High Prevalence of Work-related Musculoskeletal Disorders and Limited Evidence-based Ergonomics in Orthopaedic Surgery: A Systematic Review.

BACKGROUND: The Centers for Disease Control defines work-related musculoskeletal disorders as disorders of the nerves, muscles, tendons, joints, spinal discs, and cartilage that are caused or exacerbated by the environment or nature of work. Previous meta-analyses have characterized work-related musculoskeletal disorders among interventionists, general surgeons, and other surgical subspecialties, but prevalence estimates, prognosis, and ergonomic considerations vary by study and surgical specialty. QUESTIONS/PURPOSES: (1) What is the career prevalence of work-related musculoskeletal disorders in orthopaedic surgeons? (2) What is the treatment prevalence associated with work-related musculoskeletal disorders in orthopaedic surgeons? (3) What is the disability burden of work-related musculoskeletal disorders in orthopaedic surgeons? (4) What is the scope of orthopaedic surgical ergonomic assessments and interventions? METHODS: A systematic review of English-language studies from PubMed, MEDLINE, Embase, and Scopus was performed in December 2022 and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that presented prevalence estimates of work-related musculoskeletal disorders or assessed surgical ergonomics in orthopaedic surgery were included. Reviews, case reports, gray literature (conference abstracts and preprints), and studies with mixed-surgeon (nonorthopaedic) populations were excluded. The search yielded 5603 abstracts; 24 survey-based studies with 4876 orthopaedic surgeons (mean age 48 years; 79% of surgeons were men) were included for an analysis of work-related musculoskeletal disorders, and 18 articles were included for a descriptive synthesis of ergonomic assessment. Quality assessment using the Joanna Briggs Institute Tool revealed that studies had a low to moderate risk of bias, largely because of self-reporting survey-based methodology. Because of considerable heterogeneity and risk of bias, prevalence outcomes were not pooled and instead are presented as ranges (mean I 2 = 91.3%). RESULTS: The career prevalence of work-related musculoskeletal disorders in orthopaedic surgeons ranged from 37% to 97%. By anatomic location, the prevalence of work-related musculoskeletal disorders in the head and neck ranged from 4% to 74%; back ranged from 9% to 77%; forearm, wrist, and hand ranged from 12% to 54%; elbow ranged from 3% to 28%; shoulder ranged from 3% to 34%; hip and thigh ranged from 1% to 10%; knee and lower leg ranged from 1% to 31%; and foot and ankle ranged from 4% to 25%. Of orthopaedic surgeons reporting work-related musculoskeletal disorders, 9% to 33% had a leave of absence, practice restriction or modification, or early retirement, and 27% to 83% received some form of treatment. Orthopaedic surgeons experienced biomechanical, cardiovascular, neuromuscular, and metabolic stress during procedures. Interventions to improve orthopaedic surgical ergonomics have been limited, but have included robotic assistance, proper visualization aids, appropriate use of power tools, and safely minimizing lead apron use. In hip and knee arthroplasty, robotic assistance was the most effective in improving posture and reducing caloric expenditure. In spine surgery, proper use of surgical loupes was the most effective in improving posture. CONCLUSION: Although the reported ranges of our main findings were wide, even on the low end of the reported ranges, work-related musculoskeletal disability among orthopaedic surgeons appears to be a substantial concern. We recommend that orthopaedic residency training programs incorporate surgical ergonomics or work injury lectures, workshops, and film review (alongside existing film review of surgical skills) into their curricula. We suggest hospitals engage in shared decision-making with surgeons through anonymous needs assessment surveys to implement wellness programs specific to surgeons' musculoskeletal needs. We urge institutions to assess surgeon ergonomics during routine quality assessment of novel surgical instruments and workflows. LEVEL OF EVIDENCE: Level III, prognostic study.

Direct activation of PP2A for the treatment of tyrosine kinase inhibitor-resistant lung adenocarcinoma.

Although tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy in advanced lung adenocarcinoma (LUAD) patients with pathogenic alterations in EGFR, most patients develop acquired resistance to these agents via mechanisms enabling the sustained activation of the PI3K and MAPK oncogenic pathways downstream of EGFR. The tumor suppressor protein phosphatase 2A (PP2A) acts as a negative regulator of these pathways. We hypothesize that activation of PP2A simultaneously inhibits the PI3K and MAPK pathways and represents a promising therapeutic strategy for the treatment of TKI-resistant LUAD. After establishing the efficacy of small molecule activators of PP2A (SMAPs) in a transgenic EGFRL858R model and TKI-sensitive cell lines, we evaluated their therapeutic potential in vitro and in vivo in TKI-resistant models. PP2A activation resulted in apoptosis, significant tumor growth inhibition, and downregulation of PI3K and MAPK pathways. Combination of SMAPs and TKI afatinib resulted in an enhanced effect on the downregulation of the PI3K pathway via degradation of the PP2A endogenous inhibitor CIP2A. An improved effect on tumor growth inhibition was observed in a TKI-resistant xenograft mouse model treated with a combination of both agents. These collective data support the development of PP2A activators for the treatment of TKI-resistant LUAD.