Instrumented Upper Limb Functional Assessment Using a Robotic Exoskeleton: Normative References Intervals.

Upper-limb rehabilitation exoskeletons offer a valuable solution to support and enhance the rehabilitation path of neural-injured patients. Such devices are usually equipped with a network of sensors that can be exploited to evaluate and monitor the performances of the users. In this work, we assess the normality ranges of different motor-performance indicators on a group of 15 healthy participants, computed with the benchmark toolbox of AGREE, an upper limb motorized exoskeleton. The toolbox implements a benchmarking scheme for the evaluation of the upper limb, used to test anterior reaching at rest position height and hand-to-mouth motor skills. We selected kinematic and electromyography performance indicators to assess the different motor abilities. We performed a pilot evaluation on three neurological patients, to verify if the AGREE benchmark toolbox was able to distinguish patients from healthy subjects on the basis of the selected performance indicators. Through a comparison between results obtained by the healthy and the small group of motor-impaired users, we successfully calculated the normality ranges for the selected performance indicators, and we pilot-showed how data gathered from AGREE can be used to evaluate the current status of the patients.

Technology Acceptance Model for Exoskeletons for Rehabilitation of the Upper Limbs from Therapists' Perspectives.

Over the last few years, exoskeletons have been demonstrated to be useful tools for supporting the execution of neuromotor rehabilitation sessions. However, they are still not very present in hospitals. Therapists tend to be wary of this type of technology, thus reducing its acceptability and, therefore, its everyday use in clinical practice. The work presented in this paper investigates a novel point of view that is different from that of patients, which is normally what is considered for similar analyses. Through the realization of a technology acceptance model, we investigate the factors that influence the acceptability level of exoskeletons for rehabilitation of the upper limbs from therapists' perspectives. We analyzed the data collected from a pool of 55 physiotherapists and physiatrists through the distribution of a questionnaire. Pearson's correlation and multiple linear regression were used for the analysis. The relations between the variables of interest were also investigated depending on participants' age and experience with technology. The model built from these data demonstrated that the perceived usefulness of a robotic system, in terms of time and effort savings, was the first factor influencing therapists' willingness to use it. Physiotherapists' perception of the importance of interacting with an exoskeleton when carrying out an enhanced therapy session increased if survey participants already had experience with this type of rehabilitation technology, while their distrust and the consideration of others' opinions decreased. The conclusions drawn from our analyses show that we need to invest in making this technology better known to the public-in terms of education and training-if we aim to make exoskeletons genuinely accepted and usable by therapists. In addition, integrating exoskeletons with multi-sensor feedback systems would help provide comprehensive information about the patients' condition and progress. This can help overcome the gap that a robot creates between a therapist and the patient's human body, reducing the fear that specialists have of this technology, and this can demonstrate exoskeletons' utility, thus increasing their perceived level of usefulness.

IMU-based human activity recognition and payload classification for low-back exoskeletons.

Nowadays, work-related musculoskeletal disorders have a drastic impact on a large part of the world population. In particular, low-back pain counts as the leading cause of absence from work in the industrial sector. Robotic exoskeletons have great potential to improve industrial workers' health and life quality. Nonetheless, current solutions are often limited by sub-optimal control systems. Due to the dynamic environment in which they are used, failure to adapt to the wearer and the task may be limiting exoskeleton adoption in occupational scenarios. In this scope, we present a deep-learning-based approach exploiting inertial sensors to provide industrial exoskeletons with human activity recognition and adaptive payload compensation. Inertial measurement units are easily wearable or embeddable in any industrial exoskeleton. We exploited Long-Short Term Memory networks both to perform human activity recognition and to classify the weight of lifted objects up to 15 kg. We found a median F1 score of [Formula: see text] (activity recognition) and [Formula: see text] (payload estimation) with subject-specific models trained and tested on 12 (6M-6F) young healthy volunteers. We also succeeded in evaluating the applicability of this approach with an in-lab real-time test in a simulated target scenario. These high-level algorithms may be useful to fully exploit the potential of powered exoskeletons to achieve symbiotic human-robot interaction.

Transfer learning in hand movement intention detection based on surface electromyography signals.

Over the past several years, electromyography (EMG) signals have been used as a natural interface to interact with computers and machines. Recently, deep learning algorithms such as Convolutional Neural Networks (CNNs) have gained interest for decoding the hand movement intention from EMG signals. However, deep networks require a large dataset to train appropriately. Creating such a database for a single subject could be very time-consuming. In this study, we addressed this issue from two perspectives: (i) we proposed a subject-transfer framework to use the knowledge learned from other subjects to compensate for a target subject's limited data; (ii) we proposed a task-transfer framework in which the knowledge learned from a set of basic hand movements is used to classify more complex movements, which include a combination of mentioned basic movements. We introduced two CNN-based architectures for hand movement intention detection and a subject-transfer learning approach. Classifiers are tested on the Nearlab dataset, a sEMG hand/wrist movement dataset including 8 movements and 11 subjects, along with their combination, and on open-source hand sEMG dataset "NinaPro DataBase 2 (DB2)." For the Nearlab database, the subject-transfer learning approach improved the average classification accuracy of the proposed deep classifier from 92.60 to 93.30% when classifier was utilizing 10 other subjects' data via our proposed framework. For Ninapro DB2 exercise B (17 hand movement classes), this improvement was from 81.43 to 82.87%. Moreover, three stages of analysis in task-transfer approach proved that it is possible to classify combination hand movements using the knowledge learned from a set of basic hand movements with zero, few samples and few seconds of data from the target movement classes. First stage takes advantage of shared muscle synergies to classify combined movements, while second and third stages take advantage of novel algorithms using few-shot learning and fine-tuning to use samples from target domain to further train the classifier trained on the source database. The use of information learned from basic hand movements improved classification accuracy of combined hand movements by 10%.

AGREE: an upper-limb robotic platform for personalized rehabilitation, concept and clinical study design.

Rehabilitation exoskeletons can supplement therapist-based training allowing post-stroke patients to perform functional, high-dosage, repetitive exercises. The use of robotic devices allows providing intense rehabilitation sessions and permits clinicians to personalize the therapy according to the patient's need. In this work, we propose an upper-limb rehabilitation system developed within the AGREE project. The platform relies on a four degrees-of-freedom arm exoskeleton, capable of assisting state-of-the-art rehabilitation exercises under different training modalities while behaving transparently to user-generated and therapist-applied forces. The system is provided with a LEDs-matrix mat to guide patients during reaching tasks with visual feedback, an EMG reader to evaluate the patient's involvement during the therapy, and several software tools to help clinicians customize the treatment and monitor the patient's progress. A randomized controlled pilot study aimed at evaluating the usability and the effectiveness of the AGREE rehabilitation platform to improve arm impairment after stroke is currently ongoing.

A Backbone-Tracking Passive Exoskeleton to Reduce the Stress on the Low-Back: Proof of Concept Study.

Exoskeletons for the low-back have great potential as tools to both prevent low-back pain for healthy subjects and limit its impact for chronic patients. Here, we show a proof-of-concept evaluation of our low-back exoskeleton. Its peculiar feature is the backbone-tracking kinematic structure that allows tracking the motion of the human spine while bending the trunk. This mechanism is implemented with a rigid-yet-elongating structure that does not hinder nor constrain the motion of the wearer while providing assistance. In this work, we show the first prototype we manufactured. It is equipped with a traction spring to assist the wearer during trunk flexion/extension. Then, we report the results of a preliminary test with healthy subjects. We measured a reduction of the mean absolute value for some target muscles - including the erector spinae - when using the exoskeleton for payload manipulation tasks. This was achieved without affecting task performance, measured as task time and joints range of motion. We believe these preliminary results are encouraging, paving the way for a broader experimental campaign to evaluate our exoskeleton.

A unified scheme for the benchmarking of upper limb functions in neurological disorders.

BACKGROUND: In neurorehabilitation, we are witnessing a growing awareness of the importance of standardized quantitative assessment of limb functions. Detailed assessments of the sensorimotor deficits following neurological disorders are crucial. So far, this assessment has relied mainly on clinical scales, which showed several drawbacks. Different technologies could provide more objective and repeatable measurements. However, the current literature lacks practical guidelines for this purpose. Nowadays, the integration of available metrics, protocols, and algorithms into one harmonized benchmarking ecosystem for clinical and research practice is necessary. METHODS: This work presents a benchmarking framework for upper limb capacity. The scheme resulted from a multidisciplinary and iterative discussion among several partners with previous experience in benchmarking methodology, robotics, and clinical neurorehabilitation. We merged previous knowledge in benchmarking methodologies for human locomotion and direct clinical and engineering experience in upper limb rehabilitation. The scheme was designed to enable an instrumented evaluation of arm capacity and to assess the effectiveness of rehabilitative interventions with high reproducibility and resolution. It includes four elements: (1) a taxonomy for motor skills and abilities, (2) a list of performance indicators, (3) a list of required sensor modalities, and (4) a set of reproducible experimental protocols. RESULTS: We proposed six motor primitives as building blocks of most upper-limb daily-life activities and combined them into a set of functional motor skills. We identified the main aspects to be considered during clinical evaluation, and grouped them into ten motor abilities categories. For each ability, we proposed a set of performance indicators to quantify the proposed ability on a quantitative and high-resolution scale. Finally, we defined the procedures to be followed to perform the benchmarking assessment in a reproducible and reliable way, including the definition of the kinematic models and the target muscles. CONCLUSIONS: This work represents the first unified scheme for the benchmarking of upper limb capacity. To reach a consensus, this scheme should be validated with real experiments across clinical conditions and motor skills. This validation phase is expected to create a shared database of human performance, necessary to have realistic comparisons of treatments and drive the development of new personalized technologies.

Upper limb soft robotic wearable devices: a systematic review.

INTRODUCTION: Soft robotic wearable devices, referred to as exosuits, can be a valid alternative to rigid exoskeletons when it comes to daily upper limb support. Indeed, their inherent flexibility improves comfort, usability, and portability while not constraining the user's natural degrees of freedom. This review is meant to guide the reader in understanding the current approaches across all design and production steps that might be exploited when developing an upper limb robotic exosuit. METHODS: The literature research regarding such devices was conducted in PubMed, Scopus, and Web of Science. The investigated features are the intended scenario, type of actuation, supported degrees of freedom, low-level control, high-level control with a focus on intention detection, technology readiness level, and type of experiments conducted to evaluate the device. RESULTS: A total of 105 articles were collected, describing 69 different devices. Devices were grouped according to their actuation type. More than 80% of devices are meant either for rehabilitation, assistance, or both. The most exploited actuation types are pneumatic (52%) and DC motors with cable transmission (29%). Most devices actuate 1 (56%) or 2 (28%) degrees of freedom, and the most targeted joints are the elbow and the shoulder. Intention detection strategies are implemented in 33% of the suits and include the use of switches and buttons, IMUs, stretch and bending sensors, EMG and EEG measurements. Most devices (75%) score a technology readiness level of 4 or 5. CONCLUSION: Although few devices can be considered ready to reach the market, exosuits show very high potential for the assistance of daily activities. Clinical trials exploiting shared evaluation metrics are needed to assess the effectiveness of upper limb exosuits on target users.

Grasping learning, optimization, and knowledge transfer in the robotics field.

Service robotics is a fast-developing sector, requiring embedded intelligence into robotic platforms to interact with the humans and the surrounding environment. One of the main challenges in the field is robust and versatile manipulation in everyday life activities. An appealing opportunity is to exploit compliant end-effectors to address the manipulation of deformable objects. However, the intrinsic compliance of such grippers results in increased difficulties in grasping control. Within the described context, this work addresses the problem of optimizing the grasping of deformable objects making use of a compliant, under-actuated, sensorless robotic hand. The main aim of the paper is, therefore, finding the best position and joint configuration for the mentioned robotic hand to grasp an unforeseen deformable object based on collected RGB image and partial point cloud. Due to the complex grasping dynamics, learning-from-simulations approaches (e.g., Reinforcement Learning) are not effective in the faced context. Thus, trial-and-error-based methodologies have to be exploited. In order to save resources, a samples-efficient approach has to be employed. Indeed, a Bayesian approach to address the optimization of the grasping strategy is proposed, enhancing it with transfer learning capabilities to exploit the acquired knowledge to grasp (partially) new objects. A PAL Robotics TIAGo (a mobile manipulator with a 7-degrees-of-freedom arm and an anthropomorphic underactuated compliant hand) has been used as a test platform, executing a pouring task while manipulating plastic (i.e., deformable) bottles. The sampling efficiency of the data-driven learning is shown, compared to an evenly spaced grid sampling of the input space. In addition, the generalization capability of the optimized model is tested (exploiting transfer learning) on a set of plastic bottles and other liquid containers, achieving a success rate of the 88%.

Robotic Exoskeleton Gait Training in Stroke: An Electromyography-Based Evaluation.

The recovery of symmetric and efficient walking is one of the key goals of a rehabilitation program in patients with stroke. The use of overground exoskeletons alongside conventional gait training might help foster rhythmic muscle activation in the gait cycle toward a more efficient gait. About twenty-nine patients with subacute stroke have been recruited and underwent either conventional gait training or experimental training, including overground gait training using a wearable powered exoskeleton alongside conventional therapy. Before and after the rehabilitation treatment, we assessed: (i) gait functionality by means of clinical scales combined to obtain a Capacity Score, and (ii) gait neuromuscular lower limbs pattern using superficial EMG signals. Both groups improved their ability to walk in terms of functional gait, as detected by the Capacity Score. However, only the group treated with the robotic exoskeleton regained a controlled rhythmic neuromuscular pattern in the proximal lower limb muscles, as observed by the muscular activation analysis. Coherence analysis suggested that the control group (CG) improvement was mediated mainly by spinal cord control, while experimental group improvements were mediated by cortical-driven control. In subacute stroke patients, we hypothesize that exoskeleton multijoint powered fine control overground gait training, alongside conventional care, may lead to a more fine-tuned and efficient gait pattern.

Review on Patient-Cooperative Control Strategies for Upper-Limb Rehabilitation Exoskeletons.

Technology-supported rehabilitation therapy for neurological patients has gained increasing interest since the last decades. The literature agrees that the goal of robots should be to induce motor plasticity in subjects undergoing rehabilitation treatment by providing the patients with repetitive, intensive, and task-oriented treatment. As a key element, robot controllers should adapt to patients' status and recovery stage. Thus, the design of effective training modalities and their hardware implementation play a crucial role in robot-assisted rehabilitation and strongly influence the treatment outcome. The objective of this paper is to provide a multi-disciplinary vision of patient-cooperative control strategies for upper-limb rehabilitation exoskeletons to help researchers bridge the gap between human motor control aspects, desired rehabilitation training modalities, and their hardware implementations. To this aim, we propose a three-level classification based on 1) "high-level" training modalities, 2) "low-level" control strategies, and 3) "hardware-level" implementation. Then, we provide examples of literature upper-limb exoskeletons to show how the three levels of implementation have been combined to obtain a given high-level behavior, which is specifically designed to promote motor relearning during the rehabilitation treatment. Finally, we emphasize the need for the development of compliant control strategies, based on the collaboration between the exoskeleton and the wearer, we report the key findings to promote the desired physical human-robot interaction for neurorehabilitation, and we provide insights and suggestions for future works.

Resolvin E1 and Cytokines Environment in Skeletally Immature and Adult ACL Tears.

The intra-articular synovial fluid environment in skeletally immature patients following an ACL tear is complex and remains undefined. Levels of inflammatory and anti-inflammatory cytokines change significantly in response to trauma and collectively define the inflammatory environment. Of these factors the resolvins, with their inherent anti-inflammatory, reparative, and analgesic properties, have become prominent. This study examined the levels of resolvins and other cytokines after ACL tears in skeletally immature and adult patients in order to determine if skeletal maturity affects the inflammatory pattern. Skeletally immature and adult patients with an anterior cruciate ligament injury and meniscal tears were prospectively enrolled over a 5-month period. Synovial fluid samples were obtained before surgery quantifying Resolvin E1, IL-1ß, TNF-α, and IL-10 by ELISA. Comparisons between skeletally immature patients and adults, the influence of meniscal tear, growth plate maturity and time from trauma were analyzed. Skeletally immature patients had significantly greater levels of Resolvin E1 and IL-10 compared with adults with an isolated anterior cruciate ligament lesion. Among the injured skeletally immature patients Resolvin E1 levels were greater in the open growth plate group compared with those with closing growth plates. Moreover, levels of Resolvin E1 and IL-10 appeared to decrease with time. Our results suggest that skeletally immature patients have a stronger activation of the Resolvin pattern compared to adult patients and that synovial fluid Resolvins could play an antinflammatory role in the knee after anterior cruciate ligament lesion and that its activity may be synergistic with that of IL-10.

Brain Plasticity Mechanisms Underlying Motor Control Reorganization: Pilot Longitudinal Study on Post-Stroke Subjects.

Functional Electrical Stimulation (FES) has demonstrated to improve walking ability and to induce the carryover effect, long-lasting persisting improvement. Functional magnetic resonance imaging has been used to investigate effective connectivity differences and longitudinal changes in a group of chronic stroke patients that attended a FES-based rehabilitation program for foot-drop correction, distinguishing between carryover effect responders and non-responders, and in comparison with a healthy control group. Bayesian hierarchical procedures were employed, involving nonlinear models at within-subject level-dynamic causal models-and linear models at between-subjects level. Selected regions of interest were primary sensorimotor cortices (M1, S1), supplementary motor area (SMA), and angular gyrus. Our results suggest the following: (i) The ability to correctly plan the movement and integrate proprioception information might be the features to update the motor control loop, towards the carryover effect, as indicated by the reduced sensitivity to proprioception input to S1 of FES non-responders; (ii) FES-related neural plasticity supports the active inference account for motor control, as indicated by the modulation of SMA and M1 connections to S1 area; (iii) SMA has a dual role of higher order motor processing unit responsible for complex movements, and a superintendence role in suppressing standard motor plans as external conditions changes.

Towards a Functional Performance Validation Standard for Industrial Low-Back Exoskeletons: State of the Art Review.

While the research interest for exoskeletons has been rising in the last decades, missing standards for their rigorous evaluation are potentially limiting their adoption in the industrial field. In this context, exoskeletons for worker support have the aim to reduce the physical effort required by humans, with dramatic social and economic impact. Indeed, exoskeletons can reduce the occurrence and the entity of work-related musculoskeletal disorders that often cause absence from work, resulting in an eventual productivity loss. This very urgent and multifaceted issue is starting to be acknowledged by researchers. This article provides a systematic review of the state of the art for functional performance evaluation of low-back exoskeletons for industrial workers. We report the state-of-the-art evaluation criteria and metrics used for such a purpose, highlighting the lack of a standard for this practice. Very few studies carried out a rigorous evaluation of the assistance provided by the device. To address also this topic, the article ends with a proposed framework for the functional validation of low-back exoskeletons for the industry, with the aim to pave the way for the definition of rigorous industrial standards.

User-centred assistive SystEm for arm Functions in neUromuscuLar subjects (USEFUL): a randomized controlled study.

BACKGROUND: Upper limb assistive devices can compensate for muscular weakness and empower the user in the execution of daily activities. Multiple devices have been recently proposed but there is still a lack in the scientific comparison of their efficacy. METHODS: We conducted a cross-over multi-centric randomized controlled trial to assess the functional improvement at the upper limb level of two arms supports on 36 patients with muscular dystrophy. Participants tested a passive device (i.e., Wrex by Jaeco) and a semi-active solution for gravity compensation (i.e., Armon Ayura). We evaluated devices' effectiveness with an externally-assessed scale (i.e., Performance of the Upper Limb-PUL-module), a self-perceived scale (i.e., Abilhand questionnaire), and a usability scale (i.e., System Usability Scale). Friedman's test was used to assess significant functional gain for PUL module and Abilhand questionnaire. Moreover, PUL changes were compared by means of the Friedman's test. RESULTS: Most of the patients improved upper limb function with the use of arm supports (median PUL scores increase of 1-3 points). However, the effectiveness of each device was related to the level of residual ability of the end-user. Slightly impaired patients maintained the same independence without and with assistive devices, even if they reported reduced muscular fatigue for both devices. Moderately impaired patients enhanced their arm functionality with both devices, and they obtained higher improvements with the semi-active one (median PUL scores increase of 9 points). Finally, severely impaired subjects benefited only from the semi-active device (median PUL scores increase of 12 points). Inadequate strength was recognized as a barrier to passive devices. The usability, measured by the System Usability Scale, was evaluated by end-users "good" (70/100 points) for the passive, and "excellent" (80/100 points) for the semi-active device. CONCLUSIONS: This study demonstrated that assistive devices can improve the quality of life of people suffering from muscular dystrophy. The use of passive devices, despite being low cost and easy to use, shows limitations in the efficacy of the assistance to daily tasks, limiting the assistance to a predefined horizontal plane. The addition of one active degree of freedom improves efficacy and usability especially for medium to severe patients. Further investigations are needed to increase the evidence on the effect of arm supports on quality of life and diseases' progression in subjects with degenerative disorders. Trial registration clinicaltrials.gov, NCT03127241, Registered 25th April 2017. The clinical trial was also registered as a post-market study at the Italian Ministry of Health.

Development and Electromyographic Validation of a Compliant Human-Robot Interaction Controller for Cooperative and Personalized Neurorehabilitation.

BACKGROUND: Appropriate training modalities for post-stroke upper-limb rehabilitation are key features for effective recovery after the acute event. This study presents a cooperative control framework that promotes compliant motion and implements a variety of high-level rehabilitation modalities with a unified low-level explicit impedance control law. The core idea is that we can change the haptic behavior perceived by a human when interacting with the rehabilitation robot by tuning three impedance control parameters. METHODS: The presented control law is based on an impedance controller with direct torque measurement, provided with positive-feedback compensation terms for disturbances rejection and gravity compensation. We developed an elbow flexion-extension experimental setup as a platform to validate the performance of the proposed controller to promote the desired high-level behavior. The controller was first characterized through experimental trials regarding joint transparency, torque, and impedance tracking accuracy. Then, to validate if the controller could effectively render different physical human-robot interaction according to the selected rehabilitation modalities, we conducted tests on 14 healthy volunteers and measured their muscular voluntary effort through surface electromyography (sEMG). The experiments consisted of one degree-of-freedom elbow flexion/extension movements, executed under six high-level modalities, characterized by different levels of (i) corrective assistance, (ii) weight counterbalance assistance, and (iii) resistance. RESULTS: The unified controller demonstrated suitability to promote good transparency and render both compliant and stiff behavior at the joint. We demonstrated through electromyographic monitoring that a proper combination of stiffness, damping, and weight assistance could induce different user participation levels, render different physical human-robot interaction, and potentially promote different rehabilitation training modalities. CONCLUSION: We proved that the proposed control framework could render a wide variety of physical human-robot interaction, helping the user to accomplish the task while exploiting physiological muscular activation patterns. The reported results confirmed that the control scheme could induce different levels of the subject's participation, potentially applicable to the clinical practice to adapt the rehabilitation treatment to the subject's progress. Further investigation is needed to validate the presented approach to neurological patients.

Characterization of Synovial Cytokine Patterns in Bucket-Handle and Posterior Horn Meniscal Tears.

The specific etiology of meniscal tears, including the mechanism of lesion, location, and orientation, is considered for its contribution to subsequent joint cytokine responsiveness, healing outcomes, and by extension, appropriate lesion-specific surgical remediation. Meniscal repair is desirable to reduce the probability of development of posttraumatic osteoarthritis (PTOA) which is strongly influenced by the coordinate generation of pro- and anti-inflammatory cytokines by the injured cartilage. We now present biochemical data on variation in cytokine levels arising from two particular meniscal tears: bucket-handle (BH) and posterior horn (PH) isolated meniscal tears. We selected these two groups due to the different clinical presentations. We measured the concentrations of TNF-α, IL-1ß, IL-6, IL-8, and IL-10 in knee synovial fluid of 45 patients with isolated meniscal lesions (BH tear, n = 12; PH tear, n = 33). TNF-α levels were significantly (p < 0.05) greater in the BH group compared with the PH group, whereas IL-1ß levels were significantly greater (p < 0.05) in the PH group compared with the BH group. Both BH and PH groups were consistent in presenting a positive correlation between concentrations of IL-6 and IL-1ß. A fundamental difference in IL-10 responsiveness between the two groups was noted; specifically, levels of IL-10 were positively correlated with IL-6 in the BH group, whereas in the PH group, levels of IL-10 were positively correlated with IL-1ß. Collectively, our data suggest a possible influence of the meniscal tear pattern to the articular cytokine responsiveness. This differential expression of inflammatory cytokines may influence the risk of developing PTOA in the long term.

Test-retest reliability of the Performance of Upper Limb (PUL) module for muscular dystrophy patients.

The Performance of the Upper Limb (PUL) module is an externally-assessed clinical scale, initially designed for the Duchenne muscular dystrophy population. It provides an upper extremity functional score suitable for both weaker ambulatory and non-ambulatory phases up to the severely impaired patients. It is capable of characterizing overall progression and severity of disease and of tracking the stereotypical proximal-to-distal progressive loss of upper limb function in muscular dystrophy. Since the PUL module has been validated only with Duchenne patients, its use also for Becker and Limb-Girdle muscular dystrophy patients has been here evaluated, to verify its reliability and extend its use. In particular, two different assessors performed this scale on 32 dystrophic subjects in two consecutive days. The results showed that the PUL module has high reliability, both absolute and relative, based on the calculation of Pearson's r (0.9942), Intraclass Correlation Coefficient (0.9943), Standard Error of Measurement (1.36), Minimum Detectable Change (3.77), and Coefficient of Variation (3%). The Minimum Detectable Change, in particular, can be used in clinical trials to perform a comprehensive longitudinal evaluation of the effects of interventions with the lapse of time. According to this analysis, an intervention is effective if the difference in the PUL score between subsequent evaluation points is equal or higher than 4 points; otherwise, the observed effect is not relevant. Inter-rater reliability with ten different assessors was evaluated, and it has been demonstrated that deviation from the mean is lower than calculated Minimum Detectable Change. The present work provides evidence that the PUL module is a reliable and valid instrument for measuring upper limb ability in people with different forms of muscular dystrophy. Therefore, the PUL module might be extended to other pathologies and reliably used in multicenter settings.

The Effectiveness of Wearable Upper Limb Assistive Devices in Degenerative Neuromuscular Diseases: A Systematic Review and Meta-Analysis.

Background: This systematic review summarizes the current evidence about the effectiveness of wearable assistive technologies for upper limbs support during activities of daily living for individuals with neuromuscular diseases. Methods: Fourteen studies have been included in the meta-analysis, involving 184 participants. All included studies compared patients ability to perform functional tasks with and without assistive devices. Results: An overall effect size of 1.06 (95% CI = 0.76-1.36, p < 0.00001) was obtained, demonstrating that upper limbs assistive devices significantly improve the performance in activities of daily living in people with neuromuscular diseases. A significant interaction between studies evaluating functional improvement with externally-assessed outcome measures or self-perceived outcome measures has been detected. In particular, the effect size of the sub-group considering self-perceived scales was 1.38 (95% CI = 1.08-1.68), while the effect size of the other group was 0.77 (95% CI = 0.41-1.11), meaning that patients' perceived functional gain is often higher than the functional gain detectable through clinical scales. Conclusion: Overall, the quality of the evidence ranged from low to moderate, due to low number of studies and participants, limitations in the selection of participants and in the blindness of outcome assessors, and risk of publication bias. Significance: A large magnitude effect and a clear dose-response gradient were found, therefore, a strong recommendation, in favor of the use of assistive devices could be suggested.

Intra-Articular Cytokine Levels in Adolescent Patients after Anterior Cruciate Ligament Tear.

The treatment of anterior cruciate ligament (ACL) injuries in children and adolescents is challenging. Preclinical and clinical studies investigated ACL repairing techniques in skeletally immature subjects. However, intra-articular bioenvironment following ACL tear has not yet been defined in skeletally immature patients. The aim of this study was to measure cytokine concentrations in the synovial fluid in adolescent population. Synovial levels of IL-1ß, IL-1ra, IL-6, IL-8, IL-10, and TNF-α were measured in 17 adolescent patients (15 boys) with ACL tears who underwent ACL reconstruction including acute (5), subacute (7), and chronic (5) phases. Femoral growth plates were classified as "open" in three patients, "closing" in eight, and "closed" in six. Eleven patients presented an ACL tear associated with a meniscal tear. The mean Tegner and Lysholm scores (mean ± SD) of all patients were 8 ± 1 and 50.76 ± 26, respectively. IL-8, TNF-α, and IL-1ß levels were significantly greater in patients with "open" physes. IL-1ra and IL-1ß levels were significantly higher in patients with ACL tear associated with a meniscal tear. Poor Lysholm scores were associated with elevated IL-6 and IL-10 levels. IL-10 levels positively correlated with IL-6 and IL-8 levels, whereas TNF-α concentration negatively correlated with IL-6 levels. Skeletally immature patients with meniscal tears and open growth plates have a characteristic cytokine profile with particularly elevated levels of proinflammatory cytokines including IL-8, TNF-α, and IL-1ß. This picture suggests that the ACL tear could promote an intra-articular catabolic response in adolescent patients greater than that generally reported for adult subjects. The study lacks the comparison with synovial samples from healthy skeletally immature knees due to ethical reasons. Overall, these data contribute to a better knowledge of adolescent intra-articular bioenvironment following ACL injuries.