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Surgical techniques in amputation medicine did not change for a long time, while prosthesis technology underwent rapid development. The focus shifted to optimising the residual limb for prostheses use. At the same time, digital technologies such as gamification, virtual and mixed reality revolutionised rehabilitation. The use of gamification elements increases motivation and adherence to therapy, while immersive technologies enable realistic and interactive therapy experiences. This is particularly useful in the context of controlling modern prostheses and treating phantom pain. In addition, digital applications contribute to optimised documentation of symptoms and therapy successes. Overall, these technologies open up new, effective and personalised therapeutic approaches that can significantly improve the quality of life of amputation patients., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Restoring hand and finger function after a traumatic hand injury necessitates a regimen of consistent and conscientious exercise. However, motivation frequently wanes due to unchallenging repetitive tasks or discomfort, causing exercises to be performed carelessly or avoided completely. Introducing gamification to these repetitive tasks can make them more appealing to patients, ultimately increasing their motivation to exercise consistently., Objective: This study aims to iteratively develop a serious virtual reality game for hand and finger rehabilitation within an appealing and engaging digital environment, encouraging patient motivation for at least 2 weeks of continuous therapy., Methods: The development process comprised 3 distinct stages, each of which was subject to evaluation. Initially, a prototype was created to encompass the game's core functionalities, which was assessed by 18 healthy participants and 7 patients with impaired hand function. Subsequently, version 1 of the game was developed and evaluated with 20 patients who were divided into an investigation group and a control group. On the basis of these findings, version 2 was developed and evaluated with 20 patients who were divided into an investigation group and a control group. Motivation was assessed using the Intrinsic Motivation Inventory (IMI), while the application's quality was rated using the Mobile Application Rating Scale and the System Usability Scale. User feedback was gathered using semistructured interviews., Results: The prototype evaluation confirmed the acceptance and feasibility of the game design. Version 1 significantly increased motivation in 2 IMI subscales, effort (P<.001) and usefulness (P=.02). In version 2, a significant increase in daily performed exercises was achieved (P=.008) compared to version 1, with significantly higher motivation in the IMI subscale effort (P=.02). High Mobile Application Rating Scale scores were obtained for both versions 1 and 2, with version 2 scoring 86.9 on the System Usability Scale, indicating excellent acceptability. User feedback provided by the semistructured interviews was instrumental in the iterative development regarding improvements and the expansion of the playable content., Conclusions: This study presented a virtual reality serious game designed for hand and finger rehabilitation. The game was well received and provided an environment that effectively motivated the users. The iterative development process incorporated user feedback, confirming the game's ease of use and feasibility even for patients with severely limited hand function., (©Michael Bressler, Joachim Merk, Tanja Gohlke, Fares Kayali, Adrien Daigeler, Jonas Kolbenschlag, Cosima Prahm. Originally published in JMIR Serious Games (https://games.jmir.org), 27.08.2024.)

We present Virtual Reality Self Co-embodiment, a new method for post-stroke upper limb rehabilitation. It is inspired by mirror therapy, where the patient's healthy arm is involved in recovering the affected arm's motion. By tracking the user's head, wrists, and fingers' positions, our new approach allows the handicapped arm to control a digital avatar in order to pursue a reaching task. We apply the concept of virtual co-embodiment to use the information from the unaffected arm and complete the affected limb's impaired motion, which is our added unique feature. This requires users to mechanically involve the incapacitated area as much as possible, prioritizing actual movement rather than the sole imagination of it. As a result, subjects will see a seemingly normally functional virtual arm primarily controlled by their handicapped extremity, but with the constant support of their healthy limb's motion. Our experiment compares the task execution performance and embodiment perceived when interacting with both mirror therapy and our proposed technique. We found that our approach's provided sense of ownership is mildly impacted by users' motion planning response times, which mirror therapy does not exhibit. We also observed that mirror therapy's sense of ownership is moderately affected by the subject's proficiency while executing the assigned task, which our new method did not display. The results indicate that our proposed method provides similar embodiment and rehabilitation capabilities to those perceived from existing mirror therapy. This experiment was performed in healthy individuals to have an unbiased comparison of how mirror therapy's and VRSelfCo's task performance and degree of virtual embodiment compare, but future work explores the possibility of applying this new approach to actual post-stroke patients.

Background: The functional deficits that develop after a peripheral nerve injury mean a considerable reduction in the quality of life for the affected patients. However, interventions on the injured nerve are not always possible or effective. In this case, secondary procedures, e.g. tendon transfers, are a feasible option for functional reconstruction., Objectives: An overview of the most common secondary surgical procedures for functional reconstruction after peripheral nerve injuries., Methods: Presentation and discussion of the most common secondary surgical procedures with emphasis on tendon transfers. Illustration of the primary functions that need to be reconstructed depending on the respective nerve lesion., Results: The basic principle of secondary surgical procedures after nerve injuries is the transposition of a healthy tendomuscular unit to replace a lost function following a loss of muscle or tendon or if an intervention on the nerve is not promising. For example, by transferring flexor forearm muscles, wrist, finger and thumb extension can be reconstructed after radial nerve injury. By transposing the tibialis posterior muscle, dorsiflexion in the talocrural joint can be restored to enable the affected patient to walk safely without an orthosis., Conclusions: Secondary surgical procedures are a valuable option for functional reconstruction after nerve injury., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Arthritic disorders have become one of the main contributors to the global burden of disease. Today, they are one of the leading causes of chronic pain and disability worldwide. Current therapies are incapable of treating pain sufficiently and preventing disease progression. The lack of understanding basic mechanisms underlying the initiation, maintenance and progression of arthritic disorders and related symptoms represent the major obstacle in the search for adequate treatments. For a long time, histological evaluation of joint pathology was the predominant outcome parameter in preclinical arthritis models. Nevertheless, quantification of pain and functional limitations analogs to arthritis related symptoms in humans is essential to enable bench to bedside translation and to evaluate the effectiveness of new treatment strategies. As the experience of pain and functional deficits are often associated with altered gait behavior, in the last decades, automated gait analysis has become a well-established tool for the quantitative evaluation of the sequalae of arthritic disorders in animal models. The purpose of this review is to provide a detailed overview on the current literature on the use of the CatWalk gait analysis system in rodent models of arthritic disorders, e.g., Osteoarthritis, Monoarthritis and Rheumatoid Arthritis. Special focus is put on the assessment and monitoring of pain-related behavior during the course of the disease. The capability of evaluating the effect of distinct treatment strategies and the future potential for the application of the CatWalk in rodent models of arthritic disorders is also addressed in this review. Finally, we discuss important consideration and provide recommendations on the use of the CatWalk in preclinical models of arthritic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ritter, Menger, Herath, Histing, Kolbenschlag, Daigeler, Heinzel and Prahm.)

Background: Facial aesthetics are of great importance in social interaction. With the widespread adoption of face masks in response to the Covid-19 pandemic, there is growing interest in understanding how wearing masks might impact perceptions of attractiveness, as they partially or completely conceal facial features that are typically associated with attractiveness., Objectives: This study aimed to explore the impact of mask wearing on attractiveness and to investigate whether the color (red or blue) of the mask has any effect on the perception of a person's attractiveness, while also considering gender and age as contributing factors. Additionally, the study intended to evaluate gaze patterns, initial focus, and dwell time in response to masked and unmasked faces., Methods: 30 AI-generated images of 15 female and 15 male faces were presented to 71 participants (35 male, 36 female) in 3 conditions: not wearing any mask, wearing a red surgical mask, and wearing a blue surgical mask. The perceived attractiveness was rated on an ordinal scale of 1-10 (10 being most attractive). Gaze behavior, dwell time and initial focus were recorded using a stationary eye-tracking system., Results: The study found that wearing masks had no significant effect on the attractiveness ratings of female faces (p = .084), but it did benefit the perceived attractiveness of male faces which were initially rated lower (p = .16). Gender and age also played a significant role, as both male and female participants rated female stimuli higher than male stimuli (p < .001), and younger participants rated both genders as less attractive than older participants (p < .01). However, there was no significant influence of the mask's color on attractiveness. During the eye-tracking analysis, the periorbital region was of greater interest while masked, with the time to first fixation for the eyes being lower than the non-masked stimulus (p < .001) and showed a longer dwell time (p < .001). The lower face was shown less interest while masked as the time to first fixation was higher (p < .001) and the fixation count was less (p < .001). Mask color did not influence the scan path and there was no difference in revisits to the mask area between red or blue masks (p = .202), nor was there a difference in time to first fixation (p = .660)., Conclusions: The study findings indicate that there is an interplay between the gender and age of the participant and the facial stimuli. The color red did have an effect on the perception attractiveness, however not in female faces. The results suggest that masks, especially red ones, might be more beneficial for male faces, which were perceived as less attractive without a mask. However, wearing a mask did not significantly impact already attractive faces. The eye-tracking results revealed that the periorbital region attracted more attention and was fixated on more quickly while wearing a mask, indicating the importance of eyes in social interaction and aesthetic perception., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Sleep deprivation is known to have serious consequences, including a decrease in performance, attention and neurocognitive function. It seems common knowledge that medical residents are routinely sleep deprived, yet there is little objective research recording their average sleep times. To discern whether residents may be suffering from the abovementioned side effects, this review aimed to analyze their average sleep times. Thirty papers recording the average sleep time of medical residents were found via a literature search using the key words "resident" and "sleep". An analysis of the mean sleep times cited therein revealed a range of sleep from 4.2 to 8.6 h per night, the median being 6.2 h. A sub-analysis of papers from the USA showed barely any significant differences in sleep time between the specialties, but the mean sleep times were below 7 h. The only significant difference ( p = 0.039) was between the mean sleep times of pediatric and urology residents, with the former achieving less sleep. The comparison of methods for data collection showed no significant difference in the sleep times collected. The results of this analysis imply that residents are regularly sleep deprived and may therefore suffer from the abovementioned consequences.

Cigarette smoking (CS) leads to several adverse health effects, including diseases, disabilities, and even death. Post-operative and trauma patients who smoke have an increased risk for complications, such as delayed bone or wound healing. In clinical trials, microcurrent (MC) has been shown to be a safe, non-invasive, and effective way to accelerate wound healing. Our study aimed to investigate if MC with the strength of 100 μA may be beneficial in treating CS-related healing impairment, especially in regard to angiogenesis. In this study, we investigated the effect of human keratinocyte cells (HaCaT) on angiogenesis after 72 h of cigarette smoke extract (CSE) exposure in the presence or absence of 100 μA MC. Cell viability and proliferation were evaluated by resazurin conversion, Sulforhodamine B, and Calcein-AM/Hoechst 33342 staining; the pro-angiogenic potential of HaCaT cells was evaluated by tube formation assay and angiogenesis array assay; signaling pathway alterations were investigated using Western blot. Constant exposure for 72 h to a 100 μA MC enhanced the angiogenic ability of HaCaT cells, which was mediated through the PI3K-Akt signaling pathway. In conclusion, the current data indicate that 100 μA MC may support wound healing in smoking patients by enhancing angiogenesis.

The rat median nerve model is a well-established and frequently used model for peripheral nerve injury and repair. The grasping test is the gold-standard to evaluate functional recovery in this model. However, no comprehensive review exists to summarize the course of functional recovery in regard to the lesion type. According to PRISMA-guidelines, research was performed, including the databases PubMed and Web of Science. Groups were: (1) crush injury, (2) transection with end-to-end or with (3) end-to-side coaptation and (4) isogenic or acellular allogenic grafting. Total and respective number, as well as rat strain, type of nerve defect, length of isogenic or acellular allogenic allografts, time at first signs of motor recovery (FSR) and maximal recovery grasping strength (MRGS), were evaluated. In total, 47 articles met the inclusion criteria. Group I showed earliest signs of motor recovery. Slow recovery was observable in group III and in graft length above 25 mm. Isografts recovered faster compared to other grafts. The onset and course of recovery is heavily dependent from the type of nerve injury. The grasping test should be used complementary in addition to other volitional and non-volitional tests. Repetitive examinations should be planned carefully to optimize assessment of valid and reliable data., Competing Interests: The authors declare no conflict of interest.

Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response is normally the focus of radiation therapy, little is known about the tumor microenvironment response after irradiation. It is widely reported that increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. Aside from the classical fibrotic response, ratios of collagen isoforms have not been studied in a radiated tumor microenvironment. Here, we created one healthy co-culture of stromal fibroblasts and adipose-derived stem cells, and one triple-negative breast cancer co-culture, made of stromal fibroblasts, adipose derived stem cells, and triple-negative breast cancer cells. After irradiation, growth and decellularization of co-cultures, we reseeded the breast cancer cells for 24 h and analyzed the samples using mass spectrometry. Proteomic analysis revealed that collagen VI, a highly oncogenic collagen isoform linked to breast cancer, was decreased in the irradiated cancer co-culture. This indicates that the anti-cancer impact of radiation may be not only cell ablative, but also influential in creating a less oncogenic microenvironment.

Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7 mm segment of the right median nerve was reconstructed either with an ANG or an MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. The animals were observed for 12 weeks, and nerve regeneration was assessed using computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here, we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair.

Background: Currently used prosthetic solutions in upper extremity amputation have limited functionality, owing to low information transfer rates of neuromuscular interfacing. Although surgical innovations have expanded the functional potential of the residual limb, available interfaces are inefficacious in translating this potential into improved prosthetic control. There is currently no implantable solution for functional interfacing in extremity amputation which offers long-term stability, high information transfer rates, and is applicable for all levels of limb loss. In this study, we presented a novel neuromuscular implant, the the Myoelectric Implantable Recording Array (MIRA). To our knowledge, it is the first fully implantable system for prosthetic interfacing with a large channel count, comprising 32 intramuscular electrodes., Questions/purposes: The purpose of this study was to evaluate the MIRA in terms of biocompatibility, functionality, and feasibility of implantation to lay the foundations for clinical application. This was achieved through small- and large-animal studies as well as test surgeries in a human cadaver., Methods: We evaluated the biocompatibility of the system's intramuscular electromyography (EMG) leads in a rabbit model. Ten leads as well as 10 pieces of a biologically inert control material were implanted into the paravertebral muscles of four animals. After a 3-month implantation, tissue samples were taken and histopathological assessment performed. The probes were scored according to a protocol for the assessment of the foreign body response, with primary endpoints being inflammation score, tissue response score, and capsule thickness in µm. In a second study, chronic functionality of the full system was evaluated in large animals. The MIRA was implanted into the shoulder region of six dogs and three sheep, with intramuscular leads distributed across agonist and antagonist muscles of shoulder flexion. During the observation period, regular EMG measurements were performed. The implants were removed after 5 to 6 months except for one animal, which retained the implant for prolonged observation. Primary endpoints of the large-animal study were mechanical stability, telemetric capability, and EMG signal quality. A final study involved the development of test surgeries in a fresh human cadaver, with the goal to determine feasibility to implant relevant target muscles for prosthetic control at all levels of major upper limb amputation., Results: Evaluation of the foreign body reaction revealed favorable biocompatibility and a low-grade tissue response in the rabbit study. No differences regarding inflammation score (EMG 4.60 ± 0.97 [95% CI 4.00 to 5.20] versus control 4.20 ± 1.48 [95% CI 3.29 to 5.11]; p = 0.51), tissue response score (EMG 4.00 ± 0.82 [95% CI 3.49 to 4.51] versus control 4.00 ± 0.94 [95% CI 3.42 to 4.58]; p > 0.99), or thickness of capsule (EMG 19.00 ± 8.76 µm [95% CI 13.57 to 24.43] versus control 29.00 ± 23.31 µm [95% CI 14.55 to 43.45]; p = 0.29) were found compared with the inert control article (high-density polyethylene) after 3 months of intramuscular implantation. Throughout long-term implantation of the MIRA in large animals, telemetric communication remained unrestricted in all specimens. Further, the implants retained the ability to record and transmit intramuscular EMG data in all animals except for two sheep where the implants became dislocated shortly after implantation. Electrode impedances remained stable and below 5 kΩ. Regarding EMG signal quality, there was little crosstalk between muscles and overall average signal-to-noise ratio was 22.2 ± 6.2 dB. During the test surgeries, we found that it was possible to implant the MIRA at all major amputation levels of the upper limb in a human cadaver (the transradial, transhumeral, and glenohumeral levels). For each level, it was possible to place the central unit in a biomechanically stable environment to provide unhindered telemetry, while reaching the relevant target muscles for prosthetic control. At only the glenohumeral level, it was not possible to reach the teres major and latissimus dorsi muscles, which would require longer lead lengths., Conclusion: As assessed in a combination of animal model and cadaver research, the MIRA shows promise for clinical research in patients with limb amputation, where it may be employed for all levels of major upper limb amputation to provide long-term stable intramuscular EMG transmission., Clinical Relevance: In our study, the MIRA provided high-bandwidth prosthetic interfacing through intramuscular electrode sites. Its high number of individual EMG channels may be combined with signal decoding algorithms for accessing spinal motor neuron activity after targeted muscle reinnervation, thus providing numerous degrees of freedom. Together with recent innovations in amputation surgery, the MIRA might enable improved control approaches for upper limb amputees, particularly for patients with above-elbow amputation where the mismatch between available control signals and necessary degrees of freedom for prosthetic control is highest., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons.)

Currently, there is neither a standardized mode for the documentation of phantom sensations and phantom limb pain, nor for their visualization as perceived by patients. We have therefore created a tool that allows for both, as well as for the quantification of the patient's visible and invisible body image. A first version provides the principal functions: (1) Adapting a 3D avatar for self-identification of the patient; (2) modeling the shape of the phantom limb; (3) adjusting the position of the phantom limb; (4) drawing pain and cramps directly onto the avatar; and (5) quantifying their respective intensities. Our tool (C.A.L.A.) was evaluated with 33 occupational therapists, physiotherapists, and other medical staff. Participants were presented with two cases in which the appearance and the position of the phantom had to be modeled and pain and cramps had to be drawn. The usability of the software was evaluated using the System Usability Scale and its functional range was evaluated using a self-developed questionnaire and semi-structured interview. In addition, our tool was evaluated on 22 patients with limb amputations. For each patient, body image as well as phantom sensation and pain were modeled to evaluate the software's functional scope. The accuracy of the created body image was evaluated using a self-developed questionnaire and semi-structured interview. Additionally, pain sensation was assessed using the SF-McGill Pain Questionnaire. The System Usability Scale reached a level of 81%, indicating high usability. Observing the participants, though, identified several operational difficulties. While the provided functions were considered useful by most participants, the semi-structured interviews revealed the need for an improved pain documentation component. In conclusion, our tool allows for an accurate visualization of phantom limbs and phantom limb sensations. It can be used as both a descriptive and quantitative documentation tool for analyzing and monitoring phantom limbs. Thus, it can help to bridge the gap between the therapist's conception and the patient's perception. Based on the collected requirements, an improved version with extended functionality will be developed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bressler, Merk, Heinzel, Butz, Daigeler, Kolbenschlag and Prahm.)

Study Design: This is a Delphi study based on a scoping literature review., Introduction: Targeted muscle reinnervation (TMR) enables patients with high upper limb amputations to intuitively control a prosthetic arm with up to six independent control signals. Although there is a broad agreement regarding the importance of structured motor learning and prosthetic training after such nerve transfers, to date, no evidence-based protocol for rehabilitation after TMR exists., Purpose of the Study: We aimed at developing a structured rehabilitation protocol after TMR surgery after major upper limb amputation. The purpose of the protocol is to guide clinicians through the full rehabilitation process, from presurgical patient education to functional prosthetic training., Methods: European clinicians and researchers working in upper limb prosthetic rehabilitation were invited to contribute to a web-based Delphi study. Within the first round, clinical experts were presented a summary of recent literature and were asked to describe the rehabilitation steps based on their own experience and scientific evidence. The second round was used to refine these steps, while the importance of each step was rated within the third round., Results: Experts agreed on a rehabilitation protocol that consists of 16 steps and starts before surgery. It is based on two overarching principles, namely the necessity of multiprofessional teamwork and a careful selection and education of patients within the rehabilitation team. Among the different steps in therapy, experts rated the training with electromyographic biofeedback as the most important one., Discussion: Within this study, a first rehabilitation protocol for TMR patients based on a broad experts' consensus and relevant literature could be developed. The detailed steps for rehabilitation start well before surgery and prosthetic fitting, and include relatively novel interventions as motor imagery and biofeedback. Future studies need to further investigate the clinical outcomes and thereby improve therapists' practice., Conclusion: Graded rehabilitation offered by a multiprofessional team is needed to enable individuals with upper limb amputations and TMR to fully benefit from prosthetic reconstruction., Level of Evidence: Low., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Peripheral nerve injuries are a common clinical problem. They not only affect the physical capabilities of the injured person due to loss of motor or sensory function but also have a significant impact on psychosocial aspects of life. The aim of this work is to review the interplay of psychosocial factors and peripheral nerve lesions. By reviewing the published literature, we identified several factors to be heavily influenced by peripheral nerve lesions. In addition to psychological factors like pain, depression, catastrophizing and stress, social factors like employment status and worker's compensation status could be identified to be influenced by peripheral nerve lesions as well as serving as predictors of functional outcome themselves, respectively. This work sheds a light not only on the impact of peripheral nerve lesions on psychosocial aspects of life, but also on the prognostic values of these factors of functional outcome. Interdisciplinary, individualized treatment of patients is required to identify patient at risk for adverse outcomes and provide them with emotional support when adapting to their new life situation.

There is growing evidence that cell behaviors can be influenced by the direct current electric fields (EFs). Some behaviors may influence wound healing directly. This study aimed to investigate the effects of EF (200 mV/mm) on immortalized nontumorigenic human epidermal (HaCaT) cells. We established a setup that can transmit an EF and maintain a stable cell culture environment. An EF was applied to HaCaT cells, and scratch-assays were performed as a model of wound healing to observe cell migration. Proliferation was evaluated by mitochondrial activity, total protein, and DNA content. Secretion of healing-associated cytokines was evaluated via cytokine arrays, and Western blot was applied to investigate signaling pathway alterations. Compared with the control group, the migration of cells exposed to EFs significantly increased ( p < 0.01). After 7 days, the changes in proliferation also increased significantly ( p < 0.05). The cytokine arrays revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was the most abundant factor secreted by HaCaT following EF exposure. The signals for phospho-Erk1/2 showed a significant ( p < 0.0001) increase following EF exposure. The results demonstrate that exposure of HaCaT cells to EFs has positive effects on migration, proliferation, and cytokine secretion-three important steps in wound healing-and these effects may be partially mediated by activation of the Erk1/2 signaling pathway.

Brachial plexus injury is often debilitating because it can severely impair upper extremity function and, thus, quality of life. The surgical treatment of injuries to the brachial plexus is very demanding because it requires a profound understanding of the anatomy and expertise in microsurgery. The aim of this study was to get an overview of the landscape in adult brachial plexus injury surgery, and to understand how this has changed over the years., Methods: The most frequently cited articles in English relevant to adult brachial plexus injury were identified through the Web of Science online database., Results: The average number of citations per article was 32.8 (median 24, range 4-158). Authors from 26 countries contributed to our list, and the US was the biggest contributor. Almost half of all nerve transfer cases were described by Asian authors. Amongst nerve transfer, the spinal accessory nerve was the preferred donor overall, except in Asia, where intercostal nerves were preferred. Distal nerve transfers were described more often than plexo-plexal and extra-plexal-to-plexal transfers. The most common grafts were sural nerve grafts and vascularized ulnar nerve grafts, which became popular in the last decade., Conclusions: Our study sheds light on the regional variations in treatment trends of adult brachial plexus injury, and on the evolution of the field over the last 30 years. The articles included in our analysis are an excellent foundation for those interested in the surgical management of brachial plexus injuries., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Four patients underwent targeted sensory reinnervation (TSR), a surgical technique in which a defined skin area is first selectively denervated and then surgically reinnervated by another sensory nerve. In our case, either the area of the lateral femoral cutaneous nerve or the saphenous nerve was reinnervated by the sural nerve. Patients were then fitted with a special prosthetic device capable of transferring the sense of pressure from the sole of the prosthesis to the newly wired skin area. Pain reduction after TSR was highly significant in all patients. In three patients, permanent pain medication could even be discontinued, in one patient the pain medication has been significantly reduced. Two of the four patients were completely pain-free after the surgical intervention. Surgical rewiring of existing sensory nerves by TSR can provide the brain with new afferent signals seeming to originate from the missing limb. These signals help to reduce phantom limb pain and to restore a more normal body image. In combination with special prosthetic devices, the amputee can be provided with sensory feedback from the prosthesis, thus improving gait and balance.

The gold-standard method for reconstruction of segmental nerve defects, the autologous nerve graft, has several drawbacks in terms of tissue availability and donor site morbidity. Therefore, feasible alternatives to autologous nerve grafts are sought. Muscle-in-vein conduits have been proposed as an alternative to autologous nerve grafts almost three decades ago, given the abundance of both tissues throughout the body. Based on the anti-inflammatory effects of veins and the proregenerative environment established by muscle tissue, this approach has been studied in various preclinical and some clinical trials. There is still no comprehensive systematic summary to conclude efficacy and feasibility of muscle-in-vein conduits for reconstruction of segmental nerve defects. Given this lack of a conclusive summary, we performed a meta-analysis to evaluate the potential of muscle-in-vein conduits. This work's main findings are profound discrepancies regarding the results following nerve repair by means of muscle-in-vein conduits in a preclinical or clinical setting. We identified differences in study methodology, inter-species neurobiology and the limited number of clinical studies to be the main reasons for the still inconclusive results. In conclusion, we advise for large animal studies to elucidate the feasibility of muscle-in-vein conduits for repair of segmental defects of critical size in mixed nerves.

Computerized gait analysis is a common evaluation method in rat models of hind limb nerve injuries, but its use remains unpublished in models of segmental nerve injury of the forelimb. It was the aim of this work to investigate if computerized gait analysis is a feasible evaluation method in a rat model of segmental median nerve injury and autograft repair. Ten male Lewis rats underwent 7-mm resection of the right median nerve with immediate autograft repair. The left median nerve was resected without repair and served as an internal control. Animals were assessed for 12 weeks after surgery via CatWalk (CW) gait analysis every 2 weeks. Evaluation of motor recovery by means of the grasping test was performed weekly while electrophysiological measurements were performed at the end of the observation period. CW data were correlated with grasping strength at each post-operative time point. CW data were also correlated with electrophysiology using linear regression analysis. Principal component analysis was performed to identify clusters of outcome metrics. Recovery of motor function was observable 4 weeks after surgery, but grasping strength was significantly reduced ( p < 0.01) compared to baseline values until post-operative week 6. In terms of sensory recovery, the pain-related parameter Duty Cycle showed significant ( p < 0.05) recovery starting from post-operative week 8. The Print Area of the right paw was significantly ( p < 0.05) increased compared to the left side starting from post-operative week 10. Various parameters of gait correlated significantly ( p < 0.05) with mean and maximum grasping strength. However, only Stand Index showed a significant correlation with compound muscle action potential (CMAP) amplitude ( p < 0.05). With this work, we prove that computerized gait analysis is a valid and feasible method to evaluate functional recovery after autograft repair of the rat median nerve. We were able to identify parameters such as Print Area, Duty Cycle, and Stand Index, which allow assessment of nerve regeneration. The course of these parameters following nerve resection without repair was also assessed. Additionally, external paw rotation was identified as a valid parameter to evaluate motor reinnervation. In summary, computerized gait analysis is a valuable additional tool to study nerve regeneration in rats with median nerve injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Heinzel, Oberhauser, Keibl, Swiadek, Längle, Frick, Kolbenschlag, Prahm, Grillari and Hercher.)

Background: The human hand is the part of the body most frequently injured in work related accidents, accounting for a third of all accidents at work and often involving surgery and long periods of rehabilitation. Several applications of Augmented Reality (AR) and Virtual Reality (VR) have been used to improve the rehabilitation process. However, there is no sound evidence about the effectiveness of such applications nor the main drivers of therapeutic success., Objectives: The objective of this study was to review the efficacy of AR and VR interventions for hand rehabilitation., Methods: A systematic search of publications was conducted in October 2019 in IEEE Xplore, Web of Science, Cochrane library, and PubMed databases. Search terms were: (1) video game or videogame, (2) hand, (3) rehabilitation or therapy and (4) VR or AR. Articles were included if (1) were written in English, (2) were about VR or AR applications, (3) were for hand rehabilitation, (4) the intervention had tests on at least ten patients with injuries or diseases which affected hand function and (5) the intervention had baseline or intergroup comparisons (AR or VR intervention group versus conventional physical therapy group). PRISMA protocol guidelines were followed to filter and assess the articles., Results: From the eight selected works, six showed improvements in the intervention group, and two no statistical differences between groups. We were able to identify motivators of patients' adherence, namely real-time feedback to the patients, challenge, and increased individualized difficulty. Automated tracking, easy integration in the home setting and the recording of accurate metrics may increase the scalability and facilitate healthcare professionals' assessments., Conclusions: This systematic review provided advantages and drivers for the success of AR/VR application for hand rehabilitation. The available evidence suggests that patients can benefit from the use of AR or VR interventions for hand rehabilitation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Injuries of the peripheral nervous system are common among the population affecting around 3% of all trauma patients. This high clinical need in the field of peripheral nerve injury and regeneration has been steadily driving experimental and epidemiological research. Thereby, it is crucial to determine the exact degree of recovery of end-organ function. Regeneration after nerve injuries is assessed by a wide variety of techniques and pre-clinical model systems, where rodent models are among the most widely used. However, results from rodents are difficult to translate to human patients in general, and reproducible and comparable assessment of functional recovery is of highest importance. Computerized gait analysis allows comprehensive acquisition of locomotor function. As the animals cross the recording device voluntarily, functional recovery is assessable with a minimum degree of human interference on their behavior. This article aims to give a detailed overview on the existing literature on CatWalk gait analysis in rodent models of peripheral nerve injuries of upper and lower extremities, e.g. axonotmesis, neurotmesis or fibrosis, with special emphasis on differences between models. Researchers interested in assessment of locomotor function in such models will especially benefit from this work as it will provide them with an overview of the various experimental setups and expected outcomes. This work also addresses potential pitfalls and hurdles in order to promote well designed, comparable studies allowing for accelerated development of therapeutic strategies in peripheral repair and regeneration., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Loss of an extremity at any level has a major impact on a patient's life. Using bionic reconstruction, extremity function can be restored and the patient reintegrated into daily life. Surgical procedures including selective nerve transfer and anchoring of prostheses into bone are combined with structured rehabilitation and modern prosthetic fitting. The patient is thereby able to use the prostheses intuitively and with multiple degrees of freedom., Methods: This article presents the concept and approach for modern bionic reconstruction in detail and the relevant literature. The nerve transfer matrices for targeted muscle reinnervation (TMR) and the concept of osseointegration to optimally fit a patient with a modern prosthesis are described in detail. As a clinical example, the case of a patient who suffered from traumatic amputation and subsequently received TMR in combination with an osseointegrated implant and structured rehabilitation is presented., Results: Using bionic reconstruction, basic hand functions can be restored and bimanual dexterity can expand the range of daily activities. Besides this approach to bionic reconstruction, its advantages and disadvantages are compared to hand transplantation. The limitations and perspectives of modern bionic reconstruction are also discussed., Conclusions: Bionic reconstruction is a sophisticated method for restoring extremity function and nowadays can be considered a standard of care for all levels of upper extremity amputations. An interdisciplinary approach and structured rehabilitation are necessary to master prosthetic function to ultimately reintegrate patients into daily life.

Research on machine learning approaches for upper-limb prosthesis control has shown impressive progress. However, translating these results from the lab to patient's everyday lives remains a challenge because advanced control schemes tend to break down under everyday disturbances, such as electrode shifts. Recently, it has been suggested to apply adaptive transfer learning to counteract electrode shifts using as little newly recorded training data as possible. In this paper, we present a novel, simple version of transfer learning and provide the first user study demonstrating the effectiveness of transfer learning to counteract electrode shifts. For this purpose, we introduce the novel Box and Beans test to evaluate prosthesis proficiency and compare user performance with an initial simple pattern recognition system, the system under electrode shifts, and the system after transfer learning. Our results show that transfer learning could significantly alleviate the impact of electrode shifts on user performance in the Box and Beans test.

Even though the hand comprises only 1% of our body weight, about 30% of our central nervous systems (CNS) capacity is related to its control. The loss of a hand thus presents not only the loss of the most important tool allowing us to interact with our environment, but also leaves a dramatic sensory-motor deficit that challenges our CNS. Reconstruction of hand function is therefore not only an essential part of restoring body integrity and functional wholeness but also closes the loop of our neural circuits diminishing phantom sensation and neural pain. If biology fails to restore meaningful function, today we can resort to complex mechatronic replacement that have functional capabilities that in some respects even outperform biological alternatives, such as hand transplantation. As with replantation and transplantations, the challenge of bionic replacement is connecting the target with the CNS to achieve natural and intuitive control. In recent years, we have developed a number of strategies to improve neural interfacing, signal extraction, interpretation and stable mechanical attachment that are important parts of our current research. This work gives an overview of recent advances in bionic reconstruction, surgical refinements over technological interfacing, skeletal fixation, and modern rehabilitation tools that allow quick integration of prosthetic replacement., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Motor recovery following nerve transfer surgery depends on the successful re-innervation of the new target muscle by regenerating axons. Cortical plasticity and motor relearning also play a major role during functional recovery. Successful neuromuscular rehabilitation requires detailed afferent feedback. Surface electromyographic (sEMG) biofeedback has been widely used in the rehabilitation of stroke, however, has not been described for the rehabilitation of peripheral nerve injuries. The aim of this paper was to present structured rehabilitation protocols in two different patient groups with upper extremity nerve injuries using sEMG biofeedback. The principles of sEMG biofeedback were explained and its application in a rehabilitation setting was described. Patient group 1 included nerve injury patients who received nerve transfers to restore biological upper limb function ( n = 5) while group 2 comprised patients where biological reconstruction was deemed impossible and hand function was restored by prosthetic hand replacement, a concept today known as bionic reconstruction ( n = 6). The rehabilitation protocol for group 1 included guided sEMG training to facilitate initial movements, to increase awareness of the new target muscle, and later, to facilitate separation of muscular activities. In patient group 2 sEMG biofeedback helped identify EMG activity in biologically "functionless" limbs and improved separation of EMG signals upon training. Later, these sEMG signals translated into prosthetic function. Feasibility of the rehabilitation protocols for the two different patient populations was illustrated. Functional outcome measures were assessed with standardized upper extremity outcome measures [British Medical Research Council (BMRC) scale for group 1 and Action Research Arm Test (ARAT) for group 2] showing significant improvements in motor function after sEMG training. Before actual movements were possible, sEMG biofeedback could be used. Patients reported that this visualization of muscle activity helped them to stay motivated during rehabilitation and facilitated their understanding of the re-innervation process. sEMG biofeedback may help in the cognitively demanding process of establishing new motor patterns. After standard nerve transfers individually tailored sEMG biofeedback can facilitate early sensorimotor re-education by providing visual cues at a stage when muscle activation cannot be detected otherwise.

Background: Control of a myoelectric prostheses entails rehabilitative training, based on repetitive exercises with a physiotherapist. However, many patients lack the motivation to continue the exercises in their home environment. Mobile games on the smartphone can provide patients with long-term motivation to continue the repetitive exercises that prepare the muscles for controlling a prosthesis at home. The aim of this study was to confirm the feasibility of a myoelectrical controlled mobile application and the impact of this game-based rehabilitation on the patient's maximum voluntary contraction strength, proportionally activated muscle contraction and ability to separate muscle groups., Patients and Methods: We developed a training system that consisted of a game-based mobile rehabilitation application that is controlled by the patient's muscle signal, a tablet to play on, an electrode armband and a manual. So far two patients have participated in this study. They were asked to use the app for 4 weeks at home, 5 times a week, for 10 to 15 minutes. The intervention was designed in a randomised controlled pre-test/post-test design and patients were measured for neuromuscular parameters before the intervention and afterwards. Evaluated parameters included maximum voluntary contraction force, muscle separation, proportional control and muscle endurance, as well as user statistics., Results: After training with the app, a significant improvement (p < .01) in all examined clinical parameters for myoelectric control of a prosthesis could be achieved. The user statistics showed a high motivation to play the game and ran an additional diagnostic EMG-Test on one patient; the other participating patient, however, had played the game but neglected the EMG test and only completed half of it., Conclusion: The training app not only provides instruction and feedback on the correct execution of myoelectric commands, but also maintains patient motivation through various game modes and feedback elements. The rehabilitation process could be monitored and compared through an overview of training progress in the form of user statistics and high scores. It could be shown that patients with upper extremity amputation could significantly improve their neuromuscular control, strength and coordination after using the game-based app so that they can fully benefit from the potential of a myoelectric prosthesis., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Prosthetic motor rehabilitation usually relies on the highly repetitive training of movements. Patients might drop out of training because the rehabilitation process is long and often discouraging. Game-based interventions provide a potentially useful alternative to standard myoelectric (electromyographic [EMG]) training and can increase engagement with training., Objective: To assess the short-term impact of a game-based rehabilitation protocol on parameters for EMG control, evaluate how game-based interventions affect patient motivation, performance, and effort, and compare the game-based intervention with a standard tool in rehabilitation (MyoBoy)., Design: This randomized controlled trial included 2 patient groups and 1 control group. After establishing a baseline, the 2 patient groups received different interventions that were compared with each other and with the able-bodied control group., Setting: University hospital-based study., Participants: Fourteen patients with traumatic transradial or transhumeral upper extremity amputation and 10 able-bodied participants., Methods: For the game-based intervention, EMG proficiency was assessed before and after playing the games and 2 days later as follow-up to measure retention rate. EMG proficiency was measured using maximum voluntary contraction, proportional precision control, signal separation, and muscle endurance. Questionnaires for rating the game-based intervention and intrinsic motivation were provided after the intervention., Outcomes: Outcome measures for EMG proficiency were provisional maximum voluntary muscle contraction, precise proportional control, electrode separation, and muscle endurance. Quantitative outcome measures for participant experience were intrinsic motivation, enjoyment, pressure, exerted effort, and usefulness of the intervention. The qualitative outcome measure was the surveyed attitude toward the game-based intervention., Results: Results showed an overall improvement in EMG control, fine muscle activation, and electrode separation. Patients stated that racing games provided slightly more fun, but rhythm-based games were considered to provide better challenges for EMG control., Conclusion: Game-based interventions provide a useful addition to standard EMG training and can achieve better results in clinical outcome measures. The racing and music game genres provide solid starting points for interventions. Further studies can look at a wider range of genres and identify more specific game mechanics suitable for training., Level of Evidence: I., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Modern robotic hands/upper limbs may replace multiple degrees of freedom of extremity function. However, their intuitive use requires a high number of control signals, which current man-machine interfaces do not provide. Here, we discuss a broadband control interface that combines targeted muscle reinnervation, implantable multichannel electromyographic sensors, and advanced decoding to address the increasing capabilities of modern robotic limbs. With targeted muscle reinnervation, nerves that have lost their targets due to an amputation are surgically transferred to residual stump muscles to increase the number of intuitive prosthetic control signals. This surgery re-establishes a nerve-muscle connection that is used for sensing nerve activity with myoelectric interfaces. Moreover, the nerve transfer determines neurophysiological effects, such as muscular hyper-reinnervation and cortical reafferentation that can be exploited by the myoelectric interface. Modern implantable multichannel EMG sensors provide signals from which it is possible to disentangle the behavior of single motor neurons. Recent studies have shown that the neural drive to muscles can be decoded from these signals and thereby the user's intention can be reliably estimated. By combining these concepts in chronic implants and embedded electronics, we believe that it is in principle possible to establish a broadband man-machine interface, with specific applications in prosthesis control. This perspective illustrates this concept, based on combining advanced surgical techniques with recording hardware and processing algorithms. Here we describe the scientific evidence for this concept, current state of investigations, challenges, and alternative approaches to improve current prosthetic interfaces.

Background: A high number of upper extremity myoelectric prosthesis users abandon their devices due to difficulties in prosthesis control and lack of motivation to train in absence of a physiotherapist. Virtual training systems, in the form of video games, provide patients with an entertaining and intuitive method for improved muscle coordination and improved overall control. Complementary to established rehabilitation protocols, it is highly beneficial for this virtual training process to start even before receiving the final prosthesis, and to be continued at home for as long as needed., Objective: The aim of this study is to evaluate (1) the short-term effects of a commercially available electromyographic (EMG) system on controllability after a simple video game-based rehabilitation protocol, and (2) different input methods, control mechanisms, and games., Methods: Eleven able-bodied participants with no prior experience in EMG control took part in this study. Participants were asked to perform a surface EMG test evaluating their provisional maximum muscle contraction, fine accuracy and isolation of electrode activation, and endurance control over at least 300 seconds. These assessments were carried out (1) in a Pregaming session before interacting with three EMG-controlled computer games, (2) in a Postgaming session after playing the games, and (3) in a Follow-Up session two days after the gaming protocol to evaluate short-term retention rate. After each game, participants were given a user evaluation survey for the assessment of the games and their input mechanisms. Participants also received a questionnaire regarding their intrinsic motivation (Intrinsic Motivation Inventory) at the end of the last game., Results: Results showed a significant improvement in fine accuracy electrode activation (P<.01), electrode separation (P=.02), and endurance control (P<.01) from Pregaming EMG assessments to the Follow-Up measurement. The deviation around the EMG goal value diminished and the opposing electrode was activated less frequently. Participants had the most fun playing the games when collecting items and facing challenging game play., Conclusions: Most upper limb amputees use a 2-channel myoelectric prosthesis control. This study demonstrates that this control can be effectively trained by employing a video game-based rehabilitation protocol., (©Cosima Prahm, Ivan Vujaklija, Fares Kayali, Peter Purgathofer, Oskar C Aszmann. Originally published in JMIR Serious Games (http://games.jmir.org), 09.02.2017.)

Background: Controlling a myoelectric prosthesis for upper limbs is increasingly challenging for the user as more electrodes and joints become available. Motion classification based on pattern recognition with a multi-electrode array allows multiple joints to be controlled simultaneously. Previous pattern recognition studies are difficult to compare, because individual research groups use their own data sets. To resolve this shortcoming and to facilitate comparisons, open access data sets were analysed using components of BioPatRec and Netlab pattern recognition models., Methods: Performances of the artificial neural networks, linear models, and training program components were compared. Evaluation took place within the BioPatRec environment, a Matlab-based open source platform that provides feature extraction, processing and motion classification algorithms for prosthetic control. The algorithms were applied to myoelectric signals for individual and simultaneous classification of movements, with the aim of finding the best performing algorithm and network model. Evaluation criteria included classification accuracy and training time., Results: Results in both the linear and the artificial neural network models demonstrated that Netlab's implementation using scaled conjugate training algorithm reached significantly higher accuracies than BioPatRec., Conclusions: It is concluded that the best movement classification performance would be achieved through integrating Netlab training algorithms in the BioPatRec environment so that future prosthesis training can be shortened and control made more reliable. Netlab was therefore included into the newest release of BioPatRec (v4.0).