Innovative Techniques to Enhance Musculoskeletal Surgery Outcomes

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Longitudinal Documentation of Serum Cartilage Oligomeric Matrix Protein and Patient-Reported Outcomes in Collegiate Soccer Athletes over the Course of an Athletic Season

BACKGROUND: Serum cartilage oligomeric matrix protein (sCOMP) is a biomarker for cartilage degradation. Patient-reported outcomes (PRO) are used to document postinjury recovery and may be used to prospectively identify changes in the course of a season. It is unknown what effect intense, continuous physical activity has on sCOMP levels and PRO values in athletes over the duration of a soccer season. HYPOTHESIS/PURPOSE: The purpose of this study was to longitudinally document sCOMP levels and to determine whether changes in PROs occur in collegiate soccer athletes during a season. The hypotheses tested were that sCOMP levels and PRO scores would remain stable over the duration of the spring soccer season. STUDY DESIGN: Case series; level of evidence, 4. METHODS: Twenty-nine National Collegiate Athletic Association Division-I soccer athletes (18 men, 11 women; age, 19.6 ± 1.2 years; height, 177.8 ± 7.4 cm; mass, 73.8 ± 10.2 kg) participated in 3 (pre-[T(1)], mid-[T(2)], and postseason [T(3)]) data collection sessions. Subjects were included if they were participants in the spring soccer season and were free of severe knee injury at the time of data collection. At each session, subjects completed PROs (Lysholm, International Knee Documentation Committee scores) before serum collection. RESULTS: For sCOMP (ng/mL), there was a significant effect for time, with significant increases at T2 (1723.5 ± 257.9, P \u3c .001) and T3 (1624.7 ± 231.6, P = .002) when compared with T1(1482.9 ± 217.9). For each of the PROs, there was a significant effect for time from T1-T3, and at T2-T3 for the IKDC. CONCLUSION: These data indicate sCOMP levels increased as athletes reported an increased level of function over time. However, the differences in sCOMP levels did not reach the calculated minimal detectable change (MDC) value and the differences in PRO scores did not reach previously calculated MDC values. It is unclear whether these increases in sCOMP levels were caused by an increase in cartilage matrix breakdown or turnover. Even though these elevations may not be clinically meaningful, this biomarker may have the potential to be used for future research studies investigating the effects of exercise on overall joint health in longitudinal studies. In addition, these results indicate fluctuations in sCOMP occur during a competitive season and must be taken into consideration for future biomarker studies

The role of Wnt pathway in the pathogenesis of OA and its potential therapeutic implications in the field of regenerative medicine

Introduction. Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation, subchondral damage, and bone remodelling, affecting most commonly weight-bearing joints, such as the knee and hip. The loss of cartilage leads to joint space narrowing, pain, and loss of function which could ultimately require total joint replacement. The Wnt/beta catenin pathway is involved in the pathophysiology of OA and has been proposed as a therapeutic target. Endogenous and pharmacological inhibitors of this pathway were recently investigatedwithin innovative therapies including the use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Methods. A review of the literature was performed on the PubMed database based on the following inclusion criteria: article written in English language in the last 20 years and dealing with (1) the role of Wnt-beta catenin pathway in the pathogenesis of osteoarthritis and (2) pharmacologic or biologic strategies modulating the Wnt-beta catenin pathway in the OA setting. Results. Evidences support that Wnt signalling pathway is likely linked to OA progression and severity. Its inhibition through natural antagonists and new synthetic or biological drugs shares the potential to improve the clinical condition of the patients by affecting the pathological activity of Wnt/beta-catenin signalling. Conclusions. While further research is needed to better understand the mechanisms regulating the molecular interaction between OA regenerative therapies and Wnt, it seems that biologic therapies for OA exert modulation on Wnt/beta catenin pathway that might be relevant in achieving the beneficial clinical effect of those therapeutic strategies

Measuring the deformation of a ferrogel sphere in a homogeneous magnetic field

A sphere of a ferrogel is exposed to a homogeneous magnetic field. In accordance to theoretical predictions, it gets elongated along the field lines. The time-dependence of the elastic shear modulus causes the elongation to increase with time analogously to mechanic creep experiments, and the rapid excitation causes the sphere to vibrate. Both phenomena can be well described by a damped harmonic oscillator model. By comparing the elongation along the field with the contraction perpendicular to it, we can calculate Poisson's ratio of the gel. The magnitude of the elongation is compared with the theoretical predictions for elastic spheres in homogeneous fields.Comment: 5 pages, 8 figure

Select Biomarkers on the Day of Anterior Cruciate Ligament Reconstruction Predict Poor Patient-Reported Outcomes at 2-Year Follow-Up: A Pilot Study

Background. The majority of patients develop posttraumatic osteoarthritis within 15 years of anterior cruciate ligament (ACL) injury. Inflammatory and chondrodegenerative biomarkers have been associated with both pain and the progression of osteoarthritis; however, it remains unclear if preoperative biomarkers differ for patients with inferior postoperative outcomes. Hypothesis/Purpose. The purpose of this pilot study was to compare biomarkers collected on the day of ACL reconstruction between patients with good or poor 2-year postoperative outcomes. We hypothesized that inflammatory cytokines and chondrodegenerative biomarker concentrations would be significantly greater in patients with poorer outcomes. Study Design. Prospective cohort design. Methods. 22 patients (9 females, 13 males; age = 19.5 ± 4.1 years; BMI = 24.1 ± 3.6 kg/m2) previously enrolled in a randomized trial evaluating early anti-inflammatory treatment after ACL injury. Biomarkers of chondrodegeneration and inflammation were assessed from synovial fluid (sf) samples collected on the day of ACL reconstruction. Participants completed Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) questionnaires two years following surgery. Patients were then categorized based on whether their KOOS Quality of Life (QOL) score surpassed the Patient Acceptable Symptom State (PASS) threshold of 62.5 points or the IKDC PASS threshold of 75.9 points. Results. Patients that failed to reach the QOL PASS threshold after surgery (n = 6, 27%) had significantly greater sf interleukin-1 alpha (IL-1α; p = 0.004), IL-1 receptor antagonist (IL-1ra; p = 0.03), and matrix metalloproteinase-9 (MMP-9; p = 0.01) concentrations on the day of surgery. Patients that failed to reach the IKDC PASS threshold (n = 9, 41%) had significantly greater sf IL-1α (p = 0.02). Conclusion. These pilot data suggest that initial biochemical changes after injury may be an indicator of poor outcomes that are not mitigated by surgical stabilization alone. Biological adjuvant treatment in addition to ACL reconstruction may be beneficial; however, these data should be used for hypothesis generation and more definitive randomized clinical trials are necessary

An Expert Consensus Statement on the Management of Large Chondral and Osteochondral Defects in the Patellofemoral Joint

© The Author(s) 2020. Background: Cartilage lesions of the patellofemoral joint constitute a frequent abnormality. Patellofemoral conditions are challenging to treat because of complex biomechanics and morphology. Purpose: To develop a consensus statement on the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint using a modified Delphi technique. Study Design: Consensus statement. Methods: A working group of 4 persons generated a list of statements related to the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint to form the basis of an initial survey for rating by a group of experts. The Metrics of Osteochondral Allografts (MOCA) expert group (composed of 28 high-volume cartilage experts) was surveyed on 3 occasions to establish a consensus on the statements. In addition to assessing agreement for each included statement, experts were invited to propose additional statements for inclusion or to suggest modifications of existing statements with each round. Predefined criteria were used to refine statement lists after each survey round. Statements reaching a consensus in round 3 were included within the final consensus document. Results: A total of 28 experts (100% response rate) completed 3 rounds of surveys. After 3 rounds, 36 statements achieved a consensus, with over 75% agreement and less than 20% disagreement. A consensus was reached in 100.00% of the statements relating to functional anatomy of the patellofemoral joint, 88.24% relating to surgical indications, 100.00% relating to surgical technical aspects, and 100.00% relating to rehabilitation, with an overall consensus of 95.5%. Conclusion: This study established a strong expert consensus document relating to the functional anatomy, surgical indications, donor graft considerations for osteochondral allografts, surgical technical aspects, and rehabilitation concepts for the management of large chondral and osteochondral defects in the patellofemoral joint. Further research is required to clinically validate the established consensus statements and better understand the precise indications for surgery as well as which techniques and graft processing/preparation methods should be used based on patient- and lesion-specific factors

Resolving the Combinatorial Complexity of Smad Protein Complex Formation and Its Link to Gene Expression.

Upon stimulation of cells with transforming growth factor beta (TGF-beta), Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible Smad complexes are formed in cellular contexts and how these contribute to gene expression. By combining quantitative mass spectrometry with a computational selection strategy, we predict and provide experimental evidence for the three most relevant Smad complexes in the mouse hepatoma cell line Hepa1-6. Utilizing dynamic pathway modeling, we specify the contribution of each Smad complex to the expression of representative Smad target genes, and show that these contributions are conserved in human hepatoma cell lines and primary hepatocytes. We predict, based on gene expression data of patient samples, increased amounts of Smad2/3/4 proteins and Smad2 phosphorylation as hallmarks of hepatocellular carcinoma and experimentally verify this prediction. Our findings demonstrate that modeling approaches can disentangle the complexity of transcription factor complex formation and its impact on gene expression

The subchondral bone in articular cartilage repair: current problems in the surgical management

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed

Seaweed polysaccharide-based hydrogels used for the regeneration of articular cartilage

This manuscript provides an overview of the in vitro and in vivo studies reported in the literature focusing on seaweed polysaccharides based hydrogels that have been proposed for applications in regenerative medicine, particularly, in the field of cartilage tissue engineering. For a better understanding of the main requisites for these specific applications, the main aspects of the native cartilage structure, as well as recognized diseases that affect this tissue are briefly described. Current available treatments are also presented to emphasize the need for alternative techniques. The following part of this review is centered on the description of the general characteristics of algae polysaccharides, as well as relevant properties required for designing hydrogels for cartilage tissue engineering purposes. An in-depth overview of the most well known seaweed polysaccharide, namely agarose, alginate, carrageenan and ulvan biopolymeric gels, that have been proposed for engineering cartilage is also provided. Finally, this review describes and summarizes the translational aspect for the clinical application of alternative systems emphasizing the importance of cryopreservation and the commercial products currently available for cartilage treatment.Authors report no declarations of interest. Authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD fellowship of Elena G. Popa (SFRH/BD/64070/2009) and research project (MIT/ECE/0047/2009). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS

Role of high tibial osteotomy in chronic injuries of posterior cruciate ligament and posterolateral corner

High tibial osteotomy (HTO) is a surgical procedure used to change the mechanical weight-bearing axis and alter the loads carried through the knee. Conventional indications for HTO are medial compartment osteoarthritis and varus malalignment of the knee causing pain and dysfunction. Traditionally, knee instability associated with varus thrust has been considered a contraindication. However, today the indications include patients with chronic ligament deficiencies and malalignment, because an HTO procedure can change not only the coronal but also the sagittal plane of the knee. The sagittal plane has generally been ignored in HTO literature, but its modification has a significant impact on biomechanics and joint stability. Indeed, decreased posterior tibial slope causes posterior tibia translation and helps the anterior cruciate ligament (ACL)-deficient knee. Vice versa, increased tibial slope causes anterior tibia translation and helps the posterior cruciate ligament (PCL)-deficient knee. A review of literature shows that soft tissue procedures alone are often unsatisfactory for chronic posterior instability if alignment is not corrected. Since limb alignment is the most important factor to consider in lower limb reconstructive surgery, diagnosis and treatment of limb malalignment should not be ignored in management of chronic ligamentous instabilities. This paper reviews the effects of chronic posterior instability and tibial slope alteration on knee and soft tissues, in addition to planning and surgical technique for chronic posterior and posterolateral instability with HTO