Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital.

Platelet-rich plasma (PRP) preparations have recently become widely available in sports medicine, facilitating their use in regenerative therapy for ligament and tendon affections. Quality-oriented regulatory constraints for PRP manufacturing and available clinical experiences have underlined the critical importance of process-based standardization, a pre-requisite for sound and homogeneous clinical efficacy evaluation. This retrospective study (2013-2020) considered the standardized GMP manufacturing and sports medicine-related clinical use of autologous PRP for tendinopathies at the Lausanne University Hospital (Lausanne, Switzerland). This study included 48 patients (18-86 years of age, with a mean age of 43.4 years, and various physical activity levels), and the related PRP manufacturing records indicated a platelet concentration factor most frequently in the range of 2.0-2.5. The clinical follow-up showed that 61% of the patients reported favorable efficacy outcomes (full return to activity, with pain disappearance) following a single ultrasound-guided autologous PRP injection, whereas 36% of the patients required two PRP injections. No significant relationship was found between platelet concentration factor values in PRP preparations and clinical efficacy endpoints of the intervention. The results were in line with published reports on tendinopathy management in sports medicine, wherein the efficacy of low-concentration orthobiologic interventions appears to be unrelated to sport activity levels or to patient age and gender. Overall, this study confirmed the effectiveness of standardized autologous PRP preparations for tendinopathies in sports medicine. The results were discussed in light of the critical importance of protocol standardization for both PRP manufacturing and clinical administration to reduce biological material variability (platelet concentrations) and to enhance the robustness of clinical interventions (comparability of efficacy/patient improvement).

Current Status of PRP Manufacturing Requirements & European Regulatory Frameworks: Practical Tools for the Appropriate Implementation of PRP Therapies in Musculoskeletal Regenerative Medicine.

Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in legislation updates and enforcement between member states, and many reported gray-zone practices, notably for autologous PRP use. The levels of risk associated with blood manipulation processes generally dictate the manufacturing requirements for PRP preparations, which have gradually shifted toward good manufacturing practices (GMP) for standardization and overall quality enhancement. This work firstly outlines Western European and Swiss legislation for PRP products/preparations, providing key simplified information and recommendations for medical doctors seeking to implement this biological-based therapy for safe use in hospital settings, clinics, or private offices. This work secondly shows the importance of PRP-based product manufacturing standardization, which subsequently enables sound clinical evaluation of therapeutic interventions. Although the applicable legal bases provide guidelines for GMP manufacturing infrastructure and basic process design, paramount importance is set on the definition of workflows, technical specifications, and key parameters for PRP preparation and delivery. Overall, the development of simple and robust technologies and processes for PRP preparation is critical for guaranteeing the high therapeutic quality of the intervention, in collaboration with qualified GMP manufacturing platforms. Importantly, this work aims to serve as a practical tool for clinicians based in Western Europe who are willing to appropriately (i.e., administratively and technically) implement autologous PRP treatments in musculoskeletal regenerative medicine workflows, to ensure they make informed and optimal regulatory or process-based decisions.

Measure of efficiency and knee isokinetic strength in bike messengers and non-cyclist athletes.

BACKGROUND: Gross efficiency in cycling (GE) seems correlated with lower-body strength. This study investigated GE at four different pedaling rates and its relationship with an isokinetic strength test in bike messengers (BM) and experienced athletes non-bike messengers (NBM). METHODS: Eight BM and eight NBM completed a maximal incremental test to determine maximal aerobic power (MAP) and maximal oxygen consumption (V̇O2max). GE, V̇O2, heart rate (HR) and blood lactate concentration (BLC) were measured at different cadences (60, 70, 90 and 100 rpm) during an efficiency test at 50% of MAP and participants then performed an isokinetic test of the right knee. RESULTS: A difference in GE (except at 90 rpm), BLC and MAP/kg was found in favor of BM. The most efficient cadence was 60 rpm in both groups. Increased cadence resulted in decreased GE and increased HR and V̇O2 in both groups. BLC only increased in the NBM. We found no relationships between GE at different cadence, peak torque relative to bodyweight and muscle fatigability. CONCLUSIONS: This study is the first investigating performance and efficiency among BM. At equivalent power output, BM show a better GE than NBM. Those results are in line with previously described analysis in cyclists and explained by better aerobic capacity and training status. Isokinetic knee maximal strength and fatigability were not linked with GE, and thus does not appear appropriate for evaluating GE in cycling.

From Sedentary and Physical Inactive Behaviours to an Ultra Cycling Race: A Mixed-Method Case Report.

In faculties of health sciences, almost 30% of nursing students exercise less than once a week. This mixed-method case report presents the 38-month evolution of the physiological and psychological health parameters of a sedentary and physically inactive nursing student. During this period, she first took part in a one-semester institutional physical activity (PA) program that was offered by her university before being selected for participation in the Race Across America (RAAM) with a university relay team. In the four months leading up to the RAAM, she followed a cycling training program. After the RAAM, she was followed-up for the next 28 months. The results showed that each phase of the study had an important impact on the subject and showed that sedentary and physical inactive behaviours are reversible. Institutional PA programs, including training education in addition to concurrent strength and endurance training, can lead to physiological and psychological health improvements. For some individuals, participating in an athletic challenge can improve motivation and long-term adherence to PA participation. An individualised approach should be considered in future interventions that aim to promote PA participation. In the specific context of a university of health sciences, this kind of initiative could positively influence the general population's health by empowering students to become role models towards PA promotion.

Participating In The Race Across AMerica In A Team Of Eight Cyclists: Do Not Neglect Crew Preparation.

BACKGROUND: The Race Across AMerica (RAAM) is considered as one of the longest, and most difficult cycling races in the world. It can be performed in solo or in relay of two, four or eight persons. PURPOSE/METHOD: The aim of the present study was to investigate several physiological, perceptual and psychological responses before, during and after RAAM in a team of eight amateur cyclists. Because logistics of all team is demanding and complex, crew members have followed the same testing procedure. RESULTS: The main result is that parameters were globally not altered to a greater extent in cyclists than in crew members over the course of the RAAM, and that all variables returned to pre-race levels 1 week after the end of the race in both groups. In crew, body fat was decreased (p < 0.05) at mid-race (Mid) vs 1 week before the RAAM (Pre) (-1.5%) and total body water was increased (p < 0.05) at Mid vs Pre (+2.5%). In pre-relay quadriceps strength in cyclists was significantly lower (p < 0.05) at Mid vs Pre (41.6 ± 9.1 vs 45.0 ± 11.2 N, d = 0.36). Therefore, performing the race with eight well-prepared amateur cyclists seems to decrease potential risks on health. In crew, quadriceps strength remained stable at each assessment time but general fatigue increased all along the race. Anger was increased (p < 0.05) at Mid vs Pre in crew. CONCLUSION: The most important message of this study is that crew members for a team of eight require adequate and sufficient preparation and training. Roles and responsibilities need to be thoroughly defined; individuals need to know each other beforehand and they must be prepared for sleep deprivation. The results of this study show the importance of the preparation of two teams: crew members, as well as cyclists.

Gait analysis following single-shot hyaluronic acid supplementation: a pilot randomized double-blinded controlled trial.

OBJECTIVES: Viscosupplementation with new-generation, polyol-containing, cross-linked hyaluronic acid (HA) gels reduces joint inflammation in patients with knee osteoarthritis. Gait analysis is a complementary outcome measure to standard patient-reported scores and physical measures for testing the effect of HA injection. This three-arm, prospective, randomized, controlled, double-blind, feasibility pilot study investigated which gait parameters are more sensitive following a single bolus injection of polyol-containing HA for knee osteoarthritis. METHODS: Twenty-two patients with Ahlbäck grade II-III knee osteoarthritis were randomly allocated into three groups: (1) HA + mannitol (n = 9), (2) HA + sorbitol (n = 5), and (3) saline placebo (n = 8). Patients were assessed by blinded observers prior to injection and at 4 weeks post-injection (4W). Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society score (KSS), EuroQol in five-dimensions (EQ-5D), VAS pain, and VAS stiffness. Gait was assessed over 30 m using a portable inertial-based data logger (Physilog®). RESULTS: Differences between 4W and baseline were statistically significant for the mannitol-containing viscosupplement, with a median increase of 0.076 m/s on gait speed (p = 0.039), 0.055 m on stride length (p = 0.027), and 15 points on the KSS (p = 0.047). In contrast, the HA + sorbitol and saline groups demonstrated no significant changes from baseline to 4W in any gait parameters or self-reported outcome measures (all p > 0.3). The observed increase in gait speed is approximately 13% greater than the mean difference between healthy subjects and those with knee osteoarthritis, is clinically important, and thus is a sensitive gait parameter. CONCLUSIONS: This study demonstrated gait speed and stride length are the most relevant gait parameters to investigate when assessing the effect of polyol-containing HA viscosupplementation. This study supports the need for a larger, randomized, controlled, clinical trial to assess the effect of a single-bolus HA injection versus multiple injections in people with knee osteoarthritis using both gait performance and self-reported parameters of knee function. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov on August 20, 2018, and assigned #NCT03636971. LEVEL OF EVIDENCE: I.

[« My joints are cracking, is it serious doctor ? ¼ A review about sounds produced by joints]. / « Mes articulations craquent, c'est grave docteur ? ¼ Les bruits articulaires en question.

The sounds produced by joints are a common source of questioning for doctors and their patients. Two major types are identified : cracks and crepitus. Few investigations have been carried out on these manifestations, while they potentially have clinical implications, especially for patellar crepitus in patellofemoral osteoarthrosis, and may generate anxiety. Knuckle cracking appears to be caused by the sudden and temporary occurrence of an intra-articular gaseous cavity, called tribonucleation. Other researches on these sounds are focused on the knees and their links with osteoarthritis, as well as on the spine. Many questions still arise but it seems important to talk about it with patients without trivializing them.

Les bruits produits par les articulations sont une source de questionnements pour les médecins et leurs patients. Deux principaux types sont identifiés, les craquements et les grincements. Peu d'investigations ont été réalisées sur ces manifestations fréquentes alors qu'elles présentent potentiellement une implication clinique, notamment pour les grincements patellaires dans l'arthrose fémoro-patellaire, et qu'elles peuvent générer de l'anxiété. Les craquements des doigts semblent être provoqués par l'apparition soudaine et temporaire d'une cavité gazeuse intra-articulaire, appelée tribonucléation. Les autres recherches sur ces bruits se portent principalement sur les genoux et leurs liens avec l'arthrose, ainsi que sur le rachis. De nombreuses questions subsistent, mais il est nécessaire d'en parler avec les patients sans les banaliser.

[What do we know about the exercise-related transient abdominal pain ?] / Que sait-on sur le « point de côté ¼ lié à l'effort ?

Exercise-related transient abdominal pain or « side stitch ¼ is a very common problem among athletes, whatever their level of participation. This pain may be present in different areas of the abdomen, even in the shoulder, usually well localized, and described as cramping or stabbing depending on the severity. The etiology is still debated, with many possible theories. It is a benign problem but other pathologies, often more severe, must be excluded in case of any atypical presentation. There are simple preventive measures recommended. This pain usually disappears within minutes by slowing or stopping the effort and / or using different methods without scientific validation until now.

La douleur abdominale transitoire liée à l'effort ou « point de côté ¼ est un problème fréquemment rencontré chez les sportifs, qu'ils soient débutants ou confirmés. Cette douleur peut être présente dans différentes zones de l'abdomen, voire même les épaules, le plus souvent bien localisée, décrite comme une crampe ou « coup de couteau ¼ selon la sévérité. L'étiologie est encore débattue, avec de multiples théories possibles. Il s'agit d'un problème bénin mais d'autres pathologies, souvent plus graves, doivent être exclues devant toute présentation atypique. Il existe des mesures préventives simples à conseiller. Cette douleur disparaît généralement en quelques minutes en ralentissant ou stoppant l'effort et / ou à l'aide de différentes méthodes, sans validation scientifique à ce jour.

An inertial sensor-based system for spatio-temporal analysis in classic cross-country skiing diagonal technique.

The present study proposes a method based on ski fixed inertial sensors to automatically compute spatio-temporal parameters (phase durations, cycle speed and cycle length) for the diagonal stride in classical cross-country skiing. The proposed system was validated against a marker-based motion capture system during indoor treadmill skiing. Skiing movement of 10 junior to world-cup athletes was measured for four different conditions. The accuracy (i.e. median error) and precision (i.e. interquartile range of error) of the system was below 6 ms for cycle duration and ski thrust duration and below 35 ms for pole push duration. Cycle speed precision (accuracy) was below 0.1m/s (0.00 5m/s) and cycle length precision (accuracy) was below 0.15m (0.005 m). The system was sensitive to changes of conditions and was accurate enough to detect significant differences reported in previous studies. Since capture volume is not limited and setup is simple, the system would be well suited for outdoor measurements on snow.

Exercise efficiency relates with mitochondrial content and function in older adults.

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty-eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1-h submaximal test (55% V˙O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with (31)P-MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

[Fatigue and reduction in motor performance in sportspeople or overtraining syndrome]. / Fatigue et réduction de la performance motrice chez le sportif, syndrome de surentraînement.

The main goal of training activities is to improve motor performance. After strenuous workouts, it is physiological to experience fatigue, which relieves within two weeks, and then induce an improvement in motor capacities. An overtraining syndrome is diagnosed when fatigue is postponed beyond two weeks, and affects mainly endurance athletes. It is a condition of chronic fatigue, underperformance and an increased vulnerability to infection leading to recurrent infections. The whole observed spectrum of symptoms is physiological, psychological, endocrinogical and immunological. All play a role in the failure to recover. Monitoring of athletes activities helps to prevent the syndrome with days with no sports. Rest, patience and empathy are the only ways of treatment options.

Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.

CONTEXT: Sarcopenia is thought to be associated with mitochondrial (Mito) loss. It is unclear whether the decrease in Mito content is consequent to aging per se or to decreased physical activity. OBJECTIVES: The objective of the study was to examine the influence of fitness on Mito content and function and to assess whether exercise could improve Mito function in older adults. DESIGN AND SUBJECTS: Three distinct studies were conducted: 1) a cross-sectional observation comparing Mito content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults and sedentary (S) subjects matched for age and gender; and 3) a 4-month exercise intervention in S. SETTING: The study was conducted at a university-based clinical research center. OUTCOMES: Mito volume density (MitoVd) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins by Western blotting, mRNAs for transcription factors involved in M biogenesis by quantitative RT-PCR, and in vivo oxidative capacity (ATPmax) by (31)P-magnetice resonance spectroscopy. Peak oxygen uptake was measured by graded exercise test. RESULTS: Peak oxygen uptake was strongly correlated with MitoVd in 80 60- to 80-year-old adults. Comparison of chronically endurance-trained older adults vs S revealed differences in MitoVd, ATPmax, and some electron transport chain protein complexes. Finally, exercise intervention confirmed that S subjects are able to recover MitoVd, ATPmax, and specific transcription factors. CONCLUSIONS: These data suggest the following: 1) aging per se is not the primary culprit leading to Mito dysfunction; 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle Mito content and may prevent aging muscle comorbidities; and 3) the improvement of Mito function is all about content.

Measurement of the dynamics in ski jumping using a wearable inertial sensor-based system.

Dynamics is a central aspect of ski jumping, particularly during take-off and stable flight. Currently, measurement systems able to measure ski jumping dynamics (e.g. 3D cameras, force plates) are complex and only available in few research centres worldwide. This study proposes a method to determine dynamics using a wearable inertial sensor-based system which can be used routinely on any ski jumping hill. The system automatically calculates characteristic dynamic parameters during take-off (position and velocity of the centre of mass perpendicular to the table, force acting on the centre of mass perpendicular to the table and somersault angular velocity) and stable flight (total aerodynamic force). Furthermore, the acceleration of the ski perpendicular to the table was quantified to characterise the skis lift at take-off. The system was tested with two groups of 11 athletes with different jump distances. The force acting on the centre of mass, acceleration of the ski perpendicular to the table, somersault angular velocity and total aerodynamic force were different between groups and correlated with the jump distances. Furthermore, all dynamic parameters were within the range of prior studies based on stationary measurement systems, except for the centre of mass mean force which was slightly lower.

Characterization of lower-limbs inter-segment coordination during the take-off extension in ski jumping.

Take-off, the most important phase in ski jumping, has been primarily studied in terms of spatio-temporal parameters; little is known about its motor control aspects. This study aims to assess the inter-segment coordination of the shank-thigh and thigh-sacrum pairs using the continuous relative phase (CRP). In total 87 jumps were recorded from 33 athletes with an inertial sensor-based system. The CRP curves indicated that the thighs lead the shanks during the first part of take-off extension and that the shanks rotated faster at the take-off extension end. The thighs and sacrum first rotated synchronously, with the sacrum then taking lead, with finally the thighs rotating faster. Five characteristic features were extracted from the CRP and their relationship with jump length was tested. Three features of the shank-thigh pair and one of the thigh-sacrum pair reported a significant association with jump length. It was observed that athletes who achieved longer jumps had their thighs leading their shanks during a longer time, with these athletes also having a more symmetric movement between thighs and sacrum. This study shows that inter-segment coordination during the take-off extension is related to performance and further studies are necessary to contrast its importance with other ski jumping aspects.

Effect of hip flexion angle on hamstring optimum length after a single set of concentric contractions.

The eccentric contraction mode was proposed to be the primary stimulus for optimum angle (angle at which peak torque occurs) shift. However, the training range of motion (or muscle excursion range) could be a stimulus as important. The aim of this study was to assess the influence of the training range of motion stimulus on the hamstring optimum length. It was hypothesised that performing a single set of concentric contractions beyond optimal length (seated at 80° of hip flexion) would lead to an immediate shift of the optimum angle to longer muscle length while performing it below (supine at 0° of hip flexion) would not provide any shift. Eleven male participants were assessed on an isokinetic dynamometer. In both positions, the test consisted of 30 consecutive knee flexions at 4.19 rad · s⁻¹. The optimum angle was significantly shifted by ∼15° in the direction of longer muscle length after the contractions at 80° of hip flexion, while a non-significant shift of 3° was found at 0°. The hamstring fatigability was not influenced by the hip position. It was concluded that the training range of motion seems to be a relevant stimulus for shifting the optimum angle to longer muscle length. Moreover, fatigue appears as a mechanism partly responsible for the observed shift.

Actions of ß2-adrenoceptor agonist drug on human soleus muscle contraction.

PURPOSE: The effects of ß(2)-agonists on human skeletal muscle contractile properties, particularly on slow fibers, are unclear. Moreover, it remains to be ascertained whether central motor drive (CMD) during voluntary contractions could counter for eventual contractile alterations induced by ß(2)-agonists. This study investigated central and peripheral neuromuscular adjustments induced by ß(2)-agonist terbutaline on a predominantly slow human muscle, the soleus. METHODS: Ten recreationally active men ingested either a single dose of 8 mg of terbutaline or placebo in a randomized double-blind order (two experimental sessions). Isometric plantarflexion torque was measured during single and tetanic (10 and 100 Hz) stimulations as well as during submaximal and maximal voluntary contractions (MVC). Twitch peak torque and half-relaxation time were calculated. CMD was estimated via soleus electromyographic recordings obtained during voluntary contractions performed at approximately 50% MVC. RESULTS: MVC and twitch peak torque were not modified by terbutaline. Twitch half-relaxation time was 28% shorter after terbutaline administration compared with placebo (P < 0.001). Tetanic torques at 10 and 100 Hz were significantly lower after terbutaline intake compared with placebo (-40% and -24% respectively, P < 0.001). Despite comparable torque of submaximal voluntary contractions in the two conditions, CMD was 7% higher after terbutaline ingestion compared with placebo (P < 0.01). CONCLUSION: These results provide evidence that terbutaline modulates the contractility of the slow soleus muscle and suggest that the increased CMD during submaximal contractions may be viewed as a compensatory adjustment of the central nervous system to counter the weakening action induced by terbutaline on the contractile function of slow muscle fibers.