H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.

A new gastric impedancemeter for detecting the development of a visceral edema: a proof-of-concept study on an experimental endotoxemic shock.

Visceral congestion and edema are important features of advanced heart failure. Monitoring the evolution of fluid content in the gastric wall might provide an index of the development of this phenomenon and therefore constitute an innovative marker to early detect acute decompensated heart failure episodes. The evolution of the fluid content in the gastric wall is measured using a device implanted in the submucosa layer of the fundic region of the stomach. The device composed of two electrodes measures the bioimpedance values that reflects the water content of the tissue.An in-vivo experiment in a pig was carried out to validate the feasibility of detecting the gastric bioimpedance variations during the development of an experimental acute visceral edema caused by an endotoxemic shock. Our preliminary results confirm the possibility to monitor the bioimpedance variations due to moderate changes in tissue water content (10%) with a two-electrode configuration device implanted in the submucosa of the stomach.

High catalytic performance of laccase wired to naphthylated multiwall carbon nanotubes.

The direct electrical connection of laccase on the electrode surface is a key feature in the design of efficient and stable biocathodes. However, laccase can perform a direct electron transfer only when it is in the preferred orientation toward the electrode. Here we report the investigation of the orientation of laccase from white rot fungus on multi-walled carbon nanotube surface modified with a naphthalene group. Naphthylated multi wall carbon nanotubes were synthesized and the kinetics of laccase from white rot fungus adsorption and its direct electro-catalytic activity toward oxygen reduction was investigated by QCM and electrochemical techniques. Compared to pristine multi-walled carbon nanotubes laccase shows a high affinity to be adsorbed onto the surface of naphthylated carbon nanotubes at a very fast rate. The subsequent wiring to the naphthylated multi-walled carbon nanotubes is accompanied by a reorientation and arrangement of adsorbed laccase to create a composite biocathode that exhibits a high-performance for oxygen reduction by direct electron transfer with maximum current densities of 3 mA cm-2.

Laccase-based biocathodes: Comparison of chitosan and Nafion.

Chitosan and Nafion(®) are both reported as interesting polymers to be integrated into the structure of 3D electrodes for biofuel cells. Their advantage is mainly related to their chemical properties, which have a positive impact on the stability of electrodes such as the laccase-based biocathode. For optimal function in implantable applications the biocathode requires coating with a biocompatible semi-permeable membrane that is designed to prevent the loss of enzyme activity and to protect the structure of the biocathode. Since such membranes are integrated into the electrodes ultimately implanted, they must be fully characterized to demonstrate that there is no interference with the performance of the electrode. In the present study, we demonstrate that chitosan provides superior stability compared with Nafion(®) and should be considered as an optimum solution to enhance the biocompatibility and the stability of 3D bioelectrodes.

Toward a real-time tracking of a medical deformable needle from strain measurements.

Needles used in medical percutaneous procedures are brought to deform because of its interactions with inhomogeneous and anisotropic tissues. In this paper, the first step of the development of a new generation of tools for assistance in the realization of gestures taking into account these deformations are presented. We provide a new approach for determining, in "real time" and in 3D, the shape of an instrumented needle inserted into a complex tissue by using strain microgauges. The knowledge of the real time local deformation from these strain microgauges would improve the current navigation systems by considering not only the rigid needles but also the flexible ones. Our aim is to reconstruct in real time the instrumented needle shape in order to help tracking and steering during a medical intervention.

Single glucose biofuel cells implanted in rats power electronic devices.

We describe the first implanted glucose biofuel cell (GBFC) that is capable of generating sufficient power from a mammal's body fluids to act as the sole power source for electronic devices. This GBFC is based on carbon nanotube/enzyme electrodes, which utilize glucose oxidase for glucose oxidation and laccase for dioxygen reduction. The GBFC, implanted in the abdominal cavity of a rat, produces an average open-circuit voltage of 0.57 V. This implanted GBFC delivered a power output of 38.7 µW, which corresponded to a power density of 193.5 µW cm(-2) and a volumetric power of 161 µW mL(-1). We demonstrate that one single implanted enzymatic GBFC can power a light-emitting diode (LED), or a digital thermometer. In addition, no signs of rejection or inflammation were observed after 110 days implantation in the rat.

Evaluation of a computer-assisted navigation system for anterior cruciate ligament reconstruction: prospective non-randomized cohort study versus conventional surgery.

BACKGROUND: Conventional reconstruction of the anterior cruciate ligament (ACL) is associated with a 15% failure rate. Computer-assisted navigation systems (CANS) have been developed to improve the accuracy of tunnel positioning. HYPOTHESIS: The use of a CANS for ACL reconstruction decreases the rate of failure, defined as IKDC grade C or D, compared to conventional ACL reconstruction. MATERIALS AND METHODS: This prospective multicentre observational non-randomised open study compared two groups of patients requiring arthroscopic ACL reconstruction: one group was managed with a CANS and the other (control group) without a CANS. The primary evaluation criterion was based on the subjective and objective IKDC scores. Inclusion criteria were age older than 18 years and first ACL reconstruction procedure using autologous semitendinosus and gracilis tendons or an autologous bone-patellar tendon-bone graft. Of the 272 included patients, 214 were analysed; 100 were in the control group and 114 in the CANS group. RESULTS: No significant between-group differences were found for the fraction of patients having an IKDC grade A or B (P=0.953), the subjective IKDC score (P=0.77), differential knee laxity at 150 N (1.38 ± 1.79 mm in the control group and 1.77 ± 2.06 mmin the CANS group, P=0.384), graft-type, or graft positioning. DISCUSSION: Our results establish the large-scale feasibility of computer-assisted navigation for ACL reconstruction. However, the main outcomes at 1 year showed no significant differences between patients managed with and without computer-assisted navigation.

Automated hydraulic tensor for Total Knee Arthroplasty.

To obtain a long lifespan of knee prosthesis, it is necessary to restore the alignment of the lower limb. In some cases of severe arthrosis, the ligament envelope of the joint may be deformed, inducing an asymmetric laxity once the lower limb is realigned. Because there is not yet unanimity regarding how to optimally measure or implement soft tissue balance, we provide a means to acquire a variety of measurements. In traditional surgery, the surgeon sometimes uses a "tensor", which acts like a forceps. This system was redesigned, instrumented, actuated, and integrated into a navigation system for orthopaedic surgery. Improving the perception of the surgeon, it helps him to address the ligament balancing problem. Our first prototype has been tested on sawbones before being validated in an experiment on two cadavers. In our first attempt, the surgeon was able to assess soft tissue balance but judged the device not powerful enough, which led us to develop a new more powerful hydraulic system. In this paper, we present our approach and the first results of the new hydraulic tensor which is currently in an integration process.

Praxiteles: a miniature bone-mounted robot for minimal access total knee arthroplasty.

We have been working to develop a compact, accurate, safe, and easy-to-use surgical robot for minimally invasive total knee arthroplasty (TKA). The goal of our bone-mounted robot, named Praxiteles, is to precisely position a surgical bone-cutting guide in the appropriate planes surrounding the knee, so that the surgeon can perform the planar cuts manually using the guide. The robot architecture is comprised of 2 motorized degrees of freedom (DoF) whose axes of rotation are arranged in parallel, and are precisely aligned to the implant cutting planes with a 2 DoF adjustment mechanism. Two prototypes have been developed and tested on saw bones and cadavers--an initial one for open TKA surgery and a new version for MIS TKA, which mounts on the side of the knee. A novel bone-milling technique is also presented that uses passive guide and a side milling tool.

Synergy between medical informatics and bioinformatics: facilitating genomic medicine for future health care.

In this paper, we review the results of BIOINFOMED, a study funded by the European Commission (EC) with the purpose to analyse the different issues and challenges in the area where Medical Informatics and Bioinformatics meet. Traditionally, Medical Informatics has been focused on the intersection between computer science and clinical medicine, whereas Bioinformatics have been predominantly centered on the intersection between computer science and biological research. Although researchers from both areas have occasionally collaborated, their training, objectives and interests have been quite different. The results of the Human Genome and related projects have attracted the interest of many professionals, and introduced new challenges that will transform biomedical research and health care. A characteristic of the 'post genomic' era will be to correlate essential genotypic information with expressed phenotypic information. In this context, Biomedical Informatics (BMI) has emerged to describe the technology that brings both disciplines (BI and MI) together to support genomic medicine. In recognition of the dynamic nature of BMI, institutions such as the EC have launched several initiatives in support of a research agenda, including the BIOINFOMED study.

SURGETICA at Grenoble: from computer assisted medical interventions to quality inspired surgery.

Research on "Computer Assisted Medical Interventions" (CAMI) was initiated in Grenoble in 1984, as an attempt to take up the challenge of "Minimally Invasive Interventions", thanks to the introduction of Information and Communication Techniques in the Operating Room. In a first section, we will describe our initial vision. The corresponding achievements will then be presented. A final section will show that the challenge now is to "invert this movement": instead of moving the computer in the Operating Room, we should embed the surgeon (or at least his or her expertise) into the Information Technology based tools he or she uses.

Differences between pelvic skin and bone landmark identification in different seated positions on spinal-cord injured subjects.

The purpose of this paper was to determine the differences between internal and external pelvic landmark locations in different seating positions. A computer tool developed for the registration of two series of images was used to obtain the internal geometry. First, images of the pelvis were acquired by magnetic resonance imaging (MRI) for each subject, in a supine position; internal landmarks were then identified on the images. Second, ultrasound images of the iliac crests were acquired in four seated positions. A registration algorithm was applied to obtain the transformation matrix between the two image reference systems. The MRI anatomical landmarks were, therefore, transferred into the ultrasound referential, to obtain their three-dimensional (3-D) location in the different seating positions. The external landmarks in those seated positions were identified with a 3-D digitizer. The results revealed that generally the internal and external coordinates of corresponding landmarks are statistically different. The differences are not only due to soft tissue thickness but also to different interpretations of the landmarks' locations between the supine and the seated postures. However, these differences generally did not affect significantly the accuracy with which orientation indexes can be estimated (pelvic tilt, obliquity, transverse rotation). Correlations were found between the internal and external coordinates, implying that linear regressions can be established.

Model driven therapy - the instance of computer assisted medical interventions.

OBJECTIVES: Taking into account a priori knowledge is a key issue to meet the medical, scientific and industrial challenges of the progresses of Minimally Invasive Surgery. We propose an overview of these challenges. METHODS: Models play a major role in representing the relevant knowledge to plan and realize complex medical and surgical interventions. We analyze the three basic steps of Perception, Decision and Action, and illustrate by some instances how models may be integrated in these steps. RESULTS: We propose a selection of the results obtained in Model Driven Therapy. These results illustrate the issues of Perception (models allow accurate reconstruction of 3D objects from a limited set of X-ray projections), Decision (models allow to take into account elastic and dynamic characteristics of muscles), and Action (models allow to design innovative navigational and robotics aids to the realization of complex interventions). Likewise, models play a major role in the process of surgeon's education, which leads to the concept of Virtual Orthopedic University. CONCLUSIONS: Model Driven Therapy emerges as the way to perform optimal medical and surgical interventions, providing physicians and surgeons with the possibility to augment their capacities of sensing multi-modal information, of combining them to define optimal strategies, and of performing accurate and safe actions.

Image-guided endoscopic spine surgery: Part I. A feasibility study.

STUDY DESIGN: A feasibility study was performed to determine the efficacy of computer assistance in endoscopic spine surgery. OBJECTIVES: To assess a new method for computer assistance based on image guidance during thoracoscopic or any endoscopic spine procedure. To evaluate the reproducibility, the sensitivity and the reliability of the technique first in vitro and second in clinical use. SUMMARY OF BACKGROUND DATA: The computer-based, image-guided surgery is now a routine tool used in open spine surgery. Exposure of the anatomy of the vertebra is needed for registration. This methodology is inapplicable in endoscopic approach. Fluoroscopic-based navigation combines the technology of image-guided surgery and C-arm fluoroscopy. The navigation is based on the fluoroscopic images acquired before surgery. This technology is applicable to endoscopic surgery but the navigation is based on fluoroscopic image. The computed tomography images are not exploited. There are no published data on a technique that allows image-guided surgery based on computed tomography and magnetic resonance imaging. METHOD: A laboratory study was performed on a thoracic human spine. One vertebra was marked on the right lateral side of the body with five titanium marks. A percutaneous reference frame was specifically designed to be placed in the pedicle of the same marked vertebrae. The reference frame acted as a 3D localizer and a registration tool. The spine model was scanned including the reference frame. A standard Stealth station treatment guidance platform (Medtronic, Sofamor Danek, Memphis, TN) was used for simulation. The registration was obtained using the reference frame. Twenty navigation procedure trials were done and the error was recorded based on the distance between the anatomical point and the corresponding virtual one. RESULTS: Registration was always possible using the stealth station and a standard spine navigational software (spine 3, Medtronic Sofamor Danek, Memphis, TN). The mean error after registration given by the computer was 0.96 mm. The mean error recorded during the navigation simulation was 1.6 mm. CONCLUSIONS: This technique allows the possibility of computed tomography and magnetic resonance imaging-based, image-guided endoscopic surgery. It is probable that in the near future, as image fusion technology improves, the fluoronavigation based on fluoroscopic images would enable to navigate on multimodal images. Otherwise the technique described in this article is the only reproducible one that allows computed-tomography-based computer assistance during endoscopic procedures.

[Computer-assisted knee arthroplasty: comparison with a conventional procedure. Results of 50 cases in a prospective randomized study]. / Mise en place des prothèses totales du genou assistée par ordinateur : comparaison avec la technique conventionnelle.

PURPOSE OF THE STUDY: The aim of this work was to compare the radiographic findings after two techniques for total knee arthroplasty, one using a computer-assisted approach and the other a conventional approach. MATERIAL AND METHODS: Between January 1998 and April 1999, we conducted a prospective study randomizing 25 patients for conventional surgery (group A) and 25 for computer-assisted surgery (group B). All patients volunteered to participate in this study and gave their written informed consent. There were 35 women and 15 men, mean age 69.5 years (range 47-85). The two groups were comparable for age, gender, height, weight, orthopedic history, etiology and preoperative mobility. The preoperative hip-knee angle (HKA) was also comparable between the two groups. Mean HKA was 175 degrees, i.e. 5 degrees varus (range 162 degrees (18 degrees varus) to 210 degrees (30 degrees valgus)). Genu varum was found in 80 p. 100 of the patients in group A and in 76 p. 100 in group B, genu valgum in 16 p. 100 in group A and 24 p. 100 in group B. The same operator performed all the procedures) with the same type ok prosthesis for all patients. The goal of the operation was to position the prosthesis to produce an HKA of 180 +/- 3 degrees, a femoral angle of 90 degrees (from the mechanical axis), a tibial angle of 90 degrees and a posterior tibial slope of 0 degrees (tibial plateau at 90 degrees to the lateral tibial axis). Statview 5 PC was used for the statistical analysis. Comparisons between groups were made with the Student's t test to compare means when the validity conditions were met. RESULTS: The patients were reviewed by two surgeons, independently of the operator and the designers of the computer-assistance program. Mean duration of the procedure was longer in group B (102 mn versus 70 mn, p<0.001). There was no statistically significant difference in mean postoperative bleeding (group A=380 cc, group B=480 cc). The postoperative HKA was 181.2 +/- 2.72 degrees in group A and 179.04 +/- 2.53 degrees in group B (p > 0.05). The HKA was between 177 degrees and 183 degrees in 75 p. 100 of the patients in group A and in 84 p. 100 of those in group B. Implantation of the femoral component showed a mean angle of 91.12 +/- 2.07 degrees in group A and 89.56 +/- 1.61 degrees in group B (p=0.048). The mean tibial angle was 90.167 +/- 1.61 degrees in group A and 89.5 +/- 1.34 degrees in group B (p=0.11). On the lateral view, the femoral component was at 90 degrees to the mechanical axis in 16/21 patients in group B. These data were missing in group A. The posterior tibial slope was 90.76 +/- 2.19 degrees in group A and 89.44 +/- 2.14 in group B (p=0.18). CONCLUSION: Computer-assisted surgery for total knee arthroplasty was found to provide remarkably reliable results. Once the "growing pains" of this new material have been mastered, all surgeons should be able to expect an improvement in the positioning of prosthetic implantations.

[Measurement of carotid artery intima-media thickness. Analysis and reproducibility]. / Mesure de l'épaisseur intima-média carotidienne. Analyse de la reproductibilité.

The intima-media thickness of the carotid artery is a cardiovascular risk factor, especially in hypertensive, diabetic or dyslipidemic patients. Very accurate tools of measurement are essential in order to optimise the analysis of the severity of the vascular lesions. Present methods use computer programmes for ultrasonic image enhancement and have already been shown to be very reproducible. However, there is still room for improvement in the detection of lesions at their initial stage of development and in the follow-up of their progression with or without antihypertensive or lipid lowering drugs.

The use of a semi-customized phantom for verification of conformal plans.

We have developed a technique for inverse treatment planning of prostate therapy designed to improve the degree of conformation between the dose distribution and the target volume. We compared the inverse plan with a "standard" four-field box technique as well as a four-field technique using oblique fields ("cross technique"). We validated the dosimetry of the inverse plan using Fricke gel solution in phantom specifically designed for this purpose. The phantom is a Plexiglas tank with a cross section, which approximates the dimensions of the pelvis. Anatomical data from computed tomography (CT) images of a patient were used to simulate organs in our phantom. This allows us to calculate dose distributions with the external geometry of the phantom and internal anatomy of the patient. Dose-volume histograms (DVHs) for the three different plans were calculated. The phantom containing the Fricke gel was irradiated according to the inverse plan. Magnetic resonance (MR) images was used to determine the dose distribution delivered to the phantom. We observe, on DVHs, that the inverse plan significantly reduces the dose to the rectum and the bladder but slightly increases the inhomogeneity inside the target volume. Correlation is good between isodoses on MR images and calculated isodoses. We conclude that inverse planning software can greatly improve the conformal degree of treatment to the prostate. This technique could be applied to other complex anatomic sites at which dose to organs at risk is a limiting factor and increased dose to the target volume is indicated. Our phantom and the Fricke gel solution are convenient to carry out validation of conformal treatments.

Automated 3-dimensional computed tomographic and fluoroscopic image registration.

The registration of 3-dimensional (3-D) anatomical surfaces to sensor data such as intraoperative fluoroscopy is one of the basic problems in computer integrated surgery. The main objective is to find the relationship between 3-D preoperative computed tomographic images and a pair of intraoperative fluoroscopic images. Consequently, surgical navigation devices can use this relationship to provide improved surgical guidance. The proposed registration strategy presents a noninvasive anatomy-based (frameless) method for registration. In this article, we propose a cooperative approach between registration and contour segmentation on fluoroscopy. This approach is based on the duality between registration and segmentation in a model-based vision system. It associates a likelihood value to each pixel that corresponds to the probability that the pixel belongs to the contour of the object of interest. The registration is then achieved between backprojection lines stemming from likely contour pixels and the 3-D surface model of the object of interest. Then, in order to take into account the internal contour points extracted by the cooperative approach, we propose a new line to surface distance computation algorithm to be used during the data to model distance minimization step. Finally, we present the obtained results that demonstrate the validity of the proposed approach in carrying out accurate 3-D and 2-D registration.