No abstract

Base excision repair (BER), which is initiated by DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. The NTHL1 glycosylase, which excises DNA base damage caused by reactive oxygen species, is thought to be a tumor suppressor. However, in addition to NTHL1 loss-of-function mutations, our analysis of cancer genomic datasets reveals that NTHL1 frequently undergoes amplification or upregulation in some cancers. Whether NTHL1 overexpression could contribute to cancer phenotypes has not yet been explored. To address the functional consequences of NTHL1 overexpression, we employed transient overexpression. Both NTHL1 and a catalytically-dead NTHL1 (CATmut) induce DNA damage and genomic instability in non-transformed human bronchial epithelial cells (HBEC) when overexpressed. Strikingly, overexpression of either NTHL1 or CATmut causes replication stress signaling and a decrease in homologous recombination (HR). HBEC cells that overexpress NTHL1 or CATmut acquire the ability to grow in soft agar and exhibit loss of contact inhibition, suggesting that a mechanism independent of NTHL1 catalytic activity contributes to acquisition of cancer-related cellular phenotypes. We provide evidence that NTHL1 interacts with the multifunctional DNA repair protein XPG suggesting that interference with HR is a possible mechanism that contributes to acquisition of early cellular hallmarks of cancer.

Background: Total ankle arthroplasty (TAA) utilization is increasing in the United States. As the incidence of this procedure grows, it is important for providers to understand the future projections for ankle arthroplasty and more importantly revision total ankle arthroplasty (rTAA). Methods: The National Inpatient Sample (USA) was queried from 2005 to 2017 for all TAA and rTAA. Poisson and linear regression analysis was performed to project annual incidence of TAA and rTAA to 2030, with subgroup analyses on septic rTAA. Results: There were 5315 TAAs performed in 2017, a 564% ( P < .001) increase when compared with the TAAs performed in 2005. From 2017 to 2030, the incidence of TAAs is projected to increase from 110% to 796% ( P < .001). There were 1170 rTAAs performed in 2017, a 155% ( P < .001) increase when compared with rTAAs performed in 2005. There was a 256% increase in the incidence of septic rTAAs from 2005 to 2017 with a projected increase between 22% and 120% by 2030. Conclusions: The incidence of both TAAs and rTAAs is projected to significantly increase over the next decade. Given the known risk factors of TAA and rTAA, these findings reinforce the need for thoughtful consideration when selecting patients for TAA.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon and potentially lethal microangiopathy that carries a >90% mortality rate if not treated urgently and appropriately. Postoperative TTP after orthopaedic procedures is particularly rare with only four case reports existing in the literature. We present the case of postoperative TTP in a 57-year-old female who underwent elective total hip arthroplasty. We believe this case adds to the limited literature surrounding the topic. While rare, TTP after orthopaedic procedures poses a real and potentially fatal condition if not managed appropriately. Therefore, it is essential for orthopaedic surgeons to be cognizant of postoperative TTP for timely diagnosis and treatment.

Introduction: Spontaneous spinal epidural hematoma (SSEH) is a rare but potentially devastating condition if not appropriately identified and managed. A few case series exist regarding SSEH and certain risk factors have been described; however, much continues to be unknown regarding the pathophysiology and optimal management.Case Presentation: We present the case of SSEH in a healthy 33-year-old African American woman with no identifiable risk factors who initially presented with significant neurologic compromise. This case reports discusses pertinent clinical presentation, imaging findings, and surgical management. The patient demonstrated near-complete neurologic recovery, highlighting the need for prompt identification and intervention.Conclusions: We believe this case adds to the limited literature surrounding the topic, particularly in regard to diagnosis and surgical management. It is essential for clinicians to be cognizant of SSEH for timely diagnosis and treatment, even in patients without obvious risk factors. Cervical Spine

Objectives: To evaluate physical function and return to independence of geriatric trauma patients, to compare physical function outcomes of geriatric patients who sustained high-energy trauma with that of those who sustained low-energy trauma, and to identify predictors of physical function outcomes. Design: Retrospective. Setting: Urban Level I trauma center. Patients: Study group of 216 patients with high-energy trauma and comparison group of 117 patients with low-energy trauma. Intervention: Injury mechanism (high- vs. low-energy mechanism). Main Outcome Measurement: Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF) patient-reported outcome measure, and change in living situation and mobility. Results: Physical function outcomes and return to independence differed between patients with high-energy and low-energy injuries. High-energy geriatric trauma patients had significantly higher PROMIS PF scores compared with low-energy geriatric trauma patients (PROMIS PF score 42.2 ± 10.4 vs. 24.6 ± 10.4, P < 0.001). High-energy geriatric trauma patients were able to ambulate outdoors without an assistive device in 67% of cases and were living independently 74% of the time in comparison with 28% and 45% of low-energy geriatric trauma patients, respectively (P < 0.001, P < 0.001). Multivariate linear regression analysis demonstrated that low-energy mechanism injury was independently associated with a 13.2 point reduction in PROMIS PF score (P < 0.001). Conclusions: Geriatric patients greater than 1 year out from sustaining a high-energy traumatic injury seem to be functioning within the expected range for their age, whereas low-energy trauma patients seem to be functioning substantially worse than both age-adjusted norms and their high-energy cohorts. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

treated as inpatients at participating hospitals was obtained. RESULTS: 317 patients were identified for analysis. 22.1% of individuals received TEA for rheumatoid arthritis. 52 total adverse events were reported for all patients undergoing TEA. Rheumatoid arthritis patients experienced significantly lower rates of overall adverse events (8.57% vs 18.62%, p = 0.045). CONCLUSION: Rheumatoid arthritis patients that undergo TEA are significantly less likely to develop a 30 day post-operative complication than patients who receive TEA for other reasons.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Total ankle arthroplasty (TAA) utilization is increasing in the United States. As the incidence of this procedure grows, it is important for providers to understand the future projections for ankle arthroplasty and more importantly revision total ankle arthroplasty (rTAA). Methods: The national inpatient sample (USA) was queried from 2005 to 2017 for all TAA and rTAA. Poisson and linear regression analyses were performed to project annual incidence of TAA and rTAA to 2030, with subgroup analyses on septic rTAA. Results: There were 5315 TAAs performed in 2017, a 564% increase when compared to the TAAs performed in 2005. From 2017 to 2030, the incidence of TAAs is projected to increase from 110% to 796%. There were 1170 rTAAs performed in 2017, a 155% increase when compared to rTAAs performed in 2005. There was a 256% increase in the incidence of septic rTAAs from 2005 to 2017 with a projected increase between 22% and 120% by 2030. Conclusion: The incidence of both TAAs and rTAAs are projected to significantly increase over the next decade. Given the known risk factors of TAA and rTAA, these findings reinforce the need for thoughtful consideration when selecting patients for TAA.