[New therapeutic strategies in ARDS]. / Nouveautés thérapeutiques sur le SDRA.

Treatment of acute respiratory distress syndrome (ARDS) has been subject to many researches, sometimes leading to intense controversy. New findings in this field are varied. Effects on prognosis of commonly used treatments for ARDS have recently been investigated. Consistently, prone position, previously known to improve oxygenation without effect on mortality, has been shown to improve survival of the most severely hypoxemic patients. Administration of neuromuscular blocking agents in the acute phase of ARDS has been also shown to be beneficial on survival. In contrast, the exact place of extracorporeal membrane oxygenation (ECMO) in ARDS management remains to be defined despite data suggesting its possible efficiency. In addition, a new era of research has emerged with the advent of cell therapy. Mesenchymal stem cells are able to both promote alveolar epithelium repair and prevent infections. Their efficacy in animal models of ARDS still needs to be confirmed by clinical trials. Finally, other promising therapies including beta-2 adrenergic agonists and omega-3 fatty acids have shown significant limitations in large clinical studies on ARDS.

Confronting racially exclusionary practices in the acquisition and analyses of neuroimaging data.

Across the brain sciences, institutions and individuals have begun to actively acknowledge and address the presence of racism, bias, and associated barriers to inclusivity within our community. However, even with these recent calls to action, limited attention has been directed to inequities in the research methods and analytic approaches we use. The very process of science, including how we recruit, the methodologies we utilize and the analyses we conduct, can have marked downstream effects on the equity and generalizability of scientific discoveries across the global population. Despite our best intentions, the use of field-standard approaches can inadvertently exclude participants from engaging in research and yield biased brain-behavior relationships. To address these pressing issues, we discuss actionable ways and important questions to move the fields of neuroscience and psychology forward in designing better studies to address the history of exclusionary practices in human brain mapping.

Ultrafast and whole-body cooling with total liquid ventilation induces favorable neurological and cardiac outcomes after cardiac arrest in rabbits.

BACKGROUND: In animal models of cardiac arrest, the benefit afforded by hypothermia is closely linked to the rapidity of the decrease in body temperature after resuscitation. Because total liquid ventilation (TLV) with temperature-controlled perfluorocarbons induces a very rapid and generalized cooling, we aimed to determine whether this could limit the post-cardiac arrest syndrome in a rabbit model. We especially focused on neurological, cardiac, pulmonary, liver and kidney dysfunctions. METHODS AND RESULTS: Anesthetized rabbits were submitted to either 5 or 10 minutes of untreated ventricular fibrillation. After cardiopulmonary resuscitation and resumption of a spontaneous circulation, the animals underwent either normothermic life support (control) or therapeutic hypothermia induced by TLV. The latter procedure decreased esophageal and tympanic temperatures to 32°C to 33°C within only 10 minutes. After rewarming, the animals submitted to TLV exhibited an attenuated neurological dysfunction and decreased mortality 7 days later compared with control. The neuroprotective effect of TLV was confirmed by a significant reduction in brain histological damages. We also observed limitation of myocardial necrosis, along with a decrease in troponin I release and a reduced myocardial caspase 3 activity, with TLV. The beneficial effects of TLV were directly related to the rapidity of hypothermia induction because neither conventional cooling (cold saline infusion plus external cooling) nor normothermic TLV elicited a similar protection. CONCLUSIONS: Ultrafast cooling instituted by TLV exerts potent neurological and cardiac protection in an experimental model of cardiac arrest in rabbits. This could be a relevant approach to provide a global and protective hypothermia against the post-cardiac arrest syndrome.

[Congenital mesoblastic nephroma: diagnosis and treatment of one case]. / Le néphrome mésoblastique congénital : diagnostic et prise en charge à partir d'un cas.

The congenital mesoblastic nephroma (CMN) described by Bolande et al. in 1967 is a renal tumor often discovered in neonatal period and early childhood. It's usually considered as a benign tumor with good prognostic for which nephrectomy is the reference treatment. But some cases of local recidives and metastatic sites had been described in the literature. For these reasons histologic analysis and quality of follow up are very important. In this observation we describe a neonatal kind of CMN and we discuss this pathology.

Life-threatening hemophagocytic syndrome triggered by disseminated toxoplasmosis in a young patient with previously unknown AIDS.

Hemophagocytic syndrome is a rare life-threatening disorder that can be triggered by various conditions such as HIV infection and opportunistic agents. We report a case of disseminated toxoplasmosis complicated with severe hemophagocytic syndrome and revealing an unknown acquired immunodeficiency syndrome. The patient presented with multiple organ failure in intensive care unit. Once diagnosed, he benefitted from etoposide infusion, administration of specific anti-toxoplasmosis treatments and secondary antiretroviral therapy. He was alive at intensive care unit discharge and returned home with little sequalae. This case illustrates both the importance of rapid investigations of hemophagocytic syndrome etiologies in HIV positive patients and the necessity to prompt etoposide and specific treatments in order to improve potentially dramatic outcomes.

Study of prone positioning to reduce ventilator-associated pneumonia in hypoxaemic patients.

The aim of the present study was to examine whether prone positioning (PP) affects ventilator associated-pneumonia (VAP) and mortality in patients with acute lung injury/adult respiratory distress syndrome. 2,409 prospectively included patients were admitted over 9 yrs (2000-2008) to 12 French intensive care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction ratios <300 during the first 48 h. Controls were matched to PP patients on the PP propensity score (+/-10%), MV duration longer than that in PP patients before the first turn prone, and centre. VAP incidence was similar in the PP and control groups (24 versus 13 episodes.1,000 patient-days MV(-1) respectively, p = 0.14). After adjustment, PP did not decrease VAP occurrence (HR 1.64 (95% CI 0.70-3.84); p = 0.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39-0.79); p = 0.001), without decreasing 28-day mortality (37% in both groups). Post hoc analyses indicated that PP did not protect against VAP but, when used for >1 day, might decrease mortality and benefit the sickest patients (Simplified Acute Physiology Score >50). In ICU patients with hypoxaemic acute respiratory failure, PP had no effect on the risk of VAP. PP delayed mortality without decreasing 28-day mortality. PP >1 day might decrease mortality, particularly in the sickest patients.

[Assessment of a newly-implemented blended teaching of intensive care and emergency medicine at Paris-Diderot University]. / Évaluation d'un enseignement multimodal intégrant du e-learning dans l'apprentissage de la réanimation et de la médecine d'urgence au cours du second cycle des études médicales.

INTRODUCTION: Blended-learning methods could be a response to student nonattendance. Non-compulsory teaching combining e-learning/interactive face-to-face sessions has been implemented at Paris-Diderot Medical School for the teaching of intensive care and emergency medicine during the 2018/2019 university period. The aim of the study was to assess this newly-implemented blended teaching. METHODS: Questionnaire submitted to the 388 DFASM3 medical students present at the faculty exam of intensive care/emergency medicine. Attendance at a teaching modality was defined by the follow-up of more than half of this teaching modality. Correlations between attendance at e-learning and/or interactive face-to-face sessions, and grade were performed. RESULTS: A total of 358/388 (92%) students participated in this survey. A quarter of the students (88/321 - 25%) reported they usually attended at traditional lectures. Regarding blended-learning, 210/317 (67%) students reported having attended at e-learning courses and 84/321 (27%) attended at interactive face-to-face sessions. The distribution of students according to their attendance at e-learning and/or interactive face-to-face sessions was significantly different (P<0.01). There was a significant correlation (P<0.001) between attendance at e-learning and grade obtained at the faculty exam. Nevertheless, this correlation was also found for these students in another course taught traditionally. Overall, 309/315 (98%) students were satisfied with the blended teaching, 297/318 (93%) wanted its extent to the whole medical school's curriculum. CONCLUSION: The use of combined learning methods reached more students than traditional teachings and allowed the University to focus on its role of knowledge transfer.

[Correlation between prenatal and postnatal observations in case of gastroschisis: Experience in a prenatal referral diagnosis center]. / Corrélation des données anténatales et postnatales en cas de laparoschisis : expérience d'un CPDPN.

OBJECTIVES: Ultrasonography plays a key role in surveillance of gastroschisis. Indeed, ultrasound should allow an early diagnosis of its specific complications all the while avoiding their over-diagnosis which could induce an unnecessary prematurity in these fragile children. The aim of this study was to evaluate the relevance of ultrasonography in the surveillance of this malformation. METHODS: We conducted a retrospective single center study from 2008 until 2018 including all cases of apparently isolated gastroschisis followed during the prenatal period and surgically treated in our institution. Prenatal data gathered during the ultrasound follow-up were compared to those observed during surgery. RESULTS: Thirty-one cases of gastroschisis were included. Regarding the abdominal wall defect, the latter was described prenatally as tight in seven cases with a weak correlation, and as situated to the right of the umbilical cord insertion in 11 cases with a high correlation to the per-operative observations. Sonographic observations were responsible for inducing birth in 14 cases (45%), of which 12 due to the presence of a specific gastroschisis complication, confirmed in five cases (42%, weak correlation). Pre- and post-natal correlation for compression/atresia/stenosis and eviscerated bowel inflammation were very weak in both cases, with a respective tendency of over- and under-diagnosis. CONCLUSIONS: Diagnosing the specific complications of gastroschisis by ultrasound is difficult, even though ultrasonography is responsible for many anticipated births. Thus, this monitoring should be performed by experienced sonographers on devices with appropriate settings. In addition, reproducible parameters such as oligohydramnios or increased bowel dilations should alone be indications of anticipated birth.

[Exercise capacity in children with mild sleep-disordered breathing]. / Capacité physique de l'enfant présentant un syndrome d'apnée du sommeil léger.

INTRODUCTION: While the association between sleep-disordered breathing (SDB) and low physical activity has been reported in children, little information is available on the impact of SDB on exercise capacity. The aim of this study was to assess exercise capacity in children with SDB in order to estimate the relevance of exercise training intervention. METHODS: Twelve young patients with suspected SDB matched with 11 presumably healthy subjects of same age range (aged 13±0.5yr) were investigated. Both groups underwent physical activity assessment, full night polysomnography, incremental and all-out exercise tests. RESULTS: The respiratory disturbance index was higher in the patient group (4.6±4.7 vs 0.8±0.6; P=0.02). Children with SDB had lower VO2max (32.0±9.9 vs 42.3±5.7mL.kg-1.min-1, P=0.007) and lower peak power (8.6±3.4 vs 11.8±1.9W.kg-1, P=0.009). A significant correlation between VO2max and weekly physical activity only was found in the SDB group (P=0.005). CONCLUSION: Mild SDB may be associated with impairment of both aerobic and anaerobic exercise capacity in children, related to poor physical activity. Exercise training could bring clinical benefit in this population.

[Risks associated with the use of non-steroidal anti-inflammatory drugs during pneumonia]. / Risques associés à la prise d'anti-inflammatoires non stéroïdiens au cours de la pneumonie.

INTRODUCTION: Outpatient treatment of community-acquired pneumonia (CAP) patients with non-steroidal anti-inflammatory drugs (NSAIDs) is frequent, although this is not based on clinical recommendations and there is no scientific evidence supporting better symptom relief in comparison to acetaminophen. STATE OF THE ART: Experimental data suggest that NSAIDs alter the intrinsic functions of neutrophils, limit their locoregional recruitment, alter bacterial clearance and delay the resolution of inflammatory processes during acute bacterial pulmonary challenge. In hospitalized children and adults with CAP, observational data suggest a strong and independent association between the outpatient exposure to NSAIDs and the occurrence of pleuropulmonary complications (pleural empyema, excavation, and abscess). In the only study taking into account possible protopathic bias, the association still persists. Other markers of morbidity have been described, including delay in hospital management, prolonged antibiotic therapy, and higher transfer rate to an intensive care unit. PERSPECTIVES: Data describing the role of self-medication and the biological mechanisms involved are needed. CONCLUSIONS: Intake of NSAIDs during outpatient treatment of CAP is probably the second modifiable factor of morbidity after inadequate antibiotic therapy. In light of existing data in children and adults, health authorities should urgently reassess the risk-benefit ratio of NSAIDS in CAP.

Conservative endoscopic management for pancreatic trauma.

Traumatic pancreatic injuries are rare: their severity correlates with main pancreatic duct involvement. We report the case of a 5-year-old child who presented with complete disruption of the main pancreatic duct, treated successfully with an endoscopically inserted double pigtail stent.

[Complete resolution of inflammatory myofibroblastic tumor of the bladder after antibiotic therapy]. / Régression complète d'une tumeur myofibroblastique inflammatoire de vessie après antibiothérapie.

Inflammatory myofibroblastic tumors (IMT) are rare benign tumors, most commonly arising in the lungs and urinary bladder. Many etiologic factors are suspected in their development, but none have been formally demonstrated. Conventional treatment for bladder IMT is complete surgical resection by partial cystectomy or transurethral resection. We report the case of an 8-year-old girl with documented bladder IMT that resolved completely after antibiotic therapy.

[Computerized ranking test in three French universities: Staff experience and students' feedback]. / Épreuves informatisées de type ECNi: retour d'expérience sur un test multiuniversité.

BACKGROUND: The year 2016 will be pivotal for the evaluation of French medical students with the introduction of the first computerized National Ranking Test (ECNi). The SIDES, online electronic system for medical student evaluation, was created for this purpose. All the universities have already organized faculty exams but few a joint computerized ranking test at several universities simultaneously. We report our experience on the organization of a mock ECNi by universities Paris Descartes, Paris Diderot and Paris 13. METHODS: Docimological, administrative and technical working groups were created to organize this ECNi. Students in their fifth year of medical studies, who will be the first students to sit for the official ECNi in 2016, were invited to attend this mock exam that represented more than 50% of what will be proposed in 2016. A final electronic questionnaire allowed a docimological and organizational evaluation by students. An analysis of ratings and rankings and their distribution on a 1000-point scale were performed. RESULTS: Sixty-four percent of enrolled students (i.e., 654) attended the three half-day exams. No difference in total score and ranking between the three universities was observed. Students' feedback was extremely positive. Normalized over 1000 points, 99% of students were scored on 300 points only. Progressive clinical cases were the most discriminating test. CONCLUSION: The organization of a mock ECNi involving multiple universities was a docimological and technical success but required an important administrative, technical and teaching investment.

Peroxidase content of soybean root nodules.

A peroxidase has been isolated from soybean nodules and its main characteristics have been determined. Its molecular weight (48 000) and spectral properties are similar to those of usual plant peroxidases. Its activity is comparable to that of low-efficiency plant peroxidases. The rate constant of the reaction with H2O2 is 3 x 10(5) M-1 x s-1. In this reaction, nodule peroxidase yields an oxidized intermediate analogous to the compound I species of peroxidases already studied. A comparison is made with the pseudoperoxidatic activity of soybean leghemoglobin components. Leghemoglobins a and c react with H2O2 with rate constants of 5 x 10(3) and 2.5 x 10(3) M-1 x s-1, respectively, yielding the leghemoglobin (IV) species. During these reactions leghemoglobins are inactivated.

Proton magnetic resonance studies of peroxidases from turnip and horseradish.

Proton NMR spectra at 270 MHz have been measured for horseradish peroxidase and turnip peroxidase isoenzymes (P1, P2, P3 and P7) in both their high spin ferric native states and as the low spin ferric cyanide complexes. Resonances of amino acids near the heme have been identified and used to investigate variations in the structure of the heme crevice amongst the enzymes. Ligand proton resonances have been resolved in spectra of the cyanide complexes of the peroxidases and these provide information on the heme electronic structure. The electronic structure of the heme and the tertiary structure of the heme crevice are essentially the same in the acidic turnip isoenzymes, P1, P2 and, to a lesser extent, P3 but differ in the basic turnip enzyme, P7. The heme electronic structure and nature of the iron ligands in peroxidases are discussed. Further evidence is presented for histidine as the proximal ligand. A heme-linked ionizable group with a pK of 6.5 has been detected by NMR in the cyanide complex of horseradish peroxidase.

Hormonal control of transcription in higher plants.

1. Nucleolar RNA polymerase Ib obtained from auxin-treated lentil roots exhibits a higher transcriptional activity than the enzyme obtained from control roots. This difference is due to a change in the enzyme properties after auxin treatment. It is suggested that the hormonal effect is mediated by a factor that changes the molecular properties of nucleolar RNA polymerase. 2. Four fractions, alpha, beta, gamma and delta, that stimulate the activity of RNA polymerase Ib, have been extracted from lentil roots. Two of them, gamma and delta have been studied. Factor delta can stimulate nucleolar polymerase Ib and the nucleoplasmic enzyme II equally well, while factor gamma is specific for polymerase Ib. 3. The curve of UMP incorporation in vitro, with and without factors gamma or delta suggests that they are initiation factors. This conclusion is reinforced by the analysis of simultaneous incorporation of [gamma-32P]ATP and [3H]UMP in the RNAs synthesized in vitro. 4. Although the level of factor delta is independent of auxin treatment, that of factor gamma is doubled in auxin-treated roots. These results suggest that factor gamma is an auxin-induced protein that modulates the specific activity of the nucleolar RNA polymerase. 5. A general model of the mode of action of auxins at the molecular level is proposed. It integrates into a unified scheme the above results as well as those obtained by other workers.

TNF-alpha enhances Toxoplasma gondii cyst formation in human fibroblasts through the sphingomyelinase pathway.

The cystogenesis event of Toxoplasma gondii is poorly understood. In order to throw light on it, the effect of tumor necrosis factor-alpha (TNF-alpha) was studied in the Prugniaud strain of the organism. This showed that TNF-alpha increased the number of cysts formed in vitro in human MRC5 fibroblasts. The sphingomyelinase pathway may be involved in mediating the TNF effect, since ceramide (natural form in permeabilized cells or cell-permeable analogue) could mimic the action of TNF. More precisely, our results strongly suggest the involvement of an acidic sphingomyelinase in mediating the effect of TNF; indeed, D609 inhibited both the TNF effect and cyst formation, while arachidonic acid had no effect. Moreover, protein kinase (PKC) seems also to play a role in the process, since phorbol-12-myristate-13-acetate (PMA) enhanced the cyst formation. However, chelerythrine chloride did not prevent the TNF effect, suggesting that several host-cell pathways can affect the cystogenesis event. Taken together, these results suggest the active participation of host-cell components in the cystogenesis of Toxoplasma gondii.

EphB3 receptors function as dependence receptors to mediate oligodendrocyte cell death following contusive spinal cord injury.

We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and disturbances in EphB3-ephrinB3 protein balance acutely (days) after the initial impact creating an environment for a dependence receptor-mediated cell death to occur. Genetic ablation of EphB3 promotes OL survival associated with increased expression of myelin basic protein and improved locomotor function in mice after SCI. Moreover, administration of its ephrinB3 ligand to the spinal cord after injury also promotes OL survival. Our in vivo findings are supported by in vitro studies showing that ephrinB3 administration promotes the survival of both oligodendroglial progenitor cells and mature OLs cultured under pro-apoptotic conditions. In conclusion, the present study demonstrates a novel dependence receptor role of EphB3 in OL cell death after SCI, and supports further development of ephrinB3-based therapies to promote recovery.