Risk Factors for Progression of Cervical Congenital Scoliosis and Associated Compensatory Curve Behavior.

Background: This study investigated risk factors for progression of deformity in pediatric congenital cervical scoliosis (CCS) and evaluated the correlation between congenital cervical curves and compensatory thoracic and lumbar curves. Methods: Medical records were retrospectively reviewed for 38 pediatric patients with CCS with a minimum 2-year follow-up. Curve progression was defined as >10° increase in cervical coronal curve angle between presentation and last follow-up. Results: A total of 38 patients (16 girls, 22 boys) with a mean age at presentation of 5.6 ± 4.1 years met the inclusion criteria. Sixteen patients (42%) had curve progression with a mean follow-up of 3.1 ± 3.0 years. At presentation, T1 slope was significantly larger among children with progressive deformities (p = 0.041). A total of 18 of the 38 patients with strictly cervical spine deformity were then selected for subanalysis to evaluate the progression of compensatory curves. Cervical major coronal curves were found to significantly correlate with lumbar major coronal curves (r = 0.409), C2 central sacral vertical line (CSVL) (r = 0.407), and C7-CSVL (r = 0.403) (p < 0.05). Thoracic major coronal curves did not significantly correlate with cervical major coronal curves (r = 0.218) (p > 0.05). Conclusion: In conclusion, 42% of osseous CCS curves progressed over time in the overall cohort, and high initial T1 slope was found to be most highly correlated with progression of cervical deformity. Cervical major coronal curves significantly correlated with lumbar curve magnitude but not with thoracic curve size in isolated CCS, possibly due to the increased flexibility of the lumbar spine which may allow greater compensatory balance and thus have a greater correlation with cervical curve magnitude and possibly progression.

Learning Curve Associated With Thoracoscopic Anterior Vertebral Body Tether and Double Anterior Vertebral Body Tether for Idiopathic Scoliosis: Analysis of Three Independent Surgeons.

BACKGROUND AND OBJECTIVES: Anterior vertebral body tether (VBT) is a fusionless approach to treat idiopathic scoliosis, and surgeons are beginning to implement the technique into current practice. This study aims to evaluate the learning curve for single and double VBT. METHODS: A retrospective review of 3 surgeons' first 40 single and 20 double VBT was performed. Skeletally immature patients with idiopathic scoliosis who underwent thoracic (single) or thoracolumbar (double) VBT were included. Thoracic VBT was done via video-assisted thoracoscopic surgery and lumbar VBT through a mini-open retroperitoneal approach. Primary outcomes of interest were operative time, radiation exposure, and radiographic correction. Pooled and individual-surgeon analyses were performed. RESULTS: A total of 180 patients were included: 120 single and 60 double. Mean age was 12.7 years, and 87.8% were female. Mean segments tethered was 7.8 in single and 11.0 in double. Mean preoperative thoracic scoliosis was 51.5: single 50.5° and double 53.3°. Mean lumbar scoliosis was 36.4°: single 30.0° and double 49.0°. Average operating time was 276.2 minutes; double VBT was significantly longer (217.3 vs 394.0 minutes, P < .001). Mean blood loss was 198.5 mL, and mean fluoroscopy dose was 73.0 mGy. For single VBT, there was a decrease in operative time (283.3-174.8 minutes, P < .001) and fluoroscopy dose (70.1-53.5 mGy, P = .047) over time. Every 10 cases resulted in a 31.4 minute decrease in operative time (P < .001). There were no intraoperative complications. Single VBT resulted in 54.9% thoracic curve correction. Double VBT achieved 53.0% thoracic and 56.7% lumbar correction. There were no differences in curve correction across the learning curve. CONCLUSION: VBT is viable fusionless surgical option for scoliosis. As expected, increased experience resulted in shorter operative time; the threshold for such improvement seems to be 10 cases. Importantly, adequate and consistent curve correction can be achieved at the start of the learning curve while mitigating complications.

The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas.

ABSTRACT: Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.

Outcomes after completing growth-friendly surgical treatment for early-onset scoliosis in patients with skeletal dysplasia.

Aims: The aim of this study was to compare outcomes after growth-friendly treatment for early-onset scoliosis (EOS) between patients with skeletal dysplasias versus those with other syndromes. Methods: We retrospectively identified 20 patients with skeletal dysplasias and 292 with other syndromes (control group) who had completed surgical growth-friendly EOS treatment between 1 January 2000 and 31 December 2018. We compared radiological parameters, complications, and health-related quality of life (HRQoL) at mean follow-up of 8.6 years (SD 3.3) in the dysplasia group and 6.6 years (SD 2.6) in the control group. Results: Mean major curve correction per patient did not differ significantly between the dysplasia group (43%) and the control group (28%; p = 0.087). Mean annual spinal height increase was less in the dysplasia group (9.3 mm (SD 5.1) than in the control group (16 mm (SD 9.2); p < 0.001). Mean annual spinal growth adjusted to patient preoperative standing height during the distraction period was 11% in the dysplasia group and 14% in the control group (p = 0.070). The complication rate was 1.6 times higher (95% confidence interval (CI) 1.3 to 2.0) in the dysplasia group. The following complications were more frequent in the dysplasia group: neurological injury (rate ratio (RR) 5.1 (95% CI 2.3 to 11)), deep surgical site infection (RR 2.2 (95% CI 1.2 to 4.1)), implant-related complications (RR 2.0 (95% CI 1.5 to 2.7)), and unplanned revision (RR 1.8 (95% CI 1.3 to 2.5)). Final fusion did not provide additional spinal height compared with watchful waiting (p = 0.054). There were no significant differences in HRQoL scores between the groups. Conclusion: After growth-friendly EOS treatment, patients with skeletal dysplasias experienced a higher incidence of complications compared to those with other syndromes. Surgical growth-friendly treatment for skeletal dysplasia-associated EOS should be reserved for patients with severe, progressive deformities that are refractory to nonoperative treatment.

Pre-op considerations in neuromuscular scoliosis deformity surgery: proceedings of the half day course at the 58th annual meeting of the Scoliosis Research Society.

Scoliosis is a common complication of neuromuscular disorders. These patients are frequently recalcitrant to nonoperative treatment. When treated surgically, they have the highest risk of complications of all forms of scoliosis. While recent studies have shown an improvement in the rate of complications, they still remain high ranging from 6.3 to 75% depending upon the underlying etiology and the treatment center (Mohamad et al. in J Pediatr Orthop 27:392-397, 2007; McElroy et al. in Spine, 2012; Toll et al. in J Neurosurg Pediatr 22:207-213, 2018; Cognetti et al. in Neurosurg Focus 43:E10, 2017). For those patients who are able to recover from the perioperative period without major complications, several recent studies have shown decreased long-term mortality and improved health-related quality of life in neuromuscular patients who have undergone spine fusion (Bohtz et al. in J Pediatr Orthop 31:668-673, 2011; Ahonen et al. in Neurology 101:e1787-e1792, 2023; Jain et al. in JBJS 98:1821-1828, 2016). It is critically important to optimize patients preoperatively to minimize the risk of post-operative complications and maximize long-term outcomes. In order to do so, one must familiarize themselves with the common complications and their treatment. The most common complications are pulmonary in nature. With reported rates as high as 23-29%, pre-operative optimization should be employed for these patients to minimize the risk of post-operative complications (Sharma et al. in Eur Spine J 22:1230-1249, 2013; Rumalla et al. in J Neurosurg Spine 25:500-508, 2016). The next most common cause of complications are implant related, with 13-23% of patients experiencing an implant-related complication that may require a second procedure (Toll et al. in J Neurosurg Pediatr 22:207-213, 2018; Sharma et al. in Eur Spine J 22:1230-1249, 2013) Therefore optimization of bone quality prior to surgical intervention is important to help minimize the risk of instrumentation failure. Optimization of muscle tone and spasticity may help to decrease the risk of instrumentation complications, but may also contribute to the progression of scoliosis. While only 3% of patients have neurologic complication, significant equipoise remains regarding whether or not patients should undergo prophylactic detethering procedures to minimize those risks (Sharma et al. in Eur Spine J 22:1230-1249, 2013). Although only 1.8% of complications are classified as cardiac related, they can be among the most devastating (Rumalla et al. in J Neurosurg Spine 25:500-508, 2016). Simply understanding the underlying etiology and the potential risks associated with each condition (i.e., conduction abnormalities in a patient with Rett syndrome or cardiomyopathies patients with muscular dystrophy) can be lifesaving. The following article is a summation of the half day course on neuromuscular scoliosis from the 58th annual SRS annual meeting, summarizing the recommendations from some of the world's experts on medical considerations in surgical treatment of neuromuscular scoliosis.

Prospectively Collected Comparison of Outcomes Between Surgically and Conservatively Treated Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective review of a prospectively collected multicenter registry. OBJECTIVE: To evaluate health-related quality of life (HRQOL) measures in an operative cohort of patients (OP) and compare them with a matched nonoperative cohort (NON). SUMMARY OF BACKGROUND DATA: Historically, the surgical outcomes of adolescent idiopathic scoliosis (AIS) have been radiographically evaluated. However, the importance of HRQOL measures and their impact on surgical outcomes are increasingly being understood. METHODS: We identified 90 NON patients with curves in the operative range who were observed for at least 2 years. These patients were matched with an OP cohort of 689 patients. All patients completed the Scoliosis Research Society-22 (SRS-22) questionnaire at the initial evaluation and at a minimum of 2-year follow-up. Subgroup comparisons were based on curve type: primary thoracic (Th), primary thoracolumbar/lumbar (TL/L), and double major (DM) curves. RESULTS: The preoperative major curves in the Th, TL/L, and DM OP subgroups averaged 50.4°, 45.4°, and 51.5°, respectively, and 49.4°, 43.7°, and 48.9° in the NON cohort (P > 0.05). At 2 years postoperatively, the major curve in the Th, TL/L, and DM OP subgroups improved to 19.0°, 19.2°, and 19.3°, respectively, compared to the progression to 51.3°, 44.5°, and 49.7° in the NON group at 2-year follow-up (P < 0.05). The SRS-22 self-image, mental health, satisfaction, and total scores at the 2-year follow-up were significantly better in all OP subgroups (P < 0.001) but remained largely unchanged in the NON group. A significant percentage of patients (P < 0.001) in the OP cohort reported better SRS-22 scores at the 2-year follow-up in the self-image, mental health, and satisfaction domains than the NON group at 2 years. CONCLUSIONS: Surgically treated patients with AIS have improved HRQOL outcomes in several domains compared to age- and curve magnitude-matched nonoperatively treated patients at 2-year follow-up.

Lumbar Vertebral Body Tethering: Single Center Outcomes and Reoperations in a Consecutive Series of 106 Patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the outcomes and reoperation rates in patients with adolescent idiopathic scoliosis (AIS) undergoing lumbar anterior vertebral body tethering (AVBT). SUMMARY OF BACKGROUND DATA: Anterior vertebral body tethering (AVBT) is a viable option in growing children. The benefit of motion preservation must be balanced by a higher reoperation rate. A paucity of reports has addressed lumbar AVBT. METHODS: A single-center retrospective study was conducted to identify all patients who underwent lumbar AVBT (lowest instrumented vertebra L3 or L4) with a minimum 2 years of follow-up. Clinical and radiographic parameters, including complications and reoperations, were also collected. Statistical analysis was performed using Student's t-test for qualitative variables. RESULTS: From a dataset of 551 patients, we identified 106 patients (89% female) who underwent a lumbar AVBT (33 lumbar only, 73 bilateral thoracic/lumbar) with mean follow-up of 4.1±1.6 years at which point 85% (90/106) had reached skeletal maturity. Preoperatively, these patients were skeletally immature (age: 12.8±1.3 y, Sanders: 3.3±0.8, R=0.6±0.9) with a lumbar coronal curve angle of 49.6°±11.2 which corrected to 19.9°±11.2 (P <0.0001) at most recent follow-up. At the latest follow-up, 76.4% (81/106) of the patients harbored a coronal curve angle of < 30°. Twenty patients (18.9%) underwent 23 reoperations, with overcorrection being the most common (10/23, 43%). Broken tethers led to reoperation in 3 instances (3/23, 13%). Six patients in the cohort needed a posterior spinal fusion (6/106, 5.4%). CONCLUSIONS: Vertebral body tethering is a viable treatment option for skeletally immature patients with idiopathic scoliosis. This report is the largest to date for lumbar AVBT, highlighting that 84% of patients harbored a curve < 35° at the latest follow-up but with an 18.9% reoperation rate. LEVEL OF EVIDENCE: 3.

Patterns of progression after immune checkpoint inhibitors for Hodgkin lymphoma: implications for radiation therapy.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICIs are not well described and are essential to defining the role of local therapies in combination with ICIs. We identified patients who received ICIs for HL between 2013 and 2022. Fludeoxyglucose-18 positron emission tomography (FDG-PET) before initiating ICI and at progression on/after ICI were reviewed, and areas of active HL were recorded. An exploratory analysis of treatable progression included patients with ≤5 sites of disease on pre-ICI FDG-PET and progression only at pre-ICI sites. Ninety patients were identified; 69 had complete records, and of these, 32 (52%) had relapsed at ICI initiation, 17 (25%) were refractory, and 16 (23%) received ICI as first-line therapy. Forty-five of 69 patients had ≤5 sites of disease (limited) on pre-ICI FDG-PET. Patients with >5 sites of disease had a higher risk of progression, and every site of disease >5 sites conferred an additional 1.2x higher chance of progression. At a median follow-up of 4.0 years, 41 of 69 patients had progressed on/after ICIs (cumulative incidence 66.4%), and of these, 22 of 41 patients progressed only at pre-ICI sites (cumulative incidence 39.4%). In an exploratory analysis, the cumulative incidence of a treatable progression among 45 patients with limited disease was 34%. The cumulative incidence of any progression among this cohort was 58.9%. More than one-third of patients with limited disease before ICIs experienced progression only at pre-ICI sites of disease. These patients could be candidates for radiation during or after ICIs.

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.

The Impact of Anterior Vertebral Body Tethering on Pulmonary Function.

STUDY DESIGN: Retrospective, single-center study. OBJECTIVE: To examine pulmonary function tests (PFTs) in patients undergoing anterior vertebral body tethering (AVBT). SUMMARY OF BACKGROUND DATA: The effect of AVBT on pulmonary status remains unclear. MATERIALS AND METHODS: The authors examined preoperative and postoperative PFTs following AVBT in a retrospective, single-center cohort of patients. Outcomes were compared using percent predicted values as continuous and categorical variables (using 10% change as significant) and divided into categorical values based on the American Thoracic Society standards. RESULTS: Fifty-eight patients with adolescent idiopathic scoliosis were included, with a mean age of 12.5±1.4 years and a follow-up of 4.2±1.1 years. The mean thoracic curve was 47°±9°, which improved to 21°±12°. At baseline, the mean forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) values were 79% and 82%, respectively. Four patients had normal FEV1% (≥100%), 67% had mild restrictive disease (70%-99%) and the rest had worse FEV1%. Mean FEV1 improved from 2.2 to 2.6 L ( P <0.05) and FVC improved from 2.5 to 3.0 L ( P <0.05); however, % predicted values remained unchanged (FEV1%: 79%-80%; FVC%: 82-80%, P >0.05) with mean postoperative PFTs at 37±12 months postoperative. The use of miniopen thoracotomy was not associated with worsening PFTs, but extension of the lowest instrumented vertebra below T12 was correlated with decreasing FEV1% in the bivariate analysis ( P <0.05). Patients with worse preoperative FVC% (80±13% vs. 90±11%, P =0.03) and FEV1% (77±17% vs. 87±12%, P =0.06) also had a greater likelihood of declining postoperative FEV1%. CONCLUSION: Pulmonary function in most patients undergoing AVBT remained stable (76%) or improved (14%); however, a subset may worsen (10%). Further studies are needed to identify the risk factors for this group, but worse preoperative PFTs and extension below T12 may be risk factors for worsening pulmonary function.

Early outcomes in hybrid fixation for idiopathic scoliosis: posterior fusion combined with anterior vertebral body tethering. Patient series.

BACKGROUND: Anterior vertebral body tethering (AVBT) and posterior spinal fusion (PSF) are options for patients with idiopathic scoliosis. Combining both procedures in patients with double curves, a procedure in which PSF is performed for the thoracic curve and AVBT for the lumbar curve, provides maximal correction of the thoracic curve with a theoretical maintenance of motion in the lumbar spine. OBSERVATIONS: The authors retrospectively reviewed 20 skeletally immature patients diagnosed with idiopathic scoliosis at a single institution with an average age of 12.7 ± 1.6 years and who had undergone hybrid treatment with an average follow-up of 8 months. The PSF procedures averaged 276 ± 63 minutes with 442.8 ± 295 mL of blood loss, and the AVBT averaged 275 ± 54 minutes with 118.3 ± 80 mL of blood loss. Following the hybrid correction, the thoracic and lumbar coronal curve angles improved from 67.6° to 21.6° and from 65.2° to 24°, respectively. The three-dimensional kyphosis improved from 3.3° to 24°. LESSONS: A combined approach of PSF and AVBT is safe and effective for idiopathic scoliosis. This approach combines the gold standard of thoracic fusion with the motion preservation benefits of AVBT in the lumbar spine. This study will continue to refine indications for AVBT.

Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma.

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

Pain After Anterior Vertebral Body Tethering: Incidence, Risk Factors, and Timing.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To examine the incidence and risk factors for postoperative pain following anterior vertebral body tethering (AVBT) for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Up to 78% of patients with AIS report preoperative pain; it is the greatest patient concern surrounding surgery. Pain significantly decreases following posterior spinal fusion, but pain following AVBT is poorly understood. MATERIALS AND METHODS: We retrospectively reviewed 279 patients with a two-year follow-up after AVBT for AIS. We collected demographic, radiographic, and clinical data pertinent to postoperative pain at each time interval of preoperative and postoperative visits (6 wk, 6 mo, 1 y, and annually thereafter). RESULTS: Within our cohort, 68.1% of patients reported preoperative pain. Older age ( P =0.014) and greater proximal thoracic ( P =0.013) and main thoracic ( P =0.002) coronal curve magnitudes were associated with preoperative pain. Pain at any time point > 6 weeks postoperatively was reported in 41.6% of patients; it was associated with the female sex ( P =0.032), need for revision surgery ( P =0.019), and greater lateral displacement of the apical lumbar vertebrae ( P =0.028). The association between preoperative and postoperative pain trended toward significance ( P =0.07). At 6 months postoperatively, 91.8% had pain resolution; the same number remained pain-free at the time of last follow-up. The presence of a postoperative complication was associated with new-onset postoperative pain that resolved ( P =0.009). Only 8.2% had persistent pain, although no risk factors were found to be associated with persistent pain. CONCLUSION: In our cohort of 279 patients with a minimum 2-year follow-up after AVBT, 68.1% reported preoperative pain. Nearly 42% reported postoperative pain at any time point, but only 8.2% had persistent pain. Postoperative pain after AVBT was associated with female sex, revision surgery, and Lenke lumbar modifier. AVBT is associated with a significant reduction in pain, and few patients report long-term postoperative pain.

COL11A2 as a candidate gene for vertebral malformations and congenital scoliosis.

Human vertebral malformations (VMs) have an estimated incidence of 1/2000 and are associated with significant health problems including congenital scoliosis (CS) and recurrent organ system malformation syndromes such as VACTERL (vertebral anomalies; anal abnormalities; cardiac abnormalities; tracheo-esophageal fistula; renal anomalies; limb anomalies). The genetic cause for the vast majority of VMs are unknown. In a CS/VM patient cohort, three COL11A2 variants (R130W, R1407L and R1413H) were identified in two patients with cervical VM. A third patient with a T9 hemivertebra and the R130W variant was identified from a separate study. These substitutions are predicted to be damaging to protein function, and R130 and R1407 residues are conserved in zebrafish Col11a2. To determine the role for COL11A2 in vertebral development, CRISPR/Cas9 was used to create a nonsense mutation (col11a2L642*) as well as a full gene locus deletion (col11a2del) in zebrafish. Both col11a2L642*/L642* and col11a2del/del mutant zebrafish exhibit vertebral fusions in the caudal spine, which form due to mineralization across intervertebral segments. To determine the functional consequence of VM-associated variants, we assayed their ability to suppress col11a2del VM phenotypes following transgenic expression within the developing spine. While wildtype col11a2 expression suppresses fusions in col11a2del/+ and col11a2del/del backgrounds, patient missense variant-bearing col11a2 failed to rescue the loss-of-function phenotype in these animals. These results highlight an essential role for COL11A2 in vertebral development and support a pathogenic role for two missense variants in CS.

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.

Autofusion With Magnetically Controlled Growing Rods: A Case Report.

Magnetically controlled growing rods (MCGRs) are an effective alternative to traditional growing rods (TGRs) in the treatment of early-onset scoliosis (EOS), with comparable deformity correction despite fewer planned reoperations. This case report presents a unique case of autofusion in a patient with tetraplegic cerebral palsy, thoracic myelomeningocele, and EOS who was treated with dual MCGR instrumentation and underwent serial lengthening procedures for four years. We detail the operative and radiographic findings in a novel case of autofusion encountered after MCGR placement to treat EOS. An eight-year-old female with tetraplegic cerebral palsy causing a 94° right thoracic neuromuscular scoliosis was treated with dual MCGRs; she then underwent serial lengthenings every four months. At 12 years of age, during MCGR explantation and posterior spinal fusion, dense heterotopic autofusion was encountered around the MCGR instrumentation, limiting further deformity correction. The benefits of MCGRs make them an appealing alternative to TGRs for the treatment of EOS. Although the theoretical risk of autofusion in MCGRs is low, recent case reports propose autofusion as a possible reason for MCGRs' failure to lengthen.

What Happens After a Vertebral Body Tether Break? Incidence, Location, and Progression With Five-year Follow-up.

STUDY DESIGN: Retrospective review. OBJECTIVE: To study risk factors for anterior vertebral body tether (VBT) breakage. SUMMARY OF BACKGROUND DATA: VBT is used to treat adolescent idiopathic scoliosis in skeletally immature patients. However, tethers break in up to 48% of cases. MATERIALS AND METHODS: We reviewed 63 patients who underwent thoracic and/or lumbar VBT with a minimum five-year follow-up. We radiographically characterized suspected tether breaks as a change in interscrew angle >5°. Demographic, radiographic, and clinical risk factors for presumed VBT breaks were evaluated. RESULTS: In confirmed VBT breaks, the average interscrew angle change was 8.1°, and segmental coronal curve change was 13.6°, with a high correlation ( r =0.82). Our presumed VBT break cohort constituted 50 thoracic tethers, four lumbar tethers, and nine combined thoracic/lumbar tethers; the average age was 12.1±1.2 years and the mean follow-up was 73.1±11.7 months. Of 59 patients with thoracic VBTs, 12 patients (20.3%) had a total of 18 breaks. Eleven thoracic breaks (61.1%) occurred between two and five years postoperatively, and 15 (83.3%) occurred below the curve apex ( P <0.05). The timing of thoracic VBT breakage moderately correlated with more distal breaks ( r =0.35). Of 13 patients who underwent lumbar VBT, eight patients (61.5%) had a total of 12 presumed breaks. Six lumbar breaks (50%) occurred between one and two years postoperatively, and seven (58.3%) occurred at or distal to the apex. Age, sex, body mass index, Risser score, and curve flexibility were not associated with VBT breaks, but the association between percent curve correction and thoracic VBT breakage trended toward significance ( P =0.054). Lumbar VBTs were more likely to break than thoracic VBTs ( P =0.016). Seven of the patients with presumed VBT breaks (35%) underwent revision surgery. CONCLUSIONS: Lumbar VBTs broke with greater frequency than thoracic VBTs, and VBT breaks typically occurred at levels distal to the curve apex. Only 15% of all patients required revision. LEVEL OF EVIDENCE: 3.

Building consensus for the medical management of children with moderate and severe acute spinal cord injury: a modified Delphi study.

OBJECTIVE: The focus of this modified Delphi study was to investigate and build consensus regarding the medical management of children with moderate and severe acute spinal cord injury (SCI) during their initial inpatient hospitalization. This impetus for the study was based on the AANS/CNS guidelines for pediatric SCI published in 2013, which indicated that there was no consensus provided in the literature describing the medical management of pediatric patients with SCIs. METHODS: An international, multidisciplinary group of 19 physicians, including pediatric neurosurgeons, orthopedic surgeons, and intensivists, were asked to participate. The authors chose to include both complete and incomplete injuries with traumatic as well as iatrogenic etiologies (e.g., spinal deformity surgery, spinal traction, intradural spinal surgery, etc.) due to the overall low incidence of pediatric SCI, potentially similar pathophysiology, and scarce literature exploring whether different etiologies of SCI should be managed differently. An initial survey of current practices was administered, and based on the responses, a follow-up survey of potential consensus statements was distributed. Consensus was defined as ≥ 80% of participants reaching agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). A final meeting was held virtually to generate final consensus statements. RESULTS: Following the final Delphi round, 35 statements reached consensus after modification and consolidation of previous statements. Statements were categorized into the following eight sections: inpatient care unit, spinal immobilization, pharmacological management, cardiopulmonary management, venous thromboembolism prophylaxis, genitourinary management, gastrointestinal/nutritional management, and pressure ulcer prophylaxis. All participants stated that they would be willing or somewhat willing to change their practices based on consensus guidelines. CONCLUSIONS: General management strategies were similar for both iatrogenic (e.g., spinal deformity, traction, etc.) and traumatic SCIs. Steroids were recommended only for injury after intradural surgery, not after acute traumatic or iatrogenic extradural surgery. Consensus was reached that mean arterial pressure ranges are preferred for blood pressure targets following SCI, with goals between 80 and 90 mm Hg for children at least 6 years of age. Further multicenter study of steroid use following acute neuromonitoring changes was recommended.

Surgical Outcomes of Cerebral Palsy Patients With Scoliosis and Lumbar Hyperlordosis: A Comparative Analysis With 2-year Minimum Follow-up.

STUDY DESIGN: Retrospective review of a prospectively collected multicenter database. OBJECTIVE: To compare outcomes of patients with cerebral palsy (CP) who undergo surgery for scoliosis with normal lordosis (NL) versus hyperlordosis. SUMMARY OF BACKGROUND DATA: Surgical correction of scoliosis with lumbar hyperlordosis is challenging. Hyperlordosis may confer higher perioperative morbidity, but this is not well understood. MATERIALS AND METHODS: A multicenter database was queried for CP patients who underwent surgery from 2008 to 2017. The minimum follow-up was 2 years. Two groups were identified: lumbar lordosis <75° (NL) versus ≥ 75° hyperlordosis (HL). Perioperative, radiographic, and clinical outcomes were compared. RESULTS: Two hundred seventy-five patients were studied: 236 NL and 39 HL (-75 to -125°). The mean age was 14.1 years, and 52.4% were male. Patients with hyperlordosis had less cognitive impairment (76.9% vs. 94.0%, P =0.008) and higher CPCHILD scores (59.4 vs. 51.0, P =0.003). Other demographics were similar between the groups. Patients with hyperlordosis had greater lumbar lordosis (-90.5 vs. -31.5°, P <0.001) and smaller sagittal vertical axis (-4.0 vs. 2.6 cm, P <0.001). Patients with hyperlordosis had greater estimated blood loss (2222.0 vs. 1460.7 mL, P <0.001) but a similar perioperative complication rate (20.5% vs. 22.5%, P =0.787). Significant correction of all radiographic parameters was achieved in both groups. The HL group had postoperative lumbar lordosis of -68.2° and sagittal vertical axis of -1.0 cm. At a 2-year follow-up, patients with hyperlordosis continued to have higher CPCHILD scores and gained the greatest benefit in overall quality of life measures (20.0 vs. 6.1, P =0.008). The reoperation rate was 10.2%: implant failure (3.6%), pseudarthrosis (0.7%), and wound complications (7.3%). There were no differences in the reoperation rate between the groups. CONCLUSION: Surgical correction of scoliosis with hyperlordosis is associated with greater estimated blood loss but similar radiographic results, perioperative morbidity, and reoperation rate as normal lordosis. Patients with hyperlordosis gained greater overall health benefits. Correction of ≥25% of hyperlordosis seems satisfactory. LEVEL OF EVIDENCE: 3.