Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe ...acute kidney injury, the ideal time for initiation remains controversial.
In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days.
The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients).
Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).
Background
Exponential development of minimally invasive techniques, such as robotic-assisted devices, raises the question of how to assess robotic surgery skills. Early development of virtual ...simulators has provided efficient tools for laparoscopic skills certification based on objective scoring, high availability, and lower cost. However, similar evaluation is lacking for robotic training. The purpose of this study was to assess several criteria, such as reliability, face, content, construct, and concurrent validity of a new virtual robotic surgery simulator.
Methods
This prospective study was conducted from December 2009 to April 2010 using three simulators dV-Trainers
®
(MIMIC Technologies
®
) and one Da Vinci S
®
(Intuitive Surgical
®
). Seventy-five subjects, divided into five groups according to their initial surgical training, were evaluated based on five representative exercises of robotic specific skills: 3D perception, clutching, visual force feedback, EndoWrist
®
manipulation, and camera control. Analysis was extracted from (1) questionnaires (realism and interest), (2) automatically generated data from simulators, and (3) subjective scoring by two experts of depersonalized videos of similar exercises with robot.
Results
Face and content validity were generally considered high (77 %). Five levels of ability were clearly identified by the simulator (ANOVA;
p
= 0.0024). There was a strong correlation between automatic data from dV-Trainer and subjective evaluation with robot (
r
= 0.822). Reliability of scoring was high (
r
= 0.851). The most relevant criteria were time and economy of motion. The most relevant exercises were Pick and Place and Ring and Rail.
Conclusions
The dV-Trainer
®
simulator proves to be a valid tool to assess basic skills of robotic surgery.
Chitin is a structural polysaccharide of the cell walls of fungi and exoskeletons of insects and crustaceans
In this study, chitin was extracted, for the first time in our knowledge, from the
sloughs ...of the south-eastern French Mediterranean basin by treatment with 1 M HCl for demineralization, 1 M NaOH for deproteinization, and 1% NaClO for decolorization. The different steps of extraction were investigated by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), and Scanning Electron Microscopy (SEM). Results demonstrated that the extraction process was efficiently performed and that
sloughs of the south-eastern French Mediterranean basin have a high content of chitin (42.8%) in the α-form with a high degree of acetylation of 96% ± 3.4%. These results make
of the south-eastern French Mediterranean basin a new and promising source of chitin. Furthermore, we showed that each step of the extraction present specific characteristics (for example FTIR and XRD spectra and, consequently, distinct absorbance peaks and values of crystallinity as well as defined values of maximum degradation temperatures identifiable by TGA analysis) that could be used to verify the effectiveness of the treatments, and could be favorably compared with other natural chitin sources.
We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir–interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care ...(control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support.
We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely.
The intention-to-treat population included 583 participants—lopinavir/ritonavir (n = 145), lopinavir/ritonavir–IFN–β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)—among whom 418 (71.7%) were male, the median age was 63 years (IQR 54–71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55–1.26, p 0.39), lopinavir/ritonavir–IFN–β-1a versus control, aOR 0.69 (95%CI 0.45–1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62–1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms.
In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir–IFN–β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.
Biomaterials applied to the epicardium have been studied intensively in recent years for different therapeutic purposes. Their mechanical influence on the heart, however, has not been clearly ...identified. Most biomaterials for epicardial applications are manufactured as membranes or cardiac patches that have isotropic geometry, which is not well suited to myocardial wall motion. Myocardial wall motion during systole and diastole produces a complex force in different directions. Membrane or cardiac patches that cannot adapt to these specific directions will exert an inappropriate force on the heart, at the risk of overly restricting or dilating it. Accurately characterizing the mechanical properties of the myocardial wall is thus essential, through analysis of muscle orientation and elasticity. In this study, we investigated the Hertz contact theory for characterizing cardiac tissue, using nanoindentation measurements to distinguish different patterns in the local myocardium. We then evaluated the predictive accuracy of this model using Finite Element Analysis (FEA) to mimic the diastolic phase of the heart. Our results, extracted from instrumented nanoindentation experiments in a liquid environment using five pig hearts, revealed variations in elasticity according to the local orientation of the myocardial tissue. In addition, applying the Finite Element Method (FEM) in our model based on transverse isotropy and local tissue orientation proved able to accurately simulate the passive filling of a left ventricle (LV) in a representative 3D geometry. Our model enables improved understanding of the underlying mechanical properties of the LV wall and can serve as a guide for designing and manufacturing biomedical material better adapted to the local epicardial tissue.
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Chitin and its derivative chitosan are among the most used polysaccharides for biomedical and pharmaceutical applications. Most of the commercially available chitin is obtained from seafood wastes. ...However, the interest in alternative renewable sources of chitin and chitosan, such as insects, is growing. When new sources are identified, their stability over time has to be evaluated to allow for their commercialization. The aim of this study is to compare the physicochemical properties of chitin extracted from Cicada orni sloughs harvested in three different years (2017, 2019 and 2020) in order to assess the stability of the source and the repeatability of the extraction process. Chitin and its derivative chitosan were characterized by simple techniques such as Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Results suggest that the physicochemical properties of the extracted chitin varied from year to year, and that these differences are not due to the extraction process, but rather to intrinsic differences within the source. We showed that these differences could already be detected by analyzing the raw material (i.e., cicada sloughs) using the above-mentioned simple methods. The chitosan obtained from deacetylation of chitin had a low degree of deacetylation (66.2±1.6%). This low degree of deacetylation can be attributed to the deacetylation process, which is probably not appropriate for this source of chitin.
A myocardial infarction can cause irreversible damage to the heart muscle. A promising approach for the treatment of myocardial infarction and prevention of severe complications is the application of ...cardiac patches or epicardial restraint devices. The challenge for the fabrication of cardiac patches is the replication of the fibrillar structure of the myocardium, in particular its anisotropy and local elasticity. In this study, we developed a chitosan-gelatin-guar gum-based biomaterial ink that was fabricated using 3D printing to create patterned anisotropic membranes. The experimental results were then used to develop a numerical model able to predict the elastic properties of additional geometries with tunable elasticity that could easily match the mechanical properties of the heart tissue (particularly the myocardium).
Background
The influence of socioeconomic status on patient outcomes is unclear. We assessed the impact of socioeconomic deprivation on severity of illness at intensive care unit (ICU) admission, and ...on the risk of death at 3 months after ICU admission.
Methods
The IVOIRE study was a prospective, observational, multicentre cohort study in the ICU of 8 participating hospitals in France, including patients aged ≥ 18 years admitted to the ICU and receiving at least one life support therapy for organ failure. The primary outcomes were severity at admission (assessed by SAPSII score), and mortality at 3 months. Socioeconomic data were obtained from interviews with patients or family. Deprivation was assessed using the EPICES score.
Results
Among 1294 patents included between 2013 and 2016, 629 (48.6%) were classed as deprived and differed significantly from non-deprived subjects in terms of sociodemographic characteristics and pre-existing conditions. The mean SAPS II score at admission was 50.1 ± 19.4 in deprived patients and 52.3 ± 17.3 in non-deprived patients, with no significant difference by multivariable analysis (
β
= − 1.85 95% CI − 3.86; + 0.16,
p
= 0.072). The proportion of death was 31.1% at 3 months, without significant differences between deprived and non-deprived patients, even after adjustment for confounders.
Conclusions
Deprivation is frequent in patients admitted to the ICU and is not associated with disease severity at admission, or with mortality at 3 months between deprived and non-deprived patients.
Trial registration
The IVOIRE cohort is registered with ClinicalTrials.gov under the identifier NCT01907581, registration date 17/7/2013
The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in ...patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support.
DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948.
Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 15% of 414 in the remdesivir group vs 73 17% of 418 in the control group); (2) not hospitalised, limitation on activities (129 31% vs 132 32%); (3) hospitalised, not requiring supplemental oxygen (50 12% vs 29 7%); (4) hospitalised, requiring supplemental oxygen (76 18% vs 67 16%); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 4% vs 14 3%); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 15% vs 79 19%); (7) death (21 5% vs 24 6%). The difference between treatment groups was not significant (odds ratio 0·98 95% CI 0·77–1·25; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 33% of 406 vs control, 130 31% of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome).
No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support.
European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation.
For the French translation of the abstract see Supplementary Materials section.
Background. The teaching of implant surgery, as in other medical disciplines, is currently undergoing a particular evolution. Aim of the Study. To assess the usefulness of haptic device, a simulator ...for learning and training to accomplish basic acts in implant surgery. Materials and Methods. A total of 60 people including 40 third-year dental students without knowledge in implantology (divided into 2 groups: 20 beginners and 20 experiencing a simulator training course) and 20 experienced practitioners (experience in implantology >15 implants) participated in this study. A basic exercise drill was proposed to the three groups to assess their gestural abilities. Results. The results of the group training with the simulator tended to be significantly close to those of the experienced operators. Conclusion. Haptic simulator brings a real benefit in training for implant surgery. Long-term benefit and more complex exercises should be evaluated.
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