The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53.

p53 is an important tumor-suppressor protein that is mutated in more than 50% of cancers. Strategies for restoring normal p53 function are complicated by the oncogenic properties of mutant p53 and have not met with clinical success. To counteract mutant p53 activity, a variety of drugs with the potential to reconvert mutant p53 to an active wildtype form have been developed. However, these drugs are associated with various negative effects such as cellular toxicity, nonspecific binding to other proteins, and inability to induce a wildtype p53 response in cancer tissue. Here, we report on the effects of a curcumin analog, HO-3867, on p53 activity in cancer cells from different origins. We found that HO-3867 covalently binds to mutant p53, initiates a wildtype p53-like anticancer genetic response, is exclusively cytotoxic toward cancer cells, and exhibits high anticancer efficacy in tumor models. In conclusion, HO-3867 is a p53 mutant-reactivating drug with high clinical anticancer potential.

Congenital eccrine angiomatous hamartoma: Expanding the morphologic presentation and a review of the literature.

Eccrine angiomatous hamartoma (EAH) is a rare benign vascular hamartoma characterized histologically by an increased size and number of mature eccrine glands associated with multiple foci of dilated capillaries in the dermis and subcutis. EAH typically presents in children as discrete, solitary nodules, or plaques most commonly located on the extremities. Some cases of EAH have an agminated distribution involving classic locations, or present as solitary lesions in less common locations such as the face, scalp, or trunk. We report the case of congenital EAH in a child with atypical morphological features and pattern of distribution further expanding on the range of presentations classically described.

Quantification of functional brace forces for posterior cruciate ligament injuries on the knee joint: an in vivo investigation.

PURPOSE: Counteracting posterior translation of the tibia with an anterior force on the posterior proximal tibia has been demonstrated clinically to improve posterior knee laxity following posterior cruciate ligament (PCL) injury. This study quantified forces applied to the posterior proximal tibia by two knee braces designed for treatment of PCL injuries. METHODS: The forces applied by two knee braces to the posterior proximal tibia and in vivo three-dimensional knee kinematics of six adult, male, healthy volunteer subjects (mean ± standard deviation: height, 182.5 ± 5.2 cm; body mass, 83.2 ± 9.3 kg; body mass index, 24.9 ± 1.5 kg/m(2); age, 25.8 ± 2.9 years) were measured using a custom pressure mapping technique and traditional surface marker motion capture techniques, while subjects performed three functional activities. The activities included seated unloaded knee flexion, squatting, and stair descent in a new generation dynamic force (DF) PCL brace and a static force (SF) PCL brace. RESULTS: During unloaded flexion at the lowest force level setting, the force applied by the DF brace increased as a function of flexion angle (slope = 0.7 N/°; p < 0.001) compared to the SF brace effect. Force applied by the SF brace did not significantly change as a function of flexion angle (slope = 0.0 N/°; n.s.). By 45° of flexion, the average force applied by the DF brace (48.1 N) was significantly larger (p < 0.001) than the average force applied by the SF brace (25.0 N). The difference in force continued to increase as flexion angle increased. During stair descent, average force (mean ± standard deviation) at toe off was significantly higher (p = 0.013) for the DF brace (78.7 ± 21.6 N) than the SF brace (37.3 ± 7.2 N). Similar trends were observed for squatting and for the higher force level settings. CONCLUSIONS: The DF brace applied forces to the posterior proximal tibia that dynamically increased with increased flexion angle. Additionally, the DF brace applied significantly larger forces at higher flexion angles compared to the SF brace where the PCL is known to experience larger in situ forces. Clinical studies are necessary to determine whether the loading characteristics of the DF brace, which more closely replicated the in situ loading profile of the native PCL, results in long-term improved posterior knee laxity following PCL injury. LEVEL OF EVIDENCE: II.

Biomechanical consequences of proximal biceps tenodesis stitch location: musculotendinous junction versus tendon only.

PURPOSE: The purpose of this study was to determine the biomechanical effects of placing the biceps tenodesis stitch at the musculotendinous junction versus in the tendon only. Placing the stitch at the musculotendinous junction was hypothesized to result in a significantly weaker repair than stitching in the tendon only. METHODS: Testing was performed on two groups of six matched pairs of long head of the biceps (LHB) with enclosed musculotendinous junction and muscle belly. Specimens were randomly distributed between two groups. The same baseball whipstitch configuration was performed using the same suture material in both groups. In group 1, the stitch configuration started 1 cm proximal of the musculotendinous junction (tendon tissue only). For contralateral specimens, the baseball whipstitching included the distal 1 cm of the musculotendinous junction. Specimens were pulled to failure at a rate of 60 mm/min. Ultimate failure load and failure pattern were recorded. RESULTS: Average ultimate failure load of group 2 was significantly higher than group 1 (mean increase 18.6 %, range -9.7 to 35.8 %; p = 0.046). A cut-through failure pattern was observed for all specimens in both groups. There were highly significant correlations between ultimate failure load and tendon thickness (p = 0.004, τ = 0.636), age of the specimen (p = 0.002, τ = 0.724), and gender (p = 0.004, τ = -0.739). No significant difference between the groups regarding tendon diameter was observed. CONCLUSIONS: Baseball whipstitching of the LHB including the distal part of the tendon and the musculotendinous junction was stronger than sutures placed in the tendon alone. These results suggest that suture pattern affects initial strength of repair, and therefore may affect decisions regarding early post-operative rehabilitation or ultimate clinical outcomes. Inclusion of the musculotendinous junction should be considered clinically for improved time zero strength of the repair construct.

Biomechanical evaluation of internal fixation techniques for unstable meso-type os acromiale.

BACKGROUND: Several internal fixation surgical techniques have been described for the treatment of symptomatic os acromiale. The purpose of this study was to compare the biomechanical characteristics of different internal fixation techniques for the operative treatment of unstable meso-type os acromiale in a cadaveric model. METHODS: Testing was performed on 12 matched pairs of cadaveric acromia with simulated meso-type os acromiale. Twelve specimens were prepared with 2 cannulated 4.0-mm screws only (SO group), inserted in the anterior-posterior direction. Contralateral specimens were repaired with screws and a tension band (TB group). An inferiorly directed load to the anterior acromion was applied at a rate of 60 mm/min until failure. Ultimate failure load, stiffness, and fracture pattern were recorded and analyzed. RESULTS: Ultimate failure load was significantly higher for the TB group (mean, 336 N ± 126 N; range, 166-623 N; P = .01) than for the SO group (mean, 242 N ± 57 N; range, 186-365 N). In contrast, no significant difference in stiffness was found between the SO group (mean, 22.1 N/mm ± 4.7 N/mm; range, 13.0-33.3 N/mm; P = .94)) and the TB group (mean, 22.2 N/mm ± 2.9 N/mm; range, 18.2-26.6 N/mm). CONCLUSION: Surgical repair of simulated unstable meso-type os acromiale by a combination of cannulated screws with a tension band leads to significantly higher repair strength at time zero in a cadaveric model compared with cannulated screws alone.

The ability of massive osteochondral allografts from the medial tibial plateau to reproduce normal joint contact pressures after glenoid resurfacing: the effect of computed tomography matching.

BACKGROUND: Current techniques for resurfacing of the glenoid in the treatment of arthritis are unpredictable. Computed tomography (CT) studies have demonstrated that the medial tibial plateau has close similarity to the glenoid. The purpose of this study was to assess contact pressures of transplanted massive tibial osteochondral allografts to resurface the glenoid without and with CT matching. METHODS: Ten unmatched cadaveric tibiae were used to resurface 10 cadaveric glenoids with osteochondral allografts. Five cadaveric tibiae and glenoids were CT matched and studied. An internal control group of 4 matched pairs of glenoids, with the contralateral glenoid transplanted to the opposite glenoid, was also included as a best-case scenario to measure the effects of the surgical technique. All glenoids were tested before and after grafting at different abduction and rotation angles, with recording of peak contact pressures. RESULTS: Peak contact pressures were not different from the intact state in the autografted group but were increased in both allografted groups. CT-matched tibial grafts had lower peak pressures than unmatched grafts. Peak pressures were on average 24.8% (range [18.3%, 29.6%]) greater than in the native glenoids for unmatched allografts, 21.8% ([17.0%, 25.5%]) greater for the matched allografts, and 4.9% ([3.8%, 5.5%]) greater for matched autografts. CONCLUSION: Osteochondral grafting from the medial tibial plateau to the glenoid is feasible but results in increased peak contact pressures. The technique is reproducible as defined by the autografted group. Contact pressures between native and allografted glenoids were significantly different. The clinical significance remains unknown. Peak pressures experienced by the glenoid seem highly sensitive to deviations from the native glenoid shape.

Functional bracing of ACL injuries: current state and future directions.

PURPOSE: Functional braces are commonly prescribed to treat anterior cruciate ligament (ACL) injury. The results of the existing literature on functional brace use are mixed. The purpose of this study was to evaluate the history and current state of functional ACL bracing and to identify design criteria that could improve upon current bracing technologies. METHODS: A literature search was performed through the PubMed MEDLINE database in April 2013 for the keywords "anterior cruciate ligament" and "brace". Articles published between January 1, 1980, and April 4, 2013, were retrieved and reviewed. Current functional braces used to treat ACL injury were identified. The function of the native ACL was carefully studied to identify design requirements that could improve upon current bracing technologies. RESULTS: Biomechanical evaluations of functional brace effects at time zero have been mixed. Functional brace use reportedly does not improve long-term patient outcomes following ACL reconstruction, but has been shown to reduce subsequent injury rates while skiing in both ACL-deficient and reconstructed skiers. In situ force in the ACL varies with flexion angle and activity. Currently, no brace has been designed and validated to replicate the force-flexion behavior of the native ACL. CONCLUSIONS: Biomechanical and clinical evidence suggests current functional bracing technologies do not sufficiently restore normal biomechanics to the ACL-deficient knee, protect the reconstructed ACL, and improve long-term patient outcomes. Further research into a functional brace designed to apply forces to the knee joint similar in magnitude to the native ACL should be pursued. LEVEL OF EVIDENCE: III.

Stability of mid-shaft clavicle fractures after plate fixation versus intramedullary repair and after hardware removal.

PURPOSE: Operative treatment for middle-third clavicle fractures has been increasing as recent data has demonstrated growing patient dissatisfaction and functional deficits after non-operative management. A controlled biomechanical comparison of the characteristics of locked intramedullary (IM) fixation versus superior pre-contoured plating for fracture repair and hardware removal is warranted. Therefore, the purpose of the present study was to investigate potential differences between these devices in a biomechanical model. METHODS: Thirty fourth-generation composite clavicles were randomized to one of five groups with 6 specimens each and tested in a random order. The groups tested were intact, repair with plate, repair with IM device, plate removal, and IM device removal. The lateral end of the clavicles was loaded to failure at a rate of 60 mm/min in a cantilever bending setup. Failure mechanism, energy (J), and torque (Nm) at the site of failure were recorded. RESULTS: Failure torque of the intact clavicle (mean ± standard deviation) was 36.5 ± 7.3 Nm. Failure torques of the IM repair (21.5 ± 9.0 Nm) and plate repair (18.2 ± 1.6 Nm) were not significantly different (n.s.) but were significantly less than the intact group (P < 0.05). Failure torque following IM device removal (30.2 ± 6.5 Nm) was significantly greater than plate removal (12.9 ± 2.0 Nm) (P < 0.05). No significant differences were observed between the intact and IM device removal groups (n.s.). CONCLUSION: The results of the current study demonstrate that IM and plate devices provide similar repair strength for middle-third clavicle fractures. However, testing of the hardware removal groups found the IM device removal group to be significantly stronger than the plate removal group.

Anomalous Left Coronary Artery from the Pulmonary Artery: How to Diagnose and Treat.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare coronary anomaly that can present in childhood or adulthood with a multitude of symptoms depending on the age of presentation. It should be suspected in infants presenting with heart failure in the setting of left ventricular systolic dysfunction and associated mitral regurgitation from papillary muscle ischemia. Adults with ALCAPA may present with cardiac ischemic symptoms. Prompt diagnosis with echocardiography and cross-sectional chest imaging is important to guide surgical intervention and improve the patients' survival and prognosis. The goal of surgery is to establish a dual-coronary system with mid-term results revealing progressive recovery of left ventricular function and improvement in mitral regurgitation. Patients with ALCAPA should maintain life-long follow-up with a cardiologist with congenital heart disease expertise for surveillance of post-operative complications.

Machine learning helps predict long-term mortality and graft failure in patients undergoing heart transplant.

OBJECTIVE: We aimed to develop a risk prediction model using a machine learning to predict survival and graft failure (GF) 5 years after orthotopic heart transplant (OHT). METHODS: Using the International Society of Heart and Lung Transplant (ISHLT) registry data, we analyzed 15,236 patients who underwent OHT from January 2005 to December 2009. 342 variables were extracted and used to develop a risk prediction model utilizing a gradient-boosted machine (GBM) model to predict the risk of GF and mortality 5 years after hospital discharge. After excluding variables missing at least 50% of the observations and variables with near zero variance, 87 variables were included in the GBM model. Ten fold cross-validation repeated 5 times was used to estimate the model's external performance and optimize the hyperparameters simultaneously. Area under the receiver operator characteristic curve (AUC) for the GBM model was calculated for survival and GF 5 years post-OHT. RESULTS: The median duration of follow-up was 5 years. The mortality and GF 5 years post-OHT were 27.3% (n = 4161) and 28.1% (n = 4276), respectively. The AUC to predict 5-year mortality and GF is 0.717 (95% CI 0.696-0.737) and 0.716 (95% CI 0.696-0.736), respectively. Length of stay, recipient and donor age, recipient and donor body mass index, and ischemic time had the highest relative influence in predicting 5-year mortality and graft failure. CONCLUSION: The GBM model has a good accuracy to predict 5-year mortality and graft failure post-OHT.

ARIADNA: machine learning method for ancient DNA variant discovery.

Ancient DNA (aDNA) studies often rely on standard methods of mutation calling, optimized for high-quality contemporary DNA but not for excessive contamination, time- or environment-related damage of aDNA. In the absence of validated datasets and despite showing extreme sensitivity to aDNA quality, these methods have been used in many published studies, sometimes with additions of arbitrary filters or modifications, designed to overcome aDNA degradation and contamination problems. The general lack of best practices for aDNA mutation calling may lead to inaccurate results. To address these problems, we present ARIADNA (ARtificial Intelligence for Ancient DNA), a novel approach based on machine learning techniques, using specific aDNA characteristics as features to yield improved mutation calls. In our comparisons of variant callers across several ancient genomes, ARIADNA consistently detected higher-quality genome variants with fast runtimes, while reducing the false positive rate compared with other approaches.

Lightning-fast genome variant detection with GROM.

Current human whole genome sequencing projects produce massive amounts of data, often creating significant computational challenges. Different approaches have been developed for each type of genome variant and method of its detection, necessitating users to run multiple algorithms to find variants. We present Genome Rearrangement OmniMapper (GROM), a novel comprehensive variant detection algorithm accepting aligned read files as input and finding SNVs, indels, structural variants (SVs), and copy number variants (CNVs). We show that GROM outperforms state-of-the-art methods on 7 validated benchmarks using 2 whole genome sequencing (WGS) data sets. Additionally, GROM boasts lightning-fast run times, analyzing a 50× WGS human data set (NA12878) on commonly available computer hardware in 11 minutes, more than an order of magnitude (up to 72 times) faster than tools detecting a similar range of variants. Addressing the needs of big data analysis, GROM combines in 1 algorithm SNV, indel, SV, and CNV detection, providing superior speed, sensitivity, and precision. GROM is also able to detect CNVs, SNVs, and indels in non-paired-read WGS libraries, as well as SNVs and indels in whole exome or RNA sequencing data sets.

Evolutionary adaptation revealed by comparative genome analysis of woolly mammoths and elephants.

Comparative genomics studies typically limit their focus to single nucleotide variants (SNVs) and that was the case for previous comparisons of woolly mammoth genomes. We extended the analysis to systematically identify not only SNVs but also larger structural variants (SVs) and indels and found multiple mammoth-specific deletions and duplications affecting exons or even complete genes. The most prominent SV found was an amplification of RNase L (with different copy numbers in different mammoth genomes, up to 9-fold), involved in antiviral defense and inflammasome function. This amplification was accompanied by mutations affecting several domains of the protein including the active site and produced different sets of RNase L paralogs in four mammoth genomes likely contributing to adaptations to environmental threats. In addition to immunity and defense, we found many other unique genetic changes in woolly mammoths that suggest adaptations to life in harsh Arctic conditions, including variants involving lipid metabolism, circadian rhythms, and skeletal and body features. Together, these variants paint a complex picture of evolution of the mammoth species and may be relevant in the studies of their population history and extinction.

GROM-RD: resolving genomic biases to improve read depth detection of copy number variants.

Amplifications or deletions of genome segments, known as copy number variants (CNVs), have been associated with many diseases. Read depth analysis of next-generation sequencing (NGS) is an essential method of detecting CNVs. However, genome read coverage is frequently distorted by various biases of NGS platforms, which reduce predictive capabilities of existing approaches. Additionally, the use of read depth tools has been somewhat hindered by imprecise breakpoint identification. We developed GROM-RD, an algorithm that analyzes multiple biases in read coverage to detect CNVs in NGS data. We found non-uniform variance across distinct GC regions after using existing GC bias correction methods and developed a novel approach to normalize such variance. Although complex and repetitive genome segments complicate CNV detection, GROM-RD adjusts for repeat bias and uses a two-pipeline masking approach to detect CNVs in complex and repetitive segments while improving sensitivity in less complicated regions. To overcome a typical weakness of RD methods, GROM-RD employs a CNV search using size-varying overlapping windows to improve breakpoint resolution. We compared our method to two widely used programs based on read depth methods, CNVnator and RDXplorer, and observed improved CNV detection and breakpoint accuracy for GROM-RD. GROM-RD is available at http://grigoriev.rutgers.edu/software/.

Dimensional assessment of continuous loop cortical suspension devices and clinical implications for intraoperative button flipping and intratunnel graft length.

Continuous loop cortical suspension devices have been demonstrated to be more consistent and biomechanically superior compared to adjustable loop devices; however, continuous loop devices present unique challenges compared to adjustable loop devices, especially in short tunnel reconstruction applications. Specifically, adjustable loop devices have the advantage of a "one size fits all" approach, and the ability to tension these devices following button flipping allows for the intratunnel graft length to be maximized. Nevertheless, the reliability of continuous loop devices has sustained their widespread use. We hypothesized that continuous loop cortical suspension devices from different manufacturers would exhibit equivalent 15 mm loop lengths, as advertised. Loop length was measured using a tensile testing machine. Contrary to our hypothesis, continuous loop cortical suspension devices with equivalent advertised lengths exhibited different loop lengths (up to 27% discrepancy). Inconsistencies with regards to manufacturers' reported loop lengths for continuous loop devices could have serious clinical implications and additionally complicate technique transferal among devices. Consequently, the manufacturers' accurate and complete disclosure of the dimensions and specifications associated with each continuous loop device is critical. Furthermore, surgeon awareness of true loop length dimensions and inconsistencies among devices is needed to ensure optimal implantation and resultant clinical outcomes.

A biomechanical comparison of femoral cortical suspension devices for soft tissue anterior cruciate ligament reconstruction under high loads.

BACKGROUND: Graft healing after soft tissue anterior cruciate ligament (ACL) reconstruction requires rigid fixation to allow for soft tissue healing. Cortical suspension devices for femoral fixation should be biomechanically tested under high loads representative of early rehabilitation to evaluate whether they provide sufficient fixation. PURPOSE/HYPOTHESIS: To biomechanically compare current fixed-loop and adjustable-loop cortical suspension devices for soft tissue femoral fixation under high loads. The hypotheses were that there would be significant differences in cyclic displacement between devices, independent of loop type, and that retensioning of the adjustable-loop devices would not significantly alter the biomechanical properties of these devices. STUDY DESIGN: Controlled laboratory study. METHODS: Five different femoral ACL graft cortical suspension devices (3 fixed and 2 adjustable) were compared under high cyclic forces (100-400 N for 1000 cycles) and then pulled to failure at 50 mm/min. In addition, the effect of retensioning after simulated preconditioning was evaluated for the 2 adjustable-loop devices. RESULTS: On average, the least amount of cumulative peak cyclic displacement (mean±SD) was observed for the ENDOBUTTON (1.05±0.05 mm), followed by the RIGIDLOOP (1.09±0.16 mm), XO Button (1.65±0.43 mm), TightRope with retensioning (1.81±0.51 mm), TightRope without retensioning (2.20±0.62 mm), ToggleLoc with retensioning (3.22±1.41 mm), and ToggleLoc without retensioning (3.69±2.39 mm). The ENDOBUTTON displaced significantly less after cyclic loading than all adjustable-loop devices (TightRope and ToggleLoc, both with and without retensioning) and the XO Button. The RIGIDLOOP displaced significantly less than the TightRope without retensioning and ToggleLoc with and without retensioning. There was no significant difference in biomechanical properties after retensioning for both adjustable-loop devices. CONCLUSION: Significant differences were observed between current fixed-loop and adjustable-loop cortical suspension devices for soft tissue femoral fixation when subjected to high loads experienced during rehabilitation. Retensioning did not significantly alter the biomechanical properties of adjustable-loop devices. CLINICAL RELEVANCE: Early rehabilitation protocols subject the graft construct to higher forces than what has been previously tested biomechanically. Biomechanical testing of cortical suspension devices under simulated high rehabilitation loads demonstrated significant differences between devices. Future studies should investigate the clinical implications of these time zero results.

Consequences of tibial tunnel reaming on the meniscal roots during cruciate ligament reconstruction in a cadaveric model, Part 2: The posterior cruciate ligament.

BACKGROUND: Recent emphasis has turned to reconstructing the posterior cruciate ligament (PCL) after injury. However, single-bundle PCL reconstruction of the anterolateral bundle may potentially injure the posterior meniscal roots. PURPOSE/HYPOTHESIS: The purpose of this study was to determine if posterior meniscal root injuries occurred because of tunnel reaming for single-bundle PCL reconstruction. It was hypothesized that tibial tunnel reaming within the anterolateral bundle footprint during PCL reconstruction would result in clinically significant decreases in posteromedial (PM) root attachment areas and in ultimate failure strength for the PM root. STUDY DESIGN: Controlled laboratory study. METHODS: Testing was performed on 12 matched pairs of human cadaveric knees. For each pair of knees, one knee was left intact, while the contralateral knee was prepared with a tibial tunnel placed 5 mm anterior to the center of the tibial PCL attachment and within the previously described footprint of the anterolateral bundle of the PCL for single-bundle PCL reconstruction. The attachment areas of the posterior meniscal roots were measured with a coordinate measuring device before and after PCL tunnel reaming. The posterior meniscal roots were then pulled to failure with a dynamic tensile testing machine. RESULTS: There was a significant mean decrease in the attachment area of the PM root (%Δ, 28%; 95% CI, 16-40) after PCL tunnel reaming compared with the intact state (P=.005). The mean ultimate failure strength of the native PM root (mean, 440 N; 95% CI, 347-534) was also significantly stronger (mean, 40%; 95% CI, 18-61; P=.005) than that of the PM root after PCL tunnel reaming (mean, 243 N; 95% CI, 176-309). No changes were found for the posterolateral (PL) root after PCL tunnel reaming. CONCLUSION: Tibial tunnel reaming for single-bundle PCL reconstruction in the anterolateral bundle footprint significantly reduced the ultimate failure strength and attachment area of the PM meniscal root. The attachment area and ultimate failure strength of the PL root were unaffected by tunnel reaming. CLINICAL RELEVANCE: Tibial tunnels reamed in the footprint of the anterolateral bundle during single-bundle PCL reconstruction can cause iatrogenic damage to the PM meniscal root attachment. Thus, tibial tunnels should strive to be reamed in the center of the entire tibial PCL attachment site during PCL reconstruction.

Consequences of tibial tunnel reaming on the meniscal roots during cruciate ligament reconstruction in a cadaveric model, Part 1: The anterior cruciate ligament.

BACKGROUND: The current standard for treating complete tears of the anterior cruciate ligament (ACL) is reconstruction, which requires reaming a tibial tunnel. Based on recent anatomic and biomechanical studies, this reconstruction tunnel may cause injuries to the anterior meniscal root attachments. PURPOSE/HYPOTHESIS: The purpose was to determine if injuries occurred to the anteromedial (AM) and anterolateral (AL) meniscal root attachments because of reaming a tibial reconstruction tunnel in the anatomic center of the ACL footprint. It was hypothesized that tibial tunnel reaming for ACL reconstruction would result in significant decreases in the attachment area and in ultimate failure strength for the AL root. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve matched pairs of human cadaveric knees were tested. One knee from each pair remained intact, while the contralateral knee was reamed with a tibial tunnel for an anatomic ACL reconstruction. The attachment areas of the anterior meniscal roots were measured with a coordinate measuring device before and after tunnel reaming. The anterior meniscal roots were then pulled to failure with a dynamic tensile testing machine. RESULTS: There was a significant mean decrease in the attachment area for the AL root (%Δ, 38%; 95% CI, 25-51) after ACL tunnel reaming compared with the intact state (P=.003). The mean ultimate failure strength of the native AL root (mean, 610 N; 95% CI, 470-751) was significantly stronger (P=.015) than that of the AL root with a reamed ACL reconstruction tunnel (mean, 506 N; 95% CI, 353-659). Tunnel reaming did not significantly affect the AM root attachment area or ultimate failure strength. CONCLUSION: Tibial tunnel reaming during anatomic single-bundle ACL reconstruction significantly decreased the AL meniscal root attachment area and ultimate failure strength. The AM root was not significantly affected by reaming of the ACL reconstruction tunnel. Future studies should investigate the clinical importance of these iatrogenic injuries to the AL root. CLINICAL RELEVANCE: The ACL reconstruction tunnels reamed in the center of the ACL tibial footprint caused a significant decrease in the attachment area and ultimate strength of the AL meniscal root attachment. Clinically, repositioning guide pins placed in the lateral aspect of the ACL attachment before tibial tunnel reaming may minimize iatrogenic injuries to the AL meniscal root attachment.

Biomechanical analysis of subpectoral biceps tenodesis: effect of screw malpositioning on proximal humeral strength.

BACKGROUND: Humeral fracture after subpectoral tenodesis of the long head of biceps tendon (LHB) is a rare but devastating complication. PURPOSE: To determine whether malpositioned (laterally eccentric) tenodesis screw placement has an influence on humerus strength reduction compared with central placement. STUDY DESIGN: Controlled laboratory study. METHODS: Two groups, each consisting of 10 matched pairs of human humeri, were used for this study. Biceps tendons were fixed subpectorally with 8-mm screws in unicortical 8-mm sockets. In the first group, the socket was placed concentrically in the bicipital groove and the tendon was fixed with an interference screw. In the second group, the socket was malpositioned 30% eccentrically to the lateral (tension) side of the humerus. Contralateral humeri remained intact as positive controls. Specimens were aligned in 40° of abduction, and a uniaxial compressive force was applied to the humeral head until failure. Strength reduction was reported as percentage reduction in ultimate failure load between paired humeri. Relative defect size was calculated as a percentage of the total humeral width at the height of the tenodesis. RESULTS: Laterally eccentric malpositioned biceps tenodeses significantly decreased humeral strength compared with intact (mean change, -25%; SD, 23%; P=.017), while concentrically placed biceps tenodeses did not (mean change, -10%; SD, 15%; P=.059). A linear regression between relative defect size and strength reduction in the malpositioned group showed a significant negative linear correlation (beta=-2.577; R2=0.423; P=.042). CONCLUSION: Humeral fracture after subpectoral tenodesis of the LHB is a complication that may be minimized with careful surgical technique. Laterally eccentric malpositioned biceps tenodesis caused significant reduction (25%) in humeral strength, which might be clinically relevant and contribute to postsurgical humeral shaft fracture. Strength reduction was also significantly correlated with relative defect size. Surgeons using this technique should ensure central and orthogonal placement of the socket, especially in smaller individuals. This study lends biomechanical evidence to support the clinical procedure of a correctly, concentrically placed tenodesis screw. CLINICAL RELEVANCE: These biomechanical results indicate that in a clinical setting, special attention should be drawn to patient selection for LHB tenodesis. This study reveals that central screw positioning is critical, particularly in high-impact and overhead athletes, as well as for patients with small humeral widths or osteoporotic bone quality. Alternative surgical options such as smaller screws or other fixation methods might be considered to diminish the postoperative risk of humeral fracture.

Biomechanical consequences of a nonanatomic posterior medial meniscal root repair.

BACKGROUND: Posterior medial meniscal root tears have been reported to extrude with the meniscus becoming adhered posteromedially along the posterior capsule. While anatomic repair has been reported to restore tibiofemoral contact mechanics, it is unknown whether nonanatomic positioning of a meniscal root repair to a posteromedial location would restore the loading profile of the knee joint. PURPOSE/HYPOTHESIS: The purpose of this study was to compare the tibiofemoral contact mechanics of a nonanatomic posterior medial meniscal tear with that of the intact knee or anatomic repair. It was hypothesized that a nonanatomic root repair would not restore the tibiofemoral contact pressures and areas to that of the intact or anatomic repair state. STUDY DESIGN: Controlled laboratory study. METHODS: Tibiofemoral contact mechanics were recorded in 6 male human cadaveric knee specimens (average age, 45.8 years) using pressure sensors. Each knee underwent 5 testing conditions for the posterior medial meniscal root: (1) intact knee; (2) root tear; (3) anatomic transtibial pull-out repair; (4) nonanatomic transtibial pull-out repair, placed 5 mm posteromedially along the edge of the articular cartilage; and (5) root tear concomitant with an ACL tear. Knees were loaded with a 1000-N axial compressive force at 4 flexion angles (0°, 30°, 60°, 90°), and contact area, mean contact pressure, and peak contact pressure were calculated. RESULTS: Contact area was significantly lower after nonanatomic repair than for the intact knee at all flexion angles (mean = 44% reduction) and significantly higher for anatomic versus nonanatomic repair at all flexion angles (mean = 27% increase). At 0° and 90°, and when averaged across flexion angles, the nonanatomic repair significantly increased mean contact pressures in comparison to the intact knee or anatomic repair. When averaged across flexion angles, the peak contact pressures after nonanatomic repair were significantly higher than the intact knee but not the anatomic repair. In contrast, when averaged across all flexion angles, the anatomic repair resulted in a 17% reduction in contact area and corresponding increases in mean and peak contact pressures of 13% and 26%, respectively, compared with the intact knee. CONCLUSION: For most testing conditions, the nonanatomic repair did not restore the contact area or mean contact pressures to that of the intact knee or anatomic repair. However, the anatomic repair produced near-intact contact area and resulted in relatively minimal increases in mean and peak contact pressures compared with the intact knee. CLINICAL RELEVANCE: Results emphasize the importance of ensuring an anatomic posterior medial meniscal root repair by releasing the extruded menisci from adhesions and the posteromedial capsule. Similar caution toward preventing displacement of the meniscal root repair construct should be emphasized.