Publications by Year: 2024

2024

Kassey, V. B., Walle, M., Egan, J., Yeritsyan, D., Beeram, I., Wu, Y., Snyder, B. D., Rodriguez, E. K., Ackerman, J. L., & Nazarian, A. (2024). Quantitative 31P magnetic resonance imaging on pathologic rat bones by ZTE at 7T.. Bone, 180, 116996. https://doi.org/10.1016/j.bone.2023.116996 (Original work published 2024)

BACKGROUND: Osteoporosis is characterized by low bone mineral density (BMD), which predisposes individuals to frequent fragility fractures. Quantitative BMD measurements can potentially help distinguish bone pathologies and allow clinicians to provide disease-relieving therapies. Our group has developed non-invasive and non-ionizing magnetic resonance imaging (MRI) techniques to measure bone mineral density quantitatively. Dual-energy X-ray Absorptiometry (DXA) is a clinically approved non-invasive modality to diagnose osteoporosis but has associated disadvantages and limitations.

PURPOSE: Evaluate the clinical feasibility of phosphorus (31P) MRI as a non-invasive and non-ionizing medical diagnostic tool to compute bone mineral density to help differentiate between different metabolic bone diseases.

MATERIALS AND METHODS: Fifteen ex-vivo rat bones in three groups [control, ovariectomized (osteoporosis), and vitamin-D deficient (osteomalacia - hypo-mineralized) were scanned to compute BMD. A double-tuned (1H/31P) transmit-receive single RF coil was custom-designed and in-house-built with a better filling factor and strong radiofrequency (B1) field to acquire solid-state 31P MR images from rat femurs with an optimum signal-to-noise ratio (SNR). Micro-computed tomography (μCT) and gold-standard gravimetric analyses were performed to compare and validate MRI-derived bone mineral densities.

RESULTS: Three-dimensional 31P MR images of rat bones were obtained with a zero-echo-time (ZTE) sequence with 468 μm spatial resolution and 12-17 SNR on a Bruker 7 T Biospec having multinuclear capability. BMD was measured quantitatively on cortical and trabecular bones with a known standard reference. A strong positive correlation (R = 0.99) and a slope close to 1 in phantom measurements indicate that the densities measured by 31P ZTE MRI are close to the physical densities in computing quantitative BMD. The 31P NMR properties (resonance linewidth of 4 kHz and T1 of 67 s) of ex-vivo rat bones were measured, and 31P ZTE imaging parameters were optimized. The BMD results obtained from MRI are in good agreement with μCT and gravimetry results.

CONCLUSION: Quantitative measurements of BMD on ex-vivo rat femurs were successfully conducted on a 7 T preclinical scanner. This study suggests that quantitative measurements of BMD are feasible on humans in clinical MRI with suitable hardware, RF coils, and pulse sequences with optimized parameters within an acceptable scan time since human femurs are approximately ten times larger than rat femurs. As MRI provides quantitative in-vivo data, various systemic musculoskeletal conditions can be diagnosed potentially in humans.

Nguyen, A. T., Aris, I. M., Snyder, B. D., Harris, M. B., Kang, J. D., Murray, M., Rodriguez, E. K., & Nazarian, A. (2024). Musculoskeletal health: an ecological study assessing disease burden and research funding.. Lancet Regional Health. Americas, 29, 100661. https://doi.org/10.1016/j.lana.2023.100661 (Original work published 2024)

BACKGROUND: Exacerbated by an aging population, musculoskeletal diseases are a chronic and growing problem in the United States that impose significant health and economic burdens. The objective of this study was to analyze the correlation between the burden of diseases and the federal funds assigned to health-related research through the National Institutes of Health (NIH).

METHODS: An ecological study design was used to examine the relationship between NIH research funding and disease burden for 60 disease categories. We used the Global Burden of Disease (GBD) Study 2019 to measure disease burden and the NIH Research, Condition, and Disease Categories (RCDC) data to identify 60 disease categories aligned with available GBD data. NIH funding data was obtained from the RCDC system and the NIH Office of Budget. Using linear regression models, we observed that musculoskeletal diseases were among the most underfunded (i.e., negative residuals from the model) with respect to disease burden.

FINDINGS: Musculoskeletal diseases were underfunded, with neck pain being the most underfunded at only 0.83% of expected funding. Low back pain, osteoarthritis, and rheumatoid arthritis were also underfunded at 13.88%, 35.08%, and 66.26%, respectively. Musculoskeletal diseases were the leading cause of years lived with disability and the third leading cause in terms of prevalence and disability-adjusted life years. Despite the increasing burden of these diseases, the allocation of NIH funding to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has remained low compared to other institutes.

INTERPRETATION: Despite the increasing health burden and economic cost of $980 billion annually, the allocation of NIH funding to the NIAMS has remained low compared to other institutes. These findings suggest that the NIH may need to reassess its allocation of research funding to align with the current health challenges of our country. Furthermore, these clinically relevant observations highlight the need to increase research funding for musculoskeletal diseases and improve their prevention, diagnosis, and treatment.

FUNDING: No funding.

Villarreal-Espinosa, J. B., Kay, J., & Ramappa, A. J. (2024). Arthroscopic Bankart with remplissage results in lower rates of recurrent instability with similar range of motion compared to isolated arthroscopic Bankart for anterior glenohumeral instability: A systematic review and meta-analysis.. Knee Surgery, Sports Traumatology, Arthroscopy : Official Journal of the ESSKA, 32(2), 243-256. https://doi.org/10.1002/ksa.12054 (Original work published 2024)

PURPOSE: The addition of the remplissage procedure to an arthroscopic Bankart procedure has been shown to improve clinical outcomes, yet at the expense of potentially decreasing shoulder range of motion. The purpose of this study was to assess recurrent instability, range of motion, functional outcomes and rates of return to sport outcomes in patients undergoing an isolated arthroscopic Bankart repair compared to those undergoing arthroscopic Bankart repair in addition to the remplissage procedure.

METHODS: According to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a search was conducted using three databases (MEDLINE/OVID, EMBASE and PubMed). Retrieved studies were screened based on predefined inclusion and exclusion criteria for comparative studies. Data were extracted and meta-analysis performed using a random-effects model.

RESULTS: A total of 16 studies (13 level III studies, 2 level II studies and 1 level I) were included with a total of 507 and 704 patients in the Bankart plus remplissage and isolated Bankart repair groups, respectively. No studies reported glenoid bone loss of >20% with the least percentage of glenoid bone loss reported among studies being <1%. There was a significantly increased rate of recurrent dislocations (odds ratio [OR] = 4.22, 95% confidence interval [CI]: 2.380-7.48, p < 0.00001) and revision procedures (OR = 3.36, 95% CI: 1.52-7.41, p = 0.003) in the isolated Bankart repair group compared to the Bankart plus remplissage group. Additionally, there were no significant differences between groups in terms of external rotation at side (n.s.), in abduction (n.s.) or at forward flexion (n.s.) at final follow-up. Furthermore, return to preinjury level of sport favoured the Bankart plus remplissage group (OR = 0.54, 95% CI: 0.35-0.85, p = 0.007).

CONCLUSION: Patients undergoing arthroscopic Bankart plus remplissage for anterior shoulder instability have lower rates of recurrent instability, higher rates of return to sport, and no significant difference in range of motion at final follow-up when compared to an isolated arthroscopic Bankart repair. Further large, prospective studies are needed to further determine which patients and degree of bone loss would benefit most from augmentation with the remplissage procedure.

LEVEL OF EVIDENCE: Level III.

Mathur, V., Osei-Hwedieh, D., Hosseinian, S. H. S., Bejarano-Pineda, L., Kaiser, P., Raduan, F., Kwon, J. Y., Ashkani-Esfahani, S., & Waryasz, G. R. (2024). Use of Bio-integrative Screws for Fixation of Lisfranc Instability; Pros and Cons from Surgeons’ Point of View in a Cadaver Study.. The Archives of Bone and Joint Surgery, 12(1), 51-57. https://doi.org/10.22038/ABJS.2023.73584.3410 (Original work published 2024)

OBJECTIVES: Majority of Lisfranc fracture-dislocations require anatomic reduction and rigid internal fixation to prevent debilitating sequelae. Current methods include solid screws and flexible fixations which have been in use for many years. Biointegrative screw is a newer option that has not yet been thoroughly investigated for its effectiveness for Lisfranc injuries.

METHODS: The ligaments of the Lisfranc complex were resected in eight lower-leg cadaveric specimens. This was done by eight foot and ankle surgeons individually. Distraction forces were applied from opposite sides at the joint to replicate weight bearing conditions. Three methods of fixation - flexible fixation, metal, and biointegrative screws- were evaluated. The diastasis and area at the level of the ligament were measured at four conditions (replicated injury and each type of fixation) in neutral and distraction conditions using fluoroscopy images. The Wilcoxon test and Kruskal Wallis test were used for comparison. P value <0.05 was considered statistically significant.

RESULTS: The diastasis value for the transected ligament scenario (2.47 ± 0.51 mm) was greater than those after all three fixation methods without distraction (2.02 ± 0.5 for flexible fixation, 1.72 ± 0.63 mm for metal screw fixation and 1.67 ± 0.77 mm for biointegrative screw fixation). The transected ligament diastasis was also greater than that for metal screw (1.61 ± 1.31mm) and biointegrative screws (1.69 ± 0.64 mm) with distraction (p<0.001). The area at the level of the ligament showed higher values for transected ligament (32.7 ± 13.08 mm2) than the three fixatives (30.75 ± 7.42 mm2 for flexible fixation, 30.75 ± 17.13 mm2 for metal screw fixation and 29.53 ± 9.15 mm2 for biointegrative screw fixation; p<0.05).

CONCLUSION: Metal screws, flexible fixation and biointegrative screws showed comparable effectiveness intra-op, in the correction of diastasis created as a consequence of Lisfranc injury.

Young, J., Lee, S. W., Shariyate, M. J., Cronin, A., Wixted, J. J., Nazarian, A., Rowley, C. F., & Rodriguez, E. K. (2024). Bacteriophage therapy and current delivery strategies for orthopedic infections: A SCOPING review.. The Journal of Infection, 88(3), 106125. https://doi.org/10.1016/j.jinf.2024.106125 (Original work published 2024)

OBJECTIVES: Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized.

METHODS: Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central.

RESULTS: In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described.

CONCLUSIONS: Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.

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.

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).

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.