Combining FES and Exoskeletons in a Hybrid Haptic System for Enhancing VR Experience.

Robotic technology and functional electrical stimulation (FES) have emerged as highly effective rehabilitative techniques for individuals with neuromuscular diseases, showcasting their ability to restore motor functions. Within the proposed study, we developed and tested a new hybrid controller combining an upper-limb exoskeleton with FES to enhance haptic feedback when performing task-oriented and bimanual movement, like pick-and-place, in a virtual environment. We investigated the performance of the proposed approach on eight unimpaired participants providing haptic feedback either only by the exoskeleton or by the hybrid system. The hybrid control presents two different modalities, assistive and resistive, to modulate the perception of the load. FES intensity is calibrated to the subjects' biomechanical properties and it is adjusted in real-time according to the real-time motion of the upper limbs. Experimental results highlighted the ability of the hybrid control to improve kinematic performance: in both hybrid modalities subjects reduced the target matching error(values between 0.048±0.007 m and 0.06±0.006 m) without affecting the normal motion smoothness (SPARC values in the hybrid conditions range from -2.58±0.12 to -3.30±0.13). Moreover, the resistive approach resulted in greater metabolic consumption (1.04±0.03 W/kg), indicating a more realistic experience of lifting a virtual object through FES that increased the perceived weight. The innovation in our hybrid control relies on the modulation of muscular activation during manipulation tasks, which could be a promising approach in the clinical treatment of neuromuscular diseases.

ADRIS: The new open-source accessible driving simulator for training and evaluation of driving abilities.

BACKGROUND AND OBJECTIVE: Independent living and transportation are crucial aspects for people living with a disability. After an injury, it is important to assess driving ability, in terms of physical and psychological conditions, and to test the effects of prescribed drugs. Within this framework, driving simulators are suitable tools for training driving skills; however, available tools are expensive or lack appropriate sets of behavioral measures to fully characterize the drivers' ability. METHODS: This work presents the first step toward the development of ADRIS, a new open-source, accessible, realistic virtual reality simulator for training and testing driving skills of people with sensory-motor disability. This includes a prototype based on an open-source simulator for autonomous driving research (CARLA), with the addition of customized features such as adaptable driving controllers, a virtual reality headset, and the possibility to collect behavioral and physiological data. Also, the new system allows to set different environmental conditions, to include and control the timing of potentially dangerous situations, and to set scenarios with various difficulty levels. RESULTS: Tests on 17 healthy participants demonstrated that the simulator is well tolerated in terms of discomfort, physical fatigue, and mental effort. Also, the system is easy to use and is capable of providing a realistic driving experience, allowing the extraction of reliable behavioral parameters. CONCLUSIONS: ADRIS combines a high-fidelity virtual world, with customizable features specifically designed for the training and testing of people living with a disability, thus making it usable in many contexts such as home training, rehabilitation, education, and research.

Setup of multidisciplinary team discussions for patients with cholangiocarcinoma: current practice and recommendations from the European Network for the Study of Cholangiocarcinoma (ENS-CCA).

BACKGROUND: Cholangiocarcinomas (CCAs) are a rare group of malignancies characterized by dismal prognosis. There are currently no standardized guidelines for multidisciplinary teams (MDTs) in CCAs. MATERIAL AND METHODS: An online survey was built with the aim of defining the current practice of MDTs in CCAs and identifying possible areas of improvement, providing minimum standards of practice for an ideal CCA MDT. Analysis of the replies regarding current and ideal MDT practice was carried out by calculating weighted average (WA) of likelihood of every item. The survey was shared with members of the European Network for the Study of Cholangiocarcinoma and other medical centers with expertise in biliary tract cancer part of the EURO-CHOLANGIO-NET (European Cholangiocarcinoma Network: https://eurocholangionet.eu/) COST Action CA18122 initiative. RESULTS: The role of the MDT coordinator was a recognized priority in an ideal well-functioning MDT (WA 3.31/4), together with providing minimum clinical information before the meeting to secure adequate case preparation (WA 3.54/4). Optimal frequency of MDT meetings was weekly according to 76.92% of the participants; 73.06% believed that ideally all newly diagnosed patients and each new treatment should be discussed, although that happened only in less than half of the MDTs (46.15%) in current practice. Most participants stated that they always (46.15%) or often (50.00%) used guidelines, mainly international (61.00%) (European and American), followed by national/local (39.00%). We defined the ideal setup of a CCA MDT, identifying specialists whose presence is mandatory with WA >3.0 (oncologist, clinician responsible for patient's care, surgeon, diagnostic and interventional radiologist, hepatologist, pathologist, endoscopist and gastroenterologist) and those whose presence would be recommended with a WA <3.0 (palliative care, nurse, dietitian, basic researcher, psychologist and social worker). CONCLUSIONS: Our identified minimum requirements should be taken into account at the time of CCA MDT setup and quality assessment.

Changes in neuromuscular activity during motor training with a body-machine interface after spinal cord injury.

Body machine interfaces (BMIs) are used by people with severe motor disabilities to control external devices, but they also offer the opportunity to focus on rehabilitative goals. In this study we introduced in a clinical setting a BMI that was integrated by the therapists in the rehabilitative treatments of 2 spinal cord injured (SCI) subjects for 5 weeks. The BMI mapped the user's residual upper body mobility onto the two coordinates of a cursor on a screen. By controlling the cursor, the user engaged in playing computer games. The BMI allowed the mapping between body and cursor spaces to be modified, gradually challenging the user to exercise more impaired movements. With this approach, we were able to change our subjects' behavior, who initially used almost exclusively their proximal upper body-shoulders and arms - for using the BMI. By the end of training, cursor control was shifted toward more distal body regions - forearms instead of upper arms - with an increase of mobility and strength of all the degrees of freedom involved in the control. The clinical tests and the electromyographic signals from the main muscles of the upper body confirmed the positive effect of the training. Encouraging the subjects to explore different and sometimes unusual movement combinations was beneficial for recovering distal arm functions and for increasing their overall mobility.

A body-machine interface for training selective pelvis movements in stroke survivors: A pilot study.

The body-machine interfaces (BMIs) map the subjects' movements into the low dimensional control space of external devices to reach assistive and/or rehabilitative goals. This work is a first proof of concept of this kind of BMI as tool for rehabilitation after stroke. We designed an exercise to improve the control of selective movements of the pelvis in stroke survivors, increasing the ability to decouple the motion in the sagittal and frontal planes and decreasing compensatory adjustments at the shoulder girdle. A Kinect sensor recorded the movements of the subjects. Subjects played different games by controlling the vertical and horizontal motion of a cursor on a screen with respectively the lateral tilt and the ante/retroversion of their pelvis. We monitored also the degrees of freedom not directly involved in cursor control, thus subjects could complete the task only with a correct posture. Our preliminary results highlight significant improvement not only in cursor control, but also in the Trunk Impairment Scale (TIS) and in the Five Times Sit to Stand Test (5xSST).

Neural correlates of ankle movements during different motor tasks: A feasibility study.

This ongoing study investigates the neural correlates of ankle dorsi-plantar flexion in active, passive, and proprioceptive tasks. Specifically, we investigated two proprioceptive matching tasks that required a simple combination of active and passive ankle movements: (1) a memory-based ipsilateral matching task and (2) a contralateral concurrent matching task. As expected, during the passive tasks, subjects recruited the same brain areas involved in the correspondent active movements (primary motor cortex (M1), premotor cortex (PM) supplementary motor cortex (SMA) and primary somatosensory cortex (S1)), but the activations were lower. Instead, in both the proprioceptive matching tasks, subjects recruited more motor and sensory-motor areas of the brain and the activations were greater.

Analysis of upper limb movement in Multiple Sclerosis subjects during common daily actions.

The goal of this study was to investigate the movement and muscle activity of the upper limb during common activities of daily life in people with Multiple Sclerosis (PwMS) with low and mild-moderate level of upper limb impairments. We found significant changes in muscles activity in PwMS compared to healthy subjects when holding and lifting objects used in everyday life. These differences were particularly remarkable in subjects with moderate level of impairment, in which the disease affected also movement smoothness. Remarkably, the smoothness of the movement during the interaction with common objects of daily activities highly correlated with the subjects' ability measured with the Abilhand scale.

Functional evaluation of robot end-point assisted gait re-education in chronic stroke survivors.

Gait re-education is a primary rehabilitation goal after stroke. In this study, we used instrumented gait analysis for evaluating the outcomes of gait training assisted by an endpoint robot in a population of six chronic stroke survivors. The preliminary results, based on spatial-temporal and kinematic analysis, suggest that (a) self-placed walking speed increases, with an improvement of both length and duration of the stride, (b) balance increases during standing and walking, (c) the non-affected side becomes less involved in attempting to correct for the deficiencies of the affected side, thus reducing the importance of compensatory strategies.

Multijoint arm stiffness during movements following stroke: implications for robot therapy.

Impaired arm movements in stroke appear as a set of stereotypical kinematic patterns, characterized by abnormal joint coupling, which have a direct consequence on arm mechanics and can be quantified by the net arm stiffness at the hand. The current available measures of arm stiffness during functional tasks have limited clinical use, since they require several repetitions of the same test movement in many directions. Such procedure is difficult to obtain in stroke survivors who have lower fatigue threshold and increased variability compared to unimpaired individuals. The present study proposes a novel, fast quantitative measure of arm stiffness during movements by means of a Time-Frequency technique and the use of a reassigned spectrogram, applied on a trial-by-trial basis with a single perturbation. We tested the technique feasibility during robot mediated therapy, where a robot helped stroke survivors to regain arm mobility by providing assistive forces during a hitting task to 13 targets covering the entire reachable workspace. The endpoint stiffness of the paretic arm was estimated at the end of each hitting movements by suddenly switching of the assistive forces and observing the ensuing recoil movements. In addition, we considered how assistive forces influence stiffness. This method will provide therapists with improved tools to target the treatment to the individual's specific impairment and to verify the effects of the proposed exercises.

Body machine interface: remapping motor skills after spinal cord injury.

The goal of a body-machine interface (BMI) is to map the residual motor skills of the users into efficient patterns of control. The interface is subject to two processes of learning: while users practice controlling the assistive device, the interface modifies itself based on the user's residual abilities and preferences. In this study, we combined virtual reality and movement capture technologies to investigate the reorganization of movements that occurs when individuals with spinal cord injury (SCI) are allowed to use a broad spectrum of body motions to perform different tasks. Subjects, over multiple sessions, used their upper body movements to engage in exercises that required different operational functions such as controlling a keyboard for playing a videogame, driving a simulated wheelchair in a virtual reality (VR) environment, and piloting a cursor on a screen for reaching targets. In particular, we investigated the possibility of reducing the dimensionality of the control signals by finding repeatable and stable correlations of movement signals, established both by the presence of biomechanical constraints and by learned patterns of coordination. The outcomes of these investigations will provide guidance for further studies of efficient remapping of motor coordination for the control of assistive devices and are a basis for a new training paradigm in which the burden of learning is significantly removed from the impaired subjects and shifted to the devices.

Training stroke patients with continuous tracking movements: evaluating the improvement of voluntary control.

We report on a pilot study of robot therapy with stroke patients. Patients were requested to track a continuously moving target according to a figure-of-eight. Assistance was provided by an attractive force field, whose magnitude was regulated according to a principle of minimal assistance and a principle of consolidation of the learned memory trace. From the analysis of the assistive forces, we show that subjects improve their degree of voluntary control.

Subtle upper limb impairment in asymptomatic multiple sclerosis subjects.

We evaluated upper limb function in multiple sclerosis (MS) subjects (11 clinically definite MS patients and seven clinically isolated syndrome (CIS) subjects), with a normal upper limb standard neurological examination. Subjects performed center-out reaching movements under visual control, with and without vision of the hand. Their movements were recorded through a digitizing tablet. Motor performance was also related to lesion load, estimated from magnetic resonance imaging (MRI). We found that in MS and CIS subjects, under the hand vision condition, movements were significantly less smooth, and had a less symmetric speed profile. However, the observed impairment did not correlate with MRI findings. This result may be interpreted as evidence of a compensatory strategy, elicited by subtle alterations in sensorimotor control.

[The assessment of the operative risk in vascular surgery]. / Valutazione del rischio operatorio in chirurgia vascolare.

Atherosclerosis is a polydistrectual disease. The patients with peripheral, carotid or aortoiliac pathology suffer frequently from coronary disease; so, a careful evaluation of operative risk is indispensable related to the anatomic district that we intend submit to surgery. In this work we separately explore the risk related to peripheral revasculations, aortic surgery and carotid surgery following the current literature and our experience.

Combined chemo-immuno-hormonotherapy of advanced renal cell carcinoma.

Thirty-five patients (pts.) with advanced renal cell carcinoma were treated with a combination of vinblastine (5 mg/m2/IV) plus epirubicin (50 mg/m2/IV) every 3-4 weeks, alpha-2-A-interferon (9 x 10(6) U/IM 3 times in the 1st week, then 18 x 10(6) U/IM 3 times weekly), and medroxyprogesterone acetate (2,000 mg/os/day plus 500 mg IM/week). Thirty-one patients were males and 4 were females with a median age of 63 years (range 35-75) and median performance status of 70% (range 50-90%). We observed nine partial remissions (26%) with median duration of 40 weeks (range 20-232+). Fifteen pts. had no change (43%) while 11 pts. progressed (31%). The main side-effects were: leukopenia (29/35, 83%) with median nadir of 3,100 WBC/mm3 (range 510-3,990) and fever (32/35, 91%). Thrombocytopenia occurred in 4 pts. (11%), anemia in 5 (14%), asthenia in 12 (34%), nausea/vomiting in 12 (34%), alopecia in 8 (23%) and stomatitis in 3 (8.5%). Two patients stopped the therapy with medroxyprogesterone acetate because of muscular cramps. Median survival was 65 weeks (range 6-327+). We conclude that the combination of recombinant alpha 2A-interferon-vinblastine-epirubicin and medroxyprogesterone acetate has modest but definitive activity in patients with advanced renal cell carcinoma.

A phase II study of high-dose epirubicin plus cisplatinum in advanced non-small-cell lung cancer (NSCLC).

Thirty-seven patients with unresectable NSCLC received epirubicin (EPI) as i.v. bolus at the dose of 120 mg/sm+cisplatinum (CP) at the dose of 60 mg/sm every 28 days up to the maximum cumulative dose of 840 mg/sm of EPI. Of 35 evaluable patients, 19 (54%) (95% confidence limits: 37%-71%) achieved PR for a median duration of 10 months (range: 2-21). The majority of responsive patients experienced improvement in performance status, related-disease symptoms and body weight. Grades 3-4 leukopenia occurred in 42% of the patients. In five patients there was a > 10% reduction in the left ventricular ejection fraction as calculated by radionuclide angiocardiography. None of these patients suffered from cardiac symptoms. The median survival was 9 months (range 2-26). This study shows that inclusion of HD-EPI in a combination regimen contributes to obtaining a high remission rate in advanced NSCLC.

A phase II study on lonidamine combined with cisplatin and etoposide in the treatment of advanced non-small cell bronchogenic carcinoma (NSCBC).

A group of 28 patients with advanced non-small cell bronchogenic carcinoma (NSCBC) entered a phase II study on cisplatin (60 mg/m2, day 1) plus etoposide 120 mg/m2, day 1 to 3), every 3 weeks, in combination with lonidamine (150 mg p.o. t.i.d. continuously from day 1). Seven out of twenty-seven (26%) evaluable patients obtained a partial remission (median duration 22 weeks, range 7-47). Although the side effects were mild, three patients stopped the therapy because of them. Median survival was 14 months, range 2-19. Further studies are necessary to clarify the role of "biochemical modulators" in NSCBC.

Small cell bronchogenic carcinoma: a cyclical alternating combination of epirubicin plus cisplatin and cyclophosphamide plus etoposide.

Forty-seven patients with advanced small-cell bronchogenic carcinoma (SCLC) were treated with a combination of epirubicin (4-EPIDX) (60 mg/m2 i.v.) and cisplatin (CDDP) (50 mg/m2 i.v.) on day 1, alternated with cyclophosphamide (CTX) (800 mg/m2 i.v.) day 1 and etoposide (VP16) (120 mg/m2 i.v.) on days 21-23. Four patients (9%) obtained a complete remission and 27 (57%) a partial remission with an overall remission rate of 66%. The median duration of response was 37 weeks (range 13-150) and the median duration of survival was 43 weeks (range 10-150). No severe bone marrow depression was noted. The other side-effects were of a mild grade.

A phase III study on intermittent versus weekly cisplatin and etoposide in the treatment of advanced non-small cell bronchogenic carcinoma.

A group of 55 patients with advanced non-small cell bronchogenic carcinoma entered a random study on combined cisplatin (CDDP) and etoposide (VP16), either intermittently (I = CDDP 60 mg/m2 day 1 and VP16 120 mg/m2 day 1-3 every 3-4 weeks) or weekly (W = CDDP 20 mg/m2 and VP16 120 mg/m2). Five out of 31 (16%) evaluable patients in group I and 6/27 (22%) in group W obtained partial remission (no statistical difference). Toxicity was mild and survival was similar for both groups. The authors conclude that the weekly combination of CDDP plus VP16 is neither less toxic nor more effective than the intermittent one.

4'-Epidoxorubicin plus cisplatin as first-line therapy in the treatment of small cell bronchogenic carcinoma.

Twenty-seven patients with small cell bronchogenic carcinoma were treated with a combination of 4'-Epidoxorubicin 60 mg/m2 and cisplatin 50 mg/m2 i.v. every 3-4 weeks. Three patients (11%) had a complete remission (CR), and 12 (44%) had a partial remission (PR) with a 55% overall remission rate. The median duration of response was 36 weeks (range 11-256+). No severe bone marrow depression was noted. The other side effects were of mild grade. Because of the "minimal aggressiveness" of this combination for the patients, the results obtained in this preliminary phase can probably be improved by the integration of other drugs in the scheme.

Phase II studies on weekly cisplatinum plus epirubicin or etoposide in the treatment of advanced non-small cell bronchogenic carcinoma.

Thirty-six patients with advanced non-small cell bronchogenic carcinoma were divided in 2 groups for treatment with two different platinum-based combination therapy regimens. All 16 patients who received the weekly administered combination of 10 mg/m2 cisplatin (CDDP) plus 10 mg/m2 epirubicin (4EPIDX) experienced no clinical response. Among the 20 patients who received the combination CDDP (10 mg/m2) plus etoposide (VP16, 60 mg/m2) weekly, 4 of them (20%) showed partial remission (PR). The side effects of both combinations were of mild grade. Further study is needed to verify the effectiveness of the weekly combination of CDDP and VP16 by comparing the above regimen with the "standard" intermittent doses.