The NLRP3 Inflammasome Is Dispensable in Methicillin-Resistant Staphylococcus aureus Urinary Tract Infection.

The NLRP3 inflammasome is a cytoplasmic complex that senses molecular patterns from pathogens or damaged cells to trigger an innate immune defense response marked by the production of proinflammatory cytokines IL-1ß and IL-18 and an inflammatory death called pyroptosis. The NLRP3 inflammasome is activated in the urinary tract by a variety of infectious and non-infectious insults. In this study, we investigated the role of the NLRP3 inflammasome by comparing the pathophysiology of methicillin-resistant Staphylococcus aureus (MRSA) ascending UTI in wild-type (WT) and Nlrp3-/- mice. The difference in the bacterial burden detected in the urinary tracts of MRSA-infected WT and Nlrp3-/- was not statistically significant at 6, 24, and 72 h post-infection (hpi). The levels of pro-inflammatory cytokines and chemokines as well as the numbers of granulocytes recruited to bladder and kidney tissues at 24 hpi were also similar between Nlrp3-/- and WT mice. The histopathological analysis of MRSA-infected bladder and kidney sections from Nlrp3-/- and WT mice showed similar inflammation. Overall, these results suggest that MRSA-induced urinary NLRP3 activity does not play a role in the pathophysiology of the ascending UTI.

SHIV-C109p5 NHP induces rapid disease progression in elderly macaques with extensive GI viral replication.

CCR5-tropic simian/human immunodeficiency viruses (SHIV) with clade C transmitted/founder envelopes represent a critical tool for the investigation of HIV experimental vaccines and microbicides in nonhuman primates, although many such isolates lead to spontaneous viral control post infection. Here, we generated a high-titer stock of pathogenic SHIV-C109p5 by serial passage in two rhesus macaques (RM) and tested its virulence in aged monkeys. The co-receptor usage was confirmed before infecting five geriatric rhesus macaques (four female and one male). Plasma viral loads were monitored by reverse transcriptase-quantitative PCR (RT-qPCR), cytokines by multiplex analysis, and biomarkers of gastrointestinal damage by enzyme-linked immunosorbent assay. Antibodies and cell-mediated responses were also measured. Viral dissemination into tissues was determined by RNAscope. Intravenous SHIV-C109p5 infection of aged RMs leads to high plasma viremia and rapid disease progression; rapid decrease in CD4+ T cells, CD4+CD8+ T cells, and plasmacytoid dendritic cells; and wasting necessitating euthanasia between 3 and 12 weeks post infection. Virus-specific cellular immune responses were detected only in the two monkeys that survived 4 weeks post infection. These were Gag-specific TNFα+CD8+, MIP1ß+CD4+, Env-specific IFN-γ+CD4+, and CD107a+ T cell responses. Four out of five monkeys had elevated intestinal fatty acid binding protein levels at the viral peak, while regenerating islet-derived protein 3α showed marked increases at later time points in the three animals surviving the longest, suggesting gut antimicrobial peptide production in response to microbial translocation post infection. Plasma levels of monocyte chemoattractant protein-1, interleukin-15, and interleukin-12/23 were also elevated. Viral replication in gut and secondary lymphoid tissues was extensive.IMPORTANCESimian/human immunodeficiency viruses (SHIV) are important reagents to study prevention of virus acquisition in nonhuman primate models of HIV infection, especially those representing transmitted/founder (T/F) viruses. However, many R5-tropic SHIV have limited fitness in vivo leading to many monkeys spontaneously controlling the virus post acute infection. Here, we report the generation of a pathogenic SHIV clade C T/F stock by in vivo passage leading to sustained viral load set points, a necessity to study pathogenicity. Unexpectedly, administration of this SHIV to elderly rhesus macaques led to extensive viral replication and fast disease progression, despite maintenance of a strict R5 tropism. Such age-dependent rapid disease progression had previously been reported for simian immunodeficiency virus but not for R5-tropic SHIV infections.

Differences in spine growth potential for Sanders maturation stages 7A and 7B have implications for treatment of idiopathic scoliosis.

PURPOSE: This study aimed to clarify the differences in spine and total body height growth and curve progression between Sanders maturation stage (SMS) 7A and 7B in patients with adolescent idiopathic scoliosis (AIS). METHODS: This retrospective case-control study involving patients with AIS at SMS 7 evaluated the differential gains in the spine (T1-S1) and total body height and curve progression between SMS 7A and 7B. A validated formula was used to calculate the corrected height, accounting for height loss due to scoliosis. A multivariable non-linear and logistic regression model was applied to assess the distinct growth and curve progression patterns between the SMS 7 subtypes, adjusting for potential confounders. RESULTS: A total of 231 AIS patients (83% girls, mean age 13.9 ± 1.2 years) were included, with follow-up averaging 3.0 years. Patients at SMS 7A exhibited larger gains in spine height (9.9 mm vs. 6.3 mm) and total body height (19.8 mm vs. 13.4 mm) compared with SMS 7B. These findings remained consistent even after adjustments for curve magnitude. Non-linear regression models showed continued spine and total body height increases plateauing after 2 years, significantly greater in SMS 7A. More SMS 7A patients had curve progression over 10°, with an adjusted odds ratio of 3.31. CONCLUSION: This study revealed that patients staged SMS 7A exhibited more spine and total body growth and a greater incidence of substantial curve progression than those at 7B. These findings imply that delaying brace discontinuation until reaching 7B could be beneficial, particularly for those with larger curves. LEVEL OF EVIDENCE: Level III (Case-control study).

The Role of Liposomal Bupivacaine in Multimodal Pain Management Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: Faster and Farther With Less Opioids.

STUDY DESIGN: Retrospective controlled cohort. OBJECTIVE: To evaluate the effect of intraoperative liposomal bupivacaine (LB) infiltration on postsurgical pain management in adolescent idiopathic scoliosis (AIS) patients by analyzing postoperative opioid consumption, ambulation, and length of stay (LOS). SUMMARY OF BACKGROUND DATA: Optimal postoperative pain control for AIS patients undergoing posterior spinal fusion (PSF) is challenging. Multimodal pain management protocols provide adequate analgesia while decreasing opioid consumption. LB was recently approved for pediatric patients; however, use in AIS patients is understudied. METHODS: 119 consecutive patients with AIS who underwent PSF were included. Patients were divided into 2 groups: patients who received LB as erector spinae block in addition to the standard postoperative pain management protocol (Group A), and patients who received only the standard postoperative pain protocol (Group B). Oral morphine equivalents, intravenous opioid and valium consumption, pain scores (VAS), nausea/vomiting, ambulation distance and LOS were assessed. RESULTS: Group A experienced significantly lower total opioid consumption compared to Group B (44.5 mg vs. 70.2 mg). Morphine use was lower in Group A on postoperative day (POD) 0, and oxycodone use was lower in Group A on PODs 1 and 2. There was a higher proportion of patients who used only oral opioids in Group A (81% vs. 41%). Of patients requiring any intravenous opioids, 79% did not receive LB. A significantly higher proportion of LB patients were discharged on POD 2 (55% vs. 27%); therefore, LOS was shorter for Group A. Group A ambulated further postoperatively. There were no differences in pain scores, valium requirements or nausea/vomiting. CONCLUSIONS: LB was associated with decreased total opioid use, shorter LOS, and improved ambulation in AIS patients undergoing PSF. Including LB in multimodal pain management protocols proved effective in reducing opioid use while increasing mobilization in the immediate postoperative period. LEVEL OF EVIDENCE: 3.

Socioeconomic, Racial, and Insurance Disparities in Clinical Outcomes After Surgery Among Patients With Idiopathic Scoliosis.

BACKGROUND: Socioeconomic status (SES), race, and insurance type correlate with initial curve severity for patients with idiopathic scoliosis, but less is known regarding how these variables impact surgical outcomes. The objectives of this study were to determine the influence of SES, race, and insurance on preoperative appointment attendance, likelihood of obtaining a preoperative second opinion, brace prescription, missed 6 or 12-month postsurgical appointments, incidence of emergency department visits 0 to 90 days after surgery, and major complications within a year of surgery. METHODS: A review of 421 patients diagnosed with idiopathic scoliosis who underwent surgery at a single high-volume pediatric spinal deformity institution between May 2015 and October 2021 was conducted. Area Deprivation Index, a quantitative measure of SES, was collected. Scores were stratified by quartile; higher scores indicated a lower SES. χ 2 tests for correlation were performed to determine whether clinical outcomes were dependent upon Area Deprivation Index, race, or insurance type; P ≤0.05 was significant. RESULTS: The sample was 313 Caucasian (74%), 69 (16%) black, and 39 (9.3%) other patients. More patients had private versus public insurance (80% vs 20%) and were of higher SES. The likelihood of missing preoperative appointments was higher for black patients ( P = 0.037). Those with lower SES missed more postoperative appointments and received less bracing and second opinions ( P = 0.038, P = 0.017, P = 0.008, respectively). Being black and publicly insured correlated with fewer brace prescriptions ( P < 0.001, P = 0.050) and decreased rates of obtaining second opinions ( P = 0.004,  P = 0.001). CONCLUSION: Patients with idiopathic scoliosis surgery who were Caucasian, privately insured, and of higher SES were more likely to seek preoperative second opinions, be prescribed a brace, and attend postoperative appointments. Recognition of the inherent health care disparities prevalent within each pediatric spine surgery referral region is imperative to better inform local and national institutional level programs to educate and assist patients and families most at risk for disparate access to scoliosis care. LEVEL OF EVIDENCE: Level III; retrospective case-control study.

Do Pedicle Screws That Terminate in the Costovertebral Joint Compromise Proximal Anchor Fixation in a Dual Growing Rod Construct?

INTRODUCTION: Growing rods (GRs) are used to treat early-onset scoliosis (EOS) recalcitrant to bracing and casting. Proximal anchor pullout, a known complication of GR constructs, can result in spinal cord injury if pedicle screw anchors are placed with a lateral-to-medial trajectory. To mitigate this risk, a more straightforward and potentially safer trajectory may result in screws that terminate within the costovertebral joint (CVJ). We asked, how often does CVJ placement occur and does this technique increase the rate of failure in GR constructs? METHODS: We retrospectively reviewed 35 patients with EOS treated with dual GR with >2-year follow-up excluding patients with skeletal dysplasia or history of previous posterior instrumentation. Patient demographics, radiographic parameters, and implant constructs were assessed. RESULTS: Of patients meeting the inclusion criteria, 18/35 (51%) were females with an average age of 7.96 (range: 4.0 to 15.2) years at surgery with a follow-up of 3.7 (range: 2.0 to 7.7) years. Five (14%) patients had idiopathic EOS, 5 (14%) had congenital EOS, 12 (34%) had neuromuscular EOS, 10 (29%) had syndromic scoliosis, and 3 (9%) had another etiology for EOS. Among 195 proximal pedicle screws placed, 19 (10%) terminated within the CVJ, and 13 patients (37%) had at least 1 CVJ screw. Two patients (6%) experienced unilateral proximal pullout. In both patients, the anchors on the affected side included 1 of 2 screws within the CVJ. Both patients had constructs that included 2 screws on the side that pulled out and 3 screws on the side that did not. None of the remaining 17 CVJ screws led to implant failure. CONCLUSION: Pedicle screw placement within the CVJ is common and does not appear to significantly contribute to proximal screw pullout; however, it may contribute to unilateral implant failure in constructs employing only 2 proximal screws, where 1 of those 2 screws terminates within the CVJ. Construct modifications should be considered in this scenario. LEVEL OF EVIDENCE: Level III.

Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.

Bone alterations of pamidronate therapy in children with cerebral palsy complicating orthopedic management.

Cerebral palsy (CP) is a heterogeneous group of disorders with different clinical types and underlying genetic variants. Children with CP are at risk for fragility fractures secondary to low bone mineral density, and although bisphosphonates are prescribed for the treatment of children with bone fragility, there is limited information on long-term bone impact and safety. Children with CP usually present overtubulated bones, and the thickening of cortical bone by pamidronate treatment can potentially further narrow the medullary canal. Our purpose was to report bone alterations attributable to pamidronate therapy that impact orthopedic care in children with CP. The study consisted of 41 children with CP treated with pamidronate for low bone mineral density from 2006 to 2020. Six children presented unique bone deformities and unusual radiologic features attributed to pamidronate treatment, which affected their orthopedic care. The cases included narrowing of the medullary canal and sclerotic bone, atypical femoral fracture, and heterotopic ossification. Treatment with bisphosphonate reduced the number of fractures from 101 in the pretreatment period to seven in the post-treatment period (P < 0.001). In conclusion, children with CP treated with bisphosphonate have a reduction in low-energy fractures; however, some fractures still happen, and pamidronate treatment can lead to bone alterations including medullary canal narrowing with sclerotic bone and atypical femoral fractures. In very young children, failure to remodel may lead to thin, large femoral shafts with cystic medullary canals. More widespread use of bisphosphonates in children with CP may make these bone alterations more frequent. Level of evidence: Level IV: Case series with post-test outcomes.

Walking status and spinopelvic parameters in young children with achondroplasia: 10-year follow-up.

PURPOSE: Thoracolumbar kyphosis (TLK) is common in children with achondroplasia and resolves in 90% by 10 years of age. Our purpose was to describe the natural progression of TLK in a cohort of pre-walking children with achondroplasia. METHODS: A single-center, retrospective review identified 62 children (32 male, 30 female) with achondroplasia. Clinical information and sagittal spinopelvic parameters were collected. The children were divided into positive pelvic tilt (PT) and negative PT. All parents were routinely counseled about unsupported sitting. RESULTS: Spontaneous resolution rate was 64.5% at 1-year post-walking, 74.2% at 5 years of age, and 88.7% at 10 years of age. None of the children required posterior spinal decompression and fusion for progressive deformity or symptomatic spinal stenosis. At 1-year post-walking, the negative PT group had a higher sacral slope (p = 0.006), higher lumbar lordosis (p < 0.001), and lower pelvic incidence (p < 0.001). This relationship remained constant up to 10 years of age, and there was no association with TLK. CONCLUSION: In this largest series to date, spontaneous resolution of TLK in children with achondroplasia was 64.5% at 1-year post-walking, 74.2% at 5 years of age, and 88.7% in children followed to 10 years of age. With early identification and regular follow-up with patient education, no patient in this series required treatment or developed symptomatic spinal stenosis. While not predictive of resolution of TLK, the dichotomous presentation of PT in young children with achondroplasia persists at 5 and 10 years of age and reliably predicts the spinopelvic parameters. LEVEL OF EVIDENCE: III-retrospective comparative study.

Subclassification of Sanders Maturation Stage 3 Demonstrates Differences in Spine and Total Height Velocity Between 3A and 3B in Patients with Idiopathic Scoliosis.

STUDY DESIGN: A single-center retrospective case-control study. OBJECTIVE: To compare the spine and total height velocity between Sanders maturation stage (SMS) 3A and 3B. SUMMARY OF BACKGROUND DATA: Identifying SMS 3 is critical for treating growing children because it represents the early phase of rapid adolescent growth. However, there is limited literature available that clearly describes the growth differences between 3A and 3B. METHODS: The current study included consecutive patients with idiopathic scoliosis staged SMS 3 from January 2012 to December 2021. T1-S1 spine height, total body height, and curve magnitude were measured at the initial and follow-up visits. In addition to the spine and total height velocity calculated per month, corrected height velocity was estimated for curve magnitude using a validated formula. Mann-Whitney U test was used to compare SMS 3A and 3B outcomes, followed by a multiple linear regression model to evaluate the association of the SMS subclassifications to growth velocity adjusted for confounding factors. RESULTS: A total of 204 patients (66% girls, mean age: 12.3±1.3 y) met the inclusion criteria. Patients staged SMS 3A had higher spine height velocity (mm/month) in both girls (2.3 vs. 1.5, P<0.001) and boys (2.6 vs. 1.7, P<0.001), as well as total height velocity (mm/month; (5.8 vs. 4.3, P<0.001 for girls; 6.6 vs. 4.5, P<0.001 for boys). Corrected velocity showed similar results with greater spine and total height velocity in SMS 3A. Multivariate analysis indicated a significant association of the SMS subclassification to the spine and total height velocity. The scoliosis curve progression was comparable between SMS 3A and 3B. CONCLUSION: SMS 3A and 3B had differential growth velocity in the spine and total body height. These results advocated the significance of SMS 3 subclassification for managing scoliosis treatment, including observation, bracing, and surgical interventions with fusion and growth modulation. LEVEL OF EVIDENCE: Level III (Case-control study).

Transcranial electric motor evoked potential monitoring during scoliosis surgery in children with cerebral palsy and active seizure disorder: is it feasible and safe?

PURPOSE: Use of spinal cord monitoring in children with cerebral palsy (CP) and neuromuscular scoliosis is challenging. The previous reports suggest low success rates in the setting of CP, and it is unclear if transcranial electric motor evoked potentials (TcMEP) monitoring is contraindicated in patients with an active seizure disorder. The purpose of this study was to determine (1) are patients with CP able to be appropriately monitored with TcMEP? and (2) does TcMEP cause an increase in seizure activity? METHODS: This was an institutional review board-approved retrospective cohort study observing 304 patients from 2011 to 2020. Inclusion criteria included all patients with CP undergoing posterior spinal fusion during this time. Intraoperative data were examined for the ability to obtain monitoring and any intraoperative events. Patients were followed for 3 months postoperatively to determine any increase in seizure activity that could have been attributed to the TcMEP monitoring. RESULTS: Of the 304 patients who were observed, 21% (20.8%) were unable to be monitored due to lacking baseline signals from the extremities. Seventy-seven percent (77.5%) were successfully monitored with TcMEP. For these patients, no increased seizure activity was documented either intra- or postoperatively. CONCLUSION: A high percentage of children (77.5%) with CP were able to be successfully monitored with TcMEP during posterior spinal fusion. Furthermore, the concerns about increased seizure activity after TcMEP were not supported by the data from this cohort. Technical details of successful neuromonitoring in these patients are important and included increased stimulation voltage requirements and latency times. LEVEL OF EVIDENCE: III retrospective comparative study.

Identification of risk factors for reconstructive hip surgery after intrathecal baclofen therapy in children with cerebral palsy.

OBJECTIVE: This study aimed to determine the risk factors for reconstructive hip surgery after intrathecal baclofen pump application in children with cerebral palsy. METHODS: Inclusion criteria were children with hypertonic (spastic or mixed spastic/dystonic motor type) cerebral palsy, intrathecal baclofen implantation <8 years of age, no reconstructive osteotomies prior to or concomitant with intrathecal baclofen implantation and at least a 5-year follow-up. Exclusion criteria included reconstructive osteotomies prior to or concurrent with intrathecal baclofen implantation, lack of at least 1 hip surveillance radiograph before intrathecal baclofen, lack of a 5-year follow-up, or having selective dorsal rhizotomy. In addition, patients with bony surgery plus last follow-up migration percentage ≥50% were labeled as required reconstruction hips. RESULTS: We identified 34 patients (68 hips). The mean follow-up was 9.2 ± 2.8 years. The mean age for intrathecal baclofen application was 6.4 ± 1.2 years. Seven patients were Gross Motor Function Classification System IV, and 27 were V. Eighteen patients (52.9%) with 31 hips (45.6%) were requiring reconstruction at the final follow-up. In multivariate analysis, male sex (odds ratio 12.8, P=.012), pre-intrathecal baclofen migration percentage (odds ratio 1.1, P=0.003), age at intrathecal baclofen implantation (odds ratio 0.24, P=.002), and delta migration percentage (odds ratio 1.1, P=.002) were significant risk factors for requiring reconstruction. Patients with intrathecal baclofen <6.2 years of age had a significantly higher rate of requiring reconstruction. A pre-intrathecal baclofen migration percentage >31% had a greater risk of progression to requiring reconstruction (P=.001). Delta migration percentage higher than 15% was significantly associated with progression to requiring reconstruction (P=.043). CONCLUSION: The risk of requiring reconstruction osteotomies after intrathecal baclofen was significantly increased in males, those younger (±migration percentage >31%) at the time of intrathecal baclofen implantation and those with an increased rate of migration percentage progression after intrathecal baclofen implantation. LEVEL OF EVIDENCE: Level IV, Prognostic Study.

A Sonography-based Decision Model for Use in Treatment of Developmental Dysplasia of the Hip.

The objective of this study was to delineate a model for management of developmental dysplasia of the hip (DDH) treatment that incorporates hip ultrasound with objective/predicative parameters at key decision-making times. Hip sonograms of 74 infants (59 females, 15 males; 141 hips) with DDH were retrospectively reviewed. Hip sonographic score (HSS; ranges 0-10) was developed to reflect hip status based on sonographic position, stability, and morphology. Analysis on different management groups (i.e., no treatment, successful treatment, and failed treatment) showed that the trend of HSS is helpful in predicting course of the disease and determining effectiveness of treatment. A model for the management of DDH that utilizes an HSS and frequency schedule for hip sonography that is aligned with times of critical treatment decisions is proposed. This model illustrates how hip sonography can bring added value when timed to guide critical treatment decisions. (Journal of Surgical Orthopaedic Advances 32(1):047-054, 2023).

The Fate of the Bent Rod in Children With Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a genetic disorder characterized by brittle bones and long bone deformity. Realignment and intramedullary rodding with telescopic rods are indicated for progressive deformity and can help prevent fractures. Rod bending is a reported complication of telescopic rods and a common indication for revision; however, the fate of bent lower extremity telescopic rods in the setting of OI has not been reported. METHODS: Patients with OI at a single institution who underwent lower extremity telescopic rod placement with at least 1-year follow-up were identified. Bent rods were identified, and for these bone segments, we collected the location and angle of bend, subsequent telescoping, refracture, increasing angulation of bend, and date of revision. RESULTS: One hundred sixty-eight telescopic rods in 43 patients were identified. Forty-six rods (27.4%) bent during follow-up, with an average angulation of 7.3 (range: 1 to 24) degrees. In patients with severe OI, 15.7% of rods bent compared with 35.7% in nonsevere OI ( P =0.003). The proportion of bent rods was different between independent and nonindependent ambulators (34.1% and 20.5%; P =0.035). Twenty-seven bent rods (58.7%) were revised, with 12 rods (26.0%) revised early (within 90 d). The angulation of rods that were revised early was significantly higher than rods not (14.6 and 4.3 degrees, P <0.001). Of the 34 bent rods not revised early, the average time to revision or final follow-up was 29.1 months. Twenty-five rods (73.5%) continued to telescope, 14 (41.2%) increased in angulation (average 3.2 degrees), and 10 bones (29.4%) refractured. None of the refractures required immediate rod revision. Two bones had multiple refractures. CONCLUSIONS: Bending is a common complication of telescopic rods in the lower extremities of patients with OI. It is more common in independent ambulators and patients with nonsevere OI, possibly because of the increased demand placed on the rods. Rods with a small bend and maintained fixation can telescope and need not be an indication for immediate revision. LEVEL OF EVIDENCE: Level III-Retrospective review.

Mortality after spinal fusion in children with cerebral palsy and cerebral-palsy-like conditions: A 30-year follow-up study.

AIM: To report survival probability of a large cohort of children with cerebral palsy (CP) after spinal fusion. METHOD: All children with CP who had spinal fusion between 1988 and 2018 at the reporting facility were reviewed for survival. Death records of the institutional CP database, institutional electronic medical records, publicly available obituaries, and the National Death Index through the US Centers for Disease Control were searched. Survival probabilities with different surgical eras, comorbidities, ages, and curve severities were compared using Kaplan-Meier curves. RESULTS: A total of 787 children (402 females, 385 males) had spinal fusion at a mean age of 14 years 1 month (standard deviation 3 years 2 months). The 30-year estimated survival was approximately 30%. Survival decreased for children who had spinal fusion at younger ages, longer postoperative hospital stays, longer postoperative intensive care unit stays, gastrostomy tubes, and pulmonary comorbidities. INTERPRETATION: Children with CP who required spinal fusions had reduced long-term survival compared with an age-matched typically developing cohort; however, a substantial number survived 20 to 30 years after the surgery. This study had no comparison group of children with CP scoliosis; therefore, we do not know whether correction of scoliosis affected their survival.

Closed displaced femur fractures in children with nonambulatory cerebral palsy.

Femoral fractures in children withcerebral palsy (CP) represent a frequent medical problem, and treatment represents a challenge. The purpose of this study was to review the closed displaced femoral fractures in our population of nonambulatory children with CP to compare the results of nonoperative and operative treatment modalities to improve the care of these children. From 2006 to 2020, children with nonambulatory CP were selected with inclusion criteria of displaced femoral fracture and were divided into nonoperative and operative groups. Forty-four children met the inclusion criteria. The nonoperative group included 23 children and the operative group included 21 children. Mechanism of injury was unknown in 48% of the fractures. Fourteen (25%) fractures occurred after a femoral plate fixation during a reconstructive hip surgery, and 38 (86%) children had osteopenia. Our results reveal a high prevalence of osteopenia, low-energy trauma, malunion in nonoperative treatment, and peri-implant fractures. Suspicion of child abuse should be considered when the fracture has an unclear mechanism of the injury. Removal of proximal femoral implants may be considered to prevent peri-implant fractures. Femoral fractures should preferably be treated nonoperatively. Operative treatment should be considered for diaphyseal fractures in children capable of standing transfers, larger children, children with more severe spasticity or movement disorder or those who have suffered a high-energy fracture. Due to the high prevalence of proximal fractures in the presence of hardware, operative treatment is usually required for these fractures. In contrast, distal fractures are adequately managed nonoperatively.

Hip Displacement Does Not Change After Pelvic Obliquity Correction During Spinal Fusion in Children With Cerebral Palsy.

BACKGROUND: Children with cerebral palsy (CP) frequently develop both neuromuscular hip dysplasia and scoliosis, and occasionally, the timing of the worsening of both of these pathologies is concurrent. The question as to whether the hip or spine should be addressed first in CP remains controversial, with the majority of evidence being "expert opinion." The purpose of this project was to determine the impact of posterior spinal fusion (PSF) on the change in hip displacement for children with CP without previous reconstructive hip surgery. METHODS: This was an Institutional Review Board-approved study that observed 67 patients from 2004 to 2018. Inclusion criteria included children with CP, 18 years of age and younger, Gross Motor Function Classification System IV and V, undergoing PSF at a single tertiary care children's hospital with a minimum 2-year follow-up. The primary outcome was the change in hip displacement as quantified by the migration percentage (MP). The hip with the highest MP (worst hip) at the spine preoperative analysis were included for analysis. Triradiate cartilage (TRC) status and pelvic obliquity correction were analyzed with multivariate analysis. RESULTS: Sixty-seven patients were included for analysis, with a mean age of 12.5±2.3 years. The mean major curve angle of the major curve was 77±23 degrees and the mean preoperative pelvic obliquity was 21±12 degrees. There was no statistically significant change in MP after PSF from a mean preoperative value of 41±27%, to a mean postoperative value of 41±29% at the last follow-up, (P=0.76) The mean follow-up time was 4.1±2.7 years. TRC status (P=0.52) and the severity of pelvic obliquity (P=0.10) did not statistically impact the change in MP after PSF. CONCLUSION: PSF did not influence-either negatively or positively-the progression of hip displacement in children with CP, regardless of pelvic obliquity correction or TRC status. The lack of deterioration in hip displacement post-PSF, however, may suggest a protective effect of spine surgery. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Does intrathecal baclofen therapy decrease the progression of hip displacement in young patients with cerebral palsy?

AIM: To evaluate the effects of intrathecal baclofen pump (ITBP) therapy on hip dysplasia in young patients with cerebral palsy (CP). METHOD: This was a retrospective cohort series of prospectively collected data. Inclusion criteria were all patients with CP in Gross Motor Function Classification System (GMFCS) levels IV or V who underwent ITBP placement under 8 years old with at least 5 years of follow-up. Thirty-four patients were matched to a control group of 71 patients based on GMFCS level, motor type, medical comorbidities, worst hip migration percentage at ITBP placement, age, and Modified Ashworth scale scores. Patients were followed for at least 5 years or until they had hip reconstructive surgery. The primary outcome was the development of hip displacement as measured by the migration percentage at the latest follow-up or the preoperative migration percentage before hip reconstruction. RESULTS: The migration percentage at last follow-up was not statistically different between groups (ITBP: 36.2%, non-ITBP: 44.4%, p = 0.14). The rates of future preventative, reconstructive, and recurrent hip surgery were not different between groups. INTERPRETATION: The use of ITBP as an early treatment of spasticity did not alter the natural history of progressive hip displacement in non-ambulatory patients with CP and hip displacement is likely multifactorial, not solely due to spasticity.

Hip Displacement After Triradiate Cartilage Closure in Nonambulatory Cerebral Palsy: Who Needs Continued Radiographic Surveillance?

BACKGROUND: Recommendations with regard to the need for continued hip surveillance after skeletal maturity are based on expert opinion rather than evidence. This study aimed to determine the prevalence of and risk factors associated with progressive hip displacement in cerebral palsy (CP) after triradiate cartilage (TRC) closure. METHODS: Patients who had spastic nonambulatory CP (Gross Motor Function Classification System IV to V) and hypertonic (spastic or mixed-type) motor type and follow-up of at least 2 years after TRC closure were included. The primary outcome variable was the hip migration percentage (MP). The secondary outcome variables included patient age at the time of TRC closure, prior preventative or reconstructive surgery, a prior intrathecal baclofen pump, history of scoliosis, history of epilepsy, a prior gastrostomy tube, a previous tracheostomy, and gender. An unsuccessful hip outcome was defined as a hip with an MP of ≥40% and/or requiring a reconstructive surgical procedure after TRC closure. RESULTS: In this study, 163 patients met the inclusion criteria, with a mean follow-up of 4.8 years (95% confidence interval [CI], 4.4 to 5.1 years) after TRC closure at a mean patient age of 14.0 years (95% CI, 13.7 to 14.3 years). Of these hips, 22.1% (36 of 163) had an unsuccessful hip outcome. In multivariate analysis, the first MP at TRC closure (hazard ratio [HR] per degree, 1.04; p < 0.001) and pelvic obliquity (HR per degree, 1.06; p = 0.003) were independent risk factors for an unsuccessful hip outcome, but gender was not found to be significant (HR for male gender, 1.7 [95% CI, 0.8 to 3.58; p = 0.16]; female gender was the reference). However, the mean survival time for progression to an unsuccessful hip outcome was longer for female patients at 9.2 years [95% CI, 8.1 to 10.2 years]) compared with 6.2 years (95% CI, 5.6 to 6.9 years) for male patients (p = 0.02). There was also a significant improvement in survivorship for prior reconstructive surgical procedures (p = 0.002). The survivorship in patients who underwent reconstructive surgery performed at a patient age of ≥6 years was significantly higher compared with those who underwent surgery performed at <6 years of age (p < 0.05). A first MP at TRC closure of ≥35% was associated with an unsuccessful hip outcome, as determined by receiver operating characteristic (ROC) curve analysis (p < 0.001; area under the ROC curve of 0.891, sensitivity of 81%, and specificity of 94%). CONCLUSIONS: The risk factors for the progression of hip displacement after TRC closure in patients with CP included a higher MP and increased pelvic obliquity; there was decreased survivorship for male patients and patients with no prior reconstructive surgery. Patients with these risk factors and/or an MP of ≥35% at TRC closure should have continued radiographic surveillance to detect late hip displacement. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Femoral Head Deformity Associated With Hip Displacement in Nonambulatory Cerebral Palsy: Results at Skeletal Maturity.

BACKGROUND: Maintaining femoral head shape (FHS) and acetabular sphericity are important goals in preventing long-term osteoarthritis in hips in children with cerebral palsy (CP). As acetabular morphology has been widely studied, our objective was to determine FHS in CP after triradiate cartilage (TRC) closure, a proxy for skeletal maturity, and the risk factors associated with residual deformity and osteoarthritis. METHODS: In this retrospective cohort study, patients with CP [Gross Motor Function Classification System (GMFCS) IV to V], minimum 4 yearly hip radiographs after age 10 years, and at least 1 radiograph after age 16 years, were included. Primary outcome was FHS (Rutz), stratified as "less severe" (Rutz A to B) and "more severe" (Rutz C to D). Secondary outcomes included migration percentage (MP), age at TRC closure, previous reconstructive (femoral with/without pelvic osteotomies) surgery, previous intrathecal baclofen, Tönnis osteoarthritis grade, and GMFCS level. Statistical analyses included χ 2 analysis and multiple logistic regression. RESULTS: One hundred sixty-three patients (326 hips) met the inclusion criteria, with TRC closure at age 14.0 (SD: 1.8) years. At final follow-up of 4.4 (SD: 2.4) years after TRC closure, 17% (55 hips), had a "more severe" FHS. From TRC closure to final follow-up, the frequencies of "less severe" hips decreased (-10%, P <0.001), while "more severe" increased (+115%, P <0.001). In multiple regression analysis, MP at TRC closure was the only significant risk factor associated with a "more severe" FHS at final follow-up ( P =0.03). Receiver operating characteristic curve analysis determined MP≥30.5% to be associated with a "more severe" FHS at final follow-up ( P <0.009). The FHS was not affected by reconstructive surgery, sex, GMFCS level, or intrathecal baclofen use. "Less severe" hips had lower Tönnis grades (0 to 1) compared with "more severe" hips (Tönnis grades 2 to 3) at final follow-up ( P <0.001). CONCLUSIONS: FHS at skeletal maturity was not influenced by prior reconstructive surgery but was negatively affected when MP≥30.5% at the time of TRC closure. The extent of residual femoral head deformity correlated with the severity of osteoarthritis at final follow-up. LEVEL OF EVIDENCE: Level III.