Predicting response and toxicity to immune checkpoint inhibitors in lung cancer using antibodies to frameshift neoantigens.

PURPOSE: To evaluate a new class of blood-based biomarkers, anti-frameshift peptide antibodies, for predicting both tumor responses and adverse immune events to immune checkpoint inhibitor (ICI) therapies in advanced lung cancer patients. EXPERIMENTAL DESIGN: Serum samples were obtained from 74 lung cancer patients prior to palliative PD-(L)1 therapies with subsequently recorded tumor responses and immune adverse events (irAEs). Pretreatment samples were assayed on microarrays of frameshift peptides (FSPs), representing ~ 375,000 variant peptides that tumor cells can be informatically predicted to produce from translated mRNA processing errors. Serum-antibodies specifically recognizing these ligands were measured. Binding activities preferentially associated with best-response and adverse-event outcomes were determined. These antibody bound FSPs were used in iterative resampling analyses to develop predictive models of tumor response and immune toxicity. RESULTS: Lung cancer serum samples were classified based on predictive models of ICI treatment outcomes. Disease progression was predicted pretreatment with ~ 98% accuracy in the full cohort of all response categories, though ~ 30% of the samples were indeterminate. This model was built with a heterogeneous sample cohort from patients that (i) would show either clear response or stable outcomes, (ii) would be administered either single or combination therapies and (iii) were diagnosed with different lung cancer subtypes. Removing the stable disease, combination therapy or SCLC groups from model building increased the proportion of samples classified while performance remained high. Informatic analyses showed that several of the FSPs in the all-response model mapped to translations of variant mRNAs from the same genes. In the predictive model for treatment toxicities, binding to irAE-associated FSPs provided 90% accuracy pretreatment, with no indeterminates. Several of the classifying FSPs displayed sequence similarity to self-proteins. CONCLUSIONS: Anti-FSP antibodies may serve as biomarkers for predicting ICI outcomes when tested against ligands corresponding to mRNA-error derived FSPs. Model performances suggest this approach might provide a single test to predict treatment response to ICI and identify patients at high risk for immunotherapy toxicities.

Preventing varus collapse in proximal humerus fracture fixation: 90-90 dual plating versus endosteal fibular allograft strut.

INTRODUCTION: Screw cut out and varus collapse are the most common complication of locked plate fixation of proximal humerus fractures. The purpose of this study was to compare dual plating and endosteal fibular allograft struts as augmentation strategies to prevent varus collapse. MATERIALS AND METHODS: A trapezoidal osteotomy was created at the metaphysis to create a 2-part proximal humerus model in 18 paired shoulder specimens. Each specimen was assigned to group A, B, or C and was fixed with either a lateral locking plate, a lateral locking plate and anterior one-third tubular plate in an orthogonal 90/90 configuration, or a lateral locking plate with intramedullary fibular strut, respectively. The specimens were stressed in axial compression to failure. Displacement, elastic limit, ultimate load, and stiffness were recorded and calculated. RESULTS: There was no difference in mean cyclic displacement between the three groups (0.71 mm vs 0.89 mm vs 0.61 mm for Group A, B, C, respectively). Lateral plating demonstrated the greatest absolute and relative displacement at the elastic limit (5.3 mm ± 1.5 and 4.4 mm ± 1.3) without significance. The elastic limit or yield point was greatest for fibular allograft, Group C (1223 N ± 501 vs 1048 N ± 367 for Group B and 951 N ± 249 for Group A) without significance. CONCLUSIONS: Dual plating of proximal humerus fractures in a 90-90 configuration demonstrates similar biomechanical properties as endosteal fibular strut allograft. Both strategies demonstrate superior stiffness to isolated lateral locked plating.

Anatomic safe zones for arthroscopic snapping scapula surgery: quantitative anatomy of the superomedial scapula and associated neurovascular structures and the effects of arm positioning on safety.

BACKGROUND: Neurovascular anatomy has not been previously quantified for the arthroscopic snapping scapula approach with the patient in the most frequent patient position ("chicken-wing" position). The purposes of this study were (1) to determine anatomic relationships of the superomedial scapula and neurovascular structures at risk during arthroscopic surgical treatment of snapping scapula syndrome (SSS), (2) to compare these measurements between the arm in the neutral position and the arm in the chicken-wing position, and (3) to establish safe zones for arthroscopic treatment of SSS. METHODS: Eight fresh-frozen cadaveric hemi-torsos (mean age, 55.8 years; range, 52-66 years) were dissected to ascertain relevant anatomic structure locations including the (1) spinal accessory nerve, (2) dorsal scapular nerve, and (3) suprascapular nerve. A coordinate measuring device was used to collect data on the relationships of anatomic landmarks and at-risk structures during the surgical approach. RESULTS: The dorsal scapular nerve was a mean of 24.4 mm medial to the superomedial scapula in the neutral position and 33.1 mm medial in the chicken-wing position (P < .001); the dorsal scapular nerve was 21.7 mm medial to the medial border of the scapular spine in the neutral position and 35.5 mm medial in the chicken-wing position (P < .001). The mean distance from the superomedial angle to the spinal accessory nerve intersection at the superior scapular border was 16.5 mm in the neutral position and 15.0 mm in the chicken-wing position (P = .031). The average distance from the superomedial angle to the closest point of the spinal accessory nerve was 11.6 mm and 10.4 mm in the neutral position and chicken-wing position, respectively (P = .039). CONCLUSION: Neurologic structures around the scapula vary significantly between the neutral arm position and the chicken-wing position commonly used in the arthroscopic treatment of SSS. The chicken-wing position improves safe distances for the dorsal scapular nerve during medial-portal placement and should be considered as a primary position for arthroscopic management of SSS.

The opportunity cost of walking away in the spatial iterated prisoner's dilemma.

Previous work with the spatial iterated prisoner's dilemma has shown that the ability to respond to a partner's defection by simply "walking away" allows so-called walk away cooperators to outcompete defectors as well as cooperators that do not respond to defection. These findings are important because they suggest a relatively simple route by which cooperation can evolve. But it remains to be seen just how robust the walk away strategy is to ecologically important variables such as population density, strategic error, and offspring dispersal. The results of our simulation experiments show that the evolutionary success of walk away cooperators decreases with decreasing population density and/or with increasing error. This relationship is best explained by the ways in which population density and error jointly affect the opportunity cost of walking away. This opportunity cost also explains why naive cooperators regularly outcompete walk away cooperators in pair-wise competition, something not observed in previous studies. Our results further show that local offspring dispersal can inhibit the evolution of cooperation by negating the protection low population density affords the most vulnerable cooperators. Our research identifies socio-ecological conditions in which forgiveness trumps flight in the spatial iterated prisoner's dilemma.

HPLC-based kinetics assay facilitates analysis of systems with multiple reaction products and thermal enzyme denaturation.

Glucosinolates are plant secondary metabolites abundant in Brassica vegetables that are substrates for the enzyme myrosinase, a thioglucoside hydrolase. Enzyme-mediated hydrolysis of glucosinolates forms several organic products, including isothiocyanates (ITCs) that have been explored for their beneficial effects in humans. Myrosinase has been shown to be tolerant of non-natural glucosinolates, such as 2,2-diphenylethyl glucosinolate, and can facilitate their conversion to non-natural ITCs, some of which are leads for drug development. An HPLC-based method capable of analyzing this transformation for non-natural systems has been described. This current study describes (1) the Michaelis-Menten characterization of 2,2-diphenyethyl glucosinolate and (2) a parallel evaluation of this analogue and the natural analogue glucotropaeolin to evaluate effects of pH and temperature on rates of hydrolysis and product(s) formed. Methods described in this study provide the ability to simultaneously and independently analyze the kinetics of multiple reaction components. An unintended outcome of this work was the development of a modified Lambert W(x) which includes a parameter to account for the thermal denaturation of enzyme. The results of this study demonstrate that the action of Sinapis alba myrosinase on natural and non-natural glucosinolates is consistent under the explored range of experimental conditions and in relation to previous accounts.

Biomechanical Comparison Between Double-Row Repair and Soft Tissue Tenodesis for Treatment of Proximal Rectus Femoris Avulsions.

Background: Some patients with proximal rectus femoris (PRF) avulsions require surgical treatment after failed nonoperative treatment. There is no consensus on the superiority of suture anchor repair with the suture-bridge repair (SBR) technique versus tenodesis repair (TR) for PRF avulsions. Purpose: To compare the failure load and elongation at failure between SBR and TR and to compare the stiffness of these 2 repair techniques versus the native state. Study Design: Controlled laboratory study. Methods: Seven pairs of human cadaveric hemipelvises were dissected to the PRF and sartorius origins. Each specimen underwent preconditioning followed by a distraction test to determine the stiffness of the native specimen. One specimen of each pair received one of the repair methods (SBR or TR), while the other specimen in the pair received the other repair technique. After repair, each specimen underwent preconditioning followed by a pull to failure. The failure load, elongation at failure, stiffness, mode of failure, and stiffness as a percentage of the native state were determined for each repair. Results: The SBR group exhibited a stronger failure load (223 ± 51 N vs 153 ± 32 N for the TR group; P = .0116) and significantly higher stiffness as a percentage from the native state (70.4% ± 19% vs 33.8% ± 15.5% for the TR group; P = .0085). While the stiffness of the repair state in the SBR group (41.5 ± 9.4 N/mm) was not significantly different from that of the native state (66.2 ± 36 N/mm), the stiffness of the repair state in the TR group (20.3 ± 7.5 N/mm) was significantly lower compared with that of the native state (65.4 ± 22.1 N/mm; P < .001) and repair state in the SBR group (41.5 ± 9.4 N/mm; P = .02). The SBR group primarily failed at the repair site (71%), and the TR group primarily failed at the suture-sartorius interface (43%) and at the muscle (29%). Conclusion: SBR and TR specimens were significantly weaker than the native tendon. The stiffness of the SBR was equivalent to that of the native tendon, while TR was significantly less stiff than the native tendon. The SBR was superior to TR in terms of failure load, stiffness, and percentage stiffness from the native state. Clinical Relevance: SBR may be a better surgical option than TR to optimize failure load and stiffness for PRF avulsions.

Design of a randomized, placebo-controlled study evaluating efficacy and safety of a cancer preventative vaccine in dogs.

Preventative anti-cancer vaccination strategies have long been hampered by the challenge of targeting the diverse array of potential tumor antigens, with successes to date limited to cancers with viral etiologies. Identification and vaccination against frameshift neoantigens conserved across multiple species and tumor histologies is a potential cancer preventative strategy currently being investigated. Companion dogs spontaneously develop cancers at a similar incidence to those in people and are a complementary comparative patient population for the development of novel anti-cancer therapeutics. In addition to an intact immune system with tumors that arise in an autochthonous tumor microenvironment, dogs also have a shorter lifespan and temporally compressed tumor natural history as compared to humans, which allows for more rapid evaluation of safety, immunogenicity, and efficacy of cancer vaccination strategies. Here we describe the study protocol for the Vaccination Against Canine Cancer Study (VACCS), the largest interventional cancer clinical trial conducted in companion dogs to date. In addition to safety and immunogenicity, the primary endpoint of VACCS is the cumulative incidence (CI) of dogs developing malignant neoplasia of any type at the end of the study period. Secondary endpoints include changes in incidence of specific tumor types, survival times following neoplasia diagnosis, and all-cause mortality.

Direct measurement of three-dimensional forces at the medial meniscal root: A validation study.

The posterior medial meniscal root (PMMR) experiences variable and multiaxial forces during loading. Current methods to measure these forces are limited and fail to adequately characterize the loads in all three dimensions at the root. Our novel technique resolved these limitations with the installation of a 3-axis sensing construct that we hypothesized would not affect contact mechanics, would not impart extraneous loads onto the PMMR, would accurately measure forces, and would not deflect under joint loads. Six cadaveric specimens were dissected to the joint capsule and a sagittal-plane, femoral condyle osteotomy was performed to gain access to the root. The load sensor was placed below the PMMR and was validated across four tests. The contact mechanics test demonstrated a contact area precision of 44 mm2 and a contact pressure precision of 5.0 MPa between the pre-installation and post-installation states. The tibial displacement test indicated an average bone plug displacement of < 1 mm in all directions. The load validation test exhibited average precision values of 0.7 N in compression, 0.5 N in tension, 0.3 N in anterior-posterior shear, and 0.3 N in medial-lateral shear load. The bone plug deflection test confirmed < 2 mm of displacement in any direction when placed under a load. This is the first study to successfully validate a technique for measuring both magnitude and direction of forces experienced at the PMMR. This validated method has applications for improving surgical repair techniques and developing safer rehabilitation and postoperative protocols that decrease root loads.

In situ repair of segmental loss posterior lateral meniscal root tears outperforms meniscofemoral ligament imbrication in the ACL reconstructed knee.

PURPOSE: The purpose of this study was to compare the biomechanical effect of in-situ repair of posterior lateral meniscal root (PLMR) tear with segmental meniscal loss, with and without meniscofemoral ligament (MFL) imbrication, on anterior cruciate ligament (ACL) graft force and knee joint kinematics. METHODS: Ten fresh-frozen cadaveric knee specimens underwent kinematic evaluation in five states: 1) Native, 2) ACLR, 3) Segmental PLMR loss, 4) In-situ PLMR repair, and 5) MFL augmentation. Kinematic evaluation consisted of five tests, each performed at full extension and at 30° of flexion: 1) Anterior drawer, 2) Internal Rotation, 3) External Rotation, 4) Varus, and 5) Valgus. Additionally, a simulated pivot shift test was performed. Knee kinematics and ACL graft force were measured. RESULTS: PLMR tear did not significantly increase ACL graft force in any test. However, PLMR repair significantly reduced ACL graft force compared to the ACLR alone (over constraint -26.6 N, p = 0.001). PLMR tear significantly increased ATT during the pivot shift test (+ 2.7 mm, p = 0.0001), and PLMR repair restored native laxity. MFL augmentation did not improve the mechanics. CONCLUSIONS: In-situ PLMR repair eliminated pivot shift laxity through ATT and reduced force on the ACL graft, indicating that this procedure may be ACL graft-protective. MFL augmentation was not shown to have any effect on graft force or knee kinematics and untreated PLMR tears may place an ACL graft at higher risk. This study suggests concomitant repair to minimize additional forces on the ACL graft.

Ulnar Collateral Ligament (UCL) Reconstruction With Proximal Single-Tunnel Suspensory Fixation.

Ulnar collateral ligament (UCL) reconstruction of the medial elbow is considered to be the gold standard for treating valgus instability seen in overhead throwing athletes. The first UCL construction was performed by Frank Jobe in 1974, and this procedure has evolved over time to include multiple techniques that improved the biomechanical strength of the graft fixation and maximize the rate of return to athletic competition for these patients. The most common UCL-reconstruction technique used today is the docking technique. The purpose of this Technical Note is to describe our technique, including pearls and pitfalls, which combines the many advantages of the docking technique with a proximal single-tunnel suspensory fixation technique. This method allows for optimal tensioning of the graft, allowing for secure fixation that relies on metal implants as opposed to tying sutures over a proximal bone bridge.

The Biomechanical Role of the Deltoid Ligament on Ankle Stability: Injury, Repair, and Augmentation.

BACKGROUND: Deltoid ligament injuries occur in isolation as well as with ankle fractures and other ligament injuries. Both operative treatment and nonoperative treatment are used, but debate on optimal treatment continues. Likewise, the best method of surgical repair of the deltoid ligament remains unclear. PURPOSE: To determine the biomechanical role of native anterior and posterior components of the deltoid ligament in ankle stability and to determine the efficacy of simple suture versus augmented repair. STUDY DESIGN: Controlled laboratory study. METHODS: Ten cadaveric ankles (mean age, 51 years; age range, 34-64 years; all male specimens) were mounted on a 6 degrees of freedom robotic arm. Each specimen underwent biomechanical testing in 8 states: (1) intact, (2) anterior deltoid cut, (3) anterior repair, (4) tibiocalcaneal augmentation, (5) deep anterior tibiotalar augmentation, (6) posterior deltoid cut, (7) posterior repair, and (8) complete deltoid cut. Testing consisted of anterior drawer, eversion, and external rotation (ER), each performed at neutral and 25° of plantarflexion. A 1-factor, random-intercepts, linear mixed-effect model was created, and all pairwise comparisons were made between testing states. RESULTS: Cutting the anterior deltoid introduced ER (+2.1°; P = .009) and eversion laxity (+6.2° of eversion; P < .001) at 25 degrees of plantarflexion. Anterior deltoid repair restored native ER but not eversion. Tibiocalcaneal augmentation reduced eversion laxity, but tibiotalar augmentation provided no additional benefit. The posterior deltoid tear showed no increase in laxity. Complete tear introduced significant anterior translation, ER, and eversion laxity (+7.6 mm of anterior translation, +13.8° ER and +33.6° of eversion; P < .001). CONCLUSION: A complete deltoid tear caused severe instability of the ankle joint. Augmented anterior repair was sufficient to stabilize the complete tear, and no additional benefit was provided by posterior repair. For isolated anterior tear, repair with tibiocalcaneal augmentation was the optimal treatment. CLINICAL RELEVANCE: Deltoid repair with augmentation may reduce or avoid the need for prolonged postoperative immobilization and encourage accelerated rehabilitation, preventing stiffness and promoting earlier return to preinjury activity.

Biomechanical Analysis of Tibial Motion and ACL Graft Forces After ACLR With and Without LET at Varying Tibial Slopes.

BACKGROUND: Lateral extra-articular tenodesis (LET) is being performed more frequently with anterior cruciate ligament (ACL) reconstruction (ACLR) to decrease graft failure rates. The posterior tibial slope (PTS) affects ACL graft failure rates. The effect of ACLR + LET on tibial motion and graft forces with increasing PTS has not been elucidated. HYPOTHESIS: LET would decrease anterior tibial translation (ATT), tibial rotation, and ACL graft force versus ACLR alone with increasing tibial slope throughout knee range of motion. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve fresh-frozen cadaveric knees (mean donor age, 40.5 years; all female) were tested in 4 conditions (intact, ACL cut, ACLR, and ACLR + LET) with varying PTSs (5°, 10°, 15°, and 20°) at 3 flexion angles (0°, 30°, and 60°). Specimens were mounted to a load frame that applied a 500-N axial load with 1 N·m of internal rotation (IR) torque. The amount of tibial translation, IR, and graft force was measured. RESULTS: Increasing PTS revealed a linear and significant increase in graft force at all flexion angles. LET reduced graft force by 8.3% (-5.8 N) compared with ACLR alone at 30° of flexion. At the same position, slope reduction resulted in reduced graft force by 17% to 22% (-12.3 to -15.2 N) per 5° of slope correction, with a 46% (-40.7 N) reduction seen from 20° to 5° of slope correction. For ATT, ACLR returned tibial translation to preinjury levels, as did ACLR + LET at all flexion angles, except full extension, where ACLR + LET reduced ATT by 2.5 mm compared with the intact state (P = .019). CONCLUSION: Increased PTS was confirmed to increase graft forces linearly. Although ACLR + LET reduced graft force compared with ACLR alone, slope reduction had a larger effect across all testing conditions. No other clinically significant differences were noted between ACLR with versus without LET in regard to graft force, ATT, or IR. CLINICAL RELEVANCE: Many authors have proposed LET in the setting of ACLR, revision surgery, hyperlaxity, high-grade pivot shift, and elevated PTS, but the indications remain unclear. The biomechanical performance of ACLR + LET at varying PTSs may affect daily practice and provide clarity on these indications.

Increased Posterior Tibial Slope Increases Force on the Posterior Medial Meniscus Root.

BACKGROUND: Posterior medial meniscus root (PMMR) tears have been associated with increased posterior tibial slope, but this has not been fully evaluated biomechanically. In addition, the effects of knee flexion and rotation on the PMMR are not well understood biomechanically because of technological testing limitations. A novel multiaxial force sensor has made it possible to elucidate answers to these questions. PURPOSE: (1) To determine if increased posterior tibial slope results in increased posterior shear force and compression on the PMMR, (2) to evaluate how knee flexion angle affects PMMR forces, and (3) to assess how internal and external rotation affects force at the PMMR. STUDY DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen cadaveric knees were tested in all combinations of 3 posterior tibial slopes and 4 flexion angles. A multiaxial force sensor was connected to the PMMR and installed below the posterior tibial plateau maintaining anatomic position. The specimen underwent a 500-N compression load followed by a 5-N·m internal torque and a 5-N·m external torque. The magnitude and direction of the forces acting on the PMMR were measured. RESULTS: Under joint compression, an increased tibial slope significantly reduced the tension on the PMMR between 5° and 10° (from 13.5 N to 6.4 N), after which it transitioned to a significant increase in PMMR compression, reaching 7.6 N at 15°. Under internal torque, increased tibial slope resulted in 4.7 N of posterior shear at 5° significantly changed to 2.0 N of anterior shear at 10° and then 8.2 N of anterior shear at 15°. Under external torque, increased tibial slope significantly decreased PMMR compression (5°: 8.9 N; 10°: 4.3 N; 15°: 1.1 N). Under joint compression, increased flexion angle significantly increased medial shear forces of the PMMR (0°, 3.8 N; 30°, 6.2 N; 60°, 7.3 N; 90°, 8.4 N). Under internal torque, 90° of flexion significantly increased PMMR tension from 2.3 N to 7.5 N. Under external torque, 30° of flexion significantly increased PMMR compression from 4.7 N to 12.2 N. CONCLUSION: An increased posterior tibial slope affects compression and anterior shear forces at the PMMR. An increased flexion angle affects compression, tension, and medial shear forces at the PMMR. CLINICAL RELEVANCE: The increase in compression and posterior shear force when the knee is loaded in compression may place the PMMR under increased stress and risk potential failure after repair. This study provides clinicians with information to create safer protocols and improve repair techniques to minimize the forces experienced at the PMMR.

Meniscotibial Ligament Insufficiency Increases Force on the Posterior Medial Meniscus Root.

BACKGROUND: Posterior medial meniscus root (PMMR) tears are a challenge to assess and treat. However, the forces sustained at the PMMR are yet to be fully characterized. In addition, it has been shown that meniscotibial ligament (MTL) injuries happen before PMMR tears, suggesting that insufficiency of the MTL results in a change of forces acting on the PMMR. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the 3-dimensional forces acting on the PMMR in the intact, MTL cut, and MTL tenodesis states. It was hypothesized that the MTL cut state would increase medial shear forces seen at the PMMR, whereas the medial shear force in the MTL tenodesis state would return PMMR forces to that of the intact state. STUDY DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen cadaveric knees were tested in 3 states (intact, MTL cut, and tenodesis). A 3-axis load cell was installed below the posterior tibial plateau and attached to the enthesis of the PMMR. The specimen was mounted to a load frame that applied an axial load, an internal torque, and an external torque. The amount of compression-tension, mediolateral shear force, and anteroposterior shear force acting on the PMMR was measured. RESULTS: When the joint was loaded in compression, the MTL cut state significantly increased compression of the PMMR (P = .0368). The tenodesis state did not significantly restore forces of the PMMR (P = .008). When the joint was loaded in external torque, the MTL cut state significantly increased compression (P < .0001) and significantly decreased anterior shear on the PMMR (P = .0003). The tenodesis state did not significantly restore forces on the PMMR to the intact state (P < .0001). Increased flexion angle significantly increased medial shear forces of the PMMR when the joint was loaded in compression (P < .007 at every angle). CONCLUSION: When evaluated biomechanically, MTL insufficiency resulted in increased compressive force at the PMMR. A single-anchor centralization procedure did not restore PMMR forces to that of the intact state. Increased knee flexion angle resulted in increased medial shear force on the PMMR. CLINICAL RELEVANCE: The findings in this study provide clinicians information on PMMR forces when the MTL is disrupted. These data can aid in the decision-making for adding an MTL repair to augment PMMR repairs.

Biomechanical Analysis of Meniscotibial Ligament Tenodesis to Treat Meniscal Extrusion in the Setting of Posterior Medial Meniscus Root Repair.

BACKGROUND: Meniscal extrusion often persists after a medial meniscus root repair. If the meniscus is extruded, the function of the meniscus as a load-sharing device and secondary knee stabilizer is compromised. HYPOTHESIS: It was hypothesized that repairing the meniscotibial ligament (MTL) would decrease meniscal extrusion in the settings of both an isolated MTL tear and a repaired medial meniscus root while also improving medial compartment contact mechanics. STUDY DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen cadaveric knees (mean age, 50.5 years) were tested in 5 conditions: intact, MTL deficiency, MTL deficiency + posterior medial meniscus root deficiency, MTL deficiency + posterior medial meniscus root repair, and MTL tenodesis + posterior medial meniscus root repair. Specimens were mounted to a load frame that applied a 1000-N axial load. Joint contact pressures were measured using thin pressure sensors, and the peak and mean pressures were analyzed. Ultrasound was used to measure meniscal extrusion. RESULTS: The MTL tear in isolation resulted in significant meniscal extrusion compared with the intact state (P = 0.035) without a detectable difference in medial compartment pressures. The addition of a root tear to the MTL tear state resulted in significantly more extrusion (P = 0.001) and significant increases in medial compartment pressure (P = .030) compared to the MTL tear state. Root repair alone restored extrusion, mean contact pressure, and peak contact pressure back to the intact state (P > .05). CONCLUSION: This study showed that MTL disruption led to increased meniscal extrusion in a cadaveric model. Unlike the root tear state, MTL disruption did not change contact mechanics. Furthermore, root repair alone was sufficient in restoring intact biomechanics and extrusion. CLINICAL RELEVANCE: This study may help clinicians understand the origin of medial meniscus root tears and aid in the decision-making process for whether to add an MTL tenodesis in the setting of root repair.

Effects of Lateral Opening-Wedge Distal Femoral Osteotomy on Meniscal Allograft Transplantation: A Biomechanical Evaluation.

Background: Lateral meniscal deficiency with valgus malalignment increases the rate of lateral compartment osteoarthritis. Lateral meniscal allograft transplantation (LMAT) with a concomitant varus-producing opening-wedge distal femoral osteotomy (DFO) is an option yet to be evaluated biomechanically. Purpose/Hypothesis: The purpose of this study was to clarify the biomechanical effects of the realignment procedure in the setting of LMAT. We hypothesized that (1) given the dependence of the lateral compartment on the lateral meniscus, a DFO and increasing degrees of varus would be insufficient to restore lateral compartment pressures to normal from a lateral meniscus-deficient state, and that (2) LMAT would restore lateral compartment pressures to the intact state while DFO would decrease lateral compartment pressures for any given state of the meniscus. Study Design: Controlled laboratory study. Methods: Ten cadaveric knees underwent opening-wedge varus-producing DFO secured by an external fixator. Anatomic alignment was standardized to 6° of mechanical valgus, and each joint was tested in full extension. Submeniscal placement of thin film pressure sensors allowed for the recording of contact pressure, peak contact pressure, and contact area. The specimens were loaded on a biaxial dynamic testing machine with loading angles between 9° valgus and 6° varus of mechanical alignment. Conditions tested included intact meniscus, meniscal deficiency, and meniscal transplantation. Results: Isolated varus-producing DFO to 6° in the meniscus-deficient state failed to restore joint pressures and contact areas to the intact state, with significant changes in mean contact pressure (175%), mean peak contact pressure (135%), and contact area (-41%) (all P < .05 vs intact), while LMAT restored all outcome measures (all P > .05 compared with intact). After LMAT, every additional 1° of DFO correction contributed to a decrease in the mean contact pressure, peak pressure, and contact area of 5.6% (-0.0479 N/mm2), 5.9% (-0.154 N/mm2), and 1.4% (-6.99 mm2) for the lateral compartment and 7.3% (+0.034 N/mm2), 12.6% (+0.160 N/mm2), and 4.3% (+20.53 mm2) for the medial compartment, respectively. Conclusion: Isolated DFO was inadequate to restore load distribution in meniscus-deficient knees, while concomitant LMAT restored near normal forces and improved the lateral compartment biomechanical profile. Clinical Relevance: Our findings support the concomitant use of LMAT and varus-producing DFO in the setting of lateral meniscal deficiency with valgus malalignment. This study provides tools for the orthopaedic surgeon to individualize the correction for each patient.

Humeral Head Reconstruction With Osteochondral Allograft: Bone Plug Optimization for Hill-Sachs Lesions Using CT-Based Computer Modeling Analysis.

Background: Engaging Hill-Sachs lesions (HSLs) pose a significant risk for failure of surgical repair of recurrent anterior shoulder instability. Reconstruction with fresh osteochondral allograft (OCA) has been proposed as a treatment for large HSLs. Purpose: To determine the optimal characteristics of talus OCA bone plugs in a computer-simulated HSL model. Study Design: Descriptive laboratory study; Level of evidence, 6. Methods: Included were 132 patients with recurrent anterior instability with visible HSLs; patients who had multidirectional instability or previous shoulder surgery were excluded. Three-dimensional computed tomography models were constructed, and a custom computer optimization algorithm was generated to maximize bone plug surface area at the most superior apex (superiorization) and minimize its position relative to the most medial margin of the HSL defect (medialization). The optimal number, diameter, medialization, and superiorization of the bone plug(s) were reported. Percentages of restored glenoid track width and conversion from off- to on-track HSLs after bone plug optimization were calculated. Results: A total of 86 patients were included in the final analysis. Off-track lesions made up 19.7% of HSLs and, of these, the mean bone plug size was 9.9 ± 1.4 mm, with 2.2 mm ± 1.7 mm of medialization and 3.3 mm ± 2.9 mm of superiorization. The optimization identified 21% of HSLs requiring 1 bone plug, 65% requiring 2 plugs, and 14% requiring 3 plugs, with a mean overall coverage of 60%. The mean width of the restored HSLs was 68%, and all off-track HSLs (n = 17) were restored to on-track. A Jenks natural-breaks analysis calculated 3 ideal bone plug diameters of 8 mm (small), 10.4 mm (medium), and 12 mm (large) in order to convert this group of HSLs to on-track. Conclusion: Using a custom computer algorithm, we have demonstrated the optimal talus OCA bone plug diameters for reconstructing HSLs to successfully restore the HSL track and, on average, 60% of the HSL surface area and 68% of the HSL width. Clinical Relevance: Reconstructing HSLs with talus OCA is a promising treatment option with excellent fit and restoration of HSLs. This study will help guide surgeons to optimize OCA bone plugs from the humeral head, femoral head, and talus for varying sizes of HSLs.

Biomechanical comparison of ulnar collateral ligament reconstruction with single-tunnel proximal suspensory fixation versus modified docking technique.

Background: Despite technical advancement, elbow ulnar collateral ligament (UCL) reconstruction is a challenging procedure due to the limitations regarding the challenging tunnel placement and potential injury to the ulnar nerve. Furthermore, current techniques for reconstruction and repair are inferior functionally and biomechanically when compared to native UCL tissue. A modified docking technique using a single-tunnel proximal suspensory fixation may reduce complications and potentially provide a technique for UCL reconstruction that is biomechanically superior. Decreasing the number of bone tunnels decreases the number of places that bone tear through could occur. The purpose was to evaluate and compare the biomechanical performances for 2 elbow UCL reconstruction techniques: (1) standard docking technique (SD) and (2) a proximal single tunnel (PST) technique using a suspensory fixation. We hypothesized that the PST technique would be biomechanically superior to the SD technique. Methods: Twelve matched pairs of cadaveric elbows were dissected and fixed at 70 degrees for biomechanical testing. Gracilis grafts were used for a docking reconstruction and the modified reconstruction with a PST suspensory fixation. A cyclic valgus torque protocol was used to precondition specimens for either reconstruction technique and the ulnohumeral gapping was then assessed. Following gapping measurements, postsurgical specimens underwent a valgus rotation applied at a rate of 5°/s until the anterior band of the UCL failed or fracture occurred. Ultimate load to failure, stiffness, and mode of failure were recorded. Results: There were no statistical differences between the two groups. Mean rotational stiffness of the SD (2.3 ± 0.6 Nm/deg) compared to the PST (1.9 ± 0.7 Nm/deg) (P = .41) and mean ultimate failure torque of the SD (30.5 ± 9.2 Nm) compared to the PST (30.9 ± 8.6 Nm) (P = .86) were similar. There was also no statistically significant difference (P = .83) when comparing the native UCL ulnohumeral gapping (6.0 ± 2.0 mm) to the mean ulnohumeral gapping of the SD reconstruction (6.0 ± 1.8 mm). Conclusions: This study compares the biomechanical strength of elbow UCL reconstructions performed using the SP technique to that of a PST technique. Among all tested parameters, including ultimate failure torque, stiffness, and ulnohumeral gapping, there were no statistically significant differences between the 2 techniques.

Biomechanical Comparison of Proximal Hamstring Reconstruction Using Distal Hamstring Graft Versus Fascia Lata Graft for Treatment of Chronic Hamstring Injury.

BACKGROUND: Surgical reconstruction using autografts is often required in treating chronic proximal hamstring injuries where the hamstring has retracted >5 cm. There is a paucity of evidence that evaluates reconstructive procedures using the 2 most popular autografts, distal hamstring and fascia lata. PURPOSE: To (1) compare failure load and elongation at failure between the proximal hamstring tendon reconstruction with distal hamstring and fascia lata grafts and (2) compare the stiffness between these reconstructions and the native state. STUDY DESIGN: Controlled laboratory study. METHODS: Seven pairs of human cadaveric hemipelvises (mean age, 60.4 ± 5.0 years; 6 male, 1 female) with no evidence of previous injury or abnormality were dissected to the proximal hamstring origin. Through use of a dynamic tensile testing system, each specimen underwent preconditioning followed by a distraction test to determine the native specimen stiffness. Each pair of specimens was assigned to undergo proximal hamstring reconstruction with distal hamstring and reconstruction with fascia lata. Each specimen then underwent preconditioning followed by pull to failure. The failure load, elongation at failure, mode of failure, and stiffness were determined for each repair. RESULTS: The distal hamstring group exhibited a greater failure load (mean, 334 ± 108 N; P = .031) and higher stiffness (mean, 47.6 ± 16.0 N/mm; P = .009) compared with the fascia lata group (mean, 179 ± 78 N and 23.0 ± 11.2 N/mm, respectively). Although the stiffness of the repair state in the distal hamstring group (mean, 61.4 ± 13.4 N/mm) was not significantly different from that of the native state (mean, 47.6 ± 16.0 N/mm), the stiffness of the repair state in the fascia lata group (mean, 23.0 ± 11.2 N/mm) was significantly lower than that of the native state (mean, 60.1 ± 17.7 N/mm) (P < .0001). The elongation at failure of the distal hamstring graft group (mean, 33.0 ± 6.6 mm) was not significantly different from that of the fascia lata graft group (mean, 29.2 ± 14.9 mm) (P = .58). The most common modes of failure for the distal hamstring group (29% each) were at the repair site, at the graft-muscle interface, and at the muscle, while the most common modes of failure for the fascia lata graft were at the tendon-graft interface. CONCLUSION: The distal hamstring group achieved higher failure load and stiffness than the fascia lata group, and stiffness of the distal hamstring group was not significantly different from that of the native tendon. Elongation at failure was not different between repair techniques. Although distal hamstring graft failure predominantly occurred in 3 distinct locations, failure of the fascia lata repair occurred predominantly at the tendon-graft interface. These cadaveric results suggest that it may be more clinically appropriate to use distal hamstring versus fascia lata for proximal hamstring reconstruction. CLINICAL RELEVANCE: Our time-zero study suggests that the proximal hamstring reconstruction with distal hamstring could be the preferred surgical treatment for chronic hamstring injury over reconstruction with fascia lata. The failure load of reconstruction with distal hamstring was inferior to that of primary suture anchor, suggesting that rehabilitation after reconstruction should not be more aggressive than the standard postoperative rehabilitation protocol for acute repair.

Biomechanical Evaluation of the 2 Different Levels of Coracoid Graft Positions in the Latarjet Procedure for Anterior Shoulder Instability.

Background: In the Latarjet procedure, the ideal placement of the coracoid graft in the medial-lateral position is flush with the anterior glenoid rim. However, the ideal position of the graft in the superior-inferior position (sagittal plane) for restoring glenohumeral joint stability is still controversial. Purpose: To compare coracoid graft clockface positions between the traditional 3 to 5 o'clock and a more inferior (for the right shoulder) 4 to 6 o'clock with regard to glenohumeral joint stability in the Latarjet procedure. Study Design: Controlled laboratory study. Methods: A total of 10 fresh-frozen cadaveric shoulders were tested in a dynamic, custom-built robotic shoulder model. Each shoulder was loaded with a 50-N compressive load while an 80-N force was applied in the anteroinferior axes at 90° of abduction and 60° of shoulder external rotation. Four conditions were tested: (1) intact, (2) 6-mm glenoid bone loss (GBL), (3) Latarjet procedure fixed at 3- to 5-o'clock position, and (4) Latarjet procedure fixed at 4- to 6-o'clock position. The stability ratio (SR) and degree of lateral humeral displacement (LHD) were recorded. A 1-factor random-intercepts linear mixed-effects model and Tukey method were used for statistical analysis. Results: Compared with the intact state (1.77 ± 0.11), the SR was significantly lower after creating a 6-mm GBL (1.14 ± 0.61, P = .009), with no significant difference in SR after Latarjet 3 to 5 o'clock (1.51 ± 0.70, P = .51) or 4 to 6 o'clock (1.55 ± 0.68, P = .52). Compared with the intact state (6.48 ± 2.24 mm), LHD decreased significantly after GBL (3.16 ± 1.56 mm, P < .001) and Latarjet 4 to 6 o'clock (5.48 ± 3.39 mm, P < .001). Displacement decreased significantly after Latarjet 3 to 5 o'clock (4.78 ± 2.50 mm, P = .04) compared with the intact state but not after Latarjet 4 to 6 o'clock (P = .71). Conclusion: The Latarjet procedure in both coracoid graft positions (3-5 and 4-6 o'clock) restored the SR to the values measured in the intact state. A more inferior graft position (fixed at 4-6 o'clock) may improve shoulder biomechanics, but additional work is needed to establish clinical relevance. Clinical Relevance: An inferior coracoid graft fixation, the 4- to 6-o'clock position, may benefit in restoring normal shoulder biomechanics after the Latarjet procedure.