Microscopic colitis, a forgotten condition: a clinical case and review of the literature.

OBJECTIVE: Microscopic colitis is a not uncommon chronic inflammatory disease of the colon, characterized by watery, non-bloody diarrhea, which is often forgotten and misdiagnosed. CASE PRESENTATION: In this paper, we present a puzzling case of relapsing chronic diarrhea triggered by non-steroidal anti-inflammatory drug (NSAID) abuse, smoking, inappropriate antibiotic use, and secondary Clostridium Difficilis infection. Several tests were performed during hospitalization, all of which were negative apart from fecal calprotectin (> 6,000 mg/kg, normal values < 50 mg/kg) and a positive Clostridium Difficilis toxin test. Since Vancomycin treatment did not bring about the expected response, colonoscopy was performed, which led to diagnosis, targeted therapy, and clinical resolution. Targeted therapy with budesonide and probiotics was initiated leading to resolution of the diarrhea. CONCLUSIONS: This case study shows how actual diagnosis may be delayed not only due to having to perform differential diagnosis with chronic inflammatory diseases, but also because certainty can only come from histological evidence, which takes time to obtain, especially when the disease's multifactorial nature is considered (smoking, NSAID abuse, oral proton pump inhibitors, inappropriate antibiotic use, and Clostridium difficilis infection).

The complexity of immunology: a rare adverse event following a Pfizer-BioNTech vaccine booster shot.

OBJECTIVE: Several mRNA vaccines have been developed to tackle the global pandemic. Despite their remarkable clinical efficacy, they are not devoid of severe short- and long-term adverse events. CASE PRESENTATION: In this paper, we describe a rare delayed adverse event (arterial and venous renal thrombosis with myocardial injury) in an otherwise healthy adult female, which occurred three months after she received a booster shot of Pfizer COVID-19 vaccine.  The patient was successfully treated for subacute renal ischemia with intra-arterial urokinase, and her myocardial injury was diagnosed with imaging (contrast-enhanced thoracic CT and cardiac magnetic resonance) and percutaneous coronary intervention. Deferred post-vaccine myocarditis was diagnosed and resolved with steroid therapy. CONCLUSIONS: In this paper, we report a useful clinical case for the pharmacovigilance database. Although scientific evidence confirms that the benefits of vaccination far outweigh the risk of adverse events, we would like to point out how important watchful observation is in the medium and long term, especially when the subject belongs to a specific risk category.

Midodrine and albumin as a possible "winning pair" in managing paracentesis-induced circulatory dysfunction: a clinical case report.

BACKGROUND: Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. CASE PRESENTATION: A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. CONCLUSIONS: Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

Pharmacoeconomic management of patient with severe asthma in the Emergency Department: retrospective multicentric and cost of illness study.

OBJECTIVE: The aim of the study was to develop a cost-of-illness model that would investigate the costs associated with the management of patients suffering from asthma and severe asthma in the context of acute episodes managed in the emergency room. PATIENTS AND METHODS: A total of 795 records were collected between adults and paediatric patients. The data collection form reported an identification code for each patient included, gender, age, main discharge diagnosis, medical examinations carried out in the emergency room, the hospitalizations, and, if required by the patient condition, an outpatient visit performed by a pneumologist after the acute event that led the patient to the emergency room. In addition, the data collection form included information related to the pharmacological therapy taken by the patient. RESULTS: Among adult patients who had an admission with an asthma diagnosis, the average cost for the management of an adult patient in a green code in the emergency room is €330.39. As for the yellow code and the red code, the cost rises respectively to €444.04 and €808.25. The paediatric population has a slightly higher cost. As for the green code, the average cost stands at €355.87, for the yellow code €562.34 and €1,041.96 for the red code. CONCLUSIONS: Asthma and severe asthma impose a high burden on patients and society due to its chronicity, losses of productivity, and an increase in use of healthcare resources. We carried out the present observational retrospective analysis on asthma and severe asthma patients with the aim of assessing the economic impact from the Italian NHS perspective focusing also on the prescribed pharmacological therapies in the target conditions.

Non-implantable bone conduction device for hearing loss: a systematic review.

There are different treatment options that employ a bone conduction transmission of the sound, for different types of hearing loss, as well as hearing aids, medical intervention via prostheses and surgically implanted medical devices. A middle ear disease causes a decline in the conductive mechanism of hearing. The current possibilities of compensating Conductive Hearing Loss (CHL) solutions include both surgical and no surgical Bone Conduction Devices (BCDs). Due to the invasiveness of the implantable devices and their specific requirements in terms of the temporal bone anatomy, non-implantable BCDs are in some cases preferred in the clinical routine. The goal of this review is to investigate the beneficial effects and safety of non-implantable BC devices, analysing the different type of solutions found so far. A systematic review was performed to identify all the clinical studies evaluating the use of non-invasive BCDs. A qualitative analysis based on data extracted was conducted. From 37 articles, 11 prospective studies and 1 retrospective study were selected for a full analysis, for a total of 173 patients from 4- to 77-years-old. Eight of these studies included adult patients, while the other four are paediatric studies. All the studies analyse non-implantable BCDs commonly used in case of CHL, sensorineural HL and single side deafness. Three of them analyse an adhesive device, six compare the adhesive device with a sound processor mounted on a support fitted on the head, one compare it also with an implant, one analyse the sound processor mounted on different type of support, and one compare different type of sound processor. All the studies showed advantages from the use of non-invasive BCDs, both on adults and children. The non-invasive BCDs analysed in this review show good results both from the audiological and subjective point of view and could be considered a safe and effective solution for patients suffering from conductive hearing loss, sensorineural hearing loss or single-side deafness. More studies are required to confirm these promising results.

Intraneural electrical stimulation of median nerve: a simulation study on sensory and motor fascicles.

Neuroprostheses can be an innovative solution to improve quality of life of upper limb amputees. In this framework, the recovery of sensory feedback is a property widely requested by amputee subjects. Neural prostheses are based on neural interfaces that allow delivering direct current stimuli to the nerve fibers. The study of the interaction between the nerve and the electrode is fundamental to investigate activation properties in the nerve. Furthermore, the results could provide useful insight into improve the design of the electrodes and to advance and ameliorate tactile sensations, elicited by these interfaces, obtaining tactile feedback more like natural sensations. This work aims at studying, by means of a FEM Neuron computational model, the axon fibers activation by means of neural stimulation provided through the intraneural electrodes DS-file. Three different types of stimulation waveforms (i.e. biphasic charge balanced stimulus with inter-pulse delay, biphasic charge balanced stimulus without inter-pulse delay, biphasic charge unbalanced stimulus with inter-pulse delay), three different nerve fascicles, i.e. two sensory and one motor fascicle, and ten distances from the electrode in the fascicles, are considered. The efficacy of the stimulation expressed as the percentage of activation of the fibers, and the safety, in terms of current intensity and used waveform, are studied in the previously described different conditions and the results are compared. The obtained results show that: i. stimulating a sensory fascicle with implanted active sites can activate a fascicle close to it, but not all the fascicles belonging to the same nerve. In fact, in the nerve considered in this study, a motor fascicle cannot be activated due to the values of the electrical potential which are too low to activate the fibers; ii. the current intensity necessary to activate fibers increases according to the distance from the source of the stimulus; iii. by using a biphasic charge unbalanced stimulus, the threshold to activate the fibers is lower than using the other tested waveforms. It is an important result because the stimulation is efficient and safer since current intensity is lower than the one used for the other two waveforms.

An instrumented object for studying human grasping.

This paper proposes the use of an instrumented object for the study of the human grasping strategies. The proposed object is able to measure the grasping forces by means of three Force Sensitive Resistor (FSR) sensors and triaxial acceleration through an accelerometer. The object orientation angles (roll and pitch) can be estimated from the accelerometer output in quasi-static condition, whereas slippage events can be detected through the Power Spectrum Density (PSD) computation of the acceleration on at least one of the three axes. An experimental session on 7 healthy subjects has been performed; each subject used the instrumented object to perform 8 tripod grasp trials. All the sensory information, i.e. applied forces, object orientation and slippage, have been analyzed in order to evaluate the grasping strategies of the different subjects.

A teleoperated control approach for anthropomorphic manipulator using magneto-inertial sensors.

In this paper we propose and validate a teleoperated control approach for an anthropomorphic redundant robotic manipulator, using magneto-inertial sensors (IMUs). The proposed method allows mapping the motion of the human arm (used as the master) on the robot end-effector (the slave). We record arm movements using IMU sensors, and calculate human forward kinematics to be mapped on robot movements. In order to solve robot kinematic redundancy, we implemented different algorithms for inverse kinematics that allows imposing anthropomorphism criteria on robot movements. The main objective is to let the user to control the robotic platform in an easy and intuitive manner by providing the control input freely moving his/her own arm and exploiting redundancy and anthropomorphism criteria in order to achieve human-like behaviour on the robot arm. Therefore, three inverse kinematics algorithms are implemented: Damped Least Squares (DLS), Elastic Potential (EP) and Augmented Jacobian (AJ). In order to evaluate the performance of the algorithms, four healthy subjects have been asked to control the motion of an anthropomorphic robot arm (i.e. the Kuka Light Weight Robot 4+) through four magneto-inertial sensors (i.e. Xsens Wireless Motion Tracking sensors - MTw) positioned on their arm. Anthropomorphism indices and position and orientation errors between the human hand pose and the robot end-effector pose were evaluated to assess the performance of our approach.

Design and development of a sensorized cylindrical object for grasping assessment.

Aim of this work is to design and develop an instrumented cylindrical object equipped with force sensors, which is able to assess grasping performance of both human and robotic hands. The object is made of two concentric shells between which sixteen piezoresistive sensors have been located in order to measure the forces applied by the hand fingers during grasping. Furthermore, a magneto-inertial unit has been positioned inside the object for acquiring information about object orientation during manipulation. A wireless communication between the electronic boards, responsible for acquiring the data from the sensors, and a remote laptop has been guaranteed. The object has been conceived in such a way to be adopted for evaluating both power and precision grasps and for measuring the forces applied by each finger of the hand. In order to evaluate object performance, a finite element analysis for estimating the deformation of the external shell for different force values has been carried out. Moreover, to evaluate object sensitivity, a static analysis of the force transmitted by the external shell to the underlying sensors has been performed by varying the thickness of the shells. The obtained preliminary results have validated the feasibility of using the developed object for assessing grasping performed by human and robotic hands.

Upper-limb kinematic reconstruction during stroke robot-aided therapy.

The paper proposes a novel method for an accurate and unobtrusive reconstruction of the upper-limb kinematics of stroke patients during robot-aided rehabilitation tasks with end-effector machines. The method is based on a robust analytic procedure for inverse kinematics that simply uses, in addition to hand pose data provided by the robot, upper arm acceleration measurements for computing a constraint on elbow position; it is exploited for task space augmentation. The proposed method can enable in-depth comprehension of planning strategy of stroke patients in the joint space and, consequently, allow developing therapies tailored for their residual motor capabilities. The experimental validation has a twofold purpose: (1) a comparative analysis with an optoelectronic motion capturing system is used to assess the method capability to reconstruct joint motion; (2) the application of the method to healthy and stroke subjects during circle-drawing tasks with InMotion2 robot is used to evaluate its efficacy in discriminating stroke from healthy behavior. The experimental results have shown that arm angles are reconstructed with a RMSE of 8.3 × 10(-3) rad. Moreover, the comparison between healthy and stroke subjects has revealed different features in the joint space in terms of mean values and standard deviations, which also allow assessing inter- and intra-subject variability. The findings of this study contribute to the investigation of motor performance in the joint space and Cartesian space of stroke patients undergoing robot-aided therapy, thus allowing: (1) evaluating the outcomes of the therapeutic approach, (2) re-planning the robotic treatment based on patient needs, and (3) understanding pathology-related motor strategies.

A theoretical framework for studying the electromagnetic stimulation of nervous tissue.

In this paper we present a model for calculating the electric field, and its spatial derivatives, produced by arbitrarily shaped, oriented and placed coils carrying time-varying currents. The model has been validated by comparing its results with those obtained using FEM simulations. The model provides a simple and fast computation framework to investigate the electromagnetic stimulation of neural tissues. Some example applications are also provided.

A bio-inspired force control for cyclic manipulation of prosthetic hands.

The human hand is considered as the highest example of dexterous system capable of interacting with different objects and adapting its manipulation abilities to them. The control of poliarticulated prosthetic hands represents one important research challenge, typically aiming at replicating the manipulation capabilities of the natural hand. For this reason, this paper wants to propose a bio-inspired learning architecture based on parallel force/position control for prosthetic hands, capable of learning cyclic manipulation capabilities. To this purpose, it is focused on the control of a commercial biomechatronic hand (the IH2 hand) including the main features of recent poliarticulated prosthetic hands. The training phase of the hand was carried out in simulation, the parallel force/position control was tested in simulation whereas preliminary tests were performed on the real IH2 hand. The results obtained in simulation and on the real hand provide an important evidence of the applicability of the bio-inspired neural control to real biomechatronic hand with the typical features of a hand prosthesis.

Development and preliminary testing of an instrumented object for force analysis during grasping.

This paper presents the design and realization of an instrumented object for force analysis during grasping. The object, with spherical shape, has been constructed with three contact areas in order to allow performing a tripod grasp. Force Sensing Resistor (FSR) sensors have been employed for normal force measurements, while an accelerometer has been used for slip detection. An electronic board for data acquisition has been embedded into the object, so that only the cables for power supply exit from it. Validation tests have been carried out for: (i) comparing the force measurements with a ground truth; (ii) assessing the capability of the accelerometer to detect slippage for different roughness values; (iii) evaluating object performance in grasp trials performed by a human subject.

Comparative analysis and quantitative evaluation of ankle-foot orthoses for foot drop in chronic hemiparetic patients.

BACKGROUND: Ankle-foot-orthoses (AFOs) are frequently prescribed for hemiparetic patients to compensate for the foot drop syndrome. However, there is not a systematic study either on the effectiveness of AFOs in the gait recovery process or pointing out the therapeutic differences among the various types of AFOs available on the market. AIM: To perform a comparative evaluation of solid and dynamic Ankle-Foot-Orthoses (AFOs) on hemiparetic patients affected by foot drop syndrome by means of spatio-temporal, kinematic and electromyographic indicators. DESIGN: Crossover design with randomization for the interventions. SETTING: A rehabilitation center for adults with neurologic disorders. POPULATION: Ten chronic hemiparetic patients with foot drop syndrome met inclusion criteria and volunteered to participate. METHODS: Biomechanical gait analysis was carried out on hemiparetic subjects with foot drop syndrome under 3 conditions with randomized sequences: 1) without AFO; 2) wearing a solid AFO; 3) wearing a dynamic AFO. Significant changes in spatio-temporal, kinematic and electromyographic features of gait were investigated. RESULTS: Gait analysis outcomes showed that there were no significant differences among the solid and the dynamic AFO on the spatio-temporal parameters. Both AFOs led to a reduction of the range of motion of the ankle dorsi-plantar-flexion during stance with respect to the ambulation without AFO. They also had the effect of reducing the asymmetry between the paretic and the contralateral limb in terms of ankle angle at initial contact and hip flexion. The solid AFO generally led to an increase of the co-contraction of the couples of muscles involved in the gait. CONCLUSION: The proposed set of indicators showed that the AFOs were capable of limiting the effect of the foot-drop in hemiparetic patients and balancing the two limbs. Main differences between the two orthoses were related to muscular activity, being the level of co-contraction of the two couples of analysed muscles typically lower when the dynamic AFO was worn and closer to a normal pattern. CLINICAL REHABILITATION IMPACT: A more extensive use of the proposed indicators in the clinical practice is expected in order to enable the definition of clinical guidelines for the prescription of the two devices.

A preliminary health technology assessment of a guidance system for interventional radiology.

Disruptive innovation in biomedical devices have to be carefully assessed in order to be included in the clinical practice, especially when these new systems interact with the human body. In this scenario the guidance devices for interventional radiology represent an area of great interest. In this paper a CT-navigation system, SIRIO, used for percutaneous interventions such as biopsy, thermal ablation, percutaneous interventional, is tested and assessed. The technical features of the system in terms of efficacy and safety and the comparison with the traditional CT-guided biopsy are analyzed. According to the clinical evidences, biopsies carried out with SIRIO show an important reduction of number of CT scans, procedure's time and radiation dose absorbed by the patients. The analysis of the technology costs, the social impact related to the benefits to clinicians and patients are also reported. Although SIRIO does not have an appropriate reimbursement procedure, short- and long-term benefits introduced by this device are discussed.

A smart pill for drug delivery with sensing capabilities.

In this paper a novel system for local drug delivery is described. The actuation principle of the micropump used for drug delivery relies on the electrolysis of a water-based solution, which is separated from a drug reservoir by an elastic membrane. The electrolytically produced gases pressurize the electrolytic solution reservoir, causing the deflection of the elastic membrane. Such deflection, in turn, forces the drug out of its reservoir through a nozzle. The proposed system is integrated in a swallowable capsule, equipped with an impedance sensor useful to acquire information on the physiological conditions of the tissue. Such information can be used to control pump activation.

Muscular activity when walking in a non-anthropomorphic wearable robot.

Wearable robots should be designed not to alter human physiological motion. Perturbations introduced by a robot can be quantified by measuring EMG activity. This paper presents tests on the LENAR, an intrinsically back-drivable non-anthropomorphic lower limb wearable robot designed to provide hip and knee flexion/extension assistance. In previous works the robot was demonstrated to exhibit low mechanical impedance and to introduce minor alterations to human kinematic patterns during walking. In this paper muscular activity is assessed, demonstrating small alterations in the EMG patterns during the interaction with the robot, in both unpowered and assistive mode.

Does an intraneural interface short-term implant for robotic hand control modulate sensorimotor cortical integration? An EEG-TMS co-registration study on a human amputee.

PURPOSE: Following limb amputation, central and peripheral nervous system relays partially maintain their functions and can be exploited for interfacing prostheses. The aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. METHODS: Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject's cortico-cortical excitability, connectivity and plasticity were tested via a neuronavigated EEG-TMS experiment. RESULTS: The statistical analysis clearly demonstrated a significant modulation (with t-test p < 0.0001) of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When studying individual latencies in that time range, a global amplitude modulation was found in most of the TMS-evoked potentials; particularly, the GEE analysis showed significant differences between T0 and T1 condition at 30 ms (p < 0.0404), 46 ms (p < 0.0001) and 60 ms (p < 0.007) latencies. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. CONCLUSIONS: The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity. This reorganization strongly involves bi-hemispheric networks and intracortical and transcortical modulation of GABAergic inhibition.

An experimental protocol for the definition of upper limb anatomical frames on children using magneto-inertial sensors.

Motion capture based on magneto-inertial sensors is a technology enabling data collection in unstructured environments, allowing "out of the lab" motion analysis. This technology is a good candidate for motion analysis of children thanks to the reduced weight and size as well as the use of wireless communication that has improved its wearability and reduced its obtrusivity. A key issue in the application of such technology for motion analysis is its calibration, i.e. a process that allows mapping orientation information from each sensor to a physiological reference frame. To date, even if there are several calibration procedures available for adults, no specific calibration procedures have been developed for children. This work addresses this specific issue presenting a calibration procedure for motion capture of thorax and upper limbs on healthy children. Reported results suggest comparable performance with similar studies on adults and emphasize some critical issues, opening the way to further improvements.

An implantable neural interface with electromagnetic stimulation capabilities.

Invasive interfaces with the Peripheral Nervous System (PNS), which currently rely on electric means for both nerves stimulation and signals recording, are needed in a number of applications, including prosthetics and assistive technologies. Recent studies showed that the quality of the signal-to-noise ratio of the afferent channel might be negatively affected by physiological reactions, including fibrosis. In this paper we propose a novel approach to the development of implantable neural interfaces, where the PNS is excited electromagnetically and in situ, while electrical means are used only for neural signals recording. Electromagnetic (EM) waves, capable of overcoming fibrotic capsules, are generated by microfabricated coils. Stimulation coils and registration electrodes are deposited on the same flexible substrate, also provided with a bio-absorbable coating, which releases anti-fibrotic drugs and neurons-specific functionalized magnetic nanoparticles (NPs). The NPs are intended to improve the capability of local EM waves to elicit membranes depolarization, thus enhancing selectivity. This paper details the concept of the proposed technology and provides a preliminary in silico feasibility study.