Scoliosis Development in Spinal Muscular Atrophy: The Influences of Genetic Severity, Functional Level, and Disease-Modifying Treatments.

BACKGROUND: Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to deficiency in SMN protein and loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes, including nusinersen and gene replacement therapies, have improved gross motor and respiratory function, but their impact on scoliosis development has not been established. This study aimed to determine risk factors for scoliosis development in SMA, specifically genetic severity and DMA use. METHODS: In this retrospective cohort study, children with SMA and minimum 2-year follow-up were included. The primary outcome was the prevalence of clinically relevant scoliosis. Secondary outcomes included SMA type, SMN2 copy number, Hammersmith Functional Motor Scale (HFMS), ambulatory status [functional mobility scale at 50m (FMS50)], DMA use, and hip displacement as risk factors. Univariate/multivariate logistic regression analyses were performed to identify dependent/independent risk factors. RESULTS: One hundred sixty-five patients (51% female) with SMA types I-III met the inclusion criteria, with total follow-up of 9.8 years. The prevalence of scoliosis was 79%; age of onset 7.9 years. The major curve angle for the entire cohort at first assessment and final follow-up was 37 degrees (SD: 27 degrees) and 62 degrees (SD: 31 degrees) (P<0.0001), respectively. Significant risk factors for scoliosis by univariate analysis were SMA type (I/II, P=0.02), HFMS (>23, P<0.001), nonambulatory status (FMS50=1, P<0.0001), DMA treatment (P=0.02), and hip displacement (P<0.0001). Multivariate analysis revealed that HFMS >23 (P=0.02) and DMA (P=0.05) treatment were independent (protective) risk factors. CONCLUSIONS: The development of scoliosis in SMA is high, with risk factors associated with proxy measures of disease severity, including SMA type, nonambulatory status, hip displacement, and most notably, gross motor function (by HFMS). DMA use and HFMS >23 were associated with a decreased risk of scoliosis development. Identified risk factors can be used in the development of surveillance programs for early detection of scoliosis in SMA. LEVEL OF EVIDENCE: Level III.

Heterotopic bone formation about the hip undergoes endochondral ossification: a rabbit model.

BACKGROUND: Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma. QUESTIONS/PURPOSES: We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material. METHODS: We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale. RESULTS: Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements. CONCLUSIONS: These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation. CLINICAL RELEVANCE: By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.

Incidence of abdominal tumors in syndromic and idiopathic hemihypertrophy/isolated hemihyperplasia.

BACKGROUND: There is a reported increased risk of intra-abdominal tumors in children with both syndromic (SH) and isolated idiopathic hemihyperplasia (IH). Recommendations for tumor surveillance have been made, although there is no consensus for frequency and duration of screening. Our objective was to review the incidence of abdominal neoplasms in our pediatric population with SH and IH. METHODS: We reviewed the diagnostic criteria, imaging findings, and any associated syndrome in all patients diagnosed with hemihypertrophy over a 10-year period. RESULTS: One of 10 patients with SH, a child with Beckwith-Wiedemann syndrome, developed a hepatoblastoma resulting in a 10% tumor incidence in patients with SH. Three of the 250 (1.2%) children with IH developed an abdominal neoplasm. One was diagnosed with adrenal carcinoma and the other 2 with Wilms tumor. CONCLUSIONS: We found an increased incidence of abdominal tumors in both SH and IH, however, our incidence of tumors with IH is lower than earlier reported studies. On the basis of this lower 1.2% incidence, the current literature on IH and available molecular genetic testing, it is reasonable to recommend referral of these patients to a clinical geneticist to identify subgroups with a higher risk for tumor development that are more likely to benefit from routine imaging surveillance. LEVEL OF EVIDENCE: II-Retrospective study.

Pediatric acute leg compartment syndrome after peroneus longus rupture: a case series.

We present the case of three pediatric patients who presented with non-fracture acute lateral compartment syndrome after 'minor trauma'. All patients were male and sustained the inciting event during football. Two of the patients were able to resume play after their injury. All patients sustained intramuscular proximal avulsion ruptures of the peroneus longus muscle. At final follow-up, all but one patient had documented full neurologic recovery. A seemingly innocuous event may cause acute compartment syndrome in the adolescent male. Compartment syndrome in the absence of fracture should be promptly recognized to prevent delay in surgical treatment.

Supplemental Perioperative Oxygen to Reduce Surgical Site Infection After High-Energy Fracture Surgery (OXYGEN Study).

Supplemental perioperative oxygen (SPO) therapy has been proposed as one approach for reducing the risk of surgical site infection (SSI). Current data are mixed regarding efficacy in decreasing SSI rates and hospital inpatient stays in general and few data exist for orthopaedic trauma patients. This study is a phase III, double-blind, prospective randomized clinical trial with a primary goal of assessing the efficacy of 2 different concentrations of perioperative oxygen in the prevention of SSIs in adults with tibial plateau, pilon (tibial plafond), or calcaneus fractures at higher risk of infection and definitively treated with plate and screw fixation. Patients are block randomized (within center) in a 1:1 ratio to either treatment group (FiO2 80%) or control group (FiO2 30%) and stratified by each study injury location. Secondary objectives of the study are to compare species and antibacterial sensitivities of the bacteria in patients who develop SSIs, to validate a previously developed risk prediction model for the development of SSI after fracture surgery, and to measure and compare resource utilization and cost associated with SSI in the 2 study groups. SPO is a low cost and readily available resource that could be easily disseminated to trauma centers across the country and the world if proved to be effective.

Perioperative supplemental oxygen to reduce surgical site infection after open fixation of high-risk fractures: a randomized controlled pilot trial.

BACKGROUND: Higher concentrations of fraction of inspired oxygen (FIO2) have been shown to be associated with lower risk for surgical site infection in multiple studies outside the domain of orthopedic surgery. We evaluated the efficacy of high FIO2 administered during the perioperative period to reduce the rate of surgical site infection after open fixation of lower-extremity fractures at high risk of infection. METHODS: We conducted a randomized controlled, parallel design, double-blind study. Patients sustaining high-energy tibial plateau, tibial pilon, and calcaneus fractures treated in a staged fashion were selected for enrollment because these injuries are associated with high risk of infection. The study population included 222 patients with 235 fractures. Consenting patients were randomized by random number sequence to either the treatment or the control group. Treatment group patients received 80% FIO2 intraoperatively and for 2 hours afterward. Control group patients received 30% FIO2 during the same period. Surgeons, patients, and personnel who performed wound assessments were blinded to group assignment. The primary outcome measure was surgical site infection as defined by the Centers for Disease Control criteria for postoperative wound infection. RESULTS: The overall rates of postoperative surgical site infection were 12% (14 of 119 fractures) in the treatment group and 16% (19 of 116 fractures) in the control group (p = 0.31). Multivariate analysis, accounting for risk factors for infection, yielded the closest to a statistically significant reduction in the odds of infection with treatment (odds ratio, 0.54; p = 0.17). No treatment-associated events were observed. CONCLUSION: Use of a high concentration of FIO2 during the perioperative period is safe and shows a trend toward reduction of surgical site infection in patients undergoing open operative fixation of high-energy traumatic lower-extremity fractures. Further study in a larger patient population is indicated. LEVEL OF EVIDENCE: Therapeutic study, level III.

Predictive model for surgical site infection risk after surgery for high-energy lower-extremity fractures: development of the risk of infection in orthopedic trauma surgery score.

BACKGROUND: Current infection risk scores are not designed to predict the likelihood of surgical site infection after orthopedic fracture surgery. We hypothesized that the National Nosocomial Infections Surveillance (NNIS) System and the Study on the Efficacy of Nosocomial Infection Control (SENIC) scores are not predictive of infection after orthopedic fracture surgery and that risk factors for infection can be identified and a new score created (Emerg Infect Dis. 2003;9:196-203). METHODS: We conducted a secondary analysis of data from a trial involving internal fixation of 235 tibial plateau, pilon, and calcaneus fractures treated between 2007 and 2010 at a Level I trauma center. The predictive value of the NNIS System and SENIC scores was evaluated based on areas under the receiver operating characteristic (ROC) curve. Bivariate and multiple logistic regression analyses were used to build an improved prediction model, creating the Risk of Infection in Orthopedic Trauma Surgery (RIOTS) score. The predictive value of the RIOTS score was evaluated via the ROC curve. RESULTS: NNIS System and SENIC scores were not predictive of surgical site infection after orthopedic fracture surgery. In our final regression model, the relative odds of infection among patients with AO [Arbeitsgemeinschaft für Osteosynthesefragen] type C3 or Sanders type 4 fractures compared with fractures of lower classification was 5.40. American Society of Anesthesiologists class 3 or higher and body mass index less than 30 were also predictive of infection, with odds ratios of 2.87 and 3.49, respectively. The area under the ROC curve for the RIOTS score was 0.75, significantly higher than the areas for the NNIS System and SENIC scores. CONCLUSION: The NNIS System and SENIC scores were not useful in predicting the risk of infection after fixation of fractures. We propose a new score that incorporates fracture classification, American Society of Anesthesiologists classification, and body mass index as predictors of infection. LEVEL OF EVIDENCE: Prognostic study, level II.

Effects of non-weight-bearing on the immature femoral head following ischemic osteonecrosis: an experimental investigation in immature pigs.

BACKGROUND: Local non-weight-bearing as a treatment for Legg-Calvé-Perthes disease remains controversial since a clear scientific basis for this treatment is lacking. The purpose of this study was to determine the effects of non-weight-bearing on decreasing the femoral head deformity following ischemic osteonecrosis and to investigate its biological effects. METHODS: Unilateral femoral head ischemia was induced in sixteen piglets by placing a ligature around the femoral neck and transecting the ligamentum teres. Eight animals received a hind-limb amputation to prevent weight-bearing on the ischemic side (NWB group). The remaining eight piglets were allowed to bear weight as tolerated (WB group). The contralateral femoral heads of the WB group were used as normal controls. All animals were killed at eight weeks after induction of ischemia, when a deformity is expected in this model. Radiographic, microcomputed tomographic (micro-CT), and histomorphometric assessments were performed. RESULTS: Radiographic and micro-CT assessments showed significantly greater flattening of the infarcted epiphysis in the WB group compared with the NWB group. The mean epiphyseal quotient (ratio of femoral head height to diameter) was significantly lower in the WB group (0.29 ± 0.06) compared with the NWB group (0.41 ± 0.06, p < 0.001). Histomorphometric analyses showed that the mean percentage revascularization of the infarcted epiphysis was significantly greater in the NWB group (95% ± 14%) compared with the WB group (34% ± 33%, p < 0.0004), suggesting that revascularization was more rapid in the NWB group. Both histomorphometric and micro-CT analyses of trabecular bone parameters showed significantly decreased bone volume and decreased trabecular number in the infarcted epiphysis of the NWB group compared with the WB group (p < 0.05). CONCLUSIONS: Local non-weight-bearing decreased the deformity following ischemic femoral head osteonecrosis and increased the rates of revascularization and resorption of the infarcted epiphysis.

Locking plates in osteoporosis: a biomechanical cadaveric study of diaphyseal humerus fractures.

OBJECTIVE: To determine whether locking plates offer an advantage in fixation of fractures in osteoporotic humeral bone. DESIGN: Biomechanical testing of 18 matched pairs of osteoporotic human cadaver humeri plated posteriorly with either all locked or all nonlocked screws. An established protocol was used to test the constructs with torque applied to a peak of ±10 Nm for 1000 cycles at 0.3 Hz or until failure. Eighteen pairs were tested for failure, 11 pairs were tested for cycles survived, and 10 pairs were tested for stiffness. SETTING: University biomechanical laboratory. MAIN OUTCOME MEASUREMENTS: Percentage surviving testing, mean cycles survived, and stiffness. RESULTS: We observed catastrophic failure of the constructs in 47% of the samples. Humeri plated with nonlocking plates failed at a higher rate than those with locking plates (67% nonlocking vs 28% locking, n = 18 pairs, P = 0.008). Locking constructs also outperformed nonlocking constructs in mean cycles survived (707 cycles locking, 345 cycles nonlocking, n = 11 pairs, P < 0.05) and stiffness at 10 cycles (0.853 Nm/degree locking vs 0.416 Nm/degree nonlocking, n = 10 pairs, P < 0.001). CONCLUSIONS: Locking plates were shown to provide improved mechanical performance over nonlocking plates in torsional cyclic loading in a osteoporotic cadaveric fracture model. Our results confirm general conclusions of previous work that used a synthetic bone model of osteoporosis, but we found a high rate of catastrophic failure, questioning the validity of the previously published synthetic model of osteoporosis (overdrilling of synthetic bone) for this application.

Reduction of postoperative spinal implant infection using gentamicin microspheres.

STUDY DESIGN: Three noncontiguous spinal implant sites in 1 rabbit were challenged with Staphylococcus aureus and local antibiotic prophylaxis was given with gentamicin in controlled-release microspheres (poly(lactic-coglycolic-acid) [PLGA]). Postoperative biomaterial-centered infection on and around the titanium rods was assessed using standard bacterial quantification essays. OBJECTIVE: To assess surgical site and biomaterial-centered infection reduction with controlled release gentamicin from microspheres against S. aureus. SUMMARY OF BACKGROUND DATA: A postoperative biomaterial-centered infection can be devastating after successful thoracolumbar spinal surgery and puts a high burden on patients, families, surgeons, and hospitals, endangering both our healthcare budget and our ability to perform challenging cases in patients with increasing numbers of comorbidities. Systemic antibiotics often do not reach "dead-space" hematomas where bacteria harbor after surgery, whereas local, controlled release gentamicin prophylaxis through PLGA microspheres showed favorable pharmacokinetics data to achieve local bactericidal concentrations for up to 7 days after surgery. METHODS: A well published rabbit spinal implant model with systemic cephalosporin prophylaxis was challenged to create a baseline infection of approximately 70% in control sites. We then challenged 3 noncontiguous titanium rods inside the laminectomy defect with 10e6 colony forming units S. aureus and randomly treated 2 sites with gentamicin PLGA microspheres and 1 site with PLGA carrier only (control). Standard quantification techniques were used to assess biomaterial centered and soft tissue bacterial growth after 7 days. RESULTS: After establishing reliable infection rates in control sites, the therapeutic arm of the study was started. Surgical site infections were found in 75% of control sites, whereas gentamicin microspheres reduced the incidence down to 38% in the same rabbits. Biomaterial-centered infection was reduced from 58% to 23% only in all sites challenged with 10e6 S. aureus. CONCLUSION: Postoperative, biomaterial-centered infection was reduced at least 50% with intraoperative gentamicin microspheres in the face of systemic cephalosporin prophylaxis and high dose S. aureus in a laminectomy defect in rabbits. The data are statistically and clinically significant, and further animal testing is planned to confirm these results.

Biomechanical comparison of proximal locking plates and blade plates for the treatment of comminuted subtrochanteric femoral fractures.

OBJECTIVES: The 95 degrees angled blade plate is an accepted standard for plating subtrochanteric femoral fractures but can be technically demanding and often requires extensive soft tissue exposure. Proximal femoral locking plates (PFLPs) have been developed for subtrochanteric and pertrochanteric fractures and are potentially easier to apply with less soft tissue dissection. Clinical experience has raised concerns regarding the strength of the PFLP. The purpose of our study was to compare the relative stability of two designs of PFLP with the 95 degrees angled blade plate under loads simulating the first 3 months of progressive weight bearing after fracture fixation. METHODS: A comminuted subtrochanteric femoral fracture model was created with a 2-cm gap below the lesser trochanter in 15 synthetic femora. Fracture fixation of three plates (95 degrees angled blade plate [blade plate], the original version of the PFLP [O-PFLP], and the newest version of the PFLP [N-PFLP]), all manufactured by Synthes, Inc., Paoli, PA, was tested under progressive cyclic loading to reproduce progressive weight bearing during 3 months after fracture fixation. The force and number of cycles to reach 5 mm of displacement of the femoral head or failure of the implant were compared for each implant. RESULTS: N-PFLPs were significantly stiffer than blade plates and O-PFLPs (P = 0.01) and had a trend toward withstanding more cycles before failure (P = 0.06). All five O-PFLPs demonstrated catastrophic fatigue failure before completion of the protocol. One each of the blade plates and the N-PFLPs failed to complete the protocol (P = 0.04). CONCLUSIONS: In the model studied, N-PFLPs were shown to have biomechanical properties that were at least equivalent to those of the blade plate. The fatigue failures of O-PFLPs mirrored our clinical experience. Use of the N-PFLP might be a viable alternative fixation method for comminuted subtrochanteric femoral fractures that currently are treated with blade plates.