Optimizing Rare Disease Gait Classification through Data Balancing and Generative AI: Insights from Hereditary Cerebellar Ataxia.

The interpretability of gait analysis studies in people with rare diseases, such as those with primary hereditary cerebellar ataxia (pwCA), is frequently limited by the small sample sizes and unbalanced datasets. The purpose of this study was to assess the effectiveness of data balancing and generative artificial intelligence (AI) algorithms in generating synthetic data reflecting the actual gait abnormalities of pwCA. Gait data of 30 pwCA (age: 51.6 ± 12.2 years; 13 females, 17 males) and 100 healthy subjects (age: 57.1 ± 10.4; 60 females, 40 males) were collected at the lumbar level with an inertial measurement unit. Subsampling, oversampling, synthetic minority oversampling, generative adversarial networks, and conditional tabular generative adversarial networks (ctGAN) were applied to generate datasets to be input to a random forest classifier. Consistency and explainability metrics were also calculated to assess the coherence of the generated dataset with known gait abnormalities of pwCA. ctGAN significantly improved the classification performance compared with the original dataset and traditional data augmentation methods. ctGAN are effective methods for balancing tabular datasets from populations with rare diseases, owing to their ability to improve diagnostic models with consistent explainability.

Augmented Virtual Reality in Vestibular Assessment: A Dynamic Gait Application.

INTRODUCTION: Dizziness is a common complaint affecting up to 23% of the world population. Diagnosis is of utmost importance and routinely involves several tests to be performed in specialized centers. The advent of a new generation of technical devices would make envision their use for a valid objective vestibular assessment. Microsoft HoloLens 2 (HL2) mixed reality headset has the potential to be a valuable wearable technology that provides interactive digital stimuli and inertial measurement units (IMUs) to objectively quantify the movements of the user in response to various exercises. The aim of this study was to validate the integration of HoloLens with traditional methods used to analyze the vestibular function in order to obtain precise diagnostic values. METHODS: Twenty-six healthy adults completed the Dynamic Gait Index tests both with a traditional evaluation and while wearing HL2 headset, thus allowing to collect kinematic data of the patients' head and eyes. The subjects had to perform 8 different tasks, and the scores were independently assigned by two otolaryngology specialists. RESULTS: The maximum of the mean position of the walking axis of the subjects was found in the second task (-0.14 ± 0.23 m), while the maximum value of the standard deviation of the walking axis was found in the fifth task (-0.12 ± 0.27 m). Overall, positive results were obtained in regard to the validity of the HL2 use to analyze kinematic features. CONCLUSION: The accurate quantification of gait, movement along the walking axis, and deviation from the normality using HL2 provide an initial evidence for its useful adoption as a valuable tool in gait and mobility assessment.

A Proof of Concept Combined Using Mixed Reality for Personalized Neurorehabilitation of Cerebellar Ataxic Patients.

BACKGROUND: Guidelines for degenerative cerebellar ataxia neurorehabilitation suggest intensive coordinative training based on physiotherapeutic exercises. Scientific studies demonstrate virtual exergaming therapeutic value. However, patient-based personalization, post processing analyses and specific audio-visual feedbacks are not provided. This paper presents a wearable motion tracking system with recording and playback features. This system has been specifically designed for ataxic patients, for upper limbs coordination studies with the aim to retrain movement in a neurorehabilitation setting. Suggestions from neurologists and ataxia patients were considered to overcome the shortcomings of virtual systems and implement exergaming. METHODS: The system consists of the mixed-reality headset Hololens2 and a proprietary exergaming implemented in Unity. Hololens2 can track and save upper limb parameters, head position and gaze direction in runtime. RESULTS: Data collected from a healthy subject are reported to demonstrate features and outputs of the system. CONCLUSIONS: Although further improvements and validations are needed, the system meets the needs of a dynamic patient-based exergaming for patients with cerebellar ataxia. Compared with existing solutions, the mixed-reality system is designed to provide an effective and safe therapeutic exergaming that supports both primary and secondary goals of an exergaming: what a patient should do and how patient actions should be performed.

Analysis of Connectome Graphs Based on Boundary Scale.

The purpose of this work is to advance in the computational study of connectome graphs from a topological point of view. Specifically, starting from a sequence of hypergraphs associated to a brain graph (obtained using the Boundary Scale model, BS2), we analyze the resulting scale-space representation using classical topological features, such as Betti numbers and average node and edge degrees. In this way, the topological information that can be extracted from the original graph is substantially enriched, thus providing an insightful description of the graph from a clinical perspective. To assess the qualitative and quantitative topological information gain of the BS2 model, we carried out an empirical analysis of neuroimaging data using a dataset that contains the connectomes of 96 healthy subjects, 52 women and 44 men, generated from MRI scans in the Human Connectome Project. The results obtained shed light on the differences between these two classes of subjects in terms of neural connectivity.

Prognostic value of texture analysis of the primary tumour in high-risk neuroblastoma: An 18 F-DOPA PET study.

PURPOSE: To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography (18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL). METHODS: We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS). RESULTS: There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUVmean : p = .004) and voxel heterogeneity (entropy: p = .026; GLCM_Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM_Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p < .05) for both. CONCLUSIONS: Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival.

A Comparative Study on a Novel Quality Assessment Protocol Based on Image Analysis Methods for Color Doppler Ultrasound Diagnostic Systems.

Color Doppler (CD) imaging is widely used in diagnostics since it allows real-time detection and display of blood flow superimposed on the B-mode image. Nevertheless, to date, a shared worldwide standard on Doppler equipment testing is still lacking. In this context, the study herein proposed would give a contribution focusing on the combination of five test parameters to be included in a novel Quality Assessment (QA) protocol for CD systems testing. A first approach involving the use of the Kiviat diagram was investigated, assuming the diagram area, normalized with respect to one of the gold standards, as an index of the overall Doppler system performance. The QA parameters were obtained from the post-processing of CD data through the implementation of custom-written image analysis methods and procedures, here applied to three brand-new high-technology-level ultrasound systems. Experimental data were collected through phased and convex array probes, in two configuration settings, by means of a Doppler flow phantom set at different flow rate regimes. The outcomes confirmed that the Kiviat diagram might be a promising tool applied to quality controls of Doppler equipment, although further investigations should be performed to assess the sensitivity and specificity of the proposed approach.

Validation of SuPerSense, a Sensorized Surface for the Evaluation of Posture Perception in Supine Position.

This study aimed to validate a sensorized version of a perceptive surface that may be used for the early assessment of misperception of body midline representation in subjects with right stroke, even when they are not yet able to stand in an upright posture. This device, called SuPerSense, allows testing of the load distribution of the body weight on the back in a supine position. The device was tested in 15 patients with stroke, 15 age-matched healthy subjects, and 15 young healthy adults, assessing three parameters analogous to those conventionally extracted by a baropodometric platform in a standing posture. Subjects were hence tested on SuPerSense in a supine position and on a baropodometric platform in an upright posture in two different conditions: with open eyes and with closed eyes. Significant correlations were found between the lengths of the center of pressure path with the two devices in the open-eyes condition (R = 0.44, p = 0.002). The parameters extracted by SuPerSense were significantly different among groups only when patients were divided into those with right versus left brain damage. This last result is conceivably related to the role of the right hemisphere of the brain in the analysis of spatial information.

3D pelvimetry and biometric measurements: a surgical perspective for colorectal resections.

PURPOSE: Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution. METHODS: A 3D software was used for segmentation of DICOM data of consecutive patients aged 60 years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx's tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses. RESULTS: Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p < 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape. CONCLUSION: Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum.

Effects on Motor Control of Personalized Neuromodulation Against Multiple Sclerosis Fatigue.

Fatigue is a hidden symptom of Multiple Sclerosis (MS) disease that nevertheless impacts severely on patients' everyday life. Evidence indicates the involvement of the sensorimotor network and its inter-nodes communication at the basis of this symptom. Two randomized controlled trials (RCTs) showed that the personalized neuromodulation called Fatigue Relief in Multiple Sclerosis (FaReMuS) efficaciously fights multiple sclerosis (MS) fatigue. By this Proof of Concept study, we tested whether FaReMuS reverts the alteration of the brain-muscular synchronization previously observed occurring with fatigue. The cortico muscular coherence (CMC) was studied in 11 patients before and after FaReMuS, a 5-day tDCS (1.5 mA, 15 min per day) anodal over the whole body's somatosensory representation (S1) via a personalized MRI-based electrode (35 cm2) against the occipital cathode (70 cm2). Before FaReMuS, the CMC was observed at a mean frequency of 31.5 ± 1.6 Hz (gamma-band) and positively correlated with the level of fatigue (p = .027). After FaReMuS, fatigue reduced in average of 28% ± 33% the baseline level, and the CMC frequency reduced to 26.6 ± 1.5 Hz (p = .022), thus forthcoming the physiological beta-band as observed in healthy people. The personalized S1 neuromodulation treatment, ameliorating the central-peripheral communication that subtends simple everyday movements, supports the appropriateness of neuromodulations aiming at increasing the parietal excitability in fighting MS fatigue. The relationship between central-peripheral features and fatigue profile strengthens a central more than peripheral origin of the symptom.

There Is a Great Future in Plastics: Personalized Approach to the Management of Hilar Cholangiocarcinoma Using a 3-D-Printed Liver Model.

In recent years, three-dimensional (3-D) printing technology has become a standard tool that is used in several medical applications such as education, surgical training simulation and planning, and doctor-patient communication. Although liver surgery is ideally complemented by the use of preoperative 3-D-printed models, only a few publications have addressed this topic. We report the case of a 29-year-old Caucasian woman admitted for a Klatskin tumor infiltrating the right portal vein requiring surgery that required complex vascular reconstruction. A life-sized liver model with colorful plastic vessels and realistic looking tumor was created with the aim of planning an optimal surgical approach. According to the 3-D model, we performed a right hepatic trisectionectomy, also removing enbloc the tract of portal vein encased by the tumor and the neoplastic thrombus, followed by a complex vascular reconstruction between the main portal vein and the left portal branch. After 22 months of follow-up, the patient was alive and continuing chemotherapy. The use of the 3-D models in liver surgery helps clarify several useful preoperative issues. The accuracy of the model regarding anatomical findings was high. In the case of complex vascular reconstruction strategies, rational use of 3-D printing technology should be implemented.

Sensorized Assessment of Dynamic Locomotor Imagery in People with Stroke and Healthy Subjects.

Dynamic motor imagery (dMI) is a motor imagery task associated with movements partially mimicking those mentally represented. As well as conventional motor imagery, dMI has been typically assessed by mental chronometry tasks. In this paper, an instrumented approach was proposed for quantifying the correspondence between upper and lower limb oscillatory movements performed on the spot during the dMI of walking vs. during actual walking. Magneto-inertial measurement units were used to measure limb swinging in three different groups: young adults, older adults and stroke patients. Participants were tested in four experimental conditions: (i) simple limb swinging; (ii) limb swinging while imagining to walk (dMI-task); (iii) mental chronometry task, without any movement (pure MI); (iv) actual level walking at comfortable speed. Limb swinging was characterized in terms of the angular velocity, frequency of oscillations and sinusoidal waveform. The dMI was effective at reproducing upper limb oscillations more similar to those occurring during walking for all the three groups, but some exceptions occurred for lower limbs. This finding could be related to the sensory feedback, stretch reflexes and ground reaction forces occurring for lower limbs and not for upper limbs during walking. In conclusion, the instrumented approach through wearable motion devices adds significant information to the current dMI approach, further supporting their applications in neurorehabilitation for monitoring imagery training protocols in patients with stroke.

Performance of contrast-enhanced ultrasound (CEUS) in assessing thyroid nodules: a systematic review and meta-analysis using histological standard of reference.

BACKGROUND: The present study was undertaken to systematically review the literature on the reliability of using contrast-enhanced ultrasound (CEUS) to assess thyroid nodules. To avoid the potential bias in studies using a cytological standard of reference, here we aimed to meta-analyze data from studies adopting histological diagnosis as the gold standard. METHODS: A comprehensive literature exploration of PubMed and Scopus was conducted. The search was updated until June 2018 and references of the retrieved articles screened. Only original articles reporting the histological follow-up of nodules previously undergone CEUS evaluation were eligible for inclusion. Pooled sensitivity, specificity, PPV, and NPV of CEUS were calculated by DerSimonian and Laird method (random-effects model). RESULTS: The literature search retrieved 1885 articles, and 14 were included for the study. There were Chinese, Italian, German, and Austrian authors. All studies used SonoVue. The overall number of reported nodules was 1515, of which 775 were classified as positive at CEUS and 740 as negative. Pooled sensitivity, specificity, PPV, and NPV of CEUS were 85% (95% CI 83-88), 82% (95% CI 77-87), 83% (95% CI 77-88), and 85% (95% CI 81-88), respectively. Moderate inconsistency was present for specificity and PPV. There was publication bias for sensitivity and NPV. CONCLUSIONS: CEUS reaches good performance in discriminating between malignant and benign thyroid lesions.

The Effect of Postmastectomy Radiation Therapy on Breast Implants: Material Analysis on Silicone and Polyurethane Prosthesis.

INTRODUCTION: The pathogenic mechanism underlying capsular contracture is still unknown. It is certainly a multifactorial process, resulting from human body reaction, biofilm activation, bacteremic seeding, or silicone exposure. The scope of the present article is to investigate the effect of hypofractionated radiotherapy protocol (2.66 Gy × 16 sessions) both on silicone and polyurethane breast implants. METHODS: Silicone implants and polyurethane underwent irradiation according to a hypofractionated radiotherapy protocol for the treatment of breast cancer. After irradiation implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, infrared spectra in attenuated total reflectance mode, nuclear magnetic resonance, and field emission scanning electron microscopy. RESULTS: At superficial analysis, irradiated silicone samples show several visible secondary and tertiary blebs. Polyurethane implants showed an open cell structure, which closely resembles a sponge. Morphological observation of struts from treated polyurethane sample shows a more compact structure, with significantly shorter and thicker struts compared with untreated sample. The infrared spectra in attenuated total reflectance mode spectra of irradiated and control samples were compared either for silicon and polyurethane samples. In the case of silicone-based membranes, treated and control specimens showed similar bands, with little differences in the treated one. Nuclear magnetic resonance spectra on the fraction soluble in CDCl3 support these observations. Tensile tests on silicone samples showed a softer behavior of the treated ones. Tensile tests on Polyurethane samples showed no significant differences. CONCLUSIONS: Polyurethane implants seem to be more resistant to radiotherapy damage, whereas silicone prosthesis showed more structural, mechanical, and chemical modifications.

Experimental Investigation of Inter-element Isolation in a Medical Array Transducer at Various Manufacturing Stages.

This work presents the experimental investigation of vibration maps of a linear array transducer with 192 piezoelements by means of a laser Doppler vibrometer at various manufacturing finishing steps in air and in water. Over the years, many researchers have investigated cross-coupling in fabricated prototypes but not in arrays at various manufacturing stages. Only the central element of the array was driven at its working frequency of 5 MHz. The experimental results showed that the contributions of cross-coupling depend on the elements of the acoustic stack: Lead Zirconate Titanate (PZT), kerf, filler, matching layer, and lens. The oscillation amplitudes spanned from (6 ± 38%) nm to (110 ± 40%) nm when the energized element was tested in air and from (6 ± 57%) nm to (80 ± 67%) nm when measurements were obtained under water. The best inter-element isolation of -22 dB was measured in air after cutting the kerfs, whereas the poorest isolation was -2 dB under water with an acoustic lens (complete acoustic stack). The vibration pattern in water showed a higher standard deviation on the displacement measurements than the one obtained in air, due to the influence of acousto-optic interactions. The amount increased to 30% in water, as estimated by a comparison with the measurements in air. This work describes a valuable method for manufacturers to investigate the correspondence between the manufacturing process and the quantitative evaluations of the resulting effects.

Laparoscopic versus robotic-assisted colectomy and rectal resection: a systematic review and meta-analysis.

PURPOSE: Lately, the main technical innovations in the field of colorectal surgery have been the introduction of laparoscopic and robotic techniques; the aim of this study is to investigate the results and the advantages of these two surgical approaches. METHODS: Twenty-two studies including 1652 laparoscopic and 1120 robotic-assisted resections were analyzed and categorized into right, left, and pelvic resections of the middle/low rectum, aiming to the following outcomes: operating time, blood loss, bowel function recovery, return to oral intake, morbidity, hospital stay, and costs. RESULTS: The vast majority of the studies were non-randomized investigations (19/22 studies) enrolling small cohorts of patients (median 55.0 laparoscopic and 34.5 robotic-assisted group) with a mean age of 62.2-61.0 years. Funnel plot analysis documented heterogeneity in studies which combined cancers and benign diseases. Our meta-analysis demonstrated a significant difference in favor of laparoscopic procedures regarding costs and operating time (standardized mean difference (SMD) 0.686 and 0.493) and in favor of robotic surgery concerning morbidity rate (odds ratio (OR) 0.763), although no benefits were documented when analyzing exclusively randomized trials. When we differentiated approaches by side of resections, a significant difference was found in favor of the laparoscopic group when analyzing operating time in left-sided and pelvic procedures (SMD 0.609 and 0.529) and blood loss in pelvic resections (SMD 0.339). CONCLUSION: Laparoscopic techniques were documented as the shorter procedures, which provided lower blood loss in pelvic resections, while morbidity rate was more favorable in robotic surgery. However, these results could not be confirmed when we focused the analysis on randomized trials only.

Stability and Harmony of Gait in Patients with Subacute Stroke.

Stroke affects many gait features, such as gait stability, symmetry, and harmony. However, it is still unclear which of these features are directly altered by primary damage, and which are affected by the reduced walking speed. The aim of this study was to analyze the above gait features in patients with subacute stroke with respect to the values observed in age- and speed-matched healthy subjects. A wearable triaxial accelerometer and an optoelectronic device were used for assessing the upright gait stability, symmetry of trunk movements, and harmonic structure of gait phases by means of the root-mean-square (RMS) acceleration of the trunk, harmonic ratio (HR), and gait ratios (GRs), respectively. For healthy subjects, results showed that RMS acceleration increased with speed, HR peaked at a comfortable speed, and GRs tended towards the theoretical value of the golden ratio for speeds >1 m/s. At matched speed conditions, patients showed higher instabilities in the latero-lateral axis (p = 0.001) and reduced symmetry of trunk movements (p = 0.002). Different from healthy subjects, antero-posterior and latero-lateral acceleration harmonics were coupled in patients (R = 0.507, p = 0.023). Conversely, GRs were not more altered in patients than in slow-walking healthy subjects. In conclusion, patients with stroke showed some characteristics similar to those of the elderly when the latter subjects walk slowly, and some altered characteristics, such as increased latero-lateral instabilities coupled with movements performed along the antero-posterior axis.

Design Concepts, Fabrication and Advanced Characterization Methods of Innovative Piezoelectric Sensors Based on ZnO Nanowires.

Micro- and nano-scale materials and systems based on zinc oxide are expected to explode in their applications in the electronics and photonics, including nano-arrays of addressable optoelectronic devices and sensors, due to their outstanding properties, including semiconductivity and the presence of a direct bandgap, piezoelectricity, pyroelectricity and biocompatibility. Most applications are based on the cooperative and average response of a large number of ZnO micro/nanostructures. However, in order to assess the quality of the materials and their performance, it is fundamental to characterize and then accurately model the specific electrical and piezoelectric properties of single ZnO structures. In this paper, we report on focused ion beam machined high aspect ratio nanowires and their mechanical and electrical (by means of conductive atomic force microscopy) characterization. Then, we investigate the suitability of new power-law design concepts to accurately model the relevant electrical and mechanical size-effects, whose existence has been emphasized in recent reviews.

Development of a microfluidic-assisted open-source 3D bioprinting system (MOS3S) for the engineering of hierarchical tissues.

The engineering of new 3D bioprinting approaches has shown great promise in the field of tissue engineering and disease modelling. However, the high cost of commercial 3D bioprinters has limited their accessibility, especially to those laboratories in resource-limited settings. Moreover, the need for a 3D bioprinting system capable of dispensing multiple materials is growing apace. Therefore, the development of a Microfluidic-assisted Open Source 3D bioprinting System (MOS3S) for the engineering of hierarchical tissues is needed to progress in fabricating functional tissues, but with a technology accessible to a wider range of researchers. The MOS3S platform is designed to allow the deposition of biomaterial inks using microfluidic printheads or coaxial nozzles for the in-situ crosslinking and scaffolds fabrication. The coupling of 3D printed syringe pumps with the motion control system is used for driving the tunable extrusion of inks for the fabrication of centimeter scale hierarchical lattice constructs for tissue engineering purposes. MOS3S performance have been validated to fabricate high-resolution structures with coaxial microfluidic technology, opening to new frontiers for seminal studies in pre-clinical disease modelling and tissue regeneration.

Development and Implementation of an Innovative Framework for Automated Radiomics Analysis in Neuroimaging.

Radiomics represents an innovative approach to medical image analysis, enabling comprehensive quantitative evaluation of radiological images through advanced image processing and Machine or Deep Learning algorithms. This technique uncovers intricate data patterns beyond human visual detection. Traditionally, executing a radiomic pipeline involves multiple standardized phases across several software platforms. This could represent a limit that was overcome thanks to the development of the matRadiomics application. MatRadiomics, a freely available, IBSI-compliant tool, features its intuitive Graphical User Interface (GUI), facilitating the entire radiomics workflow from DICOM image importation to segmentation, feature selection and extraction, and Machine Learning model construction. In this project, an extension of matRadiomics was developed to support the importation of brain MRI images and segmentations in NIfTI format, thus extending its applicability to neuroimaging. This enhancement allows for the seamless execution of radiomic pipelines within matRadiomics, offering substantial advantages to the realm of neuroimaging.

Mixed Reality-Based Smart Occupational Therapy Personalized Protocol for Cerebellar Ataxic Patients.

BACKGROUND: Occupational therapy (OT) is an essential component of patient care, and it is especially beneficial if focused on meaningful activities. For ataxic patients, traditional procedures are currently the most efficient, although without specific guidelines and suggestions for virtual reality integration. In this context, this study proposes Hybrid Smart Rehabilitation (HSR) based on mixed reality (MR) as an aid in overcoming limitations of the traditional OT procedures. METHODS: MR-HSR is designed specifically for ataxic patients and developed in Unity with the Holographic Remoting setting for run-time intervention on the scene. The subject reaches a book and grabs it with their hand inside a holographic guide with audio-visive feedback. Hand trajectories acquired from eight ataxic patients and eight healthy subjects were compared and new variables were analyzed to evaluate the performance. The Trust in Automation questionnaire was submitted to assess the opinion of the patients. RESULTS: Patients confirmed their trust in the developer and in the improvement that this system can bring to their rehabilitation. The "total time" and "sway area" of the trajectory were statistically significant and, together with the deviation of the trajectory from the main axis of the guide, although not statistically significant, made it possible to build a classifier. CONCLUSIONS: The patient-specific MR-HSR can be considered as an integrative tool for assessing the subject's condition by analyzing new quantitative variables which, if matched to the Scale for the Assessment and Rating of Ataxia (SARA), could be the basis of a new index to assess the progressiveness of ataxia.