[ACL Load in Female Athletes IRB 17-001833]

Importance of the problem. Second ACL injury, whether it is an insult to the ipsilateral
graft or the contralateral ligament, is a growing problem after reconstruction. Besides
missing an additional year of athletic participation, increasing health care costs, and
increased psychological distress, re-injury and subsequent revision surgery have
significantly worse outcomes compared with those after initial reconstruction. Second
injuries have been reported to occur at a rate of 1 of 17 (6%) within the first two years of
surgery. However, a second tear prevalence of 29% has been reported. This is substantially
higher than initial ACL injuries, reported to occur at a rate of 1 in 60 to 100. Risk factors
for second injury include younger athletes 6 who return to high-level sporting activities
early. Both sexes are at risk for second ACL injury, with women reported as having higher
risk of contralateral injury, and men having an increased risk of ipsilateral injury. Thus,
it is critical to include both sexes in second ACL injury prevention programs.

Improvement in scientific knowledge and clinical practice: Patients have differential
responses after ACL injury, including their functional abilities, movement biomechanics,
neuromuscular performance, and quadriceps strength. Building from our prior funded work, the
investigators propose to prospectively evaluate these varying patient characteristics in an
attempt to identify distinct groups with differing levels of risk for second injury (Aim 1).
Our previous work revealed that there were three risk groups among uninjured female athletes.
The significance of identification of patient groups with distinct needs is profound.
Prospective identification of at-risk patients who are the most appropriate recipients of
enhanced treatment will likely reduce second ACL risk, and yield a more efficacious delivery
of health care resources after ACLR. The Cincinnati group described this differentiation in
ACL deficient patients as the 'rule of thirds,' with one third of patients able to function
without limitations and not needing to undergo surgical stabilization, one third adapting
their activity level without surgery, and one third requiring surgery to perform daily
activities without knee instability. A classification scheme described by the University of
Delaware also differentiates ACL deficient patients into groups of thirds including copers
(no limit in abilities), non-copers (unable to function without knee instability) or
potential copers (individuals who have the potential to function without ACLR). There is
evidence these differences in functional abilities and movement characteristics persist after
ACLR. A randomized clinical trial concluded individuals who exhibit poor knee stability and
function after injury may require additional time to return to pre-injury functional levels.
In addition, some may be unable to develop appropriate quadriceps strength symmetry to
support a return to high-level sports. These data indicate not all patients experience the
same magnitude or duration of impairments and symptoms after ACLR. Consequently, multiple
post-operative rehabilitation strategies may be necessary to facilitate optimum patient care
and outcomes.

Working from the rule of one-thirds, identification of distinct patient groups with unique
needs after surgery is a novel approach for integration of optimum second injury prevention
strategies. Primary-injury risk factors provide an important window into the underlying
biomechanical and neuromuscular deficits that may persist after ACL injury and
reconstruction. Using a statistical analysis clustering technique, distinct groups with
relative risk for first-time ACL injury have been identified, including low, moderate and
high risk groups. Single limb postural stability combined with biomechanical variables
including vertical ground reaction force (vGRF), frontal plane hip adduction moment minimum,
and pelvis angle during drop jump landings were identified as significant contributors to
frontal plane knee loading, a surrogate for ACL injury risk. This work has demonstrated the
existence of discernable groups of athletes that are more appropriate for targeted
neuromuscular training (TNMT) intervention to prevent first-time ACL injury.

Factors that contribute to primary ACL injury risk provide an important window into the
underlying deficits that may persist after ACL injury and reconstruction. Age and activity
level are significant factors, as young active individuals are the most likely cohort to
sustain a second ACL rupture. Surgical factors include decreased graft size, use of allograft
tissue, vertical graft position, and a lax graft. Anatomical risk factors may also contribute
to ACL injury risk and include an increase in the posterior-inferior lateral tibial plateau
slope and decreased notch width. Genetic factors also likely play a role. While it is
encouraging that so many potential factors have been identified which may contribute to
second ACL injury risk, none of these factors can be modified through non-surgical
intervention. Modifiable biomechanical and neuromuscular measures associated with second ACL
injury have been identified. Previous work by our laboratory included a prospective clinical
trial, athletes who had undergone ACLR underwent testing before a return to pivoting and
cutting sports. Thirteen athletes sustained a subsequent injury. Specific injury predictive
parameters identified during testing included a net internal rotation moment of the
uninvolved hip, an increase in total frontal plane knee movement, greater asymmetry in
internal knee extensor moment at initial contact, and deficits in single-leg postural
stability of the involved limb. These parameters predicted second injury in this population
with excellent sensitivity (0.92) and specificity (0.88).

Differences in functional abilities after ACLR may be differentiated by more than
biomechanical and neuromuscular characteristics. Clinically measured muscle weakness may
persist for years after ACLR. Quadriceps strength is strongly related to measurements of knee
function in athletes who have undergone ACLR. While hamstrings strength alone may not show a
significant effect on knee function following ACL injury and reconstruction, hamstrings
activation may be an important component in neuromuscular control of the reconstructed knee,
especially in females, who tend to be 'quadriceps dominant'. In addition, deficits in the
hamstrings-quadriceps torque production ratio also appear to be a key variable in the primary
ACL injury risk model. The relationship between muscle weakness and differential risk for
second injury has not been established. An understanding of the interplay may, however, be
critical to the development of effective, group-specific intervention programs and reduction
of second-injury risk.

It is currently unknown if biomechanical and clinical measures may effectively discern groups
of patients who are at greatest risk for second ACL injury. Evaluation of movement mechanics
and clinical characteristics, including strength, limb stability and self-reported function,
at the time a patient initiates sports-specific training may yield insight to differential
responses after ACLR. If distinct patient groups are identified, this information may be used
to provide differentiated interventions based on risk for second injury. In Aim 2 of this
proposal, the investigators will evaluate the effects of differential rehabilitation
interventions. Our Exploratory Aim will be the initial step in translating the
biomechanics-based, group algorithm into a clinical application for individualized
categorization of risk. The results of this work may instigate a paradigm shift in treatment,
and promote a more efficacious utilization of healthcare resources by providing enhanced care
to those patients who are at greatest risk for secondary injury.

Impact on patient care. One of the factors that contributes to second ACL injury is
incomplete or ineffective rehabilitation. Aberrant neuromuscular and biomechanical patterns
are commonly seen up to 2 years after ACLR and may help explain the high rate of second ACL
injury. Deficits in the neuromuscular control of both lower extremities following ACLR have
been directly implicated in the risk for second ACL injury and may not only be a result of
the initial knee injury and subsequent surgery, but may also characterize the athlete's
pre-injury movement patterns. Therefore, identification and subsequent targeted treatment of
aberrant post-ACLR movement patterns for both limbs are critical not only to maximize
functional recovery but also to reduce the risk for second ACL injury. Though neuromuscular
training programs result in a 73.4% decreased risk of a non-contact primary-ACL injury
compared to those who do not participate in neuromuscular training, the efficacy of similar
programs for reduction of second-ACL injury risk has not been examined.

An evidence-based targeted neuromuscular training (TNMT) program has been designed to prevent
second ACL injury. This training program was developed with consideration to modifiable
factors related to second-injury risk, the principles of motor learning, and careful
selection of the exercises that may most effectively modify aberrant neuromuscular programs.
In Aims 2 and 3 of this competing renewal proposal the investigators will evaluate the
effects of differential treatment interventions. Notably, the investigators will assess the
effectiveness of TNMT, including the utilization of visual and verbal biofeedback. Validation
of this evidence-based, late-phase TNMT program may significantly impact clinical practice
patterns through its integration in rehabilitation settings, and serve as a critical factor
in reduction of second injury risk. Ultimately, determining if less intensive HOME and STAN
training programs are effective interventions for patients who are at reduced risk for second
ACL injury may prove to be a tremendous time and cost savings for patients and the
health-care system.

Inclusion Criteria:

- Age, 14 ≥ 24 years

- Acute (< 6 months), first-time, isolated ACL injury

- No history of previous knee surgery to either extremity

- No low back or lower extremity injury in the year prior to ACL injury necessitating
medical care

- Pre-injury participation in cutting, jumping or pivoting sports for ≥ 50 hours/year

- Mechanism of injury did not involve a direct blow to the knee.

- Patients who sustain a medial collateral ligament (MCL) injury are eligible for study
participation if medial knee instability is resolved prior to surgery

- Patients with simple meniscus tears (i.e., 2 cm vertical longitudinal tear) that do
not necessitate alterations in rehabilitation will be eligible for study participation

Exclusion Criteria:

- History of previous knee surgery to either extremity

- Low back or lower extremity injury in the year prior to ACL injury necessitating
medical care

- Second or greater ACL injury

- Greater than 6 months since occurrence of ACL injury

- Lack of participation in cutting, jumping, or pivoting sport

- Mechanisms of injury involved a direct blow of force to the knee

- Patients with MCL injury that exhibits unresolved medial knee instability

- Patients with complex, repairable meniscus tears (i.e., radial or root repair) and
patients with full thickness articular cartilage lesions will not be eligible for
participation secondary to significant alterations to postoperative rehabilitation
protocol