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.

Reduction of Prolonged Excessive Pressure in Seated Persons With Paraplegia Using Wireless Lingual Tactile Feedback: A Randomized Controlled Trial.

Pressure ulcers (PU) are known to be a high-cost disease with a risk of severe morbidity. This paper evaluates a new clinical strategy based on an innovative medical device [Tongue Display Unit (TDU)] that implements perceptive supplementation in order to reduce prolonged excessive pressure, recognized as one of the main causes of PU. A randomized, controlled, and parallel-group trial was carried out with 12 subjects with spinal cord injuries (SCI). Subjects were assigned to the control (without TDU, [Formula: see text]) or intervention (with TDU, [Formula: see text]) group. Each subject took part in two sessions, during which the subject, seated on a pressure map sensor, watched a movie for one hour. The TDU was activated during the second session of the intervention group. Intention-to-treat analysis showed that the improvement in adequate weight shifting between the two sessions was higher in the intervention group (0.84 [0.24; 0.89]) than in the control group (0.01 [-0.01; 0.09]; [Formula: see text]) and that the ratio of prolonged excessive pressure between the two sessions was lower in the intervention group (0.74 [0.37; 1.92]) than in the control group (1.72 [1.32; 2.56]; [Formula: see text]). The pressure map sensor was evaluated as being convenient for use in daily life; however, this was not the case for the TDU. This paper shows that persons with SCI could benefit from a system based on perceptive supplementation that alerts and guides the user on how to adapt their posture in order to reduce prolonged excessive pressure, one of the main causes of PU.

CT-texture analysis of subsolid nodules for differentiating invasive from in-situ and minimally invasive lung adenocarcinoma subtypes.

PURPOSE: The purpose of this study was to evaluate the usefulness of computed tomography-texture analysis (CTTA) in differentiating between in-situ and minimally-invasive from invasive adenocarcinomas in subsolid lung nodules (SSLNs). MATERIAL AND METHODS: Two radiologists retrospectively reviewed 49 SSLNs in 44 patients. There were 27 men and 17 women with a mean age of 63±7 (SD) years (range: 47-78years). For each SSLN, type (pure ground-glass or part-solid) was assessed by consensus and CTTA was conducted independently by each observer using a filtration-histogram technique. Different filters were used before histogram quantification: no filtration, fine, medium and coarse, followed by histogram quantification using mean intensity, standard deviation (SD), entropy, mean positive pixels (MPP), skewness and kurtosis. RESULTS: We analyzed 13 pure ground-glass and 36 part-solid nodules corresponding to 16 adenocarcinomas in-situ (AIS), 5 minimally invasive adenocarcinomas (MIA) and 28 invasive adenocarcinomas (IVA). At uni- and multivariate analysis CTTA allowed discriminating between IVAs and AIS/MIA (P<0.05 and P=0.025, respectively) with the following histogram parameters: skewness using fine textures and kurtosis using coarse filtration for pure ground-glass nodules, and SD without filtration for part-solid nodules. CONCLUSION: CTTA has the potential to differentiate AIS and MIA from IVA among SSLNs. However, our results require further validation on a larger cohort.

Qualitative and quantitative assessment of cartilage degeneration using full-field optical coherence tomography ex vivo.

OBJECTIVE: The purpose of this study was to investigate the ability of full-field optical coherence tomography (FFOCT) to qualitatively and quantitatively evaluate cartilage degeneration using the qualitative evaluation of histology sections as the reference. DESIGN: Thirty-three human knee cartilage samples of variable degeneration were included in the study. A closely matching histology and FFOCT image was acquired for each sample. The cartilage degeneration was qualitatively evaluated by assigning a grade to each histology and FFOCT image. The relevance of the performed grading was assessed by calculating the intra- and inter-observer reproducibility and calculating the concordance between the histology and FFOCT grades. A near-automatic algorithm was developed to quantitatively characterize the cartilage surface in each image. The correlation between the quantitative results and the reference qualitative histology was calculated. RESULTS: An almost perfect agreement was achieved for both the intra- and inter-reproducibility of the histology and FFOCT qualitative grading (κ ≥ 0.91). A high and statistically significant level of agreement was measured between the histology and FFOCT grades (W = 0.95, P < 0.05). Strong and statistically significant correlations were measured between the quantitative results and the reference qualitative histology grades (ρ ≥ 0.75, P < 0.05). CONCLUSIONS: We have demonstrated that FFOCT is an alternative approach to conventional optical coherence tomography (OCT) that is as well adapted for the qualitative and quantitative assessment of human cartilage as the reference gold standard - histology. This study constitutes the first promising results towards developing a new diagnostic tool in the field of osteoarthritis.

Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial.

BACKGROUND: Interventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator's instruments, meaning the position and progression of the instruments are visualised in real time on the patient's images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region. METHODS/DESIGN: This study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device. DISCUSSION: This trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01896219 . Registered on 5 July 2013.

Unintended Consequences of Sensor, Signal, and Imaging Informatics: New Problems and New Solutions.

OBJECTIVES: This synopsis presents a selection for the IMIA (International Medical Informatics Association) Yearbook 2016 of excellent research in the broad field of Sensor, Signal and Imaging Informatics published in the year 2015, with a focus on Unintended consequences: new problems and new solutions. METHODS: We performed a systematic initial selection and a double blind peer review process to find the best papers in this domain published in 2015, from the PubMed and Web of Science databases. The set of MesH keywords used was provided by experts. RESULTS: The constant advances in medical technology allow ever more relevant diagnostic and therapeutic approaches to be designed. Nevertheless, there is a need to acquire expert knowledge of these innovations in order to identify precociously new associated problems for which new solutions need to be designed and developed.

[Rigid cystoscopy versus retrovision for adjustable peri-urethral balloons guidance: Comparison of precision thanks to a surgical navigation system]. / Cystoscopie rigide versus rétro-vision pour le guidage des ballonnets péri-urétraux : comparaison de la précision grâce à un système de navigation chirurgicale.

OBJECTIVES: The main goal of our phantom study was to compare the precision of adjustable periurethral balloons positioning depending whether the guidance was obtained by retrovision or rigid cystoscopy. MATERIAL AND METHODS: A navigation guidance system was used to localize the introduction mandrel which was equipped with tracking targets. Two ideal sites of implantation were predefined and recorded into the navigation system. The two points were placed symmetrically to the phantom reproducing the urethra. Four different users were asked to position the tip of the introduction mandrel as close as possible to the ideal site of implantation with the help of each method of guidance. For each attempt, the distance (mm) between the tip of the introduction mandrel and the ideal position was recorded by the navigation system. RESULTS: For each method of guidance, a total of 20 attempts on each side were made by direct puncture on one side and a symmetrical contralateral puncture. For direct puncture, the median distances were 5.20 (±3.96) and 4.38 (±1.55) mm with rigid cystoscopy and retrovision respectively (P=0.29). For symmetrical contralateral puncture, the median distance were 7,19 (±3,78) and 6,86 (±2,76) mm with rigid cystoscopy and retrovision respectively (P=0,32) CONCLUSION: This study could not demonstrate any significant difference between the two guidance systems. Nevertheless, it showed that navigation guidance system could be used to compare the precision of surgical interventions. LEVEL OF EVIDENCE: 4.

Interest of intra-operative 3D imaging in spine surgery: a prospective randomized study.

PURPOSE: We report a single-center, prospective, randomized study for pedicle screw insertion in opened and percutaneous spine surgeries, using a computer-assisted surgery (CAS) technique with three-dimensional (3D) intra-operative images intensifier (without planification on pre-operative CT scan) vs conventional surgical procedure. MATERIAL AND METHOD: We included 143 patients: Group C (conventional, 72 patients) and Group N (3D Fluoronavigation, 71 patients). We measured the pedicle screw running time, and surgeon's radiation exposure. All pedicle runs were assessed according to Heary by two independent radiologists on a post-operative CT scan. RESULTS: 3D Fluoronavigation appeared less accurate in percutaneous procedures (24 % of misplaced pedicle screws vs 5 % in Group C) (p = 0.007), but more accurate in opened surgeries (5 % of misplaced pedicle screws vs 17 % in Group C) (p = 0.025). For one vertebra, the average surgical running time reached 8 min in Group C vs 21 min in Group N for percutaneous surgeries (p = 3.42 × 10(-9)), 7.33 min in Group C vs 16.33 min in Group N (p = 2.88 × 10(-7)) for opened surgeries. The 3D navigation device delivered less radiation in percutaneous procedures [0.6 vs 1.62 mSv in Group C (p = 2.45 × 10(-9))]. For opened surgeries, it was twice higher in Group N with 0.21 vs 0.1 mSv in Group C (p = 0.022). CONCLUSION: The rate of misplaced pedicle screws with conventional techniques was nearly the same as most papers and a little bit higher with CAS. Surgical running time and radiation exposure were consistent with many studies. Our work hypothesis is partially confirmed, depending on the type of surgery (opened or closed procedure).

How Sensor, Signal, and Imaging Informatics May Impact Patient Centered Care and Care Coordination.

OBJECTIVE: This synopsis presents a selection for the IMIA (International Medical Informatics Association) Yearbook 2015 of excellent research in the broad field of Sensor, Signal, and Imaging Informatics published in the year 2014, with a focus on patient centered care coordination. METHODS: The two section editors performed a systematic initial selection and a double blind peer review process to select a list of candidate best papers in the domain published in 2014, from the PubMed and Web of Science databases. A set of MeSH keywords provided by experts was used. This selection was peer-reviewed by external reviewers. RESULTS: The review process highlighted articles illustrating two current trends related to care coordination and patient centered care: the enhanced capacity to predict the evolution of a disease based on patient-specific information can impact care coordination; similarly, better perception of the patient and his treatment could lead to enhanced personalized care with a potential impact on care coordination. CONCLUSIONS: This review shows the multiplicity of angles from which the question of patient-centered care can be addressed, with consequences on care coordination that will need to be confirmed and demonstrated in the future.

Phantom evaluation of a navigation system for out-of-plane CT-guided puncture.

OBJECTIVE: The purpose of this phantom study was to assess a new real time electromagnetically-guided navigation system and compare it to standard computed tomography (CT) guidance. MATERIAL AND METHODS: A prospective, randomized, comparative study was carried out over a two-day period. Operators without prior experience on the new navigation system sequentially attempted to puncture two 6 mm-diameter targets (one attempt for each target) with out-of-plane trajectories using both the standard CT-guided method and the new navigation station (NAV method). RESULTS: Intention-to-treat analysis was performed for 54 operators. Twenty-two operators out of 54 (40.7%) reached the target on first attempt with the NAV method versus none (0%) using CT-guidance (P<0.001). The median distance of the puncture from the center of the target was 3.7mm [Q1-Q3=2-6.7] using NAV versus 15 mm [10-20] using CT-guidance (P<0.001). Overall planning and puncture time were shorter using NAV: 76s [50-118] versus 214s [181-264] using CT-guidance (P<0.001). CONCLUSION: Novice operators consistently performed faster and more accurate phantom punctures with out-of-plane trajectories using the electromagnetically-guided navigation system than with the standard CT-guided method.

Sensor, signal, and imaging informatics: big data and smart health technologies.

OBJECTIVES: This synopsis presents a selection for the IMIA (International Medical Informatics Association) Yearbook 2014 of excellent research in the broad field of Sensor, Signal, and Imaging Informatics published in the year 2013, with a focus on Big Data and Smart Health Technologies Methods: We performed a systematic initial selection and a double blind peer review process to find the best papers in this domain published in 2013, from the PubMed and Web of Science databases. A set of MeSH keywords provided by experts was used. RESULTS: Big Data are collections of large and complex datasets which have the potential to capture the whole variability of a study population. More and more innovative sensors are emerging, allowing to enrich these big databases. However they become more and more challenging to process (i.e. capture, store, search, share, transfer, exploit) because traditional tools are not adapted anymore. CONCLUSIONS: This review shows that it is necessary not only to develop new tools specifically designed for Big Data, but also to evaluate their performance on such large datasets.

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.

Sensor, signal, and imaging informatics: evidence-based health informatics.

OBJECTIVES: This synopsis presents a selection for the IMIA (International Medical Informatics Association) Yearbook 2013 of excellent research in the broad field of Sensor, Signal, and Imaging Informatics published in the year 2012. METHODS: We performed a systematic initial selection and a double blind peer review process to find the best papers in this domain published in 2012, from the PubMed and Web of Science databases. A set of MeSH keywords provided by experts was used. RESULTS: Current research in the field of sensor signal and imaging informatics is based on innovative sensors from which relevant information (signal and imaging) can be acquired and integrated into workflow based or patient based models. This rich environment can help the medical staff in carrying out more optimal care. The demonstration of the added value of such innovations is more and more performed through evidence-based evaluations. CONCLUSIONS: The best paper selection of articles on sensors, signal, and imaging informatics illustrates the wide spectrum covered by this field in 2012, and the attention paid to evaluations.

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.

Analysis of medical prescribing practices for hepatitis B serology tests.

The aim of this survey was to study the requests written for hepatitis B virus (HBV) serology tests to ascertain their compliance with French prescription guidelines; additional costs incurred by inappropriate requests were also determined, as was the appropriateness of the physicians' interpretation of the test results. This was a cross-sectional practice inquiry involving 118 prescriptions for HBV serology tests. Data were prospectively collected in June 2005 from laboratory heads and prescribing physicians. The prescriptions were written for 188 patients (64% women), aged 35 years on average, mostly by general practitioners (65%) and gynecologists (25%). Prescribing physicians reported the following clinical situations as their main reasons for ordering HBV serology tests: pregnancy (25%); vaccination (20%); acute hepatitis (18%) and screening a patient with a risk factor (19%). Failure to comply with current guidelines was noted in 74% of the prescriptions and vague wording in 45%. The additional cost due to ordering inappropriate serology tests was 43.41 euro per prescription. The physician's interpretation of the test results was considered excellent (27%), fair (59%) or false (14%). Guidelines for the prescribing of hepatitis B serology tests need to be more rigorously applied in daily clinical practice. City hospital networks should promote further in-service training for physicians.

Pressure sensor-based tongue-placed electrotactile biofeedback for balance improvement--biomedical application to prevent pressure sores formation and falls.

We introduce the innovative technologies, based on the concept of "sensory substitution", we are developing in the fields of biomedical engineering and human disability. Precisely, our goal is to design, develop and validate practical assistive biomedical and/or technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. Proposed applications are dealing with: (1) pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia); and (2) balance control improvement to prevent fall in older and/or disabled adults. This paper describes the architecture and the functioning principle of these biofeedback systems and presents preliminary results of two feasibility studies performed on young healthy adults.

[Fourier transform spectral analysis of cutaneous blood flux in systemic sclerosis]. / Analyse spectrale par transformée de Fourier du flux sanguin cutané dans la sclérodermie systémique.

OBJECTIVES: Endothelial dysfunction is an early event and a critical step in the pathogenesis of systemic sclerosis. Accurate and sensitive tests are needed to correctly assess the degree of microvascular endothelial dysfunction. Spectral analysis of skin blood flow contains a characteristic low frequency reported to be associated with endothelial function in healthy subjects. We hypothesized that the relative amplitude of the oscillation recorded for this low frequency spectrum (0.008 to 0.021 Hz) would be less pronounced in patients with systemic sclerosis than in healthy subjects and in patients with primary Raynaud's phenomenon. PATIENTS AND METHOD: Twenty-one patients with systemic sclerosis, twenty patients with primary Raynaud phenomenon and eleven healthy subjects were enrolled. Skin perfusion was recorded at rest for 30 minutes using laser Doppler flowmetry on the pad of the left third left. Fourier transform spectral analysis was applied to obtain the mean amplitude of the cutaneous blood perfusion signal of the total spectrum from 0.008 to 1.6 Hz and the mean amplitude of each characteristic frequency in the laser Doppler flowmeter blood flow oscillations. RESULTS: The relative amplitudes of each characteristic frequency in the laser Doppler flowmeter blood flow oscillations were not statistically different in the three groups, particularly for frequency spectrum from 0.008 Hz to 0.021 Hz. CONCLUSION: Fourier transform spectral analysis of baseline cutaneous blood flow does not provide significant information. Further studies are required, perhaps using wavelet spectral analysis or stimulated conditions.

Digital thermal hyperaemia impairment does not relate to skin fibrosis or macrovascular disease in systemic sclerosis.

OBJECTIVES: Thermal hyperaemia is impaired in patients with systemic sclerosis (SSc). The objective of these studies was to determine whether this was consecutive to skin fibrosis, microangiopathy or macroangiopathy. METHODS: Using laser Doppler flowmetry, we first compared the thermal hyperaemia on the third left finger pad and on the left forearm in 21 patients with non-diffuse systemic sclerosis (SSc), in comparison with primary Raynaud's phenomenon and healthy volunteers. Second, we tested whether the altered thermal hyperaemia correlated to the digital pressure index at baseline, and following the thermal challenge. RESULTS: In the first study, thermal hyperaemia of the finger pad was impaired in terms of both amplitude and kinetics, but not on the forearm in patients with SSc. In the seven SSc patients without cutaneous fibrosis, the response was similarly altered in terms of amplitude and kinetics. In the second study, we observed a weak correlation between the digital systolic blood pressure index. However, in the 15 SSc patients tested at 44 degrees C, the median digital systolic blood pressure index was 1.04 (0.84-1.24) at baseline vs 1.08 (0.87-1.29) at 44 degrees C (NS), while seven of them had an abnormal response in terms of kinetic. Furthermore, only one patient showed a clear-cut decrease in digital systolic blood pressure at 44 degrees C. CONCLUSION: In patients with SSc, digital thermal hyperaemia is impaired, but does not relate to the skin fibrosis or to an associated macroangiopathy in most cases. Further studies are required to determine whether its impairment reflects a functional or structural microvascular damage.

Carotid remodeling in essential hypertension: role of blood pressure, indexed parameters, and association with cardiac mass and aortic stiffness.

The role of blood pressure on carotid remodeling, using no indexed and indexed parameters, was studied in essential hypertension. Carotid parameters were also compared to cardiac mass and aortic stiffness. Forty untreated hypertensive men had echocardiography, carotid ultrasonography and carotidfemoral pulse wave velocity measurements. Cross-sectional area index was associated essentially with the 24-hour systolic blood pressure whereas intima-media thickness was related especially to the 24-hour pulse pressure. Carotid intima-media thickness and cross-sectional area indexes were less related to blood pressure variables than non-indexed parameters. There is an independent association between 24-hour pulse pressure and left ventricular mass index and pulse wave velocity. To conclude, blood pressure, particularly pulse pressure, is associated with vascular and cardiac alterations. The indexation by the body surface area do not provide any additional information in the association between carotid and blood pressure parameters.