Comparison of Different Osteobiologics in Terms of Imaging Modalities and Time Frames for Fusion Assessment in Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The study's primary objective was to determine how osteobiologic choice affects fusion rates in patients undergoing anterior cervical discectomy and fusion (ACDF). The study's secondary objectives were to 1) determine the optimal timing of fusion assessment following ACDF and 2) determine if osteobiologic type affects the timing and optimal modality of fusion assessment. METHODS: A systematic search of PubMed/MEDLINE was conducted for literature published from 2000 through October 2020 comparing anterior fusion in the cervical spine with various osteobiologics. Both comparative studies and case series of ≥10 patients were included. RESULTS: A total of 74 studies met the inclusion criteria. Seventeen studies evaluated the efficacy of autograft on fusion outcomes, and 23 studies assessed the efficacy of allograft on fusion outcomes. 3 studies evaluated the efficacy of demineralized bone matrix, and seven assessed the efficacy of rhBMP-2 on fusion outcomes. Other limited studies evaluated the efficacy of ceramics and bioactive glasses on fusion outcomes, and 4 assessed the efficacy of stem cell products. Most studies utilized dynamic radiographs for the assessment of fusion. Overall, there was a general lack of supportive data to determine the optimal timing of fusion assessment meaningfully or if osteobiologic type influenced fusion timing. CONCLUSIONS: Achieving fusion following ACDF appears to remain an intricate interplay between host biology and various surgical factors, including the selection of osteobiologics. While alternative osteobiologics to autograft exist and may produce acceptable fusion rates, limitations in study methodology prevent any definitive conclusions from existing literature.

How using body mass index cutoffs to determine eligibility for total shoulder arthroplasty affects health care disparities.

BACKGROUND: The prevalence of obesity in the United States is continuously rising and is associated with increased morbidity, mortality, and health care costs. Body mass index (BMI) has been used as a risk stratification and counseling tool for patients undergoing total joint arthroplasty in an effort to focus on outcome-driven care. Although the use of BMI cutoffs may have benefits in minimizing complications when selecting patients for total shoulder arthroplasty (TSA), it may impact access to care for some patient populations and further increase disparities. The purpose of this study is to determine the implications of using BMI cutoffs on the eligibility for TSA among different ethnic and gender patient populations. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify 20,872 patients who underwent anatomic and reverse TSA between 2015 and 2019. Patient demographics, including age, sex, race and ethnicity, and BMI, were compared between eligible and ineligible patients based on BMI for 5 cutoff values: 30, 35, 40, 45, and 50 kg/m2. RESULTS: Of the total patient population studied, the mean age was 69 years, 55% were female, and the mean BMI was 31 kg/m2. For all BMI subgroups, there were more ineligible than eligible patients who were female or Black (P < .001). The relative rate of eligibility for Black patients was lower in each BMI cutoff group, whereas the relative rate of eligibility for White and Asian patients was higher for each group. There were more eligible than ineligible Asian patients for BMI cutoffs of 30 and 35 kg/m2 (both P < .001), and there were no differences in eligibility and ineligibility in Hispanic patients (P > .05). Furthermore, White patients were more eligible than ineligible for all BMI cutoff groups (P < .001). CONCLUSIONS: Enforcing BMI cutoffs for access to TSA may limit the procedure for female or Black patients for all BMI cutoffs, thus furthering the health care disparities these populations already face. However, there are more eligible than ineligible White patients for all BMI cutoff groups, which indicates a disparity in the access to TSA based on sex and race. Physicians may inadvertently increase health care disparities observed in TSA if they use BMI as the sole risk stratification tool for patients, even though BMI has been known to increase complications after TSA. Moreover, orthopedic surgeons should only use BMI as one of many factors in a more holistic process when determining if a patient should undergo TSA.

Dystonia 16 (DYT16) mutations in PACT cause dysregulated PKR activation and eIF2α signaling leading to a compromised stress response.

Dystonia 16 (DYT16) is caused by mutations in PACT, the protein activator of interferon-induced double-stranded RNA-activated protein kinase (PKR). PKR regulates the integrated stress response (ISR) via phosphorylation of the translation initiation factor eIF2α. This post-translational modification attenuates general protein synthesis while concomitantly triggering enhanced translation of a few specific transcripts leading either to recovery and homeostasis or cellular apoptosis depending on the intensity and duration of stress signals. PKR plays a regulatory role in determining the cellular response to viral infections, oxidative stress, endoplasmic reticulum (ER) stress, and growth factor deprivation. In the absence of stress, both PACT and PKR are bound by their inhibitor transactivation RNA-binding protein (TRBP) thereby keeping PKR inactive. Under conditions of cellular stress these inhibitory interactions dissociate facilitating PACT-PACT interactions critical for PKR activation. While both PACT-TRBP and PKR-TRBP interactions are pro-survival, PACT-PACT and PACT-PKR interactions are pro-apoptotic. In this study we evaluate if five DYT16 substitution mutations alter PKR activation and ISR. Our results indicate that the mutant DYT16 proteins show stronger PACT-PACT interactions and enhanced PKR activation. In DYT16 patient derived lymphoblasts the enhanced PACT-PKR interactions and heightened PKR activation leads to a dysregulation of ISR and increased apoptosis. More importantly, this enhanced sensitivity to ER stress can be rescued by luteolin, which disrupts PACT-PKR interactions. Our results not only demonstrate the impact of DYT16 mutations on regulation of ISR and DYT16 etiology but indicate that therapeutic interventions could be possible after a further evaluation of such strategies.