Extremity Trauma Research Consortium Receives Kappa Delta Elizabeth Winston Lanier Award

The 2023 Kappa Delta Elizabeth Winston Lanier Award has been bestowed upon the Major Extremity Trauma Research Consortium (METRC) for its multi-disciplinary research platform addressing challenging issues related to the evaluation, treatment and recovery of severe extremity trauma. As the largest orthopedic trauma research enterprise to date, METRC has conducted 34 studies, enrolled more than 22,000 patients across 70 sites and published 57 papers, resulting in increased awareness and funding for extremity trauma care.

The award recognizes research in musculoskeletal disease or injury with great potential to advance patient care.
 
Research Highlights
During Operation Iraqi Freedom and Operation Enduring Freedom in Afghanistan, military orthopedic surgeons were challenged by a surge of casualties with complex single or multiple extremity injures. While advanced field care and the use of body armor reduced combat mortality, it increased injuries to unprotected extremities. Critical challenges surfaced, including complex wound management, infection, bone and articular surface loss, blast-related heterotopic ossification, segmental nerve injury, volumetric muscle loss, acute compartment syndrome (ACS), and severe psychological stress that can complicate long-term recovery. At the same time, surgeons at Level I trauma centers across the country were experiencing similar challenges for treating civilian patients with high energy traumas, such as severe leg injuries with open fractures, bone loss, muscle and nerve damage, heavy contamination, and compartment syndrome.
 
With lobbying support from the American Academy of Orthopaedic Surgeons (AAOS), the U.S. Department of Defense (DOD) requested proposals for an inaugural peer-reviewed consortium grant for extremity war injury research in 2008. Rather than submit competing applications, existing trauma research teams from the Lower Extremity Assessment Project (LEAP) study, the Southeast Fracture Consortium and the Orthopaedic Trauma Research Consortium worked together to develop an inclusive and unified approach, assembling top talent nationwide. As a result, METRC was formed, and in 2009 was awarded the DOD grant to establish a clinical research platform infrastructure and initiate prospective clinical research targeted to infection, ACS and bone healing. 
 
“By establishing a military-civilian research collaboration, investigators could translate learnings across sectors, research could continue during interwar periods and the research dollars could benefit from an economy of scale by sharing resources and reducing the cost per study, while increasing productivity,” said Michael J. Bosse, M.D., FAAOS, METRC’s clinical chair emeritus.
 
METRC was anchored by a Data Coordinating Center at the Johns Hopkins Bloomberg School of Public Health and initially engaged clinical investigators at 20 Level I trauma centers and the four major military treatment facilities.
 
The success of the Consortium can be attributed to the following framework:

• Conducting randomized clinical trials and employing a “gaps driven” approach to define research that purposefully identifies challenging surgical and scientific questions
• Organizing a multi-center approach to conduct timely and clinically impactful research
• Developing a coordinated, standardized approach to protocol development and data collection
• Understanding that METRC’s growth allows for the design and execution of large pragmatic trials
• Establishing quality assessment and improvement strategies to learn, evolve and improve from each study
• Supporting individual participating investigators and academic centers to receive extremity trauma research funding

 
“We knew this initiative would not be successful unless we adopted a culture of collaboration among the researchers at our institutions,” said Ellen J. MacKenzie, Ph.D., METRC founding director of the Coordinating Center. “We worked hard to develop processes that were engaging, made everybody feel included, gave everybody a voice and recognized the collective accomplishments of the team.”
 
METRC selected seven research areas of highest importance in both military and civilian high energy trauma patients. These included:

• Prevention and management of acute and chronic musculoskeletal infections
• Early acute management of orthopedic injury
• Reconstruction surgery and nonsurgical management to improve bone healing
• Prediction, prevention and amelioration of secondary conditions and long-term physical health effects
• Management of pain and psychosocial sequelae
• Rehabilitation interventions to improve functional outcomes and quality of life
• Amputation and limb salvage outcomes including optimization of prosthetics and orthotic devices

The Consortium’s research findings include:

• The Prevent CLOT study, the largest of the METRC research efforts, enrolled more than 12,000 patients and showed that low dose aspirin was non-inferior to low-molecular-weight heparin in preventing death and was associated with a low incidence of deep-vein thrombosis and pulmonary embolism in the care of trauma patients with operatively treated extremity fractures or with any pelvic or acetabular fractures.ⁱ
• The VANCO study^ii,iii investigated an emerging low-cost topical wound antibiotic technique to reduce fracture-related infections by applying 1,000 mg of topical vancomycin to the wound prior to closure. The study demonstrated a 35% overall reduced risk of infection and a 50% reduction in gram positive infections. A study involving tobramycin targeting gram negative bacteria is currently underway. 
• The Predicting Acute Compartment Syndrome studyⁱⁱⁱ sought to gain a better understanding of diagnostic standards for ACS, a challenging condition, as it is difficult to diagnose, can occur quickly and potentially lead to amputation or death. While more research is needed, in this study, near-infrared spectroscopy was unreliable for continuous measurement of tissue oxygenation in limbs with tibia fractures^iv and was not able to reliably identify early changes in tissue oxygenation in patients at risk for ACS. Additionally, using a novel approach of having an expert panel review each case to determine whether ACS was present, the research highlighted a high incidence of unnecessary surgery when using a currently accepted standard of care to determine when fasciotomy is necessary (a surgery conducted emergently to reduce muscle pressure to maintain blood flow).^v
• The OUTLET study provided further analysis of the 2002 LEAP study cohort, which originally found that limb salvage and amputation provided similar outcomes for severe high energy trauma below the distal femur. Following reports of disappointing results from the salvage attempts of those patients with a severely injured distal tibia, ankle and/or foot, the OUTLET study found that for a subset of those with severe and complex foot and ankle injuries, early amputation was associated with a better outcome than the limb salvage patients.^vi

“Over the past decade, the Consortium has grown to over 400 investigators, and what’s really impressive is the caliber of those who are involved,” Bosse said. “They are the who’s who in orthopedic trauma in North America. Not only are they making game-changing discoveries, but they are training the next generation of residents, fellows and investigators, many of whom have gone on to start METRC-funded research centers.”
 
Since 2009, METRC has received $150 million in funding from the DOD, Patient Centered Outcomes Research Institute, and National Institutes of Health.
 
“The real advantage of the Consortium has been the ability to leverage our resources across studies, which otherwise couldn’t have been conducted had it not been for the large multi-disciplinary team spanning numerous leading trauma centers across the country,” MacKenzie said. “The funding has helped us maintain the infrastructure at the coordinating center and clinical sites to conduct this research, and a continued investment will not only advance the care of injured service members in future conflicts but contribute to the medical readiness of current forces.”
 
The Kappa Delta Sorority established the Kappa Delta Research Fellowship in Orthopaedics in 1947. The first annual award, a $1,000 stipend, was made available to the AAOS in 1949 and presented at the AAOS meeting in 1950. The Kappa Delta Awards have been presented by the AAOS to persons who have performed research in orthopedic surgery that is of high significance and impact. The sorority has since added two more awards and increased the award amounts to $20,000 each. Two awards are named for the sorority national past presidents who were instrumental in the creation of the awards: Elizabeth Winston Lanier, and Ann Doner Vaughn. The third is known as the Young Investigator Award. 
 
With more than 39,000 members, the American Academy of Orthopaedic Surgeons is the world’s largest medical association of musculoskeletal specialists. The AAOS provides comprehensive education to help orthopedic surgeons and allied health professionals best treat patients in their daily practices. The AAOS is the source for information on bone and joint conditions, treatments and related musculoskeletal healthcare issues and it leads the healthcare discussion on advancing quality.

References 
ⁱ METRC. Aspirin or low-molecular-weight heparin for thromboprophylaxis after fracture. N Engl J Med 2023;388:203-13.
ⁱⁱ Bosse, M.J., MacKenzie, E.J., Pollak, A.N., Stinner, D.J. (Eds). 2017. The Major Extremity Trauma Research Consortium. [Special Issue]. J Orthop Trauma. 31(4). 
ⁱⁱⁱ METRC. 2021. Effect of Intrawound Vancomycin Powder in Operatively Treated High- risk Tibia Fractures: A Randomized Clinical Trial. JAMA Surgery. 156(5):e207259- e207259. 
^iv Schmidt AH, Bosse MJ, Obremskey WT, et al. 2018. Continuous near-infrared spectroscopy demonstrates limitations in monitoring the development of acute compartment syndrome in patients with leg injuries. J Bone Joint Surg Am. 100(19):1645-1652. 
^v Schmidt AH, Di J, Zipunnikov V, et al. 2020. Perfusion pressure lacks diagnostic specificity for the diagnosis of acute compartment syndrome. J Orthop Trauma. 34(6):287-293. 
^vi METRC. 2021. Outcomes Following Severe Distal Tibial, Ankle, and/or Mid/Hindfoot Trauma: comparison of limb salvage and transtibial amputation (OUTLET). J Bone Joint Surg Am. 103(17):1588-1597.