Plate-only open-door laminoplasty is associated with durable, significantly improved clinical outcomes and a very low reoperation rate for progressive spondylosis or adjacent segment disease: average 8-year follow-up.

BACKGROUND CONTEXT: Multilevel cervical myelopathy is a common cause of spinal cord dysfunction in adults. Surgical intervention via laminoplasty can provide satisfactory clinical outcomes by expansive decompression of the spinal cord. Traditional suture or bone graft techniques have been associated with insufficient fixation, leading to premature closure and subsequent neurological deterioration. In contrast, plated laminoplasty has been shown to provide stable fixation to maintain canal enlargement, but longer-term outcomes are lacking. PURPOSE: To evaluate longer-term clinical outcomes and reoperations associated with plate-only open-door laminoplasty. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: Postoperative patients who underwent plate-only open door laminoplasty with minimum 5-year follow up. OUTCOME MEASURES: modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and 12-item Short Form Health Survey (SF-12). METHODS: All patients at a single academic institution who underwent plate-only open-door cervical laminoplasty from 9/1/2006 to 9/1/2016 were identified to ensure minimum 5 year follow up. Clinical outcomes included the modified Japanese Orthopaedic Association (mJOA) score, the Neck Disability Index (NDI), and the 12-item Short Form Health Survey (SF-12). The occurrence of any repeat operations on the cervical spine was evaluated, as well as its cause. The study team attempted to contact all eligible patients to achieve at least 5 years postoperative follow-up. Pairwise t tests were performed to compare clinical outcomes at preoperative, 6 months, 1-year, and final postoperative follow-up with an α level of 0.05. RESULTS: A total of 774 met the initial inclusion criteria, of which 157 were included in the study (20.3%). Most common reasons for exclusion included inability to reach after 3 attempts (49.48%), inactive phone numbers (20.28%), and patient declining (3.49%). Included patients had an average age of 60.66±10.63 and an average follow-up time of 8.37±2.57 years (minimum 5 years). mJOA scores (preoperative 11.59±2.16) improved significantly at 6-months (14.57±2.07, p<.001), 1-year (15.19±1.95, p<.001), and final follow-up (14.59±2.63, p<.001). NDI (preoperative 33.89±18.54) improved significantly at 6 months (27.89±19.72, p=.03), 1-year (25.96±19.79, p=.01) and final follow-up (17.88±17.17, p<.001). SF-12 MCS (preoperative 44.73) improved significantly at 6 months (52.01, p=.001), 1-year (51.62, p=.008), and final follow-up (52.32, p<.001). No patient underwent reoperations for plate failure or canal closure with recurrent stenosis. Reoperations for progressive spondylosis during the follow up period were rare and occurred in only three patients for new onset radiculopathy (1.9%) and two patients for myelopathy (1.3%) at an average of 3.2 years postoperative. There were no reoperations performed for adjacent segment disease. CONCLUSIONS: At a minimum of 5 years and an average of more than 8 years postoperative, laminoplasty was associated with significant and sustained improvements in mJOA, NDI, and SF-12 MCS. Importantly, no patients underwent revision surgery for plate failure or recurrent canal closure. Reoperations for new onset radiculopathy and myelopathy were also very rare over the 8-year average follow-up period, with no reoperations for adjacent segment disease. Plate-only laminoplasty is a durable means of treating multilevel myelopathy with excellent longer-term outcomes and a very low risk of reoperation, either for premature closure or the inevitable spondylotic changes that occur over time in patients with similar baseline characteristics to the study population.

Body Mass Index (BMI) Cutoffs and Racial, Ethnic, Sex, or Age Disparities in Patients Treated With Total Ankle Arthroplasty.

Background: The rising prevalence of obesity among American adults has disproportionately affected Black adults and women. Furthermore, body mass index (BMI) has historically been used as a relative contraindication to many total joint arthroplasty (TJA) procedures, including total ankle arthroplasty. The purpose of this study was to investigate potential disparities in patient eligibility for total ankle arthroplasty based on race, ethnicity, sex, and age by applying commonly used BMI cutoffs to the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Methods: Patients in the ACS-NSQIP database who underwent TAA from 2011 to 2020 were retrospectively reviewed in a cross-sectional analysis. BMI cutoffs of <50, <45, <40, and <35 were then applied. The eligibility rate for TAA was examined for each BMI cutoff, and findings were stratified by race, ethnicity, sex, and age. Independent t tests, chi-squared tests, and Fisher exact tests were performed to compare differences at an α = 0.05. Results: A total of 1215 of 1865 TAA patients (65.1%) were included after applying the exclusion criteria. Black patients had disproportionately lower rates of eligibility at the most stringent BMI cutoff of <35 (P = .004). Hispanic patients had generally lower rates of eligibility across all BMI cutoffs. In contrast, Asian American and Pacific Islander patients had higher rates of eligibility at the BMI cutoffs of <35 (P = .033) and <40 (P = .039), and White non-Hispanic patients had higher rates of eligibility across all BMI cutoffs. Females had lower eligibility rates across all BMI cutoffs. Ineligible patients were also younger compared to eligible patients across all BMI cutoffs. Conclusion: Stringent BMI cutoffs may disproportionately disqualify Black, female, and younger patients from receiving total ankle arthroplasty. Level of Evidence: Level III, retrospective cross-sectional study.

Functional and molecular effects of TNF-α on human iPSC-derived cardiomyocytes.

Proinflammatory molecule tumor necrosis factor alpha (TNF-α) is predominantly elevated in cytokine storm as well as worsening cardiac function. Here we model the molecular and functional effects of TNF-α in cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC). We found that treatment of hiPSC-CMs with TNF-α increased reactive oxygen species (ROS) and caspase 3/7 activity and caused cell death and apoptosis. TNF-α treatment also resulted in dysregulation of cardiomyocyte function with respect to the increased abnormal calcium handling, calcium wave propagation between cells and excitation-contraction coupling. We also uncovered significant changes in gene expression and protein localization caused by TNF-α treatment. Notably, TNF-α treatment altered the expression of ion channels, dysregulated cadherins, and affected the localization of gap-junction protein connexin-43. In addition, TNF-α treatment up-regulated IL-32 (a human specific cytokine, not present in rodents and an inducer of TNF-α) and IL-34 and down-regulated glutamate receptors and cardiomyocyte contractile proteins. These findings provide insights into the molecular and functional consequences from the exposure of human cardiomyocytes to TNF-α. Our study provides a model to incorporate inflammatory factors into hiPSC-CM-based studies to evaluate mechanistic aspects of heart disease.

Electrical Stimulation of pediatric cardiac-derived c-kit+ progenitor cells improves retention and cardiac function in right ventricular heart failure.

Nearly 1 in every 120 children born has a congenital heart defect. Although surgical therapy has improved survival, many of these children go on to develop right ventricular heart failure (RVHF). The emergence of cardiovascular regenerative medicine as a potential therapeutic strategy for pediatric HF has provided new avenues for treatment with a focus on repairing or regenerating the diseased myocardium to restore cardiac function. Although primarily tried using adult cells and adult disease models, stem cell therapy is relatively untested in the pediatric population. Here, we investigate the ability of electrical stimulation (ES) to enhance the retention and therapeutic function of pediatric cardiac-derived c-kit+ progenitor cells (CPCs) in an animal model of RVHF. Human CPCs isolated from pediatric patients were exposed to chronic ES and implanted into the RV myocardium of rats. Cardiac function and cellular retention analysis showed electrically stimulated CPCs (ES-CPCs) were retained in the heart at a significantly higher level and longer time than control CPCs and also significantly improved right ventricular functional parameters. ES also induced upregulation of extracellular matrix and adhesion genes and increased in vitro survival and adhesion of cells. Specifically, upregulation of ß1 and ß5 integrins contributed to the increased retention of ES-CPCs. Lastly, we show that ES induces CPCs to release higher levels of pro-reparative factors in vitro. These findings suggest that ES can be used to increase the retention, survival, and therapeutic effect of human c-kit+ progenitor cells and can have implications on a variety of cell-based therapies. Stem Cells 2019;37:1528-1541.