Prospective Observational Study of a Non-Arthroscopic Autologous Cartilage Micrografting Technology for Knee Osteoarthritis.

Autologous micrografting technology (AMT®) involves the use of autologous micrografts to stimulate/enhance the repair of damaged tissue. This study assessed the efficacy and safety of the AMT® procedure in patients with early stages of knee osteoarthritis. Briefly, the AMT® procedure involved extraction of auricular cartilage, disaggregation using the Rigeneracons® SRT in 4.0 mL of saline solution, and injection of the disaggregated micrografts into the external femorotibial compartment area of the affected knee. Ten patients (4 men, 6 women; age range: 37-84 years) were included in the study. In all patients, there was a steady improvement in knee instability, pain, swelling, mechanical locking, stair climbing, and squatting at 1- and 6-months post-procedure. Improvement in mobility was observed as early as 3 weeks post-procedure in 2 patients. Significant improvements were seen in mean scores of all five subscales of Knee Injury and Osteoarthritis Outcome Score (KOOS [KOOS symptoms, KOOS pain, KOOS ADL, KOOS sport and recreation, and KOOS quality-of-life]) between pre-procedure and 1- and 6-months post-procedure (all p ≤ 0.05). Autologous auricular cartilage micrografts obtained by AMT® procedure (using Rigenera® technology) is an effective and safe protocol in the treatment of early stage knee osteoarthritis. These encouraging findings need to be validated in a larger patient population and in a randomized clinical trial (RCT).

Adipose Tissue Stem Cells for Knee Arthritis and Cartilage Lesions: A Three-Year Follow Up.

INTRODUCTION: The purpose of this research article is to evaluate the efficacy and the safety of injections of stromal vascular fraction (SVF), obtained with mini-lipoaspiration of fat tissue for knee osteoarthritis and cartilage lesions. MATERIALS AND METHODS: Between January 2018 and February 2021, a total of 76 patients (45 females and 31 males, mean age 64 years; range 53-75 years, body mass index [BMI] no more than 30%, with symptomatic primary osteoarthritis of the knee, without previous arthroscopic intervention) underwent a local tumescent lipoaspiration procedure of 60-80cc of fat tissue from the abdomen. SVF was obtained after centrifugation according to the AdiPrep® Adipose Transfer System (Harvest-Terumo, Plymouth, Massachusetts) technique. The final product was checked with flow cytometry for absolute numbers, vitality, and the cluster of differentiation (CD) population. It was injected intraarticularly into the patients knees. Patients were divided in two groups: Group 1 had patients with knee osteoarthritis Kellgren-Lawrence grade early 4 and Group 2 with osteoarthritis K-L grade 2-3. The International Knee Documentation Committee (IKCD) and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaires were used to evaluate clinical effects and measure patient's subjective assessment of pain, joint mobility, and physical disability before the injections. They were repeated at six months, one year, two years, and three years post injections. Knee cartilage lesions patients were divided in two subgroups: Group A (11 patients with OA K-L grade 2-3 and Outerbridge cartilage lesions grade 2-3) and Group B (7 patients with OA K-L grade early 4 and cartilage lesions Outerbridge grade late 3 to early 4) were estimated with quantitive analysis of magnetic resonance imaging (MRI) at one, two, and three years post injections. RESULTS: The average IKDC score in Group 1 was 45.9, 63.2, 62.4, 60, and 52. The KOOS score of the same group was 53, 79, 72, 69, and 62 at the end of the third year. At baseline, the average total IKDC score in Group 2 was 48.3, at 6 months 78.2, at one year 77, at two years 70.4, and at three years 61. The KOOS score of this group was 57, 84, 86, 79, and 69 at three years, respectively. For the patients with cartilage lesions, Group A presented lesser volume mean numbers of the lesion: 74% at the end of the first year post injection, 61% at the second, and 52% at the end of the third year with two out of seven patients in the group. The rest had no significant difference. Lesser volume mean number of the lesions in Group B was 85-88%, 70%, and 61% at the end of the third year in 5 out of 11 patients in the group. The rest had no significant difference. CONCLUSION: Adipose-derivedSVF, injected intraarticularly in arthritic knees, seems to provide good to excellent clinical results for three years and radiological results for cartilage lesions for two years post injections. All patients were satisfied with this treatment with reduction in pain and better joint mobility, especially after two to three months and up to three years. No serious side effects or complications were reported.

Recovery kinetics following eccentric exercise is volume-dependent.

The present study compared the effect of 75 vs 150 vs 300 intensity-matched eccentric contractions on muscle damage and performance recovery kinetics. Ten healthy males participated in a randomized, cross-over study consisted of 4 experimental trials (ECC75, ECC150, ECC300 and Control - no exercise) with a 4-week washout period in-between. Performance and muscle damage, inflammatory and oxidative stress markers were evaluated at baseline, post-exercise, 24, 48 and 192 hours following each exercise protocol. Concentric and eccentric peak torque decreased similarly in ECC150 and ECC300 during the first 48 h of recovery (p < 0.05) but remained unaffected in ECC75. Countermovement jump indices decreased post-exercise and at 24 h in ECC150 and ECC300, with ECC300 inducing a more pronounced reduction (p < 0.05). Creatine kinase increased until 48 h of recovery in all trials and remained elevated up to 192 h only in ECC300 (p < 0.05). Delayed onset of muscle soreness increased, and knee-joint range of motion decreased in a volume-dependent manner during the first 48 h (p < 0.05). Likewise, a volume-dependent decline of glutathione and a rise of protein carbonyls was observed during the first 48 h of recovery (p < 0.05). Collectively, our results indicate that muscle damage and performance recovery following eccentric exercise is volume dependent, at least in lower limbs.

The role of cell therapies and hip arthroscopy in the management of osteonecrosis: an update.

The exact pathophysiology of osteonecrosis of the femoral head (ONFH) is still unknown. There is evidence to suggest that in ON there is decreased population and altered function of the mesenchymal stem cells (MSCs) of the femoral head. This could influence both the actual occurrence of ON itself and the repair process that follows. Hence, in such an environment it only is rational to consider the use of cell-based treatments to potentially regenerate lost or damaged bone. The aim of this review is to provide an up-to-date, evidence-based information in the use of cell therapies in the treatment of nontraumatic ONFH and the use of hip arthroscopy in the field.

Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation.

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation.

No difference in osteoarthritis after surgical and non-surgical treatment of ACL-injured knees after 10 years.

PURPOSE: Aim of this study was to record and compare the functional and activity level as well as the manifestations of osteoarthritis after isolated ACL ruptures between patients with conservative treatment and ACL reconstruction with hamstrings tendon graft. METHODS: Thirty-two patients diagnosed with ACL rupture were recorded. Clinical examination included the Tegner and Lysholm activity scale, the International Knee Documentation Committee Subjective Form and KT-1000 arthrometer. Narrowing of the medial and lateral joint spaces was assessed using the IKDC knee examination score. RESULTS: Median follow-up was 10.3 years (range 10-11). Fifteen patients were conservatively treated (median age 33 years, range 25-39). Seventeen patients were operated (median age 31 years, range 20-36). There was significant difference between the mean values of IKDC scores in favour of the ACL-reconstruction group of patients, 86.8 (SD 6.5) versus 77.5 (SD 13.8), respectively (p = 0.04). The mean value of anteroposterior tibial translation was 1.5 mm (SD 0.2) for ACL-reconstruction group of patients, while the corresponding mean value for ACL-conservative group was 4.5 mm (SD 0.5), p = 0.03. Four patients in ACL-reconstruction group had radiological findings of grade C or D according to IKDC form. In ACL-conservative group, five patients presented similar signs (n.s.). CONCLUSIONS: ACL reconstruction using hamstrings autograft resulted in better functional outcome and laxity measurements than ACL-conservative management. However, the incidence of radiological osteoarthritis was similar between the two groups and independent on the pre-operative grade of laxity and functional status of the patients. Equally, bone bruises were not found as a risk factor for the development of osteoarthritis after ACL rupture. LEVEL OF EVIDENCE: Prospective randomized study, Level II.

The microcycle of inflammation and performance changes after a basketball match.

Basketball incorporates intense eccentric muscle activity that induces muscle microtrauma and an inflammatory response. This study investigated time-dependent inflammatory and performance responses during a weekly microcycle after a basketball match. Twenty elite-standard players underwent a trial that comprised a match followed by a 6-day simulated in-season microcycle. The trial was preceded by a control condition that did not have a match. Blood sampling and tests of maximal-intensity exercise performance and muscle damage occurred before each condition, immediately after the match and daily thereafter for 6 consecutive days. The match induced marked increases in heart rate, lactate, ammonia, glucose, non-esterified fatty acids and triglycerides. Performance deteriorated for 24-48 h after the match, whereas knee flexor and extensor soreness increased for 48 and 24 h post-match, respectively. Inflammatory (leukocytes, C-reactive protein, creatine kinase activity, adhesion molecules, cortisol, uric acid and cytokines) and oxidative stress (malondialdehyde, protein carbonyls, oxidised glutathione, antioxidant capacity, catalase and glutathione peroxidase) markers increased for ~24 h and subsided thereafter. Reduced glutathione declined for 24 h after exercise. These results suggest that a basketball match elicits moderate and relatively brief (~24-48 h) inflammatory responses, is associated with marked but short-lived performance deterioration, but is less stressful than other intermittent-type sports.

Physical activity is associated with bone geometry of premenarcheal girls in a dose-dependent manner.

OBJECTIVE: To determine the relationship between habitual physical activity (PA) level and peripheral qualitative computed tomography-determined quantitative tibia characteristics of premenarcheal girls. METHODS: Premenarcheal girls matched for age (10-13 years), bone age and maturity level were assigned into: a) low PA group (LPA, n=25), b) moderate PA group (MPA, n=17), and c) high PA group (HPA, n=18). Participants' daily dietary intake, tibia's geometry and serum levels of calcium and vitamin D were assessed. RESULTS: Premenarcheal girls demonstrating HPA exhibited greater pericortical thickness, cross-sectional area (CSA) and bone mineral content (BMC) (p<.001) in cortical bone, greater BMC, volumetric bone density (vBMD) and polar stress strength index (SSIp) in trabecular bone (p<0.001-0.05) and greater total BMC (p<.05) and vBMD (p<.01) when compared to their physically inactive or moderately active counterparts. MPA exhibited greater values of cortical BMC (p<.01) and SSIp (p<.05) than LPA. Partial correlation analysis (adjusted for BMI) revealed modest associations between PA score and bone geometry parameters (r=0.36-0.49, p<.05) at 38% of tibia length. CONCLUSIONS: Habitual PA affects geometry of both cortical and trabecular areas of a long bone of premenarcheal girls in a dose-dependent manner. Specifically, PA increases both the density and size of cortical bone but only the density of trabecular bone during preadolescence. Given the importance of peak bone mass for future fracture risk, high levels of PA during childhood could be a major target for public health interventions aimed at optimising bone health in prepubertal children when the greatest bone gains occur.

Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise.

BACKGROUND: The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations. OBJECTIVE: The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma. DESIGN: In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg · kg(-1) · d(-1)) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise. RESULTS: NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor κB phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-α 8 d after exercise. Performance was completely recovered only in the placebo group. CONCLUSION: Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways. This trial was registered at clinicaltrials.gov as NCT01778309.

The time-frame of acute resistance exercise effects on football skill performance: the impact of exercise intensity.

The purpose of this study was to determine the recovery rate of football skill performance following resistance exercise of moderate or high intensity. Ten elite football players participated in three different trials: control, low-intensity resistance exercise (4 sets, 8-10 repetitions/set, 65-70% 1 repetition maximum [1RM]) and high-intensity resistance exercise (4 sets, 4-6 repetitions/set, 85-90% 1RM) in a counterbalanced manner. In each experimental condition, participants were evaluated pre, post, and at 24, 48, 72 h post exercise time points. Football skill performance was assessed through the Loughborough Soccer Passing Test, long passing, dribbling, shooting and heading. Delayed onset muscle soreness, knee joint range of motion, and muscle strength (1RM) in squat were considered as muscle damage markers. Blood samples analysed for creatine kinase activity, C-reactive protein, and leukocyte count. Passing and shooting performance declined (P < 0.05) post-exercise following resistance exercise. Strength declined post-exercise following high-intensity resistance exercise. Both trials induced only a mild muscle damage and inflammatory response in an intensity-dependent manner. These results indicate that football skill performance is minimally affected by acute resistance exercise independent of intensity suggesting that elite players may be able to participate in a football practice or match after only 24 h following a strength training session.

Plyometrics' trainability in preadolescent soccer athletes.

Plyometric training (PT) is a widely used method to improve muscle ability to generate explosive power. This study aimed to determine whether preadolescent boys exhibit plyometric trainability or not. Forty-five children were randomly assigned to either a control (CG, N = 21, 10.6 ± 0.5 years; participated only in regular soccer practice) or a plyometric training group (PTG, N = 24, 10.6 ± 0.6 years; participated in regular soccer practice plus a plyometric exercise protocol). Both groups trained for 12 weeks during the in-season period. The PT exercises (forward hopping, lateral hopping, shuffles, skipping, ladder drills, skipping, box jumps, low-intensity depth jumps) were performed twice a week. Preadolescence was verified by measuring Tanner stages, bone age, and serum testosterone. Speed (0-10, 10-20, 20-30 m), leg muscle power (static jumping, countermovement jumping, depth jumping [DJ], standing long jump [SLJ], multiple 5-bound hopping [MB5]), leg strength (10 repetition maximum), anaerobic power (Wingate testing), and soccer-specific performance (agility, kicking distance) were measured at baseline, midtraining, and posttraining. The CG caused only a modest (1.2-1.8%) increase in speed posttraining. The PTG induced a marked (p < 0.05) improvement in all speed tests (1.9-3.1% at midtraining and 3-5% at posttraining) and vertical jump tests (10-18.5% at midtraining and 16-23% at posttraining), SLJ (2.6% at midtraining and 4.2% at posttraining), MB5 (14.6% at midtraining and 23% at posttraining), leg strength (15% at midtraining and 28% at posttraining), agility (5% at midtraining and 23% at posttraining), and kicking distance (13.6% at midtraining and 22.5% at posttraining). Anaerobic power remained unaffected in both groups. These data indicate that (a) prepubertal boys exhibit considerable plyometric trainability, and (b) when soccer practice is supplemented with a PT protocol, it leads to greater performance gains.

Oxidative stress and inflammatory responses following an acute bout of isokinetic exercise in obese women with knee osteoarthritis.

BACKGROUND: Obesity is associated with osteoarthritis and it is accompanied by chronic inflammation and elevated oxidative stress. Strengthening-type exercise is used in knee osteoarthritis (KOA) rehabilitation. This study determined how acute isokinetic exercise influences inflammatory responses of obese middle-aged women with KOA. METHODS: Ten obese women with KOA and 10 age/weight-matched controls performed an isokinetic exercise protocol. Assessment of performance (knee extensor/flexor torque), muscle soreness (DOMS), knee flexibility (KJRM), and pain, and blood collection were performed pre-exercise, post-exercise, and at 24h post-exercise. Blood was analyzed for creatine kinase activity (CK), lactate dehydrogenase activity (LDH), CRP, leukocytes, uric acid, IL-6, TBARS, lipid hydroperoxides (LPX), protein carbonyls (PC), oxidized (GSH) and reduced glutathione (GSSG), total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase activity (GPX). RESULTS: Physical function remained unaltered by exercise (only torque at 90°/s decreased at 24h). Exercise increased DOMS throughout recovery but KJRM and pain remained unchanged. CK, LDH, and uric acid increased similarly in both groups. CRP remained unaffected by exercise while IL-6 increased only post-exercise. TBARS, PC, LPH, GSSG, and TAC increased only post-exercise in both groups. GSH and GSH/GSSG declined post-exercise and normalized thereafter. Catalase and GPX increased only in patients post-exercise. CONCLUSION: Isokinetic exercise induces only a mild inflammatory response of very short duration (<24h) without affecting physical function and pain in KOA patients suggesting that moderate strengthening-type exercise may be safe for this patient cohort. These results indicate that KOA patients may be able to receive another exercise stimulus after only 48h. CLINICAL RELEVANCE: Isokinetic exercise produces minimal inflammation and pain in knee osteoarthritis patients, could be performed every 48h during rehabilitation, and up-regulates patients' antioxidant system.