Although an increased usage and development of 3D technologies is observed in healthcare over the last decades, full integration of these technologies remains challenging. The goal of this project is to qualitatively explore challenges, pearls, and pitfalls of AR/VR/3D printing applications usage in the medical field of a university medical center. Two rounds of face-to-face interviews were conducted using a semi-structured protocol. First an explorative round was held, interviewing medical specialists (8), PhD students (7), 3D technology specialists (5), and university teachers (3). In the second round, twenty employees in high executive functions of relevant departments were interviewed on seven statements that resulted from the first interviewing round. Data analysis was performed using direct content analyses. The first interviewing round resulted in challenges and opportunities in 3D technology usage that were grouped in 5 themes: aims of using AR/VR/3D printing (1), data acquisition (2), data management plans (3), software packages and segmentation tools (4), and output data and reaching end-user (5). The second interviewing round resulted in an overview of ideas and insights on centralization of knowledge, improving implementation of 3D technology in daily healthcare, reimbursement of 3D technologies, recommendations for further studies, and requirement of using certified software. An overview of challenges and opportunities of 3D technologies in healthcare was provided. Well-designed studies on clinical effectiveness, implementation and cost-effectiveness are warranted for further implementation into the clinical setting. Since the early 1990s, innovative visualization techniques including augmented reality (AR) and virtual reality (VR) have been slowly but progressively introduced in modern medicine. Popular applications focused on visualizing complex anatomical structures and combine these online models with virtual training and operation planning features. For a review on AR/VR in anatomy education, see –5. The dDespite the rapid developments and the promising results of AR/VR/3D printing in research over many decades, full integration of these new techniques remains unaccomplished; AR/VR/3D printing is still not standard practice and is not regularly used in daily healthcare. This article qualitatively investigates the challenges, pearls, and pitfalls of AR/VR/3D printing applications in the medical field. Considering both the achievements and the remaining challenges, this study aims to identify trends towards possible future developments.This study was conducted at the Radboud University Medical Center in Nijmegen, the Netherlands. After consultation of the local ethical review board, ethical approval for this study was waived. To recruit participants, various online advertisements were placed with a 2-week interval. Also, to ensure that all eligible participants were identified, two recruiting e-mails were sent to all chairs of the departments of our university medical center. Between these two e-mails, there was an interval of 4 weeks. In these recruiting advertisements and e-mails, the researchers explained the methodology and goal of this study. Two rounds of qualitative interviewing were conducted. No strict inclusion or exclusion criteria were defined by the researchers, allowing for anyone with an interest in AR/VR/3D printing to be interviewed.The first round of interviewing concerned an exploratory round in which residents, practicing medical doctors, PhD students, 3D technology software specialists (employees Radboudumc 3Dlab), and university faculty, both junior and senior, were interviewed to express their thoughts, wishes, expectations, and views on possible challenges. Eligible participants were contacted by e-mail containing more detailed information on the purpose of the interviews and the research methodology. Participation was voluntary. After agreeing to participate, an online interview setting was arranged by using Skype. Audio-recorded informed consent to be interviewed and recorded was obtained from all participants prior to the start of the interview. Semi-structured interviews were conducted to obtain detailed descriptions and extensive data of the participants’ perspectives on AR/VR/3D printing applications. The interview schedule of the first round was structured by using topics suggested by discussion between three investigators. These topics were enriched by seemingly important topics derived from the literature . Intervihttp://atlasti.com; ATLAS.ti Scientific Software Development GmbH, Berlin, Germany). The constant comparative method was carried out after finishing the first interview following an inductive iterative process. This means that data analysis started after the first interview was completed. Codes derived from the previous interview were used as a starting point for coding the next one, adding additional codes whenever needed. This process was carried out until saturation was achieved, i.e., when no new codes arrived during an interview. Thereafter, two additional interviews were held.The data from the interviews were independently analyzed using direct content analysis by two researchers . This waAxial coding, in which codes were linked together and combined into categories, was also started and was continued throughout the first interviewing round. Out of the identified categories themes were derived.The second round of interviewing was based on the recommendations and outcomes of the first round of interviewing. By recommendation, the chairs of departments with relevant experiences with AR, VR, and/or 3D printing were contacted in which the goals and aims of this study were explained. Chairs were asked to recommend specific employees in high executive functions (including themselves) with a vision of the future of AR, VR, and/or 3D printing to take part. For this round, executives were chosen because they are the ones deciding whether or not and in what way to implant 3D technologies in daily healthcare.Reminding e-mails were sent up to three times after the initial e-mail. All interviews in the second round of interviewing were audio-recorded, and again, audio-recorded informed consent was obtained from all subjects. Based on the codes and themes resulting from the first round of interviewing, seven statements on the implementation and centralization of 3D technologies in a healthcare setting were extracted by two researchers. These statements can be viewed in Fig. http://atlasti.com; ATLAS.ti Scientific Software Development GmbH, Berlin, Germany) by two investigators.Data analysis was identical to qualitative data analysis for the first round of interviewing as described above see “” sectionTwenty-three participants, including residents, practicing medical doctors, PhD students, 3D technology software specialists, and university faculty, were interviewed during the first round of interviewing. Twenty participants were interviewed during the second round of interviewing. These employees in high executive office were appointed to several departments . Details can be viewed in Table Interviewees expressed that their goals regarding AR/VR/3D printing were threefold. With regard to educational purposes, it was reported that residents used either technique to learn specific skills, especially regarding laparoscopic surgery  could provide insight in radiomics of tissue. When aligned with artificial intelligence, these developments could predict outcomes which are directly relevant for patients. More particularly, patient education by the use of AR/VR/3D printing was discussed as an important goal. It was expressed that these new techniques were believed to enhance patient understanding of a specific disease or treatment. Besides, when comprehension was increased, interviewees expressed that this could improve therapy compliance. Including patients in this process could help to construct patient-friendly, useful, and more effective AR and/or VR applications. However, it was also expressed that AR/VR/3D printing was probably not useful in every disease; some disorders were deemed more appropriate than others. More elusive and complex diseases, as well as those conditions not visible from the external surface , were believed to benefit more from the combination of standard patient consultation and AR/VR/3D printing. Finally, it was reported that AR/VR/3D printing could help patients to explain their disease to their relatives and improve awareness and understanding.In general, interviewees used serial radiological data (computed tomography (CT) and magnetic resonance imaging (MRI) scans). In some cases, a 3D camera system, sometimes equipped with infrared light, was used. Radiological data was obtained as DICOM files, which is the standard data file for these types of images. To further process the data, the DICOM files were converted to NIfTI files. Data concerned both in vivo and ex vivo data.Data management plans needed to adhere to good clinical practice, ethical guidelines, and (inter)national jurisdiction. Privacy officers and data management specialists needed to be consulted according to most interviewees in order to ensure that data was stored safely and properly. Nevertheless, the most important factor for successful data management was the effectuation of a pipeline between the data storage space and the imaging visualization software and/or post-processing software.http://www.itksnap.org) and MeshLab (https://www.meshlab.net/)). In-house written software was also reported by the 3D technology software specialists to be used. Residents and university faculty used clinically approved software packages. All interviewees reported struggling at the beginning of their first AR/VR/3D printing project due to the vast number of possible options with regard to software and analysis techniques. In addition, highly protected computer systems within the university medical center environment did not allow for free installation of software. Only “approved” software could be installed, which complicated the pipeline from data storage spaces and the further processing of the retrieved data. In response to that, well-protected stand-alone devices are bought independently by different departments. On these stand-alone devices, the department downloads and installs the necessary software packages which are not allowed to be installed on computer systems which are part of the hospital network. Thereby, various interviewees reported to have paid for and installed identical software packages independently.A diverse variety of freeware applications was used by the PhD students and the 3D technology software specialists (mostly ITK Snap (The obtained output data comprises electronic 3D models (AR/VR) and/or the 3D-printed models. Depending on the purpose of these models, the output could differ. Electronic 3D models comprised StandardTessellationLanguage files (.stl-files) and Wavefront OBJ files (.obj-files).Regarding the question whether the AR/VR/3D printing models reach the end-users, the interviewees were divided. When the end-user was defined as the scientist or practicing medical doctors, the interviewees expressed that these end-users were enabled to see and interact with the acquired models. However, regarding patients, students, and residents, substantial improvements could still be made. The AR/VR models could not be incorporated into the electronic patient file and thereby could not be interacted with by the patients. Furthermore, AR, VR, and 3D-printed models were primarily made in experimental settings. With regard to the sparsely created 3D-printed models, most models are distributed to the patients. However, to implement this on a larger scale, a fitting reimbursement needs to be effectuated to cover the costs of production.When discussing student education, it was noted that the AR applications were finding their way towards the individuals’ devices to be used following the anytime and anywhere learning principle. The same, however, was not the case for the VR model. On the other hand, 3D models already form a cornerstone of anatomy education. The use of 3D printing to create models that are unavailable but are required according to the university faculty is being implemented progressively over time.The seven statements, as shown in Fig. When discussing centralizing all knowledge and expertise on AR, VR, and 3D printing, interviewees were in favor of this idea, but only if certain conditions would apply. The central hub would need to be a service rather than a selection committee that decides on which projects will be supported and which will not, especially if the hub itself is financed by overhead funding  and materials used, several scenarios were heard. First, if research shows that the use of AR, VR, and/or 3D prints was considered a functional, evidence-based technique that improves patients’ understanding of their disease, it would be necessary that insurance companies reimburse the costs. Second, if research, however, reports these techniques to be an add-on modality that does not result in lower costs of the healthcare processes or improved patient satisfaction, outcome, or safety, it should not be reimbursed by insurance companies. More extremely, it was said that if research shows no evidence for the use of AR, VR, and/or 3D printing, it should be avoided. However, an alternative view on this latter scenario was that when patients wanted to have a 3D model of their illness even though research had not shown an additional value, the service could still be offered. The costs, however, should be reimbursed by the patients themselves. Concerning the use of AR/VR/3D prints in educational settings, program directors were enthusiastic to aid further integration of these techniques in (bio)medical curricula. When focusing further on recommendations for future studies to help investigate the effectiveness of AR/VR/3D prints, it was stated that future clinical studies should also focus on the implementation process of the interventions to increase the effectiveness of these applications in practice. Feasibility and adequacy in the clinical setting should be assessed to elucidate which method is favorable in each setting. Additionally, the costs of creating AR, VR, and 3D prints should also be investigated, and cost-effectiveness studies are needed to elucidate whether these costs outweigh the benefits.When discussing specially designed consultation rooms in the out-patient departments, all interviewees were critical. If it were found that these techniques could be useful, the interviewees stated that the necessary changes would have to be carried out. However, as long as evidence was lacking, such permanent changes were not considered to be necessary. However, three participants wondered whether medical professionals were equipped to teach their patients by the use of such innovative models. They proposed to design special educational programs for medical professionals on how to use such models effectively to optimize patient education by the use of AR, VR, and/or 3D prints.Furthermore, all interviewees believed that well-designed, well-protected electronic environments were needed to reach the end-users of these technologies, whether they were students or patients. In addition, five interviewees stated that when patients could use the models on their own devices, no special changes were needed in the consultation rooms of the out-patient departments.The final statement regarding the use of certified software was reported to be two-sided. All interviewees agreed that for clinical practices, especially when basing healthcare decisions on 3D models, the post-processing software legally needed to be tested and approved by the relevant institutions  approved; Conformité Européenne (CE) marked). For research or educational purposes, the interviewees were less strict. They admitted that in these settings, more freedom with regard to the creation of well-designed models would be preferable.This paper provided an overview of the challenges and opportunities experienced by experienced users of AR/VR/3D prints in a university medical center in the Netherlands and used these insights to qualitatively investigate the views and opinions of employees in high executive functions with affinity to the topic to identify trends towards possible future developments. Regarding the educational and research purposes of AR/VR/3D prints, the interviewees expressed that these implementations were ongoing and extensively investigated. More specifically when focusing on the use of AR/VR/3D prints in educational settings, university faculty and program directors were enthusiastic about aiding further integration of these techniques in (bio)medical curricula. It was found that although the technological possibilities have rapidly developed over the course of 30 years, studies on clinical effectiveness, clinical implementation, and cost-effectiveness are lacking.Various papers reported improved knowledge retention in patients suffering from specific disorders –27. NeveAnother important understudied field of research concerns the cost-effectiveness of AR/VR/3D prints in medicine. This remains an important omission of the scientific literature . It has One of the strengths of the current paper is the qualitative design and the use of two rounds of interviews to include experienced users of AR/VR/3D print technologies as well as professors and visionaries with affinity about this subject. One limitation concerns the method used to select subjects for the second round of interviews, as asking single individuals in leadership roles for recommendations could have led to selection bias. Another limitation of this study is the limited generalizability of the results and recommendations regarding specific institutions, as this study was conducted in only one university medical center in the Netherlands. Nevertheless, the reported recommendations can also be useful for other institutes to improve their infrastructure with regard to AR, VR, and/or 3D printing. Furthermore, the most important omissions of the field of AR, VR, and/or 3D prints have been identified. Along with the reported trends, some suggestions for possible future developments have been made to help accelerate the integration of AR/VR/3D prints into the daily practice of modern medicine. However, to increase the likelihood of successful and relevant implementation of these new techniques in modern medicine, the patient’s perspective should not be forgotten. Although beyond the scope of the current study, more research should be conducted regarding patients’ expectations of AR/VR/3D printing in modern medicine.Qualitative exploration has provided an overview of the challenges and opportunities of AR, VR, and/or 3D prints in modern medicine and education. Especially concerning clinical usability and implementation, further developments are warranted. For further implementation into the clinical setting, well-designed studies on the clinical effectiveness, clinical implementation, and cost-effectiveness are obligatory.


Caretta caretta) at a high-use area in the eastern Big Bend, Florida, between 2016 and 2022, comprising 53 subadults, 10 adult males and 50 adult females. We calculated trophic niche metrics using established and novel methods, and constructed Bayesian ellipses and hulls, to characterize loggerhead isotopic niches. These analyses indicated that loggerheads partition their realized ecological niche by lifestage, potentially along both bionomic (e.g. trophic) and/or scenopoetic  axes, and display different characteristics of resource use within their niches. Analysis of stable isotopes from tissues with different turnover rates enabled this first characterization of intraspecific niche partitioning between and within neritic lifestages in loggerhead turtles, which has direct implications for ongoing research and conservation efforts for this and other imperiled marine species.A species may partition its realized ecological niche along bionomic and scenopoetic axes due to intraspecific competition for limited resources. How partitioning manifests depends on resource needs and availability by and for the partitioning groups. Here we demonstrate the utility of analysing short- and long-term stable carbon and nitrogen isotope ratios from imperiled marine megafauna to characterize realized niche partitioning in these species. We captured 113 loggerhead sea turtles ( Adueagris]) . Meetingin situ [Galeocerdo cuvier) and bull (Carcharhinus leucas) sharks capable of predating turtles are more abundant in waters deeper than three meters in the Big Bend  sneak into foraging territory occupied by larger brown trout  whenever the trout briefly vacate their territory [Papio hamadryas ursinus) and Trinidadian guppies (Poecilia reticulata) use sneaky mating strategies to avoid and subvert intraspecific competition [This paradigm does not explain the substantial overlap that exists between subadult and adult ecological niches. This overlap was driven by some subadults with isotopic values more similar to adults figures –4. It iserritory . Male bapetition ,121. Conpetition , and subpetition ,90,111, This characterization of intraspecific niche partitioning in loggerhead turtles has direct implications for ongoing research and conservation efforts for this and other imperiled species. Analysis of isotopic data from epidermis, a tissue with short turnover time, elucidated intraspecific partitioning by size in loggerhead turtles. Analysis of isotopic data from scute, an inert tissue that allows for multiple sampling over time, strongly supported this partitioning and allowed for additional characterization of individual resource use in the light of this partitioning. When possible, future studies of ecological niches and resource partitioning in imperiled species should incorporate short- and long-term characterizations of resource use to be able to improve confidence in, and add nuance to, their characterizations. Little is known about the life-history strategies of immature turtles , but ecoFuture studies should work to better characterize and understand intraspecific partitioning in loggerhead sea turtles in the Big Bend region and globally. The development of fine-scale carbon and nitrogen isoscapes and isotopic mixing models are important first steps towards assessing whether intraspecific partitioning might be bionomic or sceneopoetic in nature. If partitioning is scenopoetic, satellite telemetry could be used to monitor individual movements and spatial resource use characteristics. In the eastern Big Bend, this could be used to determine if any subadults make forays out of the study site. Identification and video monitoring of known shallow foraging habitats (i.e. specific patches) or the use of animal-borne cameras ,122,123 Knowledge of instraspecific partitioning and subsequent resource use strategies is crucial for effective conservation measures in sea turtles and other imperiled species ,128. Mon


Stroke is a significant cause of disability worldwide, and stroke survivors often experience severe motor impairments. Lower limb rehabilitation exoskeleton robots provide support and balance for stroke survivors and assist them in performing rehabilitation training tasks, which can effectively improve their quality of life during the later stages of stroke recovery. Lower limb rehabilitation exoskeleton robots have become a hot topic in rehabilitation therapy research. This review introduces traditional rehabilitation assessment methods, explores the possibility of lower limb exoskeleton robots combining sensors and electrophysiological signals to assess stroke survivors' rehabilitation objectively, summarizes standard human-robot coupling models of lower limb rehabilitation exoskeleton robots in recent years, and critically introduces adaptive control models based on motion intent recognition for lower limb exoskeleton robots. This provides new design ideas for the future combination of lower limb rehabilitation exoskeleton robots with rehabilitation assessment, motion assistance, rehabilitation treatment, and adaptive control, making the rehabilitation assessment process more objective and addressing the shortage of rehabilitation therapists to some extent. Finally, the article discusses the current limitations of adaptive control of lower limb rehabilitation exoskeleton robots for stroke survivors and proposes new research directions. Stroke is a major cause of disability and mortality globally  to judge muscle strength, which divides stroke survivors into five levels of muscle strength. According to the functional walking ability of stroke survivors, Hughes and Bell , which divides the walking power of stroke survivors and the need for monitoring into 0–6 levels. The Berg balance scale (BBS) evaluates the patient's ability to stand in balance to judge the possibility of falling in stroke survivors , which is now widely used in the clinical assessment of motor function in stroke survivors, covering five aspects of movement, balance, joint mobility, and pain, and the specific evaluation items reach 113 items. Although many standard scales are used for clinical diagnosis and evaluation, their functions are very similar. The specific selection mainly depends on the subjective wishes of rehabilitation physicians. Moreover, these standard scales are easy for physicians to operate, and the cost of obtaining the rehabilitation status of patients' lower limbs is low. Therefore, it is widely used in clinical practice  signals and electroencephalogram (EEG) signals  -related technologies have become more research hotspots today. AI-based lower limb exoskeleton control models are no exception . The limitation of the optical sensor is that the detection angle of the sensor is fixed, the space range of the recognition is restricted, and stroke survivors need various safety protection during exercise, so the optical positioning mark is easily blocked, which affects the motion capture. These questions have led some scholars to use optical, IMU, and pressure sensors to collect relevant signals and realize adaptive control of lower limb rehabilitation exoskeletons based on multimodal information fusion and motion intention recognition as Section 4.3. Scheme of DMPs-based control is shown in With the deepening of research in recent years, some scholars have also used optical, ultrasonic, and magnetic sensors to identify lower limb movement intentions  (Pizzolato et al., According to their acquisition methods, electrophysiological signals applied to motion intention recognition can be divided into invasive and non-invasive. The invasive acquisition method is to place electrodes into the human body. This acquisition method can obtain better signal quality, but it will cause trauma to the human body. The non-invasive acquisition method is to attach electrodes to the skin's surface. This acquisition method will not cause trauma to the human body, but the quality of the acquired signal is poor, and the signal needs to be pre-processed before the signal is used (Lew et al., Liu et al.  used a MSince the motion intention recognition model applied to the lower limb exoskeleton has high requirements for real-time action, an overly complex model will lead to too long a recognition time, which cannot meet the real-time control of the exoskeleton. Therefore, Guo et al.  uses a lHowever, long-term muscle exercise will cause muscle fatigue, which will cause the signal power spectrum to shift toward the low-frequency direction. The subsequent acquisition of sEMG will reduce the accuracy of model recognition and affect following intention recognition. For sEMG, it isn't easy to judge the starting point of the movement occurrence. The EEG has an advantage in recognition of action intentions, and the EEG is generated before the action occurs. Therefore, some scholars began to study EEG-based motion intention recognition.For example, Choi and Kim  performeToday, lower limb exoskeleton rehabilitation robots tend to use various sensors, such as combined with IMU, plantar pressure, and others. At the same time, it can also collect sEMG and EEG and recognize the movement intention of lower limbs through multi-source signals. This improves the accuracy of motion intention recognition and can also use these sensors to do more work, such as rehabilitation assessment, fatigue monitoring, etc. (Ferrarello et al., Hua et al.  have devWang et al.  built anThe kinematic provided by IMU and pressure-sensitive sensors cannot accurately identify spatial position information of stroke patients, so it is necessary to introduce motion capture to make compensation. Song et al. , built aTo ensure real-time control of exoskeletons in stroke survivors, it is necessary to incorporate electrophysiological signals with lower latency than kinematic to recognize motion intentions. Du et al.  have devLikewise, Gui et al.  obtainedSo Zheng et al.  introducSome scholars also try to recognize motion intention based only on electrophysiological signals to realize adaptive control of exoskeletons in stroke survivors, but this method also has limitations (Net'uková et al., Although motion intention recognition based on EEG and sEMG multi-source information can effectively improve the control precision of the model and the accuracy of intention recognition, the response time of different physiological signal sources is different, and there is an unavoidable delay (Zhang et al., Most adaptive control exoskeletons based on motion intention recognition now use a layered architecture to achieve control. The upper-level high-level controller is used for motion intention recognition, and the middle-level controller converts the motion pattern predicted by intention recognition into mechanical impedance control parameters. The lower-level controller uses traditional control algorithms to drive actuators to achieve closed-loop control are shown in This section collects the review of lower extremity exoskeletons in the past three years, and their main work content is summarized and compared.Gholap et al.  is a revThe work of de Miguel-Fernández et al.  is to evMasengo et al.  discusseJiyu et al.  review fLee et al.  review fWang et al.  the reviAl-Rahmani et al.  summarizWe can see that the current review research questions of lower limb exoskeletons mainly focus on the following aspects.The lower limb rehabilitation exoskeleton robots need human-machine coupling to assist or strengthen humans to complete required actions (Lee et al., Traditional approaches to rehabilitation assessment have been enumerated previously. As introduced in Section 2, the rehabilitation assessment method combined with the rehabilitation scale is still widely used in hospitals. It has crucial diagnostic significance, but the instrumental assessment has gradually become the new gold standard for rehabilitation assessment (Toro et al., Therefore, in the future, the lower limb rehabilitation exoskeleton robot based on motion intention recognition can integrate multi-source information and construct a multimodal rehabilitation evaluation model through machine learning or other technologies. Realize an objective rehabilitation assessment method based on multimodal information fusion. This can enable stroke survivors to complete rehabilitation assessments during rehabilitation training and save the assessment results. Rehabilitation therapists can directly modify the follow-up rehabilitation plan based on the evaluation opinions given by the lower limb rehabilitation exoskeleton robot, which reduces the workload of rehabilitation therapists and allows rehabilitation physicians to perform more valuable diagnostic work.Most adaptive lower limb rehabilitation exoskeleton robots based on motion intention recognition are currently researched on simple gait cycle motions, such as walking on flat ground or a flatbed. More research still needs to be done on the movement of various complex scenes. Winter et al.'s  researchFor this reason, the adaptive lower limb rehabilitation exoskeleton needs to cope with complex scenes and perform some complex movements, such as going up and down stairs. Laschowski et al. , combineCurrently, there are two common ways of the lower limb rehabilitation exoskeleton: wired and wireless. Through a wired connection, data transmission is more stable. The disadvantage is that too many wires will interfere with the subject's movement to a certain extent and limit the subject's range of activities, And there are certain requirements on the ratio of cable length (Prasad et al., When stroke survivors undergo rehabilitation training, if they rely entirely on exoskeleton rehabilitation robots for support, exercise will lead to less active participation in their movement. At this time, the muscles of the lower limbs and the knees receive less reaction from the ground and are not significantly stimulated, so the therapeutic effect is not apparent. The adaptive control exoskeleton robot using electrophysiological signals for motion intention recognition has more advantages in stimulating nerves and muscles than the adaptive control exoskeleton robot using sensors for motion intention recognition. Because the collected electrophysiological signals are mainly generated by motor imagery or muscle movement of stroke survivors, it is beneficial to the brain function remodeling of stroke survivors.To enhance the intensity of stimulation to the muscles and nerves of stroke survivors, the lower limb rehabilitation exoskeleton robot can be combined with other stroke treatment methods. For example, by combining functional electrical stimulation with the lower limb rehabilitation exoskeleton robot, through the adaptive control strategy of the exoskeleton based on functional electrical stimulation, the change of the joint angle of the subject is recognized to adjust the electrical stimulation current intensity and change the joint motion state. This not only realizes the adaptive control of the exoskeleton but also corrects the user's gait and simultaneously enhances the stimulation of the lower limb muscles to achieve better rehabilitation effects. Therefore, in the future, when designing exoskeleton-related control methods, other methods of stroke rehabilitation can be considered.The main contribution of this review is the introduction of today's instrumented rehabilitation assessment methods, emphasizing the necessity of adaptively controlled lower limb exoskeleton robots with rehabilitation assessment functions, and the study also introduces the lower limb exoskeleton based on various actuators. The exoskeleton robot control model for lower limb rehabilitation based on motion intention recognition based on multiple AI methods is mainly reviewed.In the future, in designing lower limb rehabilitation exoskeleton robots for stroke survivors, it is necessary to focus on the safety of the exoskeleton and adapt the weight reduction system to cope with stroke survivors of different muscle strength levels. At the same time, to meet the application of stroke survivors throughout the rehabilitation stage, the lower limb exoskeleton robot needs to have the function of rehabilitation assessment. To achieve a better rehabilitation effect, the training content that the exoskeleton can perform should be expanded, and some complex tasks can be performed or combined with virtual reality technology. The adaptive control model based on motion intention recognition can extract the motion intention of stroke survivors, adjust exoskeleton parameters in real-time, control exoskeleton movement, and promote brain function remodeling in stroke survivors. The multi-modal motion intention recognition can make the predicted results more accurate, so future research should focus on the multi-modal motion intention recognition adaptive control model research. In addition, the lower limb rehabilitation exoskeleton robot has a limited role in the rehabilitation treatment process, so the limb rehabilitation exoskeleton robot can be combined with other stroke rehabilitation treatment methods to achieve better efficacy. Overall, there is still much room for developing exoskeleton robots for lower limb rehabilitation for stroke survivors.DS and ZL organized the graphs and tables. DS wrote the first draft of the manuscript. PS, JW, ZL, and ZH wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.


Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti–programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors. An immunotherapeutic artificial vitreous body was developed as a crucial surgical adjunct for choroidal melanoma treatment. Choroidal melanoma is a kind of primary intraocular malignant tumor that occurs commonly in adults with a high lethality rate and poor therapeutic results  hydrogel based on highly branched polymers of tetra-armed poly(ethylene glycol) (Tetra-PEG) was developed to control the recurrence of choroidal melanoma and simultaneously preserve vision after vitrectomy . BrieflyAVB hydrogel was prepared by a two-step process . In the Considering that the ratio of Tetra-PEG-MA and Tetra-PEG-SH and the total polymer concentration in the first step are the key variables during the preparation process of AVB hydrogel, we optimized the proportion of Tetra-PEG-MA/Tetra-PEG-SH and the total mass fraction in preparing the MA nanogel and SH nanogel. As shown in To verify whether AVB would be suitable for the substitution of native vitreous body (VB) after vitrectomy, we comprehensively compared the physical properties of AVB and native VB. Both AVB and native VB appeared as transparent soft jelly  and exhiAlthough the polymer content of AVB is ultralow, it still has an abundant porous structure, allowing it excellent drug loading capacity. Mel and αPDL1 at therapeutic-relevant dosages were encapsulated into the AVB. Then, rhodamine B (RhoB)– and Cy5.5-labeled immunoglobulin G (IgG) (IgG-Cy5.5) as the substitution of Mel and αPDL1 were encapsulated into the AVB hydrogel, and drug-loaded AVB was sectioned and imaged by confocal imaging. As shown in fig. S6, strong signals from RhoB and Cy5.5 were observed, suggesting the successful encapsulation of both small and large molecules. Moreover, more than 95% of the Mel and αPDL1 could be loaded into the hydrogel tested by elution method (fig. S7). Then, RhoB- and IgG-Cy5.5–loaded AVB (RhoB&IgG-Cy5.5@AVB) was dispersed in phosphate-buffered saline (PBS). At different time points, AVB was collected, sectioned, and imaged by confocal imaging to visualize the release behaviors of encapsulated molecules (fig. S8). As expected, the fluorescence of RhoB was almost completely disappeared on the third day, and the fluorescence of IgG-Cy5.5 could still be detected on day 7, indicating that RhoB and IgG exhibited distinct release kinetics. Then, the quantitative release profiles of Mel and IgG from AVB were measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA), respectively. Approximately 74.5% of Mel was released within 1 day, while IgG exhibited more sustained release behavior, with 32.9% released in 1 day (fig. S9).Then, the distinct release kinetics of Mel and IgG were investigated in mice after intravitreal injection of free drug mixture or drug-loaded AVB by an in vivo fluorescence imaging system. Here, RhoB and IgG-Cy5.5 were still used as substitutes for Mel and αPDL1. As shown in First, we investigated the inhibitory effect of Mel on both mouse melanoma cells B16F10 and human-derived choroidal melanoma cells MuM-2B. As shown in fig. S10, the proliferation of B16F10 and MuM-2B cells was obviously inhibited in the presence of Mel. Then, we investigated whether Mel could induce ICD, a distinct cell death pathway, during which a series of damage-associated molecular patterns (DAMPs) would be released, including the exposure of calreticulin (CRT) on the cell surface, the secretion of adenosine triphosphate (ATP) and high mobility group protein 1 (HMGB1), and the release of heat shock proteins (HSP70 and HSP90) (5 to 1 × 106 p sce−1 cm−2 sr−1) from cancer cells were observed, indicating the successful establishment of choroidal melanoma model (fig. S13). Meanwhile, the mice were euthanized, and their eyes were collected for dissection. As exhibited in fig. S14, obvious infiltration of cancer cells in the vitreous cavity was observed, further indicating the successful establishment of choroidal melanoma tumors. To simulate the recurrence of choroidal melanoma after vitrectomy, we removed most of the melanoma tumors. Briefly, a specially made syringe with hooked pinpoint (fig. S15) was inserted into the posterior segment via the limbus, turned gently, and drew the mixture of VB and cancer cells. The total intensity of luminescence was less than 2 × 105 p sce−1 cm−2 sr−1 after such vitrectomy operation , Mel@AVB , αPDL1@AVB , and Mel & αPDL1@AVB . Then, the growth of tumors was monitored by an in vivo fluorescence imaging system every 2 days. According to the luminescence signals from cancer cells, we found that the melanoma tumors in mice treated with blank AVB recurred 2 days after vitrectomy, and none of the mice preserved their eyeballs on day 6 . As show+ T cells in the distant tumor were also significantly increased . These results together verified that our strategy not only could control the growth of local choroidal melanoma but also has the potential to inhibit metastatic tumor growth.To explore whether this strategy could inhibit tumor metastasis, we established primary and distant tumors in both eyes of mice according to the extensively studied subcutaneous bilateral tumor model (fig. S18A). As shown in fig. S18 (B and C), when primary tumor was treated with Vitrectomy + Mel & αPDL1@AVB , the growth of distant tumor in the left eye was also delayed. In addition, the infiltration and proliferation of antitumor CD8To further explore the advantages of Vitrectomy + Mel & αPDL1@AVB strategy, we compared it with repetitive intravitreal injections (fig. S19A). According to the results in fig. S19 (B and C), multiple intravitreal injections at the middle stage of tumor achieved negligible therapeutic results. However, the therapeutic effect of our strategy (Vitrectomy + Mel & αPDL1@AVB), achieved significantly enhanced therapeutic effect even than that of repetitive intravitreal injections at early stage. In our treatment strategy, most of the tumor tissue was removed by vitrectomy, and then the AVB with long-term release of Mel and αPDL1 was filled to prolong the retention time of drugs and inhibit the recurrence of cancer. Thus, this Vitrectomy + Mel & αPDL1@AVB strategy was more effective in treating advanced choroidal melanoma. Multiple intravitreal injection may be more suitable for early-stage choroidal melanoma, which can achieve ideal therapeutic results and avoid greater invasiveness to the patient’s eyes. However, for middle-stage choroidal melanoma, our strategy using Vitrectomy + Mel & αPDL1@AVB can achieve better therapeutic effect and preserve the eyeball of patients.To investigate the cytotoxicity of AVB hydrogel, retinal pigment epithelial (RPE) cells were incubated with different concentrations of AVB hydrogel for 24 hours, and the relative cell viability was measured by standard methyl thiazolyl tetrazolium (MTT) assay. As shown in fig. S20, AVB hydrogel induced negligible cytotoxicity to RPE cells. In addition, we further carried out the serum biochemistry and complete blood panel analysis 7 and 30 days after injection of AVB hydrogel (fig. S21). All the measured parameters after AVB hydrogel injection were in normal range, indicating that AVB hydrogel induced nearly no acute or chronic damage to mice. Moreover, H&E staining images of main organs collected from mice exhibited consistent histomorphological characteristics to those collected from healthy mice, which further proved that AVB hydrogel induced nearly no toxicity to normal organs of mice (fig. S22).+CD80+CD86+) in cervical lymph nodes in the Mel@AVB and Mel & αPDL1@AVB groups were obviously higher than those in the AVB- and αPDL1@AVB-treated groups, demonstrating that ICD induced by Mel could effectively promote the maturation of DCs in cervical lymph nodes.Encouraged by the excellent therapeutic effect achieved by Mel & αPDL1@AVB, we then evaluated the immune responses induced by Mel and αPDL1 in vivo . First, + T cells (CD3+CD8+) and actively proliferating T cells (CD8+Ki67+) were slightly increased in the Mel@AVB group, which may be attributed to the suppression of CD8+ T cells by programmed death pathway on tumor cells , a commonly used tamponade after vitrectomy in the clinic, or the AVB hydrogel (5 μl). Then, we systemically investigated the eyeball structure and retinal function of mice at different time points after surgery via a tonometer and retinal imaging microscope . As showIn addition to the normal structure, the evaluation of visual functions is also important for mice after injection with AVB. ERG was performed in scotopic condition to analyze the functions of photoreceptors of mice in different groups  and immune checkpoint inhibitors (αPDL1) with distinct release kinetics. Mel with a smaller molecular weight was released quickly from the hydrogel to induce ICD of cancer cells by releasing a large number of DAMPs to recruit various types of immune cells. Such effects working together with the subsequently released αPDL1 would be able to activate synergistic antitumor immune responses. As the result, Mel & αPDL1@AVB effectively inhibited the recurrence of the postoperative tumor and prolonged the eyeball preservation of mice bearing choroidal melanoma tumors. Meanwhile, the eyeball structure and retinal function evaluation of the implanted AVB hydrogel after 6 months indicated that the AVB should be an ideal vitreous substitute to preserve vision functions of eyes without adverse effects. Therefore, the immunotherapeutic AVB hydrogel composed of Tetra-PEG, which is the commonly used in artificial tears, has the potential to act as a crucial surgical adjunct in vitreoretinal surgery for intraocular malignant tumors in the endophytic stage of the eye. In addition, on the basis of the unique physical properties of AVB hydrogel, it has the potential to be used in a wider range of applications including retinal macular degeneration and intraocular infections.2). Human choroidal melanoma cells (MuM-2B) were also originally purchased from ATCC and cultured in RPMI 1640 medium containing 1% penicillin-streptomycin and 10% FBS under standard conditions (37°C and 5% CO2). The naive VB was donated by Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University. Female C57BL/6 mice (6 to 8 weeks) and female Balb/c mice (6 to 8 weeks) were purchased from Changzhou Cavens Experimental Animal Co Ltd. All mouse experiments were conducted following the protocol approved by the Institutional Animal Care and Use Committee of Soochow University .Tetra-PEG-MA  and Tetra-PEG-SH  were purchased from Xi’an Ruixi Biological Technology Co Ltd. Melphalan Hydrochloride (Mel)  was purchased from Shanghai J&K Scientific Chemical Technology Co Ltd. Anti-mouse PDL1  was purchased from Bio X Cell Biotech Co Ltd. The silicone oil (Oxane 5700) was purchased from Bausch & Lomb Inc. Mouse melanoma cells (B16F10) were originally purchased from American Type Culture Collection (ATCC) and cultured in Dulbecco’s modified Eagle’s medium containing 1% penicillin-streptomycin and 10% fetal bovine serum (FBS) under standard conditions (37°C and 5% COAppropriate quantities of Tetra-PEG-MA and Tetra-PEG-SH were separately dissolved in PBS (pH 7.4). For the MA nanogel solution, equal volumes of Tetra-PEG-MA (16 mg/ml) and Tetra-PEG-SH (4 mg/ml) were mixed. For the SH nanogel solution, equal volumes of Tetra-PEG-SH (16 mg/ml) and Tetra-PEG-MA (4 mg/ml) were mixed. Then, the two nanogel solutions were left at 4°C for 6 hours. Last, equal volumes of the two nanogel solutions were mixed to obtain AVB hydrogel with a total mass fraction of 1 wt %.C0) and molar proportion (p) of Tetra-PEG-SH. C0 = 0.8 wt %, p = 0.42, 0.44, 0.46, 0.48, 0.5, 0.52, 0.54, and 0.56; C0 = 1 wt %, p = 0.40, 0.42, 0.44, 0.46, 0.48, 0.56, 0.58, 0.60, 0.62, 0.64, and 0.66; C0 = 1.5 wt %, p = 0.32, 0.34, 0.36, 0.38, 0.40, 0.60, 0.62, 0.64, 0.66, 0.68, and 0.70; C0 = 2 wt %, p = 0.26, 0.28, 0.30, 0.32, 0.34, 0.68, 0.70, 0.72, 0.74, and 0.76; C0 = 3 wt %, p = 0.18, 0.20, 0.22, 0.24, 0.26, 0.76, 0.78, 0.80, 0.82, and 0.84. The corresponding set of Tetra-PEG-MA and Tetra-PEG-SH were mixed with equal volumes. After 6 hours, the gel state was determined if no flow was observed within 30 s when the vial was inverted.Tetra-PEG-MA and Tetra-PEG-SH were separately dissolved in PBS (pH 7.4) with the following total polymer concentration (Tetra-PEG-MA and Tetra-PEG-SH were separately dissolved in PBS (pH 7.4) with 1 wt % total polymer concentration. The mixing steps refer to the above “Preparation of AVB” section, and the gelation time was recorded using a stopwatch. It is worth noting that the sets of less than 0.6/0.4 molar proportions became hydrogels in the first step.TEM images were obtained using an FEI FT20 TEM. Scanning electron microscopy images were obtained using a Zeiss Gemini 500 scanning electron microscope. The photographs were shot using a smartphone in JPEG image format. The rheological behavior was measured using a Thermo Fisher Scientific HAAKE Mars40 with P20 Ti parallel plates at 25°C. The absorbance and light transmittance were recorded using a Jasco V-750 spectrophotometer over a range of visible light (380 to 780 nm). The pH was tested by a REX PHS-25 pH meter, and the density was measured by the ethanol exclusion method. The refractive index was determined by an Abbemat 500 refractometer at 25°C. The size of nanogel was determined by a Malvern Nano-ZS90 Zetasizer. The reaction conversion was calculated by measuring the characteristic absorbance of the maleimide group in Tetra-PEG-MA at 300 nm before and after mixing up using the Jasco V-750 spectrophotometer . The swelling ratio was measured by weighing the AVB immersed in PBS at different time points.The reaction conversion (proportion of Tetra-PEG-MA < 0.5) = [1 − (Tetra-PEG-MA after mixing) / (Tetra-PEG-MA before mixing)] * 100%.The reaction conversion (proportion of Tetra-PEG-MA > 0.5) = {1 – [(Tetra-PEG-MA after mixing) – (Tetra-PEG-MA before mixing)] / (Tetra-PEG-SH before mixing)} * 100%.The swelling ratio = (weight of AVB) /  * 100%.The drugs were loaded into AVB in the second mixing process. The drug release behavior was measured using a Transwell system  in PBS at 37°C to mimic the physiological environment. The AVB  encapsulated with Mel (0.3 mg) and rat IgG  was loaded into the upper chamber, and the released Mel and IgG were collected from the bottom of the chamber at different time points, which were measured using HPLC (BioLogic DuoFlow) and the rat IgG total ELISA kit  separately. In addition, AVB-encapsulated RhoB- and Cy5.5-labeled rat IgG (IgG-Cy5.5) at different time points were frozen in optimal cutting temperature medium at −80°C and then cut into slices (thickness = 15 μm) using a cryotome (Lecia CM1860) at −25°C and were sealed and imaged by a confocal microscope (Zeiss LSM 800).RhoB- and Cy5.5-labeled rat IgG (IgG-Cy5.5) were used as substitutes for Mel and αPDL1, respectively, for fluorescence imaging. Five microliters of mixture containing RhoB (30 μg) and IgG-Cy5.5 (20 μg) or 5 μl of AVB (1 wt %) encapsulating RhoB (30 μg) and IgG-Cy5.5 (20 μg) were injected separately into the right eyeballs of Balb/c mice using intravitreal injection with a microinjection needle . The mice were then monitored by an in vivo fluorescence imaging system (PerkinElmer IVIS Lumina III) at different time points.Immunofluorescence staining of CRT, HMGB1, and HSP70 was performed. For the in vitro experiment, B16F10 cells or MuM-2B cells cultured in a 24-well plate were treated with AVB (10 μl), Mel (80 μg in 1 ml of medium), or Mel@AVB (80 μg of Mel in 10 μl of AVB) for 6 hours, fixed with 0.25% paraformaldehyde, and blocked with FBS. Next, the cells were stained with anti-CRT , anti-HMGB1 , and anti-HSP70  separately overnight at 4°C with a dilution of 1:1000 (0.1% Triton X-100 was used for cell membrane perforation before staining with anti-HMGB1). Then, the slides were washed with PBS and incubated with fluorescence-labeled secondary goat anti-rabbit IgG H&L (Alexa Fluor 488) (1:400)  at room temperature for 1 hour, and the nuclei were stained with 4′,6-diamidino-2-phenylindole for 10 min. Last, the cells were sealed and imaged by a confocal microscope (Zeiss LSM 800). For the in vivo experiment, the mice were euthanized on day 2, and their tumors were collected and frozen in optimal cutting temperature medium at −80°C. After 6 hours, the tumors were cut into slices (thickness = 10 μm) using a cryotome (Lecia CM1860) at −25°C, mounted on slides, and fixed with 4% paraformaldehyde. Then, the same staining procedure was performed as in the cell experiment.For flow cytometry analysis, B16F10 cells or MuM-2B cells cultured in a 12-well plate were treated with AVB (20 μl), Mel (160 μg), or Mel@AVB (160 μg of Mel in 20 μl of AVB) for 6 hours (treated for 12 hours in terms of HMGB1). Then, the cells were collected in Eppendorf tubes, fixed with 0.25% paraformaldehyde, and blocked with anti-CD16/32  antibodies. Next, these cells were stained with anti-CRT, anti-HMGB1, and anti-HSP70 separately for 0.5 hours at room temperature at a dilution of 1:500 (0.1% Triton X-100 was used for cell membrane perforation before staining with anti-HMGB1). Then, the cells were washed with PBS and incubated with fluorescence-labeled secondary goat anti-rabbit IgG H&L (Alexa Fluor 488) (1:800) at room temperature for 0.5 hours. Last, cells for each sample were tested using a BD AccuriC6 plus flow cytometer and analyzed by FlowJo software (Ver. 10.0.7).For determination of released HMGB1 and ATP, the culture medium of B16F10 cells after different treatments was collected and measured by an ELISA kit  and an ATP assay kit .The anesthetized mice were fastened to the platform of a stereomicroscope, and then a 30-G needle was inserted with the best position, angle, and depth to ensure no effect on the normal tissue under the microscope and the guidance of ophthalmologists. Next, a specially made syringe with the hooked pinpoint (fig. S15) was inserted into the posterior segment via the pore to gently draw the mixture of VB and tumor. Last, the just mixed solution of equal amounts of MA nanogel and SH nanogel was injected into the posterior segment via the pore using a microinjection needle, followed by a drop of the antibiotic eyedrop. The next day, IOPs were measured to ensure that AVB reached equilibrium in the vitreous cavity.5 luciferase B16F10 cells were injected into the middle between the retina and choroid in the right eye of each mouse. Seven days later, the tumor cells had invaded the vitreous cavity (fig. S14). Then, the mice were randomly divided into four groups (five mice per group), and vitrectomy was performed to remove the tumor until the total intensity of luminescence was less than 2 × 105 p sce−1 cm−2 sr−1 (fig. S13). Then, 5 μl of AVB, Mel@AVB (30 μg of Mel), αPDL1@AVB (20 μg of αPDL1), or Mel & αPDL1@AVB (30 μg of Mel and 20 μg of αPDL1) were injected separately into the vitreous cavity. Last, tumors inside the eyes were monitored by an in vivo fluorescence imaging system (PerkinElmer IVIS Lumina III) every 2 days. It was deemed necessary to remove the eyeball when the total intensity of luminescence exceeded 5 × 107 p sce−1 cm−2 sr−1 because the melanoma cancer cells occupied most of the vitreous cavity space and increased the risk of metastasis (fig. S16).B16F10 or B16LS9 are two cell lines derived from murine cutaneous melanoma tissues and have been widely used to establish choroidal melanoma in previous studies , and the primary tumor was performed with Vitrectomy + Mel & αPDL1@AVB (30 μg of Mel and 20 μg of αPDL1) on day 7. The tumors inside the eyes were monitored by an in vivo fluorescence imaging system (PerkinElmer IVIS Lumina III) every 2 days.To explore the therapeutic efficacy repetitive intravitreal injections (fig. S19), mice bearing choroidal melanoma were divided into three groups: G1, untreated; G2, intravitreal injection of 30 μg of Mel and 20 μg of αPDL1 for three times at −4, −2, and 0 days (at early stage); and G3, intravitreal injection of 30 μg of Mel and 20 μg of αPDL1 for three times at 0, 2, and 4 days (at middle stage) . The tumors inside the eyes were monitored by an in vivo fluorescence imaging system (PerkinElmer IVIS Lumina III) every 2 days.Eyeballs were collected and fixed in eyeball-fixed liquid, dehydrated with ethanol, embedded in paraffin, and cut into sections (8 μm). Then, the tissue sections were stained with H&E and imaged using an optical microscope (DM 4000).5 events in the ungated flow chart in each sample were collected using a C6 plus flow cytometer and analyzed by FlowJo software (Ver. 10.0.7). The gating strategy is given in fig. S23.Tumors and cervical lymph nodes harvested from mice were collected and homogenized into the single-cell suspensions. Then, the cells were blocked with anti-CD16/32  antibodies to avoid nonspecific adsorption and stained with the following antibodies according to the manufacturer’s instructions: fluorescein isothiocyanate (FITC)–anti-CD45 , Peridinin-Chlorophyll-Protein Complex (PerCP)-CD11c , allophycocyanin (APC)–anti-CD80 , phycoerythrin (PE)–anti-CD86 , PerCP–anti-CD3 , APC–anti-CD4 , PE–anti-CD8 , and FITC–anti-Ki67 . A total of 1.0 × 10The collected tumors were ground fully in radioimmunoprecipitation assay lysis buffer at 4°C and centrifuged to remove the precipitates three times. The levels of IFN-γ and TNF-α were measured by mouse ELISA kits  according to the manufacturer’s instructions.2) for a duration of 5 ms was used to elicit the rod and mixed cone/rod responses.IOP was measured by instantaneous contact with the center of the cornea using the Icare Tonolab tonometer. Slit-lamp microscopy, FFA, OCT, and ERG were performed using a Micron IV retinal imaging microscope (Phoenix Research Laboratories Inc.) equipped with the corresponding modules. Note that the mice were dark adapted in advance for 12 hours for ERG examination, and a single-flash stimulus at an intensity of 5 log with a Tukey post hoc test was used for multiple comparisons. Survival benefit was assessed using a log-rank test. The threshold for statistical significance was *P < 0.05; **P < 0.01; ***P < 0.001. All figure illustrations were created with BioRender.com.Statistical analysis was performed via GraphPad Prism software 7. All data are presented as means ± SEM. Two-tailed Student’s


This study aimed to investigate the utilization of post-ischemic stroke rehabilitation prior to the introduction of the post-acute rehabilitation system in South Korea in 2017.Medical resources utilized for patients with cerebral infarction hospitalized at Regional Cardio-Cerebrovascular Centers (RCCVCs) of 11 tertiary hospitals were tracked until 2019. Stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS), and multivariate regression analysis was performed to analyze factors influencing the length of hospital stay (LOS).This study included 3,520 patients. Among 939 patients with stroke with moderate or greater severity, 209 (22.3%) returned home after RCCVC discharge without inpatient rehabilitation. Furthermore, 1,455 (56.4%) out of 2,581 patients with minor strokes with NIHSS scores ≤4 were readmitted to another hospital for rehabilitation. The median LOS of patients who received inpatient rehabilitation after RCCVC discharge was 47 days. During the inpatient rehabilitation period, the patients were admitted to 2.7 hospitals on average. The LOS was longer in the lowest-income group, high-severity group, and women.Before the introduction of the post-acute rehabilitation system, treatment after stroke was both over- and under-supplied, thus delaying home discharge. These results support the development of a post-acute rehabilitation system that defines the patients, duration, and intensity of rehabilitation. Stroke is known as one of the leading causes of disability worldwide –7. MoreoThe guidelines for healthcare professionals from the American Heart Association/American Stroke Association emphasize the need for sustained and coordinated efforts for stroke rehabilitation . In manyIn South Korea, a post-acute rehabilitation hospital system was not introduced until 2019 , and reiSouth Korea's post-acute rehabilitation system was launched in 2020 . MedicalTo evaluate the effects of this system in the future, it is necessary to analyze the use of medical resources related to rehabilitation services to set a baseline before its introduction. No previous studies have described the use of rehabilitation medical resources before the introduction of the post-acute rehabilitation system. Hence, the methodology of this study can serve as a useful reference for countries planning to implement a post-acute rehabilitation system in the future to evaluate the effects after the introduction of this system.This study aimed to investigate the length of hospital stay (LOS) and related factors for rehabilitation treatment after an ischemic stroke in 2017 before the introduction of the post-acute rehabilitation system.This study tracked the medical resources utilized by patients with ischemic stroke who were hospitalized and discharged from the Regional Cardio-Cerebrovascular Centers (RCCVCs) of 11 tertiary hospitals in 2017 . Data weThe Korean NHIS is a compulsory social health insurance system implemented for all citizens. The NHIS-NHID includes information on demographic and socioeconomic characteristics, births and deaths, healthcare service utilization, and specifics on medical service providers.The linkage between the RSCR and NHIS-NHID was implemented by the division of big data management within the NHIS, and the resident registration number of each patient was used as a linkage key. To protect personal information, the NHIS provided connected data to the researchers after deleting the resident registration number. The researchers could access the data only in the secure online environment provided by the NHIS.This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. H-2101-139-1192). The requirement for informed consent was waived because the data in the NHIS were anonymized and de-identified .The study population consisted of 6,703 patients with cerebral infarction  admitted to RCCVCs from 1 January 2017 to 31 December 2017. Among these, 6,550 patients were linked to the NHIS-NHID (linkage rate: 97.7%). To track medical resource utilization during the 2 years after discharge, this study analyzed NHIS-NHID data until 2019. In the 255 patients who were hospitalized in RCCVCs in 2017 but discharged in 2018, a tracking period of 2 years could not be achieved. Therefore, these were excluded from the analysis. In this study, severity was classified according to the initial NIHSS score during hospitalization. Since thrombolysis treatment can affect severity , 969 patThe primary outcome variable in this study was the LOS from ER admission to home discharge. Only hospitalization for rehabilitation treatment was investigated and presented. When a patient with a stroke was admitted to several hospitals until home discharge, the LOS at each hospital was summed.Hospital admission after stroke was also assessed. For example, one hospital was utilized when a patient was discharged home from the RCCVC, and two were used when a patient was discharged from an LTCH, followed by home discharge. The total follow-up period lasted until 31 December 2019. Therefore, all patients were followed up for 2 years after discharge from the RCCVCs.The NIHSS was used to assess stroke . In thisAdditional explanatory variables included age , sex , and income level. Income level was classified into four different groups according to the level of NHIS co-payment: quartiles 1–4. As the NHIS-NHID has no separate variable for income, NHIS co-payment was considered the patient's income. The lowest group (1st quartile) corresponded to medical aid, and no health insurance co-payment was recorded in this group .Information on the Charlson Comorbidity Index (CCI) was also collected to evaluate patients' comorbidity status before they were admitted to the RCCVCs. Based on the CCI, the severity of comorbidities was categorized as low  or high (≥2) .Two groups “not receiving inpatient rehabilitation group (home discharge from RCCVCs)” and “receiving inpatient rehabilitation group ” were compared. We performed a chi-square test and an analysis of variance for the general characteristics of the study population. For the inpatient rehabilitation group, we analyzed the LOS and number of hospital admissions during the 2-year follow-up period after discharge from the RCCVCs. For each variable, the mean and median (interquartile range [IQR]) values were calculated.Multivariate regression analysis was used to analyze the factors affecting the LOS. Independent variables included the NIHSS score, age, sex, income level, and CCI. All statistical analyses were performed using the SAS statistical software .Among the 5,188 patients linked to the NHIS-NHID, 868 died during hospitalization or within 2 years after discharge from the RCCVCs. Overall, 800 patients were readmitted to a tertiary hospital for purposes other than inpatient rehabilitation, 315 of whom experienced medical complications . A totalAnalyses were performed for the remaining 3,520 patients . Among tThe median LOS in the RCCVCs was 7  days for all 3,520 patients, 6  days for the “not receiving inpatient rehabilitation” group, and 8  days for the “receiving inpatient rehabilitation” group.P < 0.001 and P < 0.001, respectively). The proportion of women was higher in the inpatient rehabilitation group (P < 0.001).The patients in the inpatient rehabilitation group were older and had a higher severity when measured by the NIHSS than those who did not receive inpatient rehabilitation (P < 0.001). Female  and elderly  patients also had a longer LOS and a higher number of hospital admissions. The lowest income level group (Q1) had a longer LOS than that of the other income level groups (P = 0.050).The median LOS from ER admission to home discharge in the inpatient rehabilitation group was 47  days. During this period, these patients received rehabilitation treatment while being hospitalized at three hospitals sequentially at a median value , rather than being admitted to a single hospital . PatientP = 0.002 and P = 0.020, respectively).Although there are no standard guidelines on the strategies for rehabilitation treatment according to the severity of the stroke, patients with minor stroke (NIHSS 0–4) may generally undergo outpatient-based rather than intensive inpatient rehabilitation. By contrast, patients with moderate or higher stroke severity often require inpatient rehabilitation during the post-acute period . This stIn the US, inpatient rehabilitation facilities are institutions that provide intensive inpatient rehabilitation treatment after an acute period of 13 diseases, including stroke. Patients can undergo intensive multidisciplinary rehabilitation programs. They receive 3 h of treatment for 5 of 7 consecutive days , 27. PatIn our study, among 939 patients with stroke of moderate severity or above, 209 (22.3%) returned home after discharge from the RCCVCs without inpatient rehabilitation . In SoutMeanwhile, among 2,581 patients with minor stroke with an NIHSS score of ≤4, 1,455 (56.4%) were readmitted to another hospital for inpatient rehabilitation after discharge from RCCVCs . The aveAnother characteristic phenomenon demonstrated in this study was that patients with stroke in the inpatient rehabilitation group visited several hospitals after being discharged from the RCCVCs, resulting in prolonged LOS , 28. ForSeveral factors influencing LOS may be related to the specific situation in South Korea rather than being universal. First, the long LOS for women may be because women in South Korea have a higher share of household work and fewer people at home to take care of them , 30. ConThis study has some limitations. First, the NHIS-NHID does not contain information on family members or support. Therefore, information on family support could not be obtained, although this is a known factor that affects LOS , 33. SecIn future studies, the use of rehabilitation medical resources and return to home in patients with stroke that occurred after the introduction of the post-acute rehabilitation hospital system in 2020 should be investigated, and the results should be compared with those of this study.In conclusion, before the introduction of the post-acute rehabilitation system in South Korea, rehabilitation treatment after stroke was both over- and under-supplied, and return to home was delayed after discharge from acute care hospitals. Returning home after a stroke was the most delayed in the lowest-income group, high-severity group, and female patients. These results support the need for a post-acute rehabilitation system that specifies the subject, duration, and intensity of rehabilitation treatment. The data reported in this study may serve as basic evidence for planning new systems in countries where a post-acute rehabilitation system has not yet been established.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Institutional Review Board of Seoul National University Hospital. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.SB conceived and planned the study, performed the analysis, wrote the original draft with input from all authors, visualized the results, validated the study, and contributed to the interpretation of the results. JK conceived and planned the study, performed the analysis, wrote the original draft with input from all authors, and contributed to the interpretation of the results. H-IS conceived, planned, validated the study, contributed to the interpretation of the results, and supervised the entire process. All the authors have read and approved the final manuscript.


The COVID-19 pandemic brought new challenges to global healthcare systems regarding the care of acute patients and the delivery of rehabilitation programs to post-acute or chronic patients. Patients who survive severe forms of COVID-19 often report incomplete healing and long-term symptoms. The need of these patients for rehabilitation has been recognized as a public health problem. In this context, the application of tele-rehabilitation has been explored to reduce the burden on healthcare systems. The purpose of this narrative review is to present an overview of the state of the art regarding the application of remote motor rehabilitation programs for paucisymptomatic acute and post-acute COVID-19 patients, with a focus on the motor aspects of tele-rehabilitation. Following an extensive search on PubMed, the Web of Science, and Scopus, specific studies have been reviewed and compared in terms of study objectives and participants, experimental protocols and methods for home-based interventions, functional assessment, and rehabilitation outcomes. Overall, this review suggests the feasibility and the effectiveness of tele-rehabilitation as a promising tool to complement face-to-face rehabilitation interventions. However, further improvements are needed to overcome the limitations and the current lack of knowledge in the field. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic human coronavirus ,2 that wThe clinical severity spectrum of COVID-19 infection has been reported to be highly variable, ranging from asymptomatic and mild-to-moderate cases, to patients requiring admission to intensive care units (ICU), and mechanical ventilation due to acute respiratory distress and/or multiorgan failure ,5,6,7,8.Depending on the severity of the COVID-19 infection, patients may suffer several dysfunctions , are chaPost-COVID patients may thus undergo a wide and heterogeneous sequelae ,11,14,17Rehabilitation plays a key role in the functional recovery of COVID-19 patients, both at the motor and respiratory level, from the early stages of the disease, customizing the interventions and their goals according to the magnitude of the symptoms in order to restore pre-infection physical capacity ,27,28,29The pandemic greatly increased the pressure on healthcare services, requiring a massive engagement of resources and personnel for the curing of the acute patients. Rehabilitation units were often converted into acute-care units, and outpatient rehabilitation was drastically reduced because physiatrists were diverted to acute-care duties. Fear of becoming infected via face-to-face interaction, travel restrictions, and social distancing policies also contributed to a dramatic reduction in rehabilitative treatments for chronic outpatients ,32,33,34In this scenario, tele-rehabilitation appears to be a valuable tool to support health-care systems in managing the rehabilitation demand for chronic and long-COVID patients.Tele-rehabilitation is an area of telemedicine representing the clinical application of consultation, preventive actions, diagnosis, and therapy using audio-visual links and components ,35,36,37Tele-rehabilitation can be delivered synchronously or asynchronously, allowing for a wide range of multi-disciplinary personalized interventions , also mimicking virtual reality and gaming techniques ,42,43,44In the recent years, an increasing number of studies have explored the use of technologies and digital physiotherapy practices, highlighting the potential of this approach for managing chronic outpatients ,51,52. SAlthough COVID-19 primarily affects the respiratory system, survivors often report disabling motor symptoms resulting in impaired physical capacity. This may be due to muscular deconditioning ,60,61 foMotor symptoms following acute or chronic diseases, illness, or injuries can induce specific impairments that need to be addressed in order to optimize functional recovery and reduce disability. Motor tele-rehabilitation can complement other hospital-based interventions based on the rehabilitative goals.Motor tele-rehabilitation programs may include mobility and strength exercises, basic aerobic tasks, and daily recommendation . As for strength exercises, tasks using elastic bands, light dumbbells, and body weight exercises are usually prescribed. The number of sets, repetitions, and weekly sessions is adjusted according to the patient’s health condition.The aim of this narrative review is to present an overview of the state of the art regarding the application of motor tele-rehabilitation programs in the care of paucisymptomatic acute and post-acute COVID-19 patients, focusing on the administration modality and protocols, the functional motor assessment of the patients, and its effectiveness in contributing to the patients’ recovery.An extensive search of the most relevant scientific literature was conducted in December 2022, focusing on studies published during the COVID-19 pandemic years (2020–2022). The electronic search was performed on PubMed, the Web of Science, and Scopus via customized queries using specific keywords and Boolean operators in the form (((POST AND COVID) OR (LONG AND COVID) OR (ACUTE AND COVID)) AND (TELEREHABILITATION AND PROGRAM)). The selection was restricted to full articles written in English, excluding reviews, perspectives, communications, and cases studies. It was decided to include studies assessing only adult patients (≥18 years) with a previous or current COVID-19 diagnosis confirmed by a reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 . As the As a narrative review aimed at summarizing the current state of the art regarding motor tele-rehabilitation in COVID patients, in order to open a general debate on the topic, it was decided not to apply standards for the critical appraisal of the studies’ quality and selection, as these approaches are typical of systematic reviews.A total of 210 articles were retrieved from the previously mentioned electronic databases. After removing the duplicates, the screening of the titles and the abstracts led to the exclusion of 34 items. Out of the remaining 15 articles, 8 failed to meet the inclusion criteria. The selection process and the compete PRISMA flowchart are reported in The selected studies were analyzed in depth to identify methodological similarities and differences. Specifically, the studies were compared in terms of objectives and participants, experimental protocols and methods for the home-based interventions, functional assessment, and outcomes.The common aim of the selected studies was to assess the effects of a tele-rehabilitation program in order to explore its feasibility and effectiveness in the improvement of physical capacity, quality of life, and management of the symptoms in adults who experioenced COVID-19 infection.The studies targeted cohorts of patients at different stage of the disease  characterized by different magnitudes of symptoms .The studies proposed by Dalbosco-Salas et al. , EstebanA commonality among the aforementioned studies was the decision to include only patients with moderate dyspnea. Dyspnea was assessed with the modified Medical Research Council (mMRC) scale ,26,30, aIt should also be noted that due to the pandemic situation, it was not always possible to arrange a face-to-face baseline visit to assess the patients . In thesWhile most of the analyzed studies targeted post-acute patients, the tele-rehabilitation programs proposed by Rodriguez-Blanco et al. ,65 addreIn addition to inclusion criteria specifically related to the severity and the stage of the disease, it should not be forgotten that tele-rehabilitation methods require a basic knowledge and ability regarding the use of technology . For thiOf the selected studies, only those proposed by Rodriguez-Blanco et al. ,65, PehlTele-rehabilitation was performed, addressing different aspects of the rehabilitation needs of COVID-19 patients, using different tools and including different interventions with variable duration.Tele-rehabilitation allows for the delivery of multi-disciplinary interventions addressing different aspects and needs ,69. As sTele-rehabilitation programs were administered either in a synchronous or asynchronous mode, ranging in duration from a minimum of 7 days ,65 to a In the study conducted by Dalbosco-Salas et al. , patientThe program proposed by Estebanez-Perez et al.  includedA similar modality was also chosen by Kortianu et al. , who admWhile the studies analyzed so far applied an asynchronous tele-rehabilitation mode, Pehlivan et al.  chose a Regarding the studies proposed by Rodriguez-Blanco et al. ,65 on paIn all studies, the number of repetitions of each exercise was adjusted according to the patient’s condition, which was assessed using the Borg Scale ,30,64,65A functional exercise capacity assessment of the cohorts at pre- and post-treatment was carried out using various functional tests targeting motor performance and muscle strength. Either a single test or a battery of tests was performed at the baseline and after the treatment in order to detect changes in the patient’s functional capacity.Along with the functional tests, most of the reported studies assessed dyspnea perception after the execution of the tests ,30,64,65Altogether, the results of the functional tests revealed the effectiveness of the proposed approaches for COVID-19 patients in improving physical capacity, symptomatic status, and consequently, their quality of life. In particular, the outcome of the functional test was characterized by an improving trend between the baseline assessment and the end of the tele-rehabilitation program. Apart from the outcome of such tests, no other measures of physical functioning or disability indexes were provided.In the studies by Li et al.  and RodrIn a clinical setting, the test is normally performed in a flat 30 m straight corridor with a mark every 3 or 5 m, with marked turnaround points ,76,77. IDalbosco-Salas et al. , EstebanWith respect to the 1 min STS, the number of repetitions increased significantly after tele-rehabilitation, ranging from a minimum of 3  to a maxAlong with the STS test, Estebanez-Perez et al.  and KortPehlivan et al.  also appThe 3 min step test (3MST)  and the The aim of this review was to provide an overview of the state of the art regarding the application of remote motor rehabilitation programs in the care of paucisymptomatic acute and post-acute COVID-19 patients and an evaluation of their effectiveness in the recovery of functional capacity.Despite heterogeneity in the duration and intervention protocols, the motor tele-rehabilitation programs reviewed seem to be effective in improving functional exercise capacity and long-lasting symptoms.The care of post-COVID-19 survivors is a recent challenge for healthcare systems, and there is still no consensus in the literature regarding the therapeutic interventions and functional tests to be used. Although reference values for COVID-19 patients are not available, adopting widely used functional tests allowed for a comparison of the data in the literature. In particular, the 1 min STST has already proven to be an excellent follow-up measure in both face-to-face and remote rehabilitation programs ,30,64,87The comparison of the results achieved by the patients who followed the tele-rehabilitation program with those in the control group showed a difference in the recovery of functional capacity. The difference found in the outcomes of non-hospitalized versus hospitalized patients and non-ICU versus ICU patients reported by Estebanez-Perez et al.  is also Regarding the two studies concerning acute COVID-19 patients with mild-to-moderate symptoms ,65, the The dropout rates, between 10 and 32%, are in line with those reported in the literature for tele-rehabilitation programs for chronic obstructive pulmonary disease (COPD) . DropoutDespite the promising results, the application of the proposed programs requires further exploration. In particular, the limitations could be related to study design and patient assessment, as well as to the use of the technology and to environmental factors.The main downside related to the study design could be related to the absence of a control group ,30,64. IA risk of bias may be also related to the exclusion of patients with severe dyspnea from tele-rehabilitation. Although this choice was made for safety reasons and to limit the occurrence of adverse events during tele-rehabilitation , it seemIn addition, it should also be noted that since no information was provided on the administration of other rehabilitative interventions prior to tele-rehabilitation, it is difficult to determine whether the improvement in functional exercise capacity is due to tele-rehabilitation, to the natural evolution of the disease, or to the long-term effects of a previous treatment. The pandemic caused the suspension of most inpatient and outpatient rehabilitation services, but it is not known whether this suspension affected the rehabilitation path of these patients before tele-rehabilitation and their baseline status. Additionally, due to the restriction of access to healthcare facilities, it was difficult to achieve a complete assessment of the actual functional state of the patients via clinical tests, such as complete spirometry to evaluate pulmonary function .Another bias could be related to the age group of the participants. Only adult patients >18 years) were assessed, but it seems that only a few studies dealt with patients older than 70 years. For example, in the study of Kortianu et al. , the upp years weAs for environmental factors, the main drawback is related to the assessment environment. In fact, among the reported studies, only Li et al.  assessedThis is a narrative review and therefore, quantitative approaches to assess the quality of the studies commonly used in systematic reviews were not used ,94. In aThe difference between studies applying only motor interventions and those applying either motor and respiratory interventions was not explored in the present work. Since in the work of Rodriguez-Blanco et al. , the stuSeveral case series and studies have been proposed, aiming to improve the respiratory system in COVID-19 patients ,71,72. FGiven the benefits emerging from these studies at both motor and respiratory levels, as well as the close link between exercise capacity and respiratory function reported in literature ,97, in tThe mechanisms underlying the functional recovery of post-COVID-19 patients are not yet fully elucidated, and the individual differences in terms of ongoing symptoms makes it difficult to define standardized rehabilitation protocols. Currently, tele-rehabilitation seems to be a feasible, safe, and effective complementary tool in managing the rehabilitation needs of post-COVID patients, opening new perspectives for a tele-health care-delivery model ,99, but


BackgroundSeveral studies suggested that artificial intelligence (AI), including virtual reality (VR) and augmented reality (AR), may help improve visualization, diagnostic, and therapeutic abilities and reduce medical and surgical errors. These technologies have been revolutionary in Saudi Arabia. We aimed to elucidate physicians' perceptions toward these technologies.MethodologyWe carried out a cross-sectional electronic questionnaire-based study in November 2021. The study targeted doctors of different medical and surgical specialties in the western region of Saudi Arabia.ResultsIn our study, 53.2% of the participants were 25-30 years old. Most participants were residents (53.6%) with career experiences <5 years. Only 32.3% had a good familiarity with AR and VR technologies. However, 64.5% agreed that AR and VR technologies had practical applications in the medical field. Moreover, 35% agreed that the diagnostic and therapeutic ability was superior to the clinical experience of a human doctor. About 41.4% agreed they would always use AR and VR technologies for future medical decisions.ConclusionDoctors are open to using AR and VR technologies in healthcare. Although most people are unfamiliar with these technologies, most agree that they positively impact healthcare. Artificial intelligence (AI), augmented reality (AR), virtual reality (VR), and machine learning are permeating all aspects of healthcare . The useRecent technological developments have improved the portability, realism, and real-time navigation of VR and AR systems and expanded the sensory range by adding sensory and occasionally olfactory aspects . VR is aOn the other hand, the closely linked AR uses VR components to overlay them in the real world using live videos presented on an electronic device . AR has Study design and settingsThis cross-sectional electronic questionnaire-based study was carried out in November 2021. This study targeted doctors of different medical and surgical specialties in the western region of Saudi Arabia. The research team collected data using an online questionnaire conducted via social media websites.Sample populationThe total sample size was 220 people. The questionnaire links were sent to each participant. Each specialist received the same connection to ensure each participant was represented correctly.Questionnaire instrumentThe questionnaire's content was identical across all links. In addition to the link to social media, a brief introduction was provided regarding the study's objectives and goals. We informed the participants that the participation was voluntary and anonymous and that all information would be kept strictly confidential. The participants then had to confirm their involvement in the study by selecting either "agree" to continue the research or "disagree" with the participant's anonymous identities. The study's primary inclusion criteria were (1) doctors who work in different specialties of medicine in Saudi Arabia, (2) those who confirm their agreement to answer the questionnaire, and (3) those who completed the questionnaire. The study's primary exclusion criteria were (1) undergraduate medical students, (2) healthcare workers other than doctors , (2) those who did not confirm their agreement to answer the questionnaire, and (3) those who did not complete the questionnaire. Using the Google questionnaire, we designed an electronic questionnaire consisting of three parts. The first part was the participants’ personal information, including the participants’ place of residence, gender, age, years of experience as a carrier, professional title, and specialty. The second part was about the participant's basic understanding of AR and VR, including whether the participant had sufficient information about AR and VR technologies. The third part was about the participant's attitudes to AR and VR, including whether they thought the AR anthologies would replace doctors.Face validity check and piloting phaseThe questionnaire was piloted on a group of students (n = 20) to analyze its validity and ensure a proper interpretation of the questions. The results of the pilot questions appeared satisfactory and valid.Statistical analysisThe results of the questionnaires were displayed in Excel version 16.16.23 , while the data were analyzed statistically using SPSS Statistics version 26 . The questionnaire used in this study included questions on Saudi doctors' perceptions of using logics in medicine. The questionnaire items were derived from previous studies in ,11. A stEthical approvalTaif University's ethics committee approved this study and approved the research proposal. The National Committee for Bioethics accredits the committee with No. HAO-02-T-105.About 53.2% of the participants were 25-30 years old, 54.1% were males, and 47.7% had a career experience <5 years. Among them, 53.6% were residents  and 35% agreed that AR and VR technologies' diagnostic and therapeutic abilities are superior to human doctors' clinical experience, respectively. Only 24.6% agreed that AR and VR technologies could replace their jobs, and 41.4% agreed that they would always use AR and VR technologies for medical decisions in the future. More than half (58.1% and 60.9%) agreed that AR and VR technologies could increase the speed of processes in healthcare and reduce medical errors, respectively. Approximately 53% (53.2%) agreed that AR and VR technologies could reduce burnout among doctors, and 35.4% agreed that these technologies have no physical limitations . In comparison, a nonsignificant relationship was observed between the participants' demographic and work characteristics (p >0.05) Table .Approximately 44% (44.6%) of the participants had sufficient general information about AR and VR technologies. Moreover, 39.1% reported knowing about AR and VR applications in the medical field Figures .The most common concerns of the participants regarding the application of AR and VR technologies in medicine were the cost (65.5%) and non-flexibility for application to every patient (59.5%). They cannot be used to provide opinions in unpredictable situations owing to inadequate information (55%) Figure .The most commonly reported medical applications, the AR and VR technologies, will be most helpful, according to the participants' opinions, in diagnosis (57.3%) and medical assistance in underserved areas (53.2%) Figure .The most common medical fields were general surgery (48.2%), radiology (39.1%), and neurosurgery 35.5%)  in their medical practices . FurtherThese technologies are superior regarding many physicians' diagnoses and clinical experience. A study in Germany showed that more than half of the students felt more integrated, which would improve the radiological field. Similarly, Buchanan showed that students trained with VR exhibited better and faster learning experiences, almost at the same level as traditional medical practice trainees .In our study, some individuals agreed that VR and AR technologies could accelerate healthcare. Similar results were obtained in a survey by Hui et al., where the subjects exhibited significant improvements in their cognitive function and processing speed . AnotherAccording to our findings, a minority of respondents believed these technologies are useful in medical decisions. Approximately half of the individuals were confident they could help reduce medical errors. Similar studies demonstrated that practitioners who practiced surgery with VR and AR technologies before the surgery performed better with fewer errors than their fellow residents . SimilarApproximately half of the individuals believed that they could relieve the burnout of practitioners. A study at Mount Sinai demonstrated that using VR technologies on their residents for two months can significantly reduce emotional exhaustion (P = 0.027) and residents' burnout rate . A minorDoctors are open to the use of AR and VR technologies in healthcare. Although most people are unfamiliar with these technologies, the majority agree that they positively impact healthcare. They believe that these technologies will help reduce medical errors and practitioner burnout. However, current barriers must be resolved to increase the awareness and use of these technologies for some healthcare professionals in the future.