Patient-oriented and performance-based outcomes after knee autologous chondrocyte implantation: a timeline for the first year of recovery

It is well established that autologous chondrocyte implantation (ACI) can require extended recovery postoperatively; however, little information exists to provide clinicians and patients with a timeline for anticipated function during the first year after ACI. Objective: To document the recovery of functional performance of activities of daily living after ACI. Patients: ACI patients (n = 48, 29 male 35.1 ± 8.0 y). Intervention: All patients completed functional tests (weight-bearing squat, walk-across, sit-to-stand, step-up/over, and forward lunge) using the NeuroCom long force plate (Clackamas, OR) and completed patient-reported outcome measures (International Knee Documentation Committee Subjective Knee Evaluation Form, Lysholm, Western Ontario and McMaster Osteoarthritis Index WOMAC, and 36-Item Short-Form Health Survey) preoperatively and 3, 6, and 12 mo postoperatively. Main Outcome Measures: A covariance pattern model was used to compare performance and self-reported outcome across time and provide a timeline for functional recovery after ACI. Results: Participants demonstrated significant improvement in walk-across stride length from baseline (42.0% ± 8.9% height) at 6 (46.8% ± 8.1%) and 12 mo (46.6% ± 7.6%). Weight bearing on the involved limb during squatting at 30°, 60°, and 90° was significantly less at 3 mo than presurgery. Step-up/over time was significantly slower at 3 mo (1.67 ± 0.69 s) than at baseline (1.49 ± 0.33 s), 6 mo (1.51 ± 0.36 s), and 12 mo (1.40 ± 0.26 s). Step-up/over lift-up index was increased from baseline (41.0% ± 11.3% body weight BW) at 3 (45.0% ± 11.7% BW), 6 (47.0% ± 11.3% BW), and 12 mo (47.3% ± 11.6% BW). Forward-lunge time was decreased at 3 mo (1.51 ± 0.44 s) compared with baseline (1.39 ± 0.43 s), 6 mo (1.32 ± 0.05 s), and 12 mo (1.27 ± 0.06). Similarly, forward-lunge impact force was decreased at 3 mo (22.2% ± 1.4% BW) compared with baseline (25.4% ± 1.5% BW). The WOMAC demonstrated significant improvements at 3 mo. All patient-reported outcomes were improved from baseline at 6 and 12 mo postsurgery. Conclusions: Patients' perceptions of improvements may outpace physical changes in function. Decreased function for at least the first 3 mo after ACI should be anticipated, and improvement in performance of tasks requiring weight-bearing knee flexion, such as squatting, going down stairs, or lunging, may not occur for a year or more after surgery

Patient Experiences of Recovery After Autologous Chondrocyte Implantation: A Qualitative Study

Context: The recovery process after autologous chondrocyte implantation (ACI) can be challenging for patients and clinicians alike due to significant functional limitations and a lengthy healing time. Understanding patients\u27 experiences during the recovery process may assist clinicians in providing more individualized care. Objective: To explore and describe patients\u27 experiences during the recovery process after ACI. Design: Qualitative study. Setting: Orthopaedic clinic. Patients or Other Participants: Participants from a single orthopaedic practice who had undergone ACI within the previous 12 months were purposefully selected. Data Collection and Analysis: Volunteers participated in 1-on-1 semistructured interviews to describe their recovery experiences after ACI. Data were analyzed using the process of horizontalization. Results: Seven patients (2 men, 5 women; age = 40.7 ± 7.5 years, time from surgery = 8.7 ± 4.2 months) participated. Four themes and 6 subthemes emerged from the data and suggested that the recovery process is a lengthy and emotional experience. Therapy provides optimism for the future but requires a collaborative effort among the patient, surgeon, rehabilitation provider, and patient\u27s caregiver(s). Furthermore, patients expressed frustration that their expectations for recovery did not match the reality of the process, including greater dependence on caregivers than expected. Conclusions: Patients\u27 expectations should be elicited before surgery and managed throughout the recovery process. Providing preoperative patient and caregiver education and encouraging preoperative rehabilitation can assist in managing expectations. Establishing realistic goals and expectations may improve rehabilitation adherence, encourage optimism for recovery, and improve outcomes in the long term

Comparing Responsiveness of Six Common Patient-Reported Outcomes to Changes Following Autologous Chondrocyte Implantation: A Systematic Review and Meta-Analysis of Prospective Studies

Objective: To compare the responsiveness of six common patient-reported outcomes (PROs) following autologous chondrocyte implantation (ACI). Design: A systematic search was conducted to identify reports of PROs following ACI. Study quality was evaluated using the modified Coleman Methodology Score (mCMS). For each outcome score, pre- to postoperative paired Hedge\u27s g effect sizes were calculated with 95% confidence intervals (CIs). Random effects meta-analyses were performed to provide a summary response for each PRO at time points (TP) I (\u3c1 year), II (1 year to \u3c2 years), III (2 years to \u3c4 years), IV (\u3e= 4 years), and overall. Results: The mean mCMS for the 42 articles included was 50.9 +/- 9.2. For all evaluated instruments, none of the mean effect size CIs encompassed zero. The International Knee Documentation Committee Subjective Knee Form (IKDC) had increasing responsiveness over time with TP-IV, demonstrating greater mean effect size [confidence interval] (1.78 [1.33, 2.24]) than TP-I (0.88 [0.69, 1.07]). The Knee Injury and Osteoarthritis Outcome Score-Sports and recreation subscale (KOOS-Sports) was more responsive at TP-III (1.76 [0.87, 2.64]) and TP-IV (0.98 [0.81, 1.15]) than TP-I (0.61 [0.44, 0.78]). Overall, the Medical Outcomes Study 36-Item Short Form Health Survey Physical Component Scale (0.60 [0.46, 0.74]) was least responsive. Both the Lysholm Scale (1.42 [1.14, 1.72]) and the IKDC (1.37 [1.13, 1.62]) appear more responsive than the KOOS-Sports (0.90 [0.73, 1.07]). All other KOOS subscales had overall effect sizes ranging from 0.90 (0.74, 1.22) (Symptoms) to 1.15 (0.76, 1.54) (Quality of Life). Conclusions: All instruments were responsive to improvements in function following ACI. The Lysholm and IKDC were the most responsive instruments across time. IKDC and KOOS-Sports may be more responsive to long-term outcomes, especially among active individuals

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

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

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

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

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

Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship