Outcome of life-threatening malaria in African children requiring endotracheal intubation

BACKGROUND: Little is known about children undergoing critical care for malaria. The purpose of this survey was to evaluate the outcome in African children requiring endotracheal intubation for life-threatening malaria. METHODS: All children with a primary diagnosis of severe malaria (2000 WHO definition) requiring endotracheal intubation, hospitalised over a five-year period, within a tertiary-care hospital in Dakar, Senegal, were enrolled in a retrospective cohort study. RESULTS: 83 consecutive patients were included (median PRISM h(24 )score: 14; IQR: 10–19, multiple organ dysfunctions: 91.5%). The median duration of ventilation was 36 hrs (IQR: 4–72). Indications for intubation were deep coma (Glasgow score ≤7, n = 16), overt cortical or diencephalic injury, i.e, status epilepticus/decorticate posturing (n = 20), severe brainstem involvement, i.e., decerebrate posturing/opisthotonus (n = 15), shock (n = 15), cardiac arrest (n = 13) or acute lung injury (ALI) (PaO(2)/FiO(2 )<300 Torr, n = 4). Death occurred in 50 cases (case fatality rate (CFR), 60%) and was associated with multiple organ dysfunctions (median PELOD(h24 )scores: 12.5 among non-survivors versus 11 among survivors, p = 0.02). Median PRISM(h24 )score was significantly lower when testing deep coma against other indications (10 vs 15, p < 0.001), ditto for PELOD(h24 )score (2.5 vs 13, p = 0.02). Multivariate analysis identified deep coma as having a better outcome than other indications (CFR, 12.5% vs 40.0 to 93.3%, p < 0.0001). Decerebrate posturing/opisthotonus (CFR 73.3%, adjusted relative risk (aRR) 10.7, 95% CI 2.3–49.5) were associated with a far worse prognosis than status epilepticus/decorticate posturing (CFR 40.0%, aRR 5.7, 95% CI 1.2–27.1). Thrombocytopaenia (platelet counts <100,000/mm(3)) was associated with death (aRR 2.6, 95% CI 1.2–5.8) and second-line anticonvulsant use (clonazepam or thiopental) with survival (aRR 0.4, 95% CI 0.2–0.9). Complications, mostly nosocomial infections (n = 20), ALI/ARDS (n = 9) or sub-glottic stenosis (n = 3), had no significant prognostic value. CONCLUSION: In this study, the outcome of children requiring intubation for malaria depends more on clinical presentation and progression towards organ failures than on critical care complications per se. In sub-Saharan Africa, mechanical ventilation for life-threatening childhood malaria is feasible, but seems unlikely to dramatically improve the prognosis

Homing and Navigation Using one Transponder for AUV, Post-Processing Comparisons Results with Long Base-Line Navigation

International audienc

Navigation et positionnement sur une balise d'engins sous-marins autonomes

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

A New Design of AUV for Shallow Water Applications: H160

International audienceThis paper focuses on the design and control of a new Autonomous Underwater Vehicle (AUV) named H160. The first prototype of this AUV has been designed through a collaboration of two partners, which are the LIRMM laboratory and ECA-HYTEC company. We present an overview of this project regarding the development of this vehicle including the software and hardware architecture, modelling and control. In addition, the first experimental results relying on real experimental conditions are displayed and commented

Coastal Karst Aquifers in Mediterranean Regions. 2. A Methodology for Exploring, Exploiting and monitoring Submarine Springs

International audienceIn coastal regions, the study of karst aquifers and the ground water resource exploitation require a specific methodology and exploration and monitoring techniques. Two directions are investigated, leading to new technological and methodological developments. The first investigation axis deals with the exploration of fresh water plumes from submarine karst springs. An Autonomous Underwater Vehicle (AUV) is being developed and tested in order to collect all data (salinity, temperature and depth) along its trajectory. The submarine discharge may be estimated by modelling. The second axis deals with the water works for collecting the submarine fresh water discharge. The capture system is designed for monitoring the spring discharge, salinity, temperature, radon concentration and turbidity. The data time series will be analysed in order to determine the aquifer functioning. Discharge data will be used for simulating the spring flow in function of rain series. The prototypes are presently being developed and tested

Dynamics of the digestive acquisition of bacterial carriage and integron presence by French preterm newborns according to maternal colonization: The DAIR3N multicentric study

ObjectivesThe study aimed to describe the dynamics and risk factors of Gram-negative bacteria (GNB) acquisition in preterm infants.MethodsThis prospective multicenter French study included mothers hospitalized for preterm delivery and their newborns, followed until hospital discharge. Maternal feces and vaginal fluids at delivery, and neonatal feces from birth to discharge were tested for cultivable GNB, potential acquired resistance, and integrons. The primary outcome was the acquisition of GNB and integrons in neonatal feces, and their dynamics, evaluated by survival analysis using the actuarial method. Risk factors were analyzed using Cox models.ResultsTwo hundred thirty-eight evaluable preterm dyads were included by five different centers over 16 months. GNB were isolated in 32.6% of vaginal samples, with 15.4% of strains producing extended-spectrum beta-lactamase (ESBL) or hyperproducing cephalosporinase (HCase), and in 96.2% of maternal feces, with 7.8% ESBL-GNB or HCase-GNB. Integrons were detected in 40.2% of feces and 10.6% of GNB strains. The mean (SD) length of stay of newborns was 39.5 (15.9) days; 4 died in the hospital. At least one infection episode occurred in 36.1% of newborns. The acquisition of GNB and integrons was progressive from birth to discharge. At discharge, half of newborns had ESBL-GNB or HCase-GNB, independently favored by a premature rupture of membranes (Hazard Ratio (HR), 3.41, 95% confidence interval (CI), 1.71; 6.81), and 25.6% had integrons (protective factor: multiple gestation, HR, 0.367, 95% CI, 0.195; 0.693).ConclusionIn preterm newborns, the acquisitions of GNB, including resistant ones, and integrons are progressive from birth to discharge. A premature rupture of membranes favored the colonization by ESBL-GNB or Hcase-GNB

Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients

Background: The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate-CoA ligase, caused by mutations in SUCLA2 or SUCLG1. We report here 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings in these and 46 previously reported patients. Patients and results: Of the 71 patients, 50 had SUCLA2 mutations and 21 had SUCLG1 mutations. In the newly-reported 20 SUCLA2 patients we found 16 different mutations, of which nine were novel: two large gene deletions, a 1\ua0bp duplication, two 1\ua0bp deletions, a 3\ua0bp insertion, a nonsense mutation and two missense mutations. In the newly-reported SUCLG1 patients, five missense mutations were identified, of which two were novel. The median onset of symptoms was two months for patients with SUCLA2 mutations and at birth for SUCLG1 patients. Median survival was 20\ua0years for SUCLA2 and 20\ua0months for SUCLG1. Notable clinical differences between the two groups were hepatopathy, found in 38\ua0% of SUCLG1 cases but not in SUCLA2 cases, and hypertrophic cardiomyopathy which was not reported in SUCLA2 patients, but documented in 14\ua0% of cases with SUCLG1 mutations. Long survival, to age 20\ua0years or older, was reported in 12\ua0% of SUCLA2 and in 10\ua0% of SUCLG1 patients. The most frequent abnormality on neuroimaging was basal ganglia involvement, found in 69\ua0% of SUCLA2 and 80\ua0% of SUCLG1 patients. Analysis of respiratory chain enzyme activities in muscle generally showed a combined deficiency of complexes I and IV, but normal histological and biochemical findings in muscle did not preclude a diagnosis of succinate-CoA ligase deficiency. In five patients, the urinary excretion of methylmalonic acid was only marginally elevated, whereas elevated plasma methylmalonic acid was consistently found. Conclusions: To our knowledge, this is the largest study of patients with SUCLA2 and SUCLG1 deficiency. The most important findings were a significantly longer survival in patients with SUCLA2 mutations compared to SUCLG1 mutations and a trend towards longer survival in patients with missense mutations compared to loss-of-function mutations. Hypertrophic cardiomyopathy and liver involvement was exclusively found in patients with SUCLG1 mutations, whereas epilepsy was much more frequent in patients with SUCLA2 mutations compared to patients with SUCLG1 mutations. The mutation analysis revealed a number of novel mutations, including a homozygous deletion of the entire SUCLA2 gene, and we found evidence of two founder mutations in the Scandinavian population, in addition to the known SUCLA2 founder mutation in the Faroe Islands

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency

International audienceIntroduction This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB). Methods Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. Results The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group. Conclusion This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management

Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection