Autofusion in early-onset scoliosis growing constructs: occurrence, risk factors, and impacts.

PURPOSES: Autofusion (AF) during growing rod (GR) instrumentation for early-onset scoliosis (EOS) has been reported, but AF incidence, causation, and clinical implications remain unknown. This article aims to (1) quantify frequency and severity of AF, (2) determine risk factors for AF, and (3) assess the influence of AF on final curve correction and spinal lengthening. METHODS: EOS patients were prospectively enrolled (2016-2021). Patients underwent evaluation, GR implantation, lengthenings, and posterior spinal fusion (PSF). Cobb angle and spinal length measurements were collected. AF was assessed and graded, with grades I-II being low-grade and III-V being high-grade. Exposure analysis quantified risk factors' impact via odds ratios and Pearson regression correlates. Statistical significance was p ≤ 0.05 or ≥ 0.95. RESULTS: 28 patients, with variable EOS diagnoses, were included. On average, GR were implanted at 8.54-year-old and lengthened over 4.66 years. 53.6% of patients received magnetically controlled GR (MCGR) and 46.4% traditional GR (TGR). The average construct bridged 13.4 levels. Over the lengthening period, for all indications, patients averaged 2.9 total open procedures. Curves corrected from 68.5º preoperatively to 35.3º after index GR to 35.6º after PSF. Spinal length increased from 30.0 cm preoperatively to 33.9 cm after index GR to 39.5 cm after PSF. AF grading was: 28.6% Grade I, 25.0% Grade II, 17.9% Grade III, 25.0% Grade IV, and 3.6% Grade V. Idiopathic EOS tended to have lower AF grades (p = 0.37). AF risk factors included GR age < 8 (10.4×, p = 0.01), any interval open procedures (6.3×, p = 0.05), and residual curve > 30º after index GR (13.7×, p = 0.02). Protective factors included preoperative spinal length of > 30.0 cm (0.11×, p = 0.01) and index MCGR (0.16×, p = 0.03). Maintenance of Cobb angles from index GR through PSF was relatively better in low-grade patients (p = 0.08). Spinal length gained was no different between low- and high-grade AF (p = 0.50). CONCLUSIONS: This largest-to-date evaluation found AF is nearly ubiquitous in GR constructs, but with variable severity. Both risk factors and protective factors coincide with AF. Ultimately, even in high-grade AF, curve correction was maintained, and spinal lengthening was achieved. LEVEL OF EVIDENCE: Level II-prospective cohort study.

Utilizing two surgeons for neuromuscular scoliosis suggests improved operative efficiency.

PURPOSE: Neuromuscular scoliosis (NMS) patients tend to have significant comorbidities with complex medical and surgical histories. When undergoing posterior spinal fusion (PSF), NMS risks can be much higher than the idiopathic population. This study aimed to identify the impact of two experienced pediatric cosurgeons (CS) compared to a single spine surgeon (SS) on the intra- and postoperative results of NMS PSF. METHODS: A database of NMS patients who had undergone PSF 2016-2021 identified 53 patients, of which 32 were CS, while 21 were SS. Patients' sex, age, weight, diagnosis, curve severity, fusion performed, estimated blood loss (EBL), transfusion rates, hemoglobin, anesthesia and surgical times, length of stay, and complications were collected. RESULTS: Patient demographics were similar between groups. Curves were more severe in the CS group (p = 0.013). Intraoperatively, CS patients underwent larger corrections (p = 0.089) but in significantly shorter anesthetic (p = 0.0018) and operative (p = 0.0025) times. Blood loss and transfusions were similar. Postoperatively, intensive-care unit (ICU) admission and length of stay (LOS) were similar, but SS had higher rates of both unplanned ICU admissions (p = 0.36) and 30 day readmissions (p = 0.053). Complications overall were similar between the groups both within 30 days (p = 0.40) and in the short-term period (31-90 days, p = 0.76), though the CS cohort had less Grade 2 immediate postoperative pulmonary complications (p = 0.16). CONCLUSION: Utilizing CS for NMS PSF has been found to reduce operative times. Downstream, additional potential impacts trended toward fewer unplanned ICU admissions, less-frequent postoperative pulmonary complications, and reduced 30-day readmission rates.

Effects of race on blood loss in spinal fusions for adolescent idiopathic scoliosis.

OBJECTIVE: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) can be associated with significant blood loss. It has been suggested that blood loss is greater in different racial groups. The purpose of this study was to evaluate differences in blood loss between African American and Caucasian patients undergoing PSF for AIS. METHODS: A retrospective review was performed of patients aged 10-18 years with AIS who were treated with PSF from 2014 to 2017 at a single children's healthcare system. Patient demographic, radiographic, and operative data were obtained from medical records. Intraoperative blood loss was calculated using the formula described by Waters et al. Patients who declined reporting their race or had prior spinal surgery, neuromuscular or syndromic diagnoses, a history of cardiac or thoracic surgery, or a bleeding disorder were excluded. Blood loss variables were log-transformed for normality and modeled using multivariable linear regression. RESULTS: A total of 433 PSFs for AIS qualified for the analysis. The average age was 14.1 years, and 73.7% of the patients were female. With respect to race, 44.6% identified themselves as African American. There was no significant difference in blood loss (p = 0.31) or blood loss per level fused (p = 0.36) in African American patients. African American patients, however, did have significantly lower preoperative hemoglobin and hematocrit levels and greater operating room time than Caucasian patients (p < 0.001). There was no difference between race and transfusion rate. CONCLUSIONS: There appears to be no relationship between race and blood loss during PSF for AIS. Standardized protocols for minimizing perioperative blood loss can be applied to both Caucasian and African American patients.

Blood cell microparticles as biomarkers of hemostatic abnormalities in patients with implanted cardiac assist devices.

For heart failure patients unable to undergo cardiac transplantation, mechanical circulatory support with left ventricular assist devices can be utilized. These devices improve quality of life and prolong life expectancy, but they are associated with bleeding and thrombotic complications impacting patient survival. Little is known of the relevant mechanisms of these hemostatic issues, hindering identification of a clinically useful biomarker. However, there is suggestive evidence that blood cell-derived microparticles may fulfill this unmet clinical need. Recent publications have shown an association of up regulated microparticle production with implanted left ventricular assist devices and the potential to use this as a biomarker to predict thrombosis (and perhaps other adverse events) with an onset time earlier than currently used clinical indicators.

High specificity targeting and detection of human neuroblastoma using multifunctional anti-GD2 iron-oxide nanoparticles.

AIM: To develop biocompatible, tumor-specific multifunctional iron-oxide nanoconstructs targeting neuroblastoma, an aggressive pediatric malignancy. MATERIALS & METHODS: Clinical-grade humanized monoclonal antibody (hu14.18K322A), designed to target GD2 antigen on neuroblastoma with reduced nonspecific immune interactions, was conjugated to hydroxyethyl starch-coated iron-oxide nanoparticles. Targeting capability in vitro and in vivo was assessed by immunofluorescence, electron microscopy, analytical spectrophotometry, histochemistry and magnetic resonance R2* relaxometry. RESULTS: The biocompatible nanoconstructs demonstrated high tumor specificity in vitro and in vivo, and low background uptake in a mouse flank xenograft model. Specific accumulation in tumors enabled particle visualization and quantification by magnetic resonance R2* mapping. CONCLUSION: Our findings support the further development toward clinical application of this anti-GD2 iron-oxide nanoconstruct as diagnostic and therapeutic scaffold for neuroblastoma and potentially other GD2-positive malignancies.

Tumor-selective anti-cancer effects of the synthetic alkyl phosphocholine analog CLR1404 in neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor in children and is associated with high mortality in advanced stages. Survivors suffer from long-term treatment-related sequelae. Thus, new targeted treatment options are urgently needed. 18-(p-[(127)I] iodophenyl) octadecyl phosphocholine (CLR1404) is a novel, broadly tumor targeted small molecule drug suitable for intravenous injection with highly selective tumor uptake. As a carrier molecule for radioactive iodine, CLR1404 is in clinical trials as cancer imaging agent and radiotherapeutic drug. Chemically, CLR1404 belongs to the anti-tumor alkyl phospholipids, a class of drugs known to have intrinsic cytotoxic effects on cancer cells. Therefore, we hypothesized that CLR1404 could be a tumor-targeted anti-cancer agent for neuroblastoma, and investigated its effect in vitro and in vivo. CLR1404 was taken up by NB cells in a highly tumor-selective manner both in vitro and in vivo, confirmed by flow cytometry and PET/CT imaging of mouse flank xenografts with (124)I-CLR1404, respectively. Using flow cytometry, MTT assay, Western blotting and caspase 3/7 assay, we confirm that in vitro treatment with CLR1404 leads to robust apoptosis and cell death in multiple NB cell lines and is associated with Akt inhibition, while sparing normal cells. Treatment with CLR1404 in doses of 10 or 30 mg/kg administered by intravenous injection once weekly for 7 weeks significantly inhibited the tumor growth rate in a mouse flank xenograft model of NB (P<0.001) when compared to control cohorts, without causing drug-related hematotoxicity or other noticeable adverse effects, which was determined by serial tumor volume measurements, complete blood counts, and monitoring of animal-specific health parameters. We conclude that CLR1404 warrants clinical exploration as a novel, tumor selective anticancer agent in NB and potentially other cancers.