Faculty Bibliography

BACKGROUND:The prolonged turnaround time for next-generation sequencing (NGS) results may be a barrier to the timely selection of therapeutics in myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) with mutated TP53. Biomarker validation for early detection of TP53 mutation may have a significant impact on clinical decision-making. METHODS:In this study, p53 immunohistochemistry (IHC) (index test) and TP53 NGS (referent test) were performed on 145 bone marrow specimens from 82 unique patients with TP53-mutant MDS or AML to validate IHC as an early surrogate for NGS, and to assess the prognostic relevance of IHC. RESULTS:p53 IHC testing was able to correctly identify 95.5% of patients with TP53-mutant MDS and 100% of patients with TP53-mutant AML in this cohort. The mean p53 stain positivity was higher for AML compared to MDS (28% ± 3.67% vs. 8.8% ± 1.61%; p < .001), as well as for multihit TP53 compared to monoallelic TP53. Bootstrap analysis with 2000 iterations showed that a p53 IHC of 7% was the threshold best associated with multihit TP53. False-negative results were obtained with IHC in all TP53 sole nonsense or frameshift mutations. IHC positivity was inversely correlated with overall survival (OS), with the highest quintile of p53 positivity showing a median OS of just 2.53 months. CONCLUSIONS:IHC is a useful biomarker for the early detection of TP53-mutant MDS or AML and for prediction of TP53 allelic state. The results suggest a role for IHC across global markets, especially in geographic areas with inaccessibility to NGS testing.

BACKGROUND:The prognostic impact of cohesin mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is controversial. METHODS:In patients with AML and MDS who underwent next-generation sequencing at the authors' center during 2017-2023, the authors assessed the landscape of cohesin mutations and the impact of co-occurring mutations on overall survival (OS) and compared outcomes between patients with cohesin mutations and those with wild-type (WT) cohesin genes. RESULTS:The study included 83 patients, 36 with cohesin mutations (STAG2, n = 28; SMC1A, n = 7; SMC3, n = 3; co-expression of cohesin mutations, n = 2) and 47 with WT cohesin genes. Of the 36 patients with cohesin mutations, 17 (47%) had AML (six de novo and 11 secondary), and 19 (53%) had MDS. Patients who had STAG2 mutations had better median OS than patients who had only SMC1A and SMC3 mutations (26 vs. 10 months; p = .043). SRSF2 mutation was the most frequent co-occurring mutation (n = 12; 33%) and was associated with worse median OS than WT SRSF2 (13 vs. 43 months; p = .016). Seven patients (19%) with cohesin mutations underwent hematopoietic transplantation; their median OS was 70 months. Compared with the WT cohesin group, patients who had cohesin mutations were more likely to have adverse-risk AML (82% vs. 53%). The median OS was similar among patients with adverse-risk AML in the cohesin-mutation and WT cohesin groups (10 vs. 14 months, respectively; p = .9). CONCLUSIONS:The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.

The cost of healthcare spending in foot and ankle surgery continues to rise. Several recent studies about cost effectiveness have been published. These may be difficult to understand and analyze without a background in business and healthcare economics. The goal of this narrative review is to provide the fundamentals for understanding and interpreting healthcare economic studies by defining key terminology and providing examples in the field of foot and ankle surgery. Foot and ankle surgeons should be familiar with the elements that comprise cost-effectiveness for providers, clinicians, researchers, and economists in caring for patients and making healthcare-related decisions.

BACKGROUND:The effect of spinopelvic fixation in addition to lumbar spinal fusion (LSF) on dislocation/instability and revision in patients undergoing primary total hip arthroplasty (THA) has not been reported previously. METHODS:The PearlDiver Research Program was used to identify patients aged 30 and above undergoing primary THA who received (1) THA only, (2) THA with prior single-level LSF, (3) THA with prior 2-5 level LSF, or (4) THA with prior LSF with spinopelvic fixation. The incidence of THA revision and dislocation/instability was compared through logistic regression and Chi-squared analysis. All regressions were controlled for age, gender, and Elixhauser Comorbidity Index (ECI). RESULTS:Between 2010 and 2018, 465,558 patients without history of LSF undergoing THA were examined and compared to 180 THA patients with prior spinopelvic fixation, 5,299 with prior single-level LSF, and 1,465 with prior 2-5 level LSF. At 2 years, 7.8% of THA patients with prior spinopelvic fixation, 4.7% of THA patients with prior 2-5 level LSF, 4.2% of THA patients with prior single-level LSF, and 2.2% of THA patients undergoing only THA had a dislocation event or instability (P < .0001). After controlling for length of fusion, pelvic fixation itself was associated with higher independent risk of revision (at 2 years: 2-5 level LSF + spinopelvic fixation: aHR = 3.15, 95% CI 1.77-5.61, P < .0001 vs 2-5 level LSF with no spinopelvic fixation: aOR = 1.39, 95% CI 1.10-1.76, P < .0001). CONCLUSION/CONCLUSIONS:At 2 years, spinopelvic fixation in THA patients were associated with a greater than 3.5-fold increase in hip dislocation risk compared to those without LSF, and an over 2-fold increase in THA revision risk compared to those with LSF without spinopelvic fixation. LEVEL OF EVIDENCE/METHODS:III.

Rising health care costs in the United States, besides evolving payment models that place emphasis on value instead of volume, have led to an increasing number of studies evaluating hand surgery from an economic perspective. To better understand such economics-based studies, this review provides a foundational understanding of what value entails by defining its features of quality and cost. Principles of evaluating value through cost-benefit, cost-effectiveness, and cost-utility analyses are discussed. Models of discounting and clinical decision analyses are also discussed. Understanding such concepts and their evaluation in economic analyses will provide greater insight into the economic landscape of hand surgery and improving patient care.

The number of arthroplasty procedures has been rising at a significant rate, contributing to a notable portion of the nation's health care spending. This growth has contributed to an increase in the number of health care economic studies in the field of adult reconstruction surgery. Although these articles are filled with important information, they can be difficult to understand without a background in business or economics. The goal of this review is to define the common terminology used in health care economic studies, assess their value and benefit in the context of total joint arthroplasty, and highlight shortcomings in the current literature. [Orthopedics. 2022;45(4):e174-e182.].

Background/UNASSIGNED:Surgical volunteer organizations have been severely limited during the ongoing coronavirus disease pandemic. Our purpose was to identify obstacles to surgical volunteer organizations secondary to COVID-19 and their responses. Methods/UNASSIGNED:= 24). Univariate analyses were used to compare the two cohorts. Results/UNASSIGNED:= 0.02). The three leading obstacles were finances/donations (78%), fewer volunteers (38%), and inadequate personal protective equipment (30%). In response, 39% of surgical volunteer organizations developed novel E-volunteering opportunities. For support, 85% of surgical volunteer organizations suggested monetary donations, 78% promotion through social media platforms, and 54% donation of personal protective equipment. Conclusion/UNASSIGNED:The majority of surgical volunteer organizations were unable to maintain full functionality due to stressors caused by COVID-19, including limitations on finances, volunteers, and personal protective equipment.