Bilateral vertebral body tethering: identifying key factors associated with successful outcomes.

PURPOSE: The treatment of operative double major pediatric spinal deformities (e.g., Lenke 3 or 6) with bilateral vertebral body tethering (VBT) can be significantly more challenging when compared to other deformity patterns (e.g., Lenke 1) or treatment with a posterior spinal fusion. We aimed to identify preoperative and perioperative characteristics that were associated with successful postoperative outcomes in patients treated with both a thoracic and thoracolumbar (e.g., bilateral) tether. METHODS: We retrospectively assessed radiographic and clinical data from patients enrolled in a large multi-center study who had a minimum postoperative follow-up of two years. Standard radiographic parameters were extracted from standing spine and left hand-wrist radiographs at various timepoints. We classified patients based on their preoperative deformity pattern (Primary Thoracic [TP] vs. Primary Thoracolumbar [TLP]) and assessed: (1) deformity balance, (2) tilt of the transitional vertebra, and (3) postoperative success. RESULTS: We analyzed data from thirty-six patients (TP: 19 and TLP: 17). We observed no relationship between deformity balance at first erect and postoperative success (p = 0.354). Patients with a horizontal transitional vertebra at first erect were significantly (p = 0.001) more likely to exhibit a successful outcome when compared to those who exhibited a tilted transitional vertebra (83% vs. 62%). Patients who had TLP were also more likely to exhibit a successful outcome when compared to patients who exhibited TP (76% vs. 50%). CONCLUSION: These data indicate that double major deformities can be successfully treated with VBT, particularly for those who exhibit TLP.

Incidence of Tether Breakage in Anterior Vertebral Body Tethering.

BACKGROUND: Thoracic anterior vertebral body tethering (TAVBT) is an emerging treatment for adolescent idiopathic scoliosis. Tether breakage is a known complication of TAVBT with incompletely known incidence. We aim to define the incidence of tether breakage in patients with adolescent idiopathic scoliosis who undergo TAVBT. The incidence of tether breakage in TAVBT is hypothesized to be high and increase with time postoperatively. METHODS: All patients with right-sided, thoracic curves who underwent TAVBT with at least 2 and up to 3 years of radiographic follow-up were included. Tether breakage between 2 vertebrae was defined a priori as any increase in adjacent screw angle >5 degrees from the minimum over the follow-up period. The presence and timing of tether breakage were noted for each patient. A Kaplan-Meier survival analysis was performed to calculate expected tether breakage up to 36 months. χ 2 analysis was performed to examine the relationship between tether breakage and reoperations. Independent t test was used to compare the average final Cobb angle between cohorts. RESULTS: In total, 208 patients from 10 centers were included in our review. Radiographically identified tether breakage occurred in 75 patients (36%). The initial break occurred at or beyond 24 months in 66 patients (88%). Kaplan-Meier survival analysis estimated the cumulative rate of expected tether breakage to be 19% at 24 months, increasing to 50% at 36 months. Twenty-one patients (28%) with a radiographically identified tether breakage went on to require reoperation, with 9 patients (12%) requiring conversion to posterior spinal fusion. Patients with a radiographically identified tether breakage went on to require conversion to posterior spinal fusion more often than those patients without identified tether breakage (12% vs. 2%; P =0.004). The average major coronal curve angle at final follow-up was significantly larger for patients with radiographically identified tether breakage than for those without tether breakage (31 deg±12 deg vs. 26 deg±12 deg; P =0.002). CONCLUSIONS: The incidence of tether breakage in TAVBT is high, and it is expected to occur in 50% of patients by 36 months postoperatively. LEVEL OF EVIDENCE: Level IV.

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.

Physeal fusion status and lesion size are more important than patient age for healing of juvenile osteochodritis dessicans lesions of the distal femur.

PURPOSE: The purpose of the study was to evaluate the effect of skeletal age and lesion size, location, and grade on the success of nonoperative treatment for juvenile osteochondritis dissecans (OCD). It is hypothesized that skeletal maturity, including a combination of maturation phenotypes, correlates with nonoperative lesion healing. METHODS: The clinical and radiographic data on 52 patients aged 7-20 years treated for OCD of the distal femur between 2010 and 2019 were retrospectively reviewed. Knee radiographs were assessed for number of lesions present and lesion location, size, and stage. Assessments of skeletal maturation were performed on all antero-posterior knee radiographs using the Roche, Wainer, and Thissen (RWT) method. Patients were categorized as healed if they demonstrated no pain on clinical examination. The relationship between skeletal maturity and nonoperative lesion healing was determined using Spearman rank correlations on available variables. RESULTS: Neither chronological nor skeletal age was associated with surgical status (Rho = 0.03, n.s., and Rho = 0.13, n.s., respectively) or the healing status of nonoperatively treated OCD lesions (Rho = 0.44, n.s., and Rho = 0.03, n.s., respectively). Epiphyseal fusion status of the distal femoral physis was moderately correlated with nonoperative healing, but was not statistically significant (lateral femoral physis: Rho = 0.43, p = 0.05; medial femoral physis: Rho = 0.43, n.s.). Lesion length correlated with surgical status (Rho = - 0.38, p = 0.009). CONCLUSION: The extent of fusion of the distal femoral physis (multi-stage grading) may be more strongly correlated with nonoperative healing than other markers of skeletal maturity or chronological age. Clinicians can use this as an additional radiographic sign when considering nonoperative treatment for juvenile OCD lesions in the distal femur. OCD lesion length and physeal fusion status appear to be more important for healing than patient age.

Household Income and Parental Educational Level Affect Post-Operative Opioid Usage in Pediatric Orthopaedic Patients.

Opioid medications are commonly prescribed after pediatric orthopaedic surgery, but there is a critical need to optimize prescribing practice. This study identifies socio-economic characteristics, surgical characteristics, and patient reported psychological factors influencing postoperative opioid use in this population and found that post-operative opioid use in this pediatric orthopaedic population is multifactorial. Physicians should consider implementing protocols for initial opioid prescriptions to cover two to three days following common orthopaedic surgeries for most pediatric patients.

Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study.

PURPOSE: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control. METHODS: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing. RESULTS: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was -2.5 for girls and -3.2 for boys and decreased up to the age 5 years (-5.3 for girls; -4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward. CONCLUSION: This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.

Vertebral Body Tethering: Rationale, Results, and Revision.

Vertebral body tethering is a nonfusion technique for the surgical correction of adolescent idiopathic scoliosis. For skeletally immature patients for whom vertebral body tethering is indicated, it is an alternative option to the gold standard posterior spinal fusion (PSF) and may at least partially preserve motion in instrumented segments of the spine. Benefits of the procedure include the possibility of avoiding the long-term sequelae of PSF such as adjacent segment disease and proximal junctional kyphosis. Recent retrospective case series of vertebral body tethering have shown promising results with correction rates up to 70% but greater variability in outcomes compared with PSF. The complication profile of the procedure also appears to differ from PSF with tether breakage and overcorrection as primary concerns in addition to approach-related complications. Although early outcomes have been promising, additional studies to optimize surgical timing, long-term outcomes, and the possible role of tethering in the more skeletally mature patient are required.

As Vertebral Body Tethering Impacts Missouri, New Technology Grows in the Right Direction.

All eleven-year-old girls want to do is play and be active like every other child her age. Yet, the ability to have a normal childhood for one of our patients became a concern when she and her parents noticed an abnormal lateral curvature in her spine, which was later diagnosed as adolescent idiopathic scoliosis. In February 2014, she presented with a 45° thoracic deformity with a high risk of progression. At that time, the gold standard for the treatment of her deformity was a posterior spinal fusion - a surgical treatment she nor her parents were interested in pursuing. After their initial appointment, her parents scoured the internet and discovered a new non-fusion surgical technique, known as vertebral body tethering, that might correct their daughter's deformity without the need for titanium rods in her spine. In April 2014, that same eleven-year-old girl underwent vertebral body tethering of her main thoracic deformity from T5 to L1 under the care and management of Dr. Daniel Hoernschemeyer, a pediatric orthopaedic surgeon, with the University of Missouri's Department of Orthopaedic Surgery. Today, she is a healthy young adult who is thinking more about prom than about her scoliosis.

Team Integrated Enhanced Recovery (TIGER) Protocol after Adolescent Idiopathic Scoliosis Correction Lowers Direct Cost and Length of Stay While Increasing Daily Contribution Margins.

Introduction: Posterior spinal fusion (PSF) is the gold standard procedure for curve correction in Adolescent Idiopathic Scoliosis (AIS). Enhanced recovery protocols (ERPs) have been found to decrease pain and hospital length of stay (LOS) resulting in decreased total hospital charges. Methods: We identified all adolescent idiopathic scoliosis patients treated with a posterior spinal fusion at our children's hospital between 2015-2019. Length of stay, pain scores, and hospital direct costs were calculated to determine the pathway's efficacy. Results: Hospital LOS was reduced by 26% and post-op pain scores did not significantly change when using the Team Integrated Enhanced Recovery (TIGER) protocol (P<0.05). Total hospital costs decreased by 7.9%, daily contribution margins increased 7.9%, and daily net income increased 10.6% after TIGER protocol implementation. Conclusion: TIGER protocol resulted in decreased hospital LOS as well as direct costs for the hospital without increasing postoperative pain scores.

Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial.

BACKGROUND: There are no effective therapies for achondroplasia. An open-label study suggested that vosoritide administration might increase growth velocity in children with achondroplasia. This phase 3 trial was designed to further assess these preliminary findings. METHODS: This randomised, double-blind, phase 3, placebo-controlled, multicentre trial compared once-daily subcutaneous administration of vosoritide with placebo in children with achondroplasia. The trial was done in hospitals at 24 sites in seven countries (Australia, Germany, Japan, Spain, Turkey, the USA, and the UK). Eligible patients had a clinical diagnosis of achondroplasia, were ambulatory, had participated for 6 months in a baseline growth study and were aged 5 to less than 18 years at enrolment. Randomisation was done by means of a voice or web-response system, stratified according to sex and Tanner stage. Participants, investigators, and trial sponsor were masked to group assignment. Participants received either vosoritide 15·0 µg/kg or placebo, as allocated, for the duration of the 52-week treatment period administered by daily subcutaneous injections in their homes by trained caregivers. The primary endpoint was change from baseline in mean annualised growth velocity at 52 weeks in treated patients as compared with controls. All randomly assigned patients were included in the efficacy analyses (n=121). All patients who received one dose of vosoritide or placebo (n=121) were included in the safety analyses. The trial is complete and is registered, with EudraCT, number, 2015-003836-11. FINDINGS: All participants were recruited from Dec 12, 2016, to Nov 7, 2018, with 60 assigned to receive vosoritide and 61 to receive placebo. Of 124 patients screened for eligibility, 121 patients were randomly assigned, and 119 patients completed the 52-week trial. The adjusted mean difference in annualised growth velocity between patients in the vosoritide group and placebo group was 1·57 cm/year in favour of vosoritide (95% CI [1·22-1·93]; two-sided p<0·0001). A total of 119 patients had at least one adverse event; vosoritide group, 59 (98%), and placebo group, 60 (98%). None of the serious adverse events were considered to be treatment related and no deaths occurred. INTERPRETATION: Vosoritide is an effective treatment to increase growth in children with achondroplasia. It is not known whether final adult height will be increased, or what the harms of long-term therapy might be. FUNDING: BioMarin Pharmaceutical.

Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.

PURPOSE: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. METHODS: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 µg/kg/day. RESULTS: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. CONCLUSION: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

A preliminary assessment of intervertebral disc health and pathoanatomy changes observed two years following anterior vertebral body tethering.

PURPOSE: Vertebral body tethering (VBT) has been reported as a safe and effective non-fusion surgical technique for the treatment of adolescent idiopathic scoliosis, but the postoperative health of the bone and soft tissues of the spine following instrumentation remains unknown. We aimed to evaluate pathoanatomy and degenerative changes of the spine in adolescent idiopathic scoliosis patients both prior to and two years following VBT. METHODS: We prospectively enrolled nine patients who underwent VBT for the treatment of progressive adolescent idiopathic scoliosis. All patients received preoperative and two-year postoperative magnetic resonance imaging of their spine; images were assessed for pathoanatomy (e.g. nucleus pulposus positioning and muscle atrophy) and degenerative changes (e.g. Schmorl nodes, endplate oedema, disc degeneration, and osteoarthritis) at each vertebral level between T1 and S1. RESULTS: Four patients (44%) exhibited a shift of the nucleus pulposus from an eccentric position at baseline towards midline at three or more levels, most of which were in the tethered region. Tethering did not affect preexisting fatty atrophy of multifidus. No patients exhibited postoperative Schmorl nodes, endplate oedema, or disc degeneration in either the tethered or untethered regions. Four patients (44%) presented with mild facet osteoarthritis in the lower lumbar spine, which did not change postoperatively. One patient developed moderate facet osteoarthritis at L5-S1. CONCLUSIONS: These preliminary data indicate that VBT may not result in significant degenerative changes in either the intervertebral discs or the posterior facets two years following instrumentation.

Effect of NSAID Use on Bone Healing in Pediatric Fractures: A Preliminary, Prospective, Randomized, Blinded Study.

BACKGROUND: This study aimed to investigate if nonsteroidal anti-inflammatory drugs (NSAIDs) used in the acute phase of bone healing in children with fractures result in delayed union or nonunion as compared with patients who do not take NSAIDs for pain control during this same time period. METHODS: In this prospective, randomized, parallel, single-blinded study, skeletally immature patients with long bone fractures were randomized to 1 of 2 groups for their postfracture pain management. The NSAID group was prescribed weight-based ibuprofen, whereas the control group was not allowed any NSAID medication and instead prescribed weight-based acetaminophen. Both groups were allowed to use oxycodone for breakthrough pain. The primary outcome was fracture healing assessed at 2, 6, and 10 weeks. RESULTS: One-hundred-two patients were enrolled between February 6, 2014 and September 23, 2016. Ninety-five patients (with 97 fractures) completed a 6-month follow-up (46 patients with 47 fractures in the control group and 49 patients 50 fractures in the NSAID group). None achieved healing at 1 to 2 weeks. By 6 weeks, 37 of 45 patients (82%) of control group and 46 out of 50 patients (92%) of ibuprofen group had healed fractures (P=0.22). At 10 to 12 week follow-up, 46 (98%) of the control group fractures were healed and 50 (100%) of the ibuprofen group fractures were healed. All were healed by 6 months. Healing was documented at a mean of 40 days in the control group and 31 days in the ibuprofen group (P=0.76). The mean number of days breakthrough oxycodone was used was 2.4 days in the control group and 1.9 days in the NSAID group (P=0.48). CONCLUSION: Ibuprofen is an effective medication for fracture pain in children and its use does not impair clinical or radiographic long bone fracture healing in skeletally immature patients. LEVEL OF EVIDENCE: Level I-therapeutic.

Automated extraction of biplanar stereo-radiographic image measurements: Mizzou 3D SPinE.

PURPOSE: Although several studies have reported on the application of biplanar stereo-radiographic technology in pediatric clinical practice, few have performed large-scale analyses. The manual extraction of these types of data is time-consuming, which often precludes physicians and scientists from effectively utilizing these valuable measurements. To fill the critical gap between clinical assessments and large-scale evidence-based research, we have addressed one of the primary hurdles in using data derived from these types of imaging modalities in pediatric clinical practice by developing an application to automatically transcribe and aggregate three-dimensional measurements in a manner that facilitates statistical analyses. METHODS: Mizzou 3D SPinE was developed using R software; the application, instructions, and process were beta tested with four separate testers. We compared 1309 manually compiled three-dimensional deformity measurements derived from thirty-five biplanar three-dimensional reconstructions (image sets) from ten pediatric patients to those derived from Mizzou 3D SPinE. We assessed the difference between manually entered values and extracted values using a Fisher's exact test. RESULTS: Mizzou 3D SPinE significantly reduced the duration of data entry (95.8%) while retaining 100% accuracy. Manually compiled data resulted in an error rate of 1.58%, however, the magnitude of errors ranged from 5.97 to 2681.82% significantly increased the transcription accuracy (p value < 0.0001) while also significantly reducing transcription time (0.33 vs. 8.08 min). CONCLUSION: Mizzou 3D SPinE is an essential component in improving evidence-based patient care by allowing clinicians and scientists to quickly compile three-dimensional data at regular intervals in an automated, efficient manner without transcription errors.

Effect of Antibiotic Prophylaxis on Infection Rates in Pediatric Supracondylar Humerus Fractures Treated with Closed Reduction and Percutaneous Pinning: A Prospective Double-Blinded Randomized Controlled Trial.

BACKGROUND: Supracondylar humerus fractures (SCHFs) are the most common elbow fracture in the pediatric population. In the case of displaced fractures, closed reduction and percutaneous Kirschner wire pinning (CRPP) is commonly performed. Infection rates are between 0 and 7%; however, retrospective studies have shown no benefit of preoperative antibiotics. There continues to be notable variability in antibiotic usage based on surgeon preference and local institutional policy. We conducted a double-blinded, randomized controlled trial to evaluate whether antibiotic prophylaxis reduces the risk of infection in pediatric SCHF patients treated with CRPP. METHODS: Pediatric patients with displaced SCHF who presented to a pediatric hospital were enrolled and randomized into two groups. Group I received one dose of prophylactic antibiotics (25 mg/kg cefazolin IV up to 1g or clindamycin 10 mg/kg up to 600 mg/kg IV in the case of cefazolin allergy). Group II received placebo (10-mL prefilled syringe of normal saline). All patients underwent CRPP and casting followed by pin removal 3 to 6 weeks after the initial procedure. The presence of pin-site infection, erythema, drainage, septic arthritis, and osteomyelitis was recorded. RESULTS: One hundred sixty patients were enrolled in the study. Eighty-two patients were randomized to receive antibiotics, and 78 patients were randomized to placebo. No difference was seen in the rate of infection between the treatment groups (1.2% in the antibiotic group versus 1.3% in the placebo group; P = 1.00). Presence of purulent drainage (0.0% versus 1.3%; P = 0.49), septic arthritis (0.0% versus 0.0%; P = 1.00), and osteomyelitis (1.2% versus 0.0%; P = 1.00) was similar in both groups. No difference in the need for additional antibiotics (1.2% versus 1.3%; P = 1.00) or additional surgery (1.2% versus 0.0%; P = 1.00) was found between groups. DISCUSSION: The use of antibiotic prophylaxis did not affect the risk of infection in pediatric patients who underwent CRPP for displaced SCHF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03261830. LEVEL OF EVIDENCE: Therapeutic Level I.

Anterior vertebral body tethering shows clinically comparable shoulder balance outcomes to posterior spinal fusion.

PURPOSE: Posterior spinal fusion (PSF) is the current gold standard in surgical treatment for adolescent idiopathic scoliosis. Vertebral body tethering (VBT) is a fusionless alternative. Shoulder balance is an important metric for outcomes and patient satisfaction. Here we compare shoulder balance outcomes between PSF and VBT. METHODS: In this retrospective review, the pre-operative and post-operative absolute radiographic shoulder height (|RSH|) of 45 PSF patients were compared to 46 VBT patients. Mean values were compared and then collapsed into discrete groups (|RSH| GROUP) and compared. Patients were propensity score matched. Regression models based on pretest-posttest designs were used to compare procedure type on post-operative outcomes. RESULTS: Pre-operatively there were no differences in |RSH| between PSF and VBT, however, at latest post-operative follow-up PSF maintained a larger |RSH| imbalance compared to VBT (0.91 cm vs 0.63 cm, p = 0.021). In an ANCOVA regression, PSF was associated with a larger |RSH| imbalance compared to VBT, F(1, 88) = 5.76, p = 0.019. An ordinal logistic regression found that the odds ratio of being in a worse |RSH| GROUP for PSF vs VBT is 2.788 (95% CI = 1.099 to 7.075), a statistically significant effect χ2(1) = 4.658, p = 0.031. Results were similar in subgroup analyses of Lenke 1 and Lenke 2 patients, though to less statistical significance. CONCLUSION: While PSF was found to be associated with worse |RSH| outcomes, the actual numbers (2-3 mm) are unlikely to be clinically meaningful. Thus, in this analysis, VBT can be said to show comparable shoulder balance outcomes to PSF.

Double major curvature treated with vertebral body tethering of both curves: how do outcomes compare to posterior spinal fusion?

PURPOSE: Vertebral body tethering (VBT) is a non-fusion alternative to posterior spinal fusion (PSF). There have been few reports on VBT of two curvatures. We aim to compare the radiographic outcomes between VBT and PSF in patients with double curvatures in which both curves were instrumented. METHODS: 29 AIS patients matched by Lenke, age (± 2 years), triradiate cartilage closure status, major Cobb angle (± 8°), and T5-T12 kyphosis (± 10°). Variables were compared using Wilcoxon rank-sum tests, Student's t tests, and chi-Square. Clinical success was defined as major curve < 35°. RESULTS: Group baseline demographics were similar. Major thoracic (T) curve types had significantly better major (VBT 51.5 ± 7.9° to 31.6 ± 12.0° [40%] vs. PSF 54.3 ± 7.4° to 17.4 ± 6.5° [68%]; p = 0.0002) and secondary curve correction in the PSF group. 71% of major T VBT patients were clinically successful versus 100% of PSF. Major thoracolumbar (TL) curve types experienced comparable major (VBT 52.3 ± 7.0° to 18.3 ± 11.4° (65%) vs. PSF 53.0 ± 5.2° to 23.8 ± 10.9° (56%); p = 0.2397) and secondary curve correction. 92% of major TL VBT patients were clinically successful versus 75% in the PSF group. There was no difference in T5-12 kyphosis or lumbar lordosis between groups for any curve type. There were 4 patients (13.8%) with major complications in the VBT group compared to 0 (0%) in the PSF. CONCLUSION: Patients with double major AIS who underwent VBT with major T curve types had less correction than PSF; however, those with major TL curves experienced similar radiographic outcomes regardless of procedure. Complications were greater for VBT.

Central Airway Obstruction with Persistent Pulmonary Decline After Vertebral Body Tethering: A Case Report.

CASE: An 11-year-old girl with pectus excavatum presented with an acute airway obstruction and persistent pulmonary compromise after vertebral body tethering (VBT). The anterior instrumentation was occluding her right basilar bronchus, resulting in hyperinflation. Removal of the instrumentation reversed the hyperinflation. CONCLUSION: This case illustrates the difficulty of performing VBT in a small patient with severe scoliosis and significant asymmetric pectus excavatum. We recommend using low-profile instrumentation and ensuring the trajectory of the instrumentation is anterior to the rib head and parallel to the articular facets.

Outcomes of vertebral body tethering in the lumbar spine.

PURPOSE: The use of vertebral body tethering (VBT) for the treatment of main thoracic deformities in adolescent idiopathic scoliosis patients is becoming increasingly more common, but limited data exist on its safety and efficacy in thoracolumbar deformities. We aimed to evaluate the postoperative outcomes of patients with thoracolumbar (TL) deformities that were treated with VBT. METHODS: We assessed clinical and radiographic data from twenty-eight consecutive patients that were surgically managed with VBT, all of whom exhibited a TL deformity with at least two years (mean: 44.7 ± 14.5 months) of postoperative follow-up. Standard radiographic parameters were extracted from left hand wrist and standing posterior-anterior and lateral spine radiographs at various timepoints. Outcome variables were assessed based on preoperative Lenke Classification and included: deformity measures, complications, surgical revisions, and postoperative success. RESULTS: The mean age at the time of instrumentation was 13.4 ± 1.3 years, with an average preoperative Sanders Stage of 4.6 ± 1.4. A significant reduction in preoperative deformities was observed at most postoperative timepoints. A perioperative complication was observed in three patients and surgical revision was required in another four patients. A suspected broken tether was observed in sixteen patients, most of which occurred at the apex of the lumbar deformity. Only one patient required surgical revision due to a suspected broken tether. We observed an overall success rate of 57%, regardless of Lenke Classification. CONCLUSIONS: These data indicate that VBT can successfully correct TL deformity patterns in 57% of patients without an increase in the rate of perioperative complications, suspected broken tethers, or surgical revisions.

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial.

Background: TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia. Methods: ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 µg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety and annualised growth velocity (AGV). ACcomplisH is registered with ClinicalTrials.gov (NCT04085523) and Eudra (CT 2019-002754-22). Findings: Forty-two participants received TransCon CNP at doses of 6 µg (n = 10; 7 female), 20 µg (n = 11; 3 female), 50 µg (n = 10; 3 female), or 100 µg (n = 11; 6 female) CNP/kg/week, with 15 receiving placebo (5 female). Treatment-emergent adverse events (TEAEs) were mild or moderate with no grade 3/4 events reported. There were 2 serious TEAEs that were assessed as not related to TransCon CNP. Eleven injection site reactions occurred in 8 participants receiving TransCon CNP and no symptomatic hypotension occurred. TransCon CNP demonstrated a dose-dependent improvement in AGV. At 52 weeks, TransCon CNP 100 µg CNP/kg/week significantly improved AGV vs placebo (least squares mean [95% CI] 5.42 [4.74-6.11] vs 4.35 [3.75-4.94] cm/year; p = 0.0218), and improved achondroplasia-specific height SDS from baseline (least squares mean [95% CI] 0.22 [0.02-0·41] vs -0·08 [-0.25 to 0.10]; p = 0.0283). All participants completed the randomised period and continued in the ongoing open-label extension period receiving TransCon CNP 100 µg CNP/kg/week. Interpretation: This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment option for children with achondroplasia. These results support TransCon CNP at 100 µg CNP/kg/week in the ongoing pivotal trial. Funding: Ascendis Pharma, A/S.