Racial Disparities in Postoperative Outcomes Following Operative Management of Pediatric Developmental Dysplasia of the Hip.

BACKGROUND: Developmental dysplasia of the hip in pediatric patients can be managed conservatively or operatively. Understanding patient risk factors is important to optimize outcomes following surgical treatment of developmental dysplasia of the hip. Racial disparities in procedural outcomes have been studied, however, there is scarce literature on an association between race and complications following pediatric orthopaedic surgery. Our study aimed to determine the association between pediatric patients' race and outcomes following operative management of hip dysplasia by investigating 30-day postoperative complications and length of hospital stay. METHODS: The National Surgical Quality Improvement Program-Pediatric database was utilized from the years 2012 to 2019 to identify all pediatric patients undergoing surgical treatment for hip dysplasia. Patients were stratified into 2 groups: patients who were White and patients from underrepresented minority (URM) groups. URM groups included those who were Black or African American, Hispanic, Native American or Alaskan, and Native Hawaiian or Pacific Islander. Differences in patient demographics, comorbidities, and postoperative outcomes were compared between the 2 cohorts using bivariate and multivariate analyses. RESULTS: Of the 9159 pediatric patients who underwent surgical treatment for hip dysplasia between 2012 and 2019, 6057 patients (66.1%) were White and 3102 (33.9%) were from URM groups. In the bivariate analysis, compared with White patients, patients from URM groups were more likely to experience deep wound dehiscence, pneumonia, unplanned reintubation, cardiac arrest, and extended length of hospital stay. Following multivariate analysis, patients from URM groups had an increased risk of unplanned reintubation (odds ratio: 3.583; P=0.018). CONCLUSIONS: Understanding which patient factors impact surgical outcomes allows health care teams to be more aware of at-risk patient groups. Our study found that pediatric patients from URM groups who underwent surgery for correction of hip dysplasia had greater odds of unplanned reintubation when compared with patients who were White. Further research should investigate the relationship between multiple variables including race, low socioeconomic status, and language barriers on surgical outcomes following pediatric orthopaedic procedures. LEVEL OF EVIDENCE: Level III-retrospective cohort analysis.

Discrimination of low- and high-grade appendiceal mucinous neoplasms by targeted sequencing of cancer-related variants.

DNA was obtained from matching micro-dissected, primary tumor cells, paired metastases, and peripheral blood mononuclear cells (germline) from patients with appendiceal mucinous neoplasms. We compared specimens from patient cohorts comprising low-grade adenomucinous neoplasm versus high-grade mucinous adenocarcinoma using a targeted, amplicon sequencing panel of 409 cancer related genes (Ion Torrent Comprehensive Cancer Panel, Thermo-Fisher, Waltham, MA). Copy number variants, single nucleotide variants and small insertions/deletions were identified using a multiplex algorithm pipeline (GATK, VarScan2, MuTect2, SIFT, SIFT-INDEL, PolyPhen-2, Provean). There were significantly more damaging variants in high-grade versus low-grade tumor cohorts. Both cohorts contained damaging, heterozygous germline variants (catenin ß1; notch receptor 1 and 4) in pathways associated with cell-lineage specification (WNT, NOTCH). Damaging, somatic KRAS proto-oncogene, GTPase mutations were present in both cohorts, while somatic GNAS complex locus mutations were confined to low-grade neoplasms. Variants predominantly affected transcription factors, kinases, and stem cell signaling molecules in canonical pathways including epithelial to mesenchymal transition, stem cell pluripotency, p53, PTEN, and NF-қB signaling pathways. High-grade tumors demonstrated MYC proto-oncogene, bHLH transcription factor (MYC) and death domain associated protein (DAXX) amplification and damaging somatic variants in tumor protein p53 (TP53), likely to amplify an aggressive phenotype. Damaging APC, WNT signaling pathway regulator (APC) deletions were identified in metastatic tissue of both cohorts suggesting a role in invasive disease. Our data suggest that germline dysregulation of WNT and/or NOTCH pathways predisposes patients toward a secretory cell phenotype (i.e., goblet-like cells) upon acquisition of somatic KRAS mutations. Additional somatically acquired variants activating oncogenes MYC and DAXX and inhibiting the critical tumor suppressor, tumor protein TP53, were consistent with manifestation of a high-grade phenotype. These additional changes within the epithelial to mesenchymal transition signaling network (WNT, NOTCH, RAS/ERK/PI3K, PTEN, NF-қB), produce aggressive high-grade tumor characteristics by actively driving cells towards dedifferentiation, proliferation, and migration.