Publications

2024

Garcia, M., Momenzadah, K., Shariyate, M. J., Kheir, N., Khak, M., Villarreal, J. B., Abbasian, M., Flaherty, A. F., Hanna, P., Ramappa, A., Paschos, N. K., & Nazarian, A. (2024). Plastic and elastic biomechanical properties of anterior cruciate ligament autografts.. BMC Musculoskeletal Disorders, 25(1), 157. https://doi.org/10.1186/s12891-024-07262-y (Original work published 2024)

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common orthopedic injury, occurring in roughly 68.6 per 100,000 persons annually, with the primary treatment option being ACL reconstruction. However, debate remains about the appropriate graft type for restoring the native biomechanical properties of the knee. Furthermore, plastic graft elongation may promote increased knee laxity and instability without rupture. This study aims to investigate the plastic properties of common ACL-R graft options.

METHODS: Patellar tendon (PT), hamstring tendon (HT), and quadriceps tendon (QT) grafts were harvested from 11 cadaveric knees (6 male and 5 female) with a mean age of 71(range 55-81). All grafts were mechanically tested under uniaxial tension until failure to determine each graft's elastic and plastic biomechanical properties.

RESULTS: Mechanically, the QT graft was the weakest, exhibiting the lowest failure force and the lowest failure stress (QT < HT, p = 0.032). The PT was the stiffest of the grafts, having a significantly higher stiffness (PT > QT, p = 0.0002) and Young's modulus (PT > QT, p = 0.001; PT > HT, p = 0.041). The HT graft had the highest plastic elongation at 4.01 ± 1.32 mm (HT > PT, p = 0.002). The post-yield behavior of the HT tendon shows increased energy storage capabilities with the highest plastic energy storage (HT > QT, p = 0.012) and the highest toughness (HT > QT, p = 0.032).

CONCLUSION: Our study agrees with prior studies indicating that the failure load of all grafts is above the requirements for everyday activities. However, grafts may be susceptible to yielding before failure during daily activities. This may result in the eventual loss of functionality for the neo-ACL, resulting in increased knee laxity and instability.

Brameier, D. T., Tischler, E. H., Ottesen, T. D., McTague, M. F., Appleton, P. T., Harris, M. B., Weaver, M. J., & Suneja, N. (2024). Use of Direct Oral Anticoagulants Among Patients With Hip Fracture Is Not an Indication to Delay Surgical Intervention.. Journal of Orthopaedic Trauma, 38(3), 148-154. https://doi.org/10.1097/BOT.0000000000002753 (Original work published 2024)

OBJECTIVES: To compare outcomes in patients on direct oral anticoagulants (DOACs) treated within 48 hours of last preoperative dose with those with surgical delays >48 hours.

DESIGN: Retrospective cohort study.

SETTING: Three academic Level 1 trauma centers.

PATIENT SELECTION CRITERIA: Patients 65 years of age or older on DOACs before hip fracture treated between 2010 and 2018. Patients were excluded if last DOAC dose was >24 hours before admission, patient suffered from polytrauma, and/or delay to surgery was not attributed to DOAC.

OUTCOME MEASURES AND COMPARISONS: Primary outcome measures were the postoperative complication rate as determined by diagnosis of deep venous thrombosis or pulmonary embolus, wound breakdown, drainage, or infection. Secondary outcomes included transfusion requirement, perioperative bleeding, length of stay, reoperation rates, readmission rates, and mortality.

RESULTS: Two hundred five patients were included in this study, with a mean cohort age of 81.9 years (65-100 years), 64% were (132/205) female, and a mean Charlson Comorbidity Index of 6.4 (2-20). No significant difference was observed among age, sex, Charlson Comorbidity Index, or fracture pattern between cohorts (P > 0.05 for all comparisons). Seventy-one patients had surgery <48 hours after final preoperative DOAC dose; 134 patients had surgery >48 hours after. No significant difference in complication rate between the 2 cohorts was observed (P = 0.30). Patients with delayed surgical management were more likely to require transfusion (OR 2.39, 95% CI, 1.05-5.44; P = 0.04). Patients with early surgical management had significantly shorter lengths of stay (5.9 vs. 7.6 days, P < 0.005). There was no difference in estimated blood loss, anemia, reoperations, readmissions, 90-day mortality, or 1-year mortality (P > 0.05 for all comparisons).

CONCLUSIONS: Geriatric patients with hip fracture who underwent surgical management within 48 hours of their last preoperative DOAC dose required less transfusions and had decreased length of stay, with comparable mortality and complication rates with patients with surgery delayed beyond 48 hours. Providers should consider early intervention in this population rather than adherence to elective procedure guidelines.

LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Chainani, P. H., Mena, M. B., Yeritsyan, D., Caro, D., Momenzadeh, K., Galloway, J. L., DeAngelis, J. P., Ramappa, A. J., & Nazarian, A. (2024). Successive tendon injury in an in vivo rat overload model induces early damage and acute healing responses.. Frontiers in Bioengineering and Biotechnology, 12, 1327094. https://doi.org/10.3389/fbioe.2024.1327094 (Original work published 2024)

Introduction: Tendinopathy is a degenerative condition resulting from tendons experiencing abnormal levels of multi-scale damage over time, impairing their ability to repair. However, the damage markers associated with the initiation of tendinopathy are poorly understood, as the disease is largely characterized by end-stage clinical phenotypes. Thus, this study aimed to evaluate the acute tendon responses to successive fatigue bouts of tendon overload using an in vivo passive ankle dorsiflexion system. Methods: Sprague Dawley female rats underwent fatigue overloading to their Achilles tendons for 1, 2, or 3 loading bouts, with two days of rest in between each bout. Mechanical, structural, and biological assays were performed on tendon samples to evaluate the innate acute healing response to overload injuries. Results: Here, we show that fatigue overloading significantly reduces in vivo functional and mechanical properties, with reductions in hysteresis, peak stress, and loading and unloading moduli. Multi-scale structural damage on cellular, fibril, and fiber levels demonstrated accumulated micro-damage that may have induced a reparative response to successive loading bouts. The acute healing response resulted in alterations in matrix turnover and early inflammatory upregulations associated with matrix remodeling and acute responses to injuries. Discussion: This work demonstrates accumulated damage and acute changes to the tendon healing response caused by successive bouts of in vivo fatigue overloads. These results provide the avenue for future investigations of long-term evaluations of tendon overload in the context of tendinopathy.

Chainani, P. H., Williamson, P. M., Yeritsyan, D., Momenzadeh, K., Kheir, N., DeAngelis, J. P., Ramappa, A. J., & Nazarian, A. (2024). A Passive Ankle Dorsiflexion Testing System for an In Vivo Model of Overuse-induced Tendinopathy.. Journal of Visualized Experiments : JoVE, 205. https://doi.org/10.3791/65803 (Original work published 2024)

Tendinopathy is a chronic tendon condition that results in pain and loss of function and is caused by repeated overload of the tendon and limited recovery time. This protocol describes a testing system that cyclically applies mechanical loads via passive dorsiflexion to the rat Achilles tendon. The custom-written code consists of pre- and post-cyclic loading measurements to assess the effects of the loading protocol along with the feedback control-based cyclic fatigue loading regimen. We used 25 Sprague-Dawley rats for this study, with 5 rats per group receiving either 500, 1,000, 2,000, 3,600, or 7,200 cycles of fatigue loads. The percentage differences between the pre- and post-cyclic loading measurements of the hysteresis, peak stress, and loading and unloading moduli were calculated. The results demonstrate that the system can induce varying degrees of damage to the Achilles tendon based on the number of loads applied. This system offers an innovative approach to apply quantified and physiological varying degrees of cyclic loads to the Achilles tendon for an in vivo model of fatigue-induced overuse tendon injury.

Kanumuri, S., Subhansab, S. K., Agarwal-Harding, K. J., & Krishna, S. V. (2024). Open Exploration and Reduction of Paediatric Supracondylar Humerus Fracture with Pink, Pulseless Hand in Resource-Limited Settings.. The Journal of Hand Surgery Asian-Pacific Volume, 29(2), 118-124. https://doi.org/10.1142/S2424835524500139 (Original work published 2024)

Background: Supracondylar humerus fractures (SHFs) are common paediatric injuries, with high risk of vascular compromise. Some patients present with a 'pink, pulseless hand', caused by occlusion of brachial artery flow but with collateral circulation preserving distal perfusion. Management of these patients remains controversial, especially when resources may be limited for prolonged hospitalisation and serial monitoring by skilled staff. The aim of this study is to present the intraoperative findings, surgical procedures done and outcomes at 6 weeks for patients with paediatric supracondylar fractures with a pink pulseless hand. Methods: We retrospectively identified 13 patients who presented to a public hospital between January 2019 and May 2023 with a displaced SHF and pink, pulseless hand. All patients underwent an open reduction with an anterior approach allowing for exploration, protection and repair of neurovascular structures. Distal flow was restored in the brachial artery either with topical lidocaine application, thrombectomy or artery reconstruction. Results: Out of 13 patients, all had intact median nerves and 10 had intact arteries (69%), of which seven were interposed at the fracture site and four were in vasospasm. Of the three patients with true arterial injury (23%), two had a crushed artery and one had thrombosis of the artery. Peripheral pulses were restored within an hour of fracture open reduction in all patients. At final follow-up, a mean 6 weeks postoperatively, all patients had recovered without neurovascular deficit, compartment syndrome or Volkmann ischemic contracture. Conclusions: In resource-limited settings, we recommend performing open exploration and reduction for patients with SHFs with pink, pulseless hand. This approach prevents iatrogenic neurovascular injury during closed reduction attempts, allows for immediate repair of a brachial artery injury and avoids unnecessary hospitalisation and serial monitoring. Level of Evidence: Level IV (Therapeutic).

Evans, A. R., Tetsworth, K., Quinnan, S., & Wixted, J. J. (2024). Transcutaneous osseointegration for amputees.. OTA International : The Open Access Journal of Orthopaedic Trauma, 7(2 Suppl), e326. https://doi.org/10.1097/OI9.0000000000000326 (Original work published 2024)

Transcutaneous osseointegration for amputees (TOFA) is an evolving technology that has the potential to revolutionize the interface between the amputee and their prosthesis, showing potential at many levels of amputation. While no amputation is without its challenges, TOFA requires a highly specialized prosthesis and a multidisciplinary team that includes specialized surgeons, physical therapists, wound care teams, and social workers who guide the amputee through surgery, postoperative rehabilitation, and the chronic wound care that goes into maintaining the prosthesis. The infrastructure required to facilitate care pathways that lead to reliable, successful outcomes are unique in each health care setting, including those in advanced health care systems such as the United States and Australia. This article details the emerging evidence supporting the use of this prosthetic interface design and many of the challenges that providers face when establishing programs to offer this type of care in the United States.

Kassey, V. B., Walle, M., Egan, J., Yeritsyan, D., Beeram, I., Kassey, S. P., Wu, Y., Snyder, B. D., Rodriguez, E. K., Ackerman, J. L., & Nazarian, A. (2024). Quantitative 1H Magnetic Resonance Imaging on Normal and Pathologic Rat Bones by Solid-State 1H ZTE Sequence with Water and Fat Suppression.. Journal of Magnetic Resonance Imaging : JMRI, 60(6), 2423-2432. https://doi.org/10.1002/jmri.29361 (Original work published 2024)

BACKGROUND: Osteoporosis (OP) and osteomalacia (OM) are metabolic bone diseases characterized by mineral and matrix density changes. Quantitative bone matrix density differentiates OM from OP. MRI is a noninvasive and nonionizing imaging technique that can measure bone matrix density quantitatively in ex vivo and in vivo.

PURPOSE: To demonstrate water + fat suppressed 1H MRI to compute bone matrix density in ex vivo rat femurs in the preclinical model.

STUDY TYPE: Prospective.

ANIMAL MODEL: Fifteen skeletally mature female Sprague-Dawley rats, five per group (normal, ovariectomized (OVX), partially nephrectomized/vitamin D (Vit-D) deficient), 250-275 g, ∼15 weeks old.

FIELD STRENGTH/SEQUENCE: 7T, zero echo time sequence with water + fat (VAPOR) suppression capability, μCT imaging, and gravimetric measurements.

ASSESSMENT: Cortical and trabecular bone segments from normal and disease models were scanned in the same coil along with a dual calibration phantom for quantitative assessment of bone matrix density.

STATISTICAL TESTS: ANOVA and linear regression were used for data analysis, with P-values <0.05 statistically significant.

RESULTS: The MRI-derived three-density PEG pellet densities have a strong linear relationship with physical density measures (r2 = 0.99). The Vit-D group had the lowest bone matrix density for cortical bone (0.47 ± 0.16 g cm-3), whereas the OVX had the lowest bone matrix density for trabecular bone (0.26 ± 0.04 g cm-3). Gravimetry results confirmed these MRI-based observations for Vit-D cortical (0.51 ± 0.07 g cm-3) and OVX trabecular (0.26 ± 0.03 g cm-3) bone groups.

DATA CONCLUSION: Rat femur images were obtained using a modified pulse sequence and a custom-designed double-tuned (1H/31P) transmit-receive solenoid-coil on a 7T preclinical MRI scanner. Phantom experiments confirmed a strong linear relation between MRI-derived and physical density measures and quantitative bone matrix densities in rat femurs from normal, OVX, and Vit-D deficient/partially nephrectomized animals were computed.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Chen, A., Garvey, S. R., Saxena, N., Bustos, V. P., Jia, E., Morgenstern, M., Nanda, A. D., Dowlatshahi, A. S., & Cauley, R. P. (2024). Is Diabetes a Contraindication to Lower Extremity Flap Reconstruction? An Analysis of Threatened Lower Extremities in the NSQIP Database (2010-2020).. Archives of Plastic Surgery, 51(2), 234-250. https://doi.org/10.1055/a-2233-2617 (Original work published 2024)

Background  The impact of diabetes on complication rates following free flap (FF), pedicled flap (PF), and amputation (AMP) procedures on the lower extremity (LE) is examined. Methods  Patients who underwent LE PF, FF, and AMP procedures were identified from the 2010 to 2020 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP®) database using Current Procedural Terminology and International Classification of Diseases-9/10 codes, excluding cases for non-LE pathologies. The cohort was divided into diabetics and nondiabetics. Univariate and adjusted multivariable logistic regression analyses were performed. Results  Among 38,998 patients undergoing LE procedures, 58% were diabetic. Among diabetics, 95% underwent AMP, 5% underwent PF, and <1% underwent FF. Across all procedure types, noninsulin-dependent (NIDDM) and insulin-dependent diabetes mellitus (IDDM) were associated with significantly greater all-cause complication rates compared with absence of diabetes, and IDDM was generally higher risk than NIDDM. Among diabetics, complication rates were not significantly different across procedure types (IDDM: p  = 0.5969; NIDDM: p  = 0.1902). On adjusted subgroup analysis by diabetic status, flap procedures were not associated with higher odds of complications compared with amputation for IDDM and NIDDM patients. Length of stay > 30 days was statistically associated with IDDM, particularly those undergoing FF (AMP: 5%, PF: 7%, FF: 14%, p  = 0.0004). Conclusion  Our study highlights the importance of preoperative diabetic optimization prior to LE procedures. For diabetic patients, there were few significant differences in complication rates across procedure type, suggesting that diabetic patients are not at higher risk of complications when attempting limb salvage instead of amputation.

Dworkin, M., Harrison, W. J., Chidothi, P., Mbowuwa, F., Martin, C., Agarwal-Harding, K., & Chokotho, L. (2024). Epidemiology and Treatment of Distal Radius Fractures at Four Public Hospitals in Malawi.. Journal of the American Academy of Orthopaedic Surgeons. Global Research & Reviews, 8(4). https://doi.org/10.5435/JAAOSGlobal-D-23-00282 (Original work published 2024)

BACKGROUND: Little is known about the burden or management of distal radius fractures (DRFs) in low- and middle-income countries. The purpose of this study was to describe the care of DRFs in Malawi.

METHODS: We retrospectively reviewed a registry of all patients with fractures who presented to the orthopaedic departments at four public hospitals in Malawi.

RESULTS: Totally, 1,440 patients (14.5%) were with a DRF. Average age was 40, and 888 (62.0%) were male. Surgery was done for 122 patients (9.5%). Patients presenting to Queen Elizabeth Hospital, patients presenting after a fall, and patients initially evaluated by an orthopaedic registrar or orthopaedic clinical officer had lower odds of receiving surgical treatment. Meanwhile, open injuries had the greatest odds of receiving surgery.

CONCLUSION: The most common musculoskeletal injury among patients in the Malawi Fracture Registry was fractures of the distal radius. These most affected young adult male patients may benefit from surgery; however, the majority were managed nonsurgically. Lack of access to surgical fixation and conservative follow-up may have long-term functional consequences in a predominantly agrarian society. Outcomes-based research is needed to help guide management decisions and standardize patient care and referral protocols.

Nourmahnad, A., Shariyate, M. J., Khak, M., Grinstaff, M. W., Nazarian, A., & Rodriguez, E. K. (2024). Relaxin as a treatment for musculoskeletal fibrosis: What we know and future directions.. Biochemical Pharmacology, 225, 116273. https://doi.org/10.1016/j.bcp.2024.116273 (Original work published 2024)

Fibrotic changes in musculoskeletal diseases arise from the abnormal buildup of fibrotic tissue around the joints, leading to limited mobility, compromised joint function, and diminished quality of life. Relaxin (RLX) attenuates fibrosis by accelerating collagen degradation and inhibiting excessive extracellular matrix (ECM) production. Further, RLX disrupts myofibroblast activation by modulating the TGF-β/Smads signaling pathways, which reduces connective tissue fibrosis. However, the mechanisms and effects of RLX in musculoskeletal pathologies are emerging as increasing research focuses on relaxin's impact on skin, ligaments, tendons, cartilage, joint capsules, connective tissues, and muscles. This review delineates the actions of relaxin within the musculoskeletal system and the challenges to its clinical application. Relaxin shows significant potential in both in vivo and in vitro studies for broadly managing musculoskeletal fibrosis; however, challenges such as short biological half-life and sex-specific responses may pose hurdles for clinical use.