Publications

2023

Karczewski, D., Gonzalez, M. R., Bedi, A., Ready, J. E., Anderson, M. E., & Lozano-Calderon, S. A. (2023). Giant cell-rich osteosarcoma: A match pair analysis of 11 new cases and literature review of 56 patients.. Journal of Surgical Oncology, 128(5), 877-890. https://doi.org/10.1002/jso.27368 (Original work published 2023)

BACKGROUND: Limited remains known on giant cell-rich osteosarcoma (GCRO) with current studies being case reports or smaller series. This investigation compared GCRO and conventional osteoblastic osteosarcoma (OOS) with regard to demographics and survival.

METHODS: An institutional tumor registry was used to identify 11 patients (six males) treated for GCRO. Mean age was 43 years. Staging showed American Joint Committee on Cancer (AJCC) stages IIA in four and IIB in seven patients. Mean follow-up was 14 years. Study initiatives were: (1) Comparison of demographics between GCRO and 167 OOS from our institutional registry, (2) Differences in survival between GCRO and 33 OOS case controls (based on sex and AJCC stage), as well as 10 OOS using an age-based propensity match, and (3) Summary of all GCRO cases reported in the literature.

RESULTS: (1) Sex (p = 0.53), grading (p = 0.56), AJCC stage (p = 0.42), and chemotherapeutic response rate (p = 0.67) did not differ between groups. Age was significantly increased in GCRO (p = 0.001). (2) Case-control and propensity-matched groups revealed no difference in disease-free survival, local recurrence, and distant disease-free survival at 2 years (p > 0.05). (3) Mean age of 56 patients (50% males) reported in the literature was 26 years. After merging with our 11 cases, the 2-year disease-free survival was 66%.

CONCLUSIONS: GCRO remains a rare disease with high short-term mortality. Although affecting older patients more than conventional osteosarcoma, GCRO should not be viewed as a predictor of survival compared to OOS.

Mandeville, R., Sanchez, B., Johnston, B., Bazarek, S., Thum, J. A., Birmingham, A., See, R. H. B., Leochico, C. F. D., Kumar, V., Dowlatshahi, A. S., Brown, J., Stashuk, D., & Rutkove, S. B. (2023). A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration, and regeneration: part 1, neurophysiology.. Journal of Neural Engineering, 20(4). https://doi.org/10.1088/1741-2552/acdbeb (Original work published 2023)

Peripheral neuroregeneration research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures that can serve as biomarkers of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, such biomarkers can elucidate regeneration mechanisms and open new avenues for research. Without these measures, clinical decision-making falls short, and research becomes more costly, time-consuming, and sometimes infeasible. As a companion to Part 2, which is focused on non-invasive imaging, Part 1 of this two-part scoping review systematically identifies and critically examines many current and emerging neurophysiological techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

Williamson, P. M., Yeritsyan, D., Peacock, T., Chainani, P., Momenzadeh, K., Asciutto, D., Pathirana, P., Avakian, C., Stewart, I., Kheir, N., Abbasian, M., DeAngelis, J. P., Ramappa, A. J., & Nazarian, A. (2023). A passive ankle dorsiflexion testing system to assess mechanobiological and structural response to cyclic loading in rat Achilles tendon.. Journal of Biomechanics, 156, 111664. https://doi.org/10.1016/j.jbiomech.2023.111664 (Original work published 2023)

Tendinopathy is thought to be caused by repeated overload of the tendon with insufficient recovery time, leading to an inadequate healing response and incomplete recovery of preinjury material strength and function. The etiology of tendinopathy induced by mechanical load is being explored with a variety of mechanical load scenarios in small animals. This study establishes a testing system that applies passive ankle dorsiflexion to a rat hindlimb, estimates the force applied to the tendon during cyclic loading and enables the assessment of subsequent structural and biological changes. We demonstrated that the system had no drift in the applied angle, and the registered maximum angle and torque inputs and outputs were consistent between tests. We showed that cyclic loading decreased hysteresis and loading and unloading moduli with increasing cycles applied to the tendon. Histology showed gross changes to tendon structure. This work establishes a system for passively loading the rat Achilles tendon in-vivo in a physiological manner, facilitating future studies that will explore how mechanics, structure, and biology are altered by mechanical repetitive loading.

Williams, C. T., Whyman, J., Loewenthal, J., & Chahal, K. (2023). Managing Geriatric Patients with Falls and Fractures.. The Orthopedic Clinics of North America, 54(3S), e1-e12. https://doi.org/10.1016/j.ocl.2023.04.001 (Original work published 2023)

Orthopedic fractures in adults 65 and older are common and can lead to functional decline and increased morbidity and mortality. Falls are often the precipitating event for fractures in this population, linked to common aging physiology with increasing comorbid conditions and advancing frailty. Managing falls and orthopedic fractures in the geriatric population is complex, requiring a systematic and collaborative approach spearheaded by a multidisciplinary team focused on improving patient outcomes.

Shariyate, M. J., Kheir, N., Caro, D., Abbasian, M., Rodriguez, E. K., Snyder, B. D., & Nazarian, A. (2023). Assessment of Bone Healing: Opportunities to Improve the Standard of Care.. The Journal of Bone and Joint Surgery. American Volume, 105(15), 1193-1202. https://doi.org/10.2106/JBJS.22.01224 (Original work published 2023)

➤ Bone healing is commonly evaluated by clinical examination and serial radiographic evaluation. Physicians should be mindful that personal and cultural differences in pain perception may affect the clinical examination. Radiographic assessment, even with the Radiographic Union Score, is qualitative, with limited interobserver agreement.➤ Physicians may use serial clinical and radiographical examinations to assess bone healing in most patients, but in ambiguous and complicated cases, they may require other methods to provide assistance in decision-making.➤ In complicated instances, clinically available biomarkers, ultrasound, and magnetic resonance imaging may determine initial callus development. Quantitative computed tomography and finite element analysis can estimate bone strength in later callus consolidation phases.➤ As a future direction, quantitative rigidity assessments for bone healing may help patients to return to function earlier by increasing a clinician's confidence in successful progressive healing.

Kim, E. J., Stearns, S. A., Bustos, V. P., Dowlatshahi, A. S., Lee, B. T., & Cauley, R. (2023). Impact of financial well-being on gender affirmation surgery access and hospital course.. Journal of Plastic, Reconstructive & Aesthetic Surgery : JPRAS, 85, 174-181. https://doi.org/10.1016/j.bjps.2023.06.059 (Original work published 2023)

BACKGROUND: Although gender affirmation surgery (GAS) can effectively treat gender dysphoria, it remains one of the most expensive components of gender affirming care. This study aims to identify the impact of financial well-being on GAS access and hospital course in the United States.

METHODS: The National Inpatient Sample database was queried from 2012 to 2019. US transgender patients undergoing GAS were identified. Predictors included patient sociodemographic variables. Outcomes included hospitalization course variables. Regression modeling was used to assess the relationship between predictor and outcome variables. Significance was set at α = 0.05.

RESULTS: A total of 5620 weighted GAS encounters were identified (genital surgery 92.3%, chest surgery 16.6%). 1825 (32.5%) patients were in the highest income bracket, compared with 1120 (19.9%) patients in the lowest bracket. Higher income was associated with younger age at the time of GAS. Patients in the highest income quartile were also 3.7 times more likely to be funded by private insurance and self-pay options than those in the lowest income quartile (95% confidence interval [CI]: 3.1-4.4, p < 0.0001). Additionally, patients in the lowest income quartile were 4.2 times more likely to require either home healthcare or transfer to a nursing facility post discharge than those in the highest income quartile (95% CI: 3.1-5.8, p < 0.001).

CONCLUSIONS: To promote equitable care to transgender patients, efforts to reduce financial barriers to healthcare access are much needed, particularly through broader insurance coverage of GAS procedures. Broadly, our results highlight the impact of socioeconomic variables on healthcare access and outcomes.

Mandeville, R., Deshmukh, S., Tan, E. T., Kumar, V., Sanchez, B., Dowlatshahi, A. S., Luk, J., See, R. H. B., Leochico, C. F. D., Thum, J. A., Bazarek, S., Johnston, B., Brown, J., Wu, J., Sneag, D., & Rutkove, S. (2023). A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration and regeneration: part 2, non-invasive imaging.. Journal of Neural Engineering, 20(4). https://doi.org/10.1088/1741-2552/ace217 (Original work published 2023)

Peripheral neuroregenerative research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, novel biomarkers can elucidate regenerative mechanisms and open new avenues for research. Without such measures, clinical decision-making is impaired, and research becomes more costly, time-consuming, and sometimes infeasible. Part 1 of this two-part scoping review focused on neurophysiology. In part 2, we identify and critically examine many current and emerging non-invasive imaging techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

Chaudhury, A. S., Bernstein, D. N., Harper, C. M., Hammert, W. C., & Rozental, T. D. (2023). Bringing Patient-Reported Outcome Measures (PROMs) Into Practice: A Review of the Latest Developments in PROM Use in the Evaluation and Treatment of Carpal Tunnel Syndrome.. Journal of Hand Surgery Global Online, 5(4), 492-497. https://doi.org/10.1016/j.jhsg.2022.06.005 (Original work published 2023)

As health care systems globally shift toward optimizing value, defined as health outcomes achieved per dollar spent across a full cycle of care, there has been increasing focus on using patient-reported outcome measures (PROMs) to gauge success. Patient-reported outcome measures are validated questionnaires that allow patients to share their health status across several domains (eg, pain or physical function). This trend has been particularly notable in hand surgery, with PROM use investigated for many common hand conditions, including carpal tunnel syndrome, Dupuytren contracture, trigger finger, osteoarthritis, and wrist ganglion. The purpose of this article is to review recent developments in the use of PROM instruments, including the Boston Carpal Tunnel Questionnaire; Michigan Hand Outcomes Questionnaire; Disabilities of the Arm, Shoulder, and Hand; and Patient-Reported Outcomes Measurement Information System, for the evaluation and treatment of patients with carpal tunnel syndrome. The considerable progress in establishing PROMs for use in carpal tunnel syndrome is reviewed, and future improvements are proposed to standardize PROM use and bring PROMs into day-to-day clinical practice for individualized patient treatment decision-making and counseling.

Dworkin, M., Agarwal-Harding, K. J., Joseph, M., Cahill, G., Konadu-Yeboah, D., Makasa, E., Mock, C., & Group, M. I. (2023). Indicators for the evaluation of musculoskeletal trauma systems: A scoping review and Delphi study.. PloS One, 18(8), e0290816. https://doi.org/10.1371/journal.pone.0290816 (Original work published 2023)

BACKGROUND: Trauma is a leading cause of mortality and morbidity, disproportionately affecting low- and middle-income countries. Musculoskeletal trauma results in the majority of post-traumatic morbidity and disability globally. The literature has reported many performance indicators relating to trauma care, but few specific to musculoskeletal injuries.

STUDY OBJECTIVES: The purpose of this study was to establish a practical list of performance indicators to evaluate and monitor the quality and equity of musculoskeletal trauma care delivery in health systems worldwide.

METHODS: A scoping review was performed that identified performance indicators related to musculoskeletal trauma care. Indicators were organized by phase of care (general, prevention, pre-hospital, hospital, post-hospital) within a modified Donabedian model (structure, process, outcome, equity). A panel of 21 experts representing 45 countries was assembled to identify priority indicators utilizing a modified Delphi approach.

RESULTS: The scoping review identified 1,206 articles and 114 underwent full text review. We included 95 articles which reported 498 unique performance indicators. Most indicators related to the hospital phase of care (n = 303, 60%) and structural characteristics (n = 221, 44%). Mortality (n = 50 articles) and presence of trauma registries (n = 16 articles) were the most frequently reported indicators. After 3 rounds of surveys our panel reached consensus on a parsimonious list of priority performance indicators. These focused on access to trauma care; processes and key resources for polytrauma triage, patient stabilization, and hemorrhage control; reduction and immobilization of fractures and dislocations; and management of compartment syndrome and open fractures.

CONCLUSIONS: The literature has reported many performance indicators relating to trauma care, but few specific to musculoskeletal injuries. To create quality and equitable trauma systems, musculoskeletal care must be incorporated into development plans with continuous monitoring and improvement. The performance indicators identified by our expert panel and organized in a modified Donabedian model can serve as a method for evaluating musculoskeletal trauma care.

Lechtig, A., Hanna, P., Nagy, J. A., Wixted, J., Nazarian, A., & Rutkove, S. B. (2023). Electrical impedance myography for the early detection of muscle ischemia secondary to compartment syndrome: a study in a rat model.. Scientific Reports, 13(1), 18252. https://doi.org/10.1038/s41598-023-45209-w (Original work published 2023)

Acute Compartment Syndrome (ACS) is one of the most devastating orthopedic conditions, affecting any of the body's many compartments, which, if sufficiently severe, may result in disability and amputation. Currently, intra-compartmental pressure measurements serve as the gold standard for diagnosing ACS. Diagnosing limbs at risk for ACS before irreversible damage to muscle and nerve is critical. Standard approaches for diagnosing impending compartment syndrome include clinical evaluation of the limb, such as assessment for "tightness" of the overlying skin, reduced pulses distally, and degree of pain, none of which are specific or sensitive. We have proposed a novel method to detect ACS via electrical impedance myography (EIM), where a weak, high-frequency alternating current is passed between one pair of electrodes through a region of tissue, and the resulting surface voltages are measured via a second pair. We evaluated the ability of EIM to detect early muscle ischemia in an established murine model of compression-induced muscle injury, where we collected resistance, reactance, and their dimensionless product, defined as Relative Injury Index (RII) during the study. Our model generated reproducible hypoxia, confirmed by Hypoxyprobe™ staining of endothelial regions within the muscle. Under conditions of ischemia, we demonstrated a reproducible, stable, and significant escalation in resistance, reactance, and RII values, compared to uninjured control limbs. These data make a reasonable argument for additional investigations into using EIM for the early recognition of muscle hypoperfusion and ischemia. However, these findings must be considered preliminary steps, requiring further pre-clinical and clinical validation.