogenesis and could be leveraged in therapeutic strategies to improve bone mass.