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Browsing by Author "Flanigan, David C."
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Item Mechanosignaling in bone health, trauma and inflammation(Mary Ann Liebert, Inc., 2014-02-20) Knapik, Derrick M.; Perera, Priyangi; Nam, Jin; Blazek, Alisa D.; Rath, Bjorn; Leblebicioglu, Binnaz; Das, Hiranmoy; Chu Wu, Lai; Hewett, Timothy E.; Agarwal, Suresh K. Jr.; Robling, Alexander G.; Flanigan, David C.; Lee, Beth S.; Agarwal, Sudha; Department of Anatomy & Cell Biology, IU School of MedicineSIGNIFICANCE: Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. RECENT ADVANCES: In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-κB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-κB signaling cascade. CRITICAL ISSUES: Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. FUTURE DIRECTIONS: Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health.Item Positive Reframing: An Important but Underutilized Coping Strategy in Athletes Undergoing Sport-Related Knee Surgery(National Athletic Trainers' Associaton, 2021-05-26) Flanigan, David C.; Everhart, Joshua S.; DiBartola, Alex C.; Blough, Christian; Schiele, Steven E.; Harris, Kristie M.; Emery, Charles F.; Orthopaedic Surgery, School of MedicineContext: It is unknown how specific coping strategies are associated with the short-term outcomes among athletes following knee surgery. Objective: 1) To determine whether specific coping strategies are associated with satisfaction, return to sport, self-reported knee function, or kinesiophobia following sports-related knee surgery. 2) To determine whether these associations vary by age, sex, or surgical procedure. Study design: Case series. Methods: Athletes (n=184 total; n=104 men, n=80 women; n=38 age <20 years, n=35 age 20-25, n=36 age 26-31, n=36 age 32-40, n=39 age >40) who underwent outpatient knee surgery were enrolled from a single center. Utilization of specific coping strategies (self-distraction, use of emotional or instrumental support, venting, positive reframing, and acceptance) was assessed pre-operatively with the Brief-COPE inventory. Relationship between coping strategies and post-operative satisfaction, return to sport, International Knee Documentation Committee-subjective (IKDC-S) and Tampa Scale for Kinesiophobia scores at median 10.7 months follow-up were determined with consideration for age, sex, and surgical procedure. Results: Return to prior level of sport was 72%, and satisfaction was 86%. Most coping strategies had age-specific utilization rates; positive reframing was utilized least frequently in ages <20 years. Satisfaction increased with greater positive reframing among ages <20 years and decreased with greater self-distraction among men. Return to sport was higher with greater positive reframing in ages <32 years. No coping strategies predicted IKDC-S scores. Greater positive reframing correlated with lower kinesiophobia in ages <20 years. Greater instrumental support correlated with lower kinesiophobia in ages >40 years. No other coping strategies were associated with outcomes. Surgical procedure was not related to association between coping strategies and outcomes. Conclusion: Coping strategies have age-specific associations with outcomes after knee surgery in athletes. Positive reframing is infrequently utilized in younger athletes. Greater use of positive reframing in this group may improve satisfaction, return to sport, and lower fear of re-injury.Item Time Matters: Knee Cartilage Defect Expansion and High-Grade Lesion Formation while Awaiting Autologous Chondrocyte Implantation(Sage, 2021) Pettit, Robert J.; Everhart, Joshua S.; DiBartola, Alex C.; Blackwell, Ryan E.; Flanigan, David C.; Orthopaedic Surgery, School of MedicineObjective: The objective of this study was to assess potential risk factors, including time delay until implantation, for knee cartilage defect expansion or new high-grade defect formation between biopsy and Autologous Chondrocyte Implantation (ACI) or Matrix Autologous Chondrocyte Implantation (MACI). Study design: Consecutive knee ACI and MACI cases by a single surgeon (n = 111) were reviewed. The relationship between time between biopsy and staged implantation and (1) progression in primary cartilage defect size and (2) development of a new high-grade (Outerbridge grade ≥3) cartilage defect were determined with adjustment for demographics, body mass index, smoking status, coronal alignment, initial cartilage status, and prior surgery. Results: Average size of the primary defect at time of biopsy was 4.50 cm2. Mean time to chondrocyte implantation was 155 days. Defect expansion increased 0.11 cm2 (standard error = 0.03) per month delay to implantation (P = 0.001). Independent predictors of defect expansion were male sex, smaller initial defect size, and delay to implantation (adjusted mean = 0.15 cm2 expansion per month). A total of 16.2% of patients (n = 18/111) developed a new high-grade defect. Independent predictors of a new secondary defect were Outerbridge grade 2 changes (vs. 0-1) on the surface opposing the index defect and delayed implantation (per month increase, adjusted odds ratio = 1.21, 95% confidence interval: 1.01-1.44; P = 0.036). Conclusions: Patients undergoing 2-stage cell-based cartilage restoration with either ACI or MACI demonstrated long delays between stages of surgery, placing them at risk for expanding defects and development of new high-grade cartilage defects. Patients who were male, had smaller initial defect size, and longer time between surgeries were at greater risk for defect expansion.