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

Development of a Mind Body Program for Obese Knee Osteoarthritis Patients with Comorbid Depression

Knee osteoarthritis (OA) is the most common joint disorder in the U.S. and a leading cause of disability. Depression and obesity are highly comorbid among knee OA patients, and the combination of obesity and depression is associated with decreased physical activity, higher pain and disability, and more rapid cartilage degradation. Depression, obesity and OA exacerbate one another and share a common pathophysiology involving systemic inflammation and pro-inflammatory cytokines, reflecting a complex mind-body interaction. Current treatments for knee OA offer little to no benefit over placebo, and do not emphasize mind-body practices or physical activity to target the underlying pathophysiology. Mind-body interventions to lessen depressive symptoms and increase physical activity offer the ability to target biological, mechanical and psychological mechanisms of OA progression. Our long-term goals are to evaluate the mechanisms by which the Relaxation Response Resiliency Program (3RP) delivered via secure telehealth, and adapted for patients with depression, obesity and knee OA (GetActive-OA) promotes increases in physical activity and improved knee health. We hypothesize that the synergistic interaction between mindfulness, adaptive thinking, positive psychology and healthy living skills of the GetActive-OA will slow the progression of symptomatic knee OA by reducing pro-inflammatory cytokine expression and promoting optimal mechanical loading of the cartilage. Here we present the protocol for a mixed methods study that will adapt the 3RP for the needs of knee OA patients with depression and obesity with a focus on increasing physical activity (GetActive-OA), and iteratively maximize the feasibility, credibility and acceptability of the programs and research procedures

Multimodal nonlinear imaging of atherosclerotic plaques differentiation of triglyceride and cholesterol deposits

Cardiovascular diseases in general and atherothrombosis as the most common of its individual disease entities is the leading cause of death in the developed countries. Therefore, visualization and characterization of inner arterial plaque composition is of vital diagnostic interest, especially for the early recognition of vulnerable plaques. Established clinical techniques provide valuable morphological information but cannot deliver information about the chemical composition of individual plaques. Therefore, spectroscopic imaging techniques have recently drawn considerable attention. Based on the spectroscopic properties of the individual plaque components, as for instance different types of lipids, the composition of atherosclerotic plaques can be analyzed qualitatively as well as quantitatively. Here, we compare the feasibility of multimodal nonlinear imaging combining two-photon fluorescence (TPF), coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy to contrast composition and morphology of lipid deposits against the surrounding matrix of connective tissue with diffraction limited spatial resolution. In this contribution, the spatial distribution of major constituents of the arterial wall and atherosclerotic plaques like elastin, collagen, triglycerides and cholesterol can be simultaneously visualized by a combination of nonlinear imaging methods, providing a powerful label-free complement to standard histopathological methods with great potential for in vivo application

Immunohistochemical Identification of Human Skeletal Muscle Macrophages

Macrophages have well-characterized roles in skeletal muscle repair and regeneration. Relatively little is known regarding the role of resident macrophages in skeletal muscle homeostasis, extracellular matrix remodeling, growth, metabolism and adaptation to various stimuli including exercise and training. Despite speculation into macrophage contributions during these processes, studies characterizing macrophages in non-injured muscle are limited and methods used to identify macrophages vary. A standardized method for the identification of human resident skeletal muscle macrophages will aide in the characterization of these immune cells and allow for the comparison of results across studies. Here, we present an immunohistochemistry (IHC) protocol, validated by flow cytometry, to distinctly identify resident human skeletal muscle macrophage populations. We show that CD11b and CD206 double IHC effectively identifies macrophages in human skeletal muscle. Furthermore, the majority of macrophages in non-injured human skeletal muscle show a ‘mixed’ M1/M2 phenotype, expressing CD11b, CD14, CD68, CD86 and CD206. A relatively small population of CD11b+/CD206- macrophages are present in resting skeletal muscle. Changes in the relative abundance of this population may reflect important changes in the skeletal muscle environment. CD11b and CD206 IHC in muscle also reveals distinct morphological features of macrophages that may be related to the functional status of these cells

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

Insights into the Evolution of Multicellularity from the Sea Lettuce Genome

We report here the 98.5 Mbp haploid genome (12,924 protein coding genes) of Ulva mutabilis, a ubiquitous and iconic representative of the Ulvophyceae or green seaweeds. Ulva’s rapid and abundant growth makes it a key contributor to coastal biogeochemical cycles; its role in marine sulfur cycles is particularly important because it produces high levels of dimethylsulfoniopropionate (DMSP), the main precursor of volatile dimethyl sulfide (DMS). Rapid growth makes Ulva attractive biomass feedstock but also increasingly a driver of nuisance “green tides.” Ulvophytes are key to understanding the evolution of multicellularity in the green lineage, and Ulva morphogenesis is dependent on bacterial signals, making it an important species with which to study cross-kingdom communication. Our sequenced genome informs these aspects of ulvophyte cell biology, physiology, and ecology. Gene family expansions associated with multicellularity are distinct from those of freshwater algae. Candidate genes, including some that arose following horizontal gene transfer from chromalveolates, are present for the transport and metabolism of DMSP. The Ulva genome offers, therefore, new opportunities to understand coastal and marine ecosystems and the fundamental evolution of the green lineage

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

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