Diagnostics inattendus découverts par les urgentistes grâce à l'échocardiographie ciblée dans un service d'urgence

Introduction
:
 L'utilité
 de
 l'échocardiographie
 (EC)
 dans
 la
 prise
 en
 charge
 des
 maladies
 cardiorespiratoires
 n'est
 plus
 à
 prouver.
 Dans
 la
 mesure
 où
 l'EC
 est
 un
 outil
 non
 invasif
 et
 réalisable
 au
 lit
 du
 malade,
 il
 est
 dès
 lors
 intéressant
 de
 l'employer
 comme
 complément
 à
 l'examen
 standard
 du
 patient
 cardiaque
 et
 pas
 uniquement
 comme
 examen
 accessoire.
 Son
 utilisation
 dans
 des
 situations
 où
 il
 faut
 établir
 rapidement
 un
 diagnostic
 chez
 un
 patient
 hémodynamiquement
 instable,
 ou
 qui
 présente
 des
 plaintes
 suggestives
 d'une
 pathologie
 menaçant
 la
 vie,
 circonstances
 fréquemment
 retrouvées
 aux
 urgences,
 est
 déjà
 bien
 reconnue.
 Néanmoins,
 la
 subtilité
 et
 la
 multiplicité
 de
 la
 présentation
 des
 pathologies
 cardiaques
 masquent
 fréquemment
 des
 diagnostics.
 Ce
 travail
 a
 donc
 pour
 but
 d'évaluer
 le
 bénéfice
 des
 EC
 effectuées
 par
 des
 urgentistes
 sur
 des
 patients 
atteints de
 troubles 
cardiorespiratoires 
dans
 le
 service
 d'urgence
 du
 CHUV.
 Méthodologie : Pour qu’un dossier ait été inclus, il fallait que l’EC ait été pratiquée par un urgentiste du CHUV formé à cette intention, dans le service d’urgence et qu’aucun compte‐rendu n’ait été lacunaire. Ensuite, les dossiers dont l’EC a apporté un diagnostic inattendu (DI) ont été sélectionnés. Enfin, l’impact du DI sur la prise en charge du patient a été analysé. Résultats : Parmi les 511 dossiers sélectionnés, il y a eu 79 DI, ce qui correspond à 15,5% des EC réalisées par les urgentistes. Au sein de ces DI, 53,2% des EC ont eu une conséquence majeure sur la prise en charge du patient, 27,8% un impact mineur, les 19,0% restants n’ont eu aucun effet. La majorité des DI ayant un impact majeur a eu pour résultat de modifier radicalement le traitement du patient (31,0 %) ou de changer son orientation (19,0%), par exemple en l’hospitalisant. La plupart des malades ayant eu une EC révélant un DI se sont présentés aux urgences du CHUV avec une dyspnée (29,1%), une douleur thoracique (19,0%), une tachypnée (12,7%) ou un malaise (12,7%). Par ailleurs, les symptômes suivants sont ceux qui présentent les plus grandes proportions de DI après EC. La dyspnée a conduit à 25,3% de DI, la douleur thoracique à 21,7%, la tachypnée à 20,0% et les malaises à 17,9%. Les trois DI les plus fréquents révélé par les EC sont l’insuffisance cardiaque (34,2 %), l’épanchement péricardique (31,2%) et les insuffisances valvulaires (13,9%). Ces pathologies ont eu plus fréquemment des DI que les autres EC. Il y a eu 48,1% de DI parmi les épanchements péricardiques, 35,5% parmi les insuffisances cardiaques et 21,1% parmi les insuffisances valvulaires. Conclusion : Le nombre de DI est élevé et leur impact sur la prise en charge des patients est important. De plus, les symptômes et pathologies fréquemment découverts par l’EC sont couramment retrouvés aux urgences et il est alors indispensable d’avoir à disposition un examen complémentaire pouvant accélérer leur diagnostic et donc améliorer leur prise en charge. La pratique de l’EC par les urgentistes apporte une réelle plus‐value dans la prise en charge des patients atteints de maladies cardiorespiratoires

The improvement of the best practice guidelines for preimplantation genetic diagnosis of cystic fibrosis: toward an international consensus

Cystic fibrosis (CF) is one of the most common indications for preimplantation genetic diagnosis (PGD) for single gene disorders, giving couples the opportunity to conceive unaffected children without having to consider termination of pregnancy. However, there are no available standardized protocols, so that each center has to develop its own diagnostic strategies and procedures. Furthermore, reproductive decisions are complicated by the diversity of disease-causing variants in the CFTR (cystic fibrosis transmembrane conductance regulator) gene and the complexity of correlations between genotypes and associated phenotypes, so that attitudes and practices toward the risks for future offspring can vary greatly between countries. On behalf of the EuroGentest Network, eighteen experts in PGD and/or molecular diagnosis of CF from seven countries attended a workshop held in Montpellier, France, on 14 December 2011. Building on the best practice guidelines for amplification-based PGD established by ESHRE (European Society of Human Reproduction and Embryology), the goal of this meeting was to formulate specific guidelines for CF-PGD in order to contribute to a better harmonization of practices across Europe. Different topics were covered including variant nomenclature, inclusion criteria, genetic counseling, PGD strategy and reporting of results. The recommendations are summarized here, and updated information on the clinical significance of CFTR variants and associated phenotypes is presented

Large genomic rearrangements in the CFTR gene contribute to CBAVD

<p>Abstract</p> <p>Background</p> <p>By performing extensive scanning of whole coding and flanking sequences of the <it>CFTR (Cystic Fibrosis Transmembrane Conductance Regulator</it>) gene, we had previously identified point mutations in 167 out of 182 (91.7%) males with isolated congenital bilateral absence of the vas deferens (CBAVD). Conventional PCR-based methods of mutation analysis do not detect gross DNA lesions. In this study, we looked for large rearrangements within the whole <it>CFTR </it>locus in the 32 CBAVD patients with only one or no mutation.</p> <p>Methods</p> <p>We developed a semi-quantitative fluorescent PCR assay (SQF-PCR), which relies on the comparison of the fluorescent profiles of multiplex PCR fragments obtained from different DNA samples. We confirmed the gross alterations by junction fragment amplification and identified their breakpoints by direct sequencing.</p> <p>Results</p> <p>We detected two large genomic heterozygous deletions, one encompassing exon 2 (c.54-5811_c.164+2186del8108ins182) [or <it>CFTRdele2</it>], the other removing exons 22 to 24 (c.3964-3890_c.4443+3143del9454ins5) [or <it>CFTRdele 22_24</it>], in two males carrying a typical CBAVD mutation on the other parental <it>CFTR </it>allele. We present the first bioinformatic tool for exon phasing of the <it>CFTR </it>gene, which can help to rename the exons and the nomenclature of small mutations according to international recommendations and to predict the consequence of large rearrangements on the open reading frame.</p> <p>Conclusion</p> <p>Identification of large rearrangements further expands the <it>CFTR </it>mutational spectrum in CBAVD and should now be systematically investigated. We have designed a simple test to specifically detect the presence or absence of the two rearrangements identified in this study.</p

Green Urbanism and its Application to Singapore

Green urbanism has been applied to cities but not in Asia. Seven characteristics of green urbanism are outlined and then applied to Singapore. The Renewable City is not yet a concept for Singapore. The Carbon Neutral City is being developed for an island Palau Ubin and by some firms but not to significant sectors or parts of urban Singapore. The Distributed City is being developed around Singapore’s polycentric model but needs specific infrastructure plans similar to ones developed by Singapore for Tianjin Eco-City. The Biophillic City is being developed as a world first through its Skyrise Greenery initiative and urban landscaping. The Eco-Efficient City is also being demonstrated through Singapore closing the loop on their water and solid waste systems. The Place Based City is very evident in all its 22 sub centres. And the Sustainable Transport City is an Asian leader in integrated transport planning though there are signs of this becoming harder to achieve

A microplate technique to simultaneously assay calcium accumulation in endoplasmic reticulum and SERCA release of inorganic phosphate

Traditional analyses of calcium homeostasis have separately quantified either calcium accumulation or release mechanisms. To define the system as a whole, however, requires multiple experimental techniques to examine both accumulation and release. Here we describe a technique that couples the simultaneous quantification of radio-labeled calcium accumulation in endoplasmic reticulum (ER) microsomes with the release of inorganic phosphate (Pi) by the hydrolytic activity of sarco-endoplasmic reticulum calcium ATPase (SERCA) all in the convenience of a 96-well format

Diurnal Rhythms in Neurexins Transcripts and Inhibitory/Excitatory Synapse Scaffold Proteins in the Biological Clock

The neurexin genes (NRXN1/2/3) encode two families (α and β) of highly polymorphic presynaptic proteins that are involved in excitatory/inhibitory synaptic balance. Recent studies indicate that neuronal activation and memory formation affect NRXN1/2/3α expression and alternative splicing at splice sites 3 and 4 (SS#3/SS#4). Neurons in the biological clock residing in the suprachiasmatic nuclei of the hypothalamus (SCN) act as self-sustained oscillators, generating rhythms in gene expression and electrical activity, to entrain circadian bodily rhythms to the 24 hours day/night cycles. Cell autonomous oscillations in NRXN1/2/3α expression and SS#3/SS#4 exons splicing and their links to rhythms in excitatory/inhibitory synaptic balance in the circadian clock were explored. NRXN1/2/3α expression and SS#3/SS#4 splicing, levels of neurexin-2α and the synaptic scaffolding proteins PSD-95 and gephyrin (representing excitatory and inhibitory synapses, respectively) were studied in mRNA and protein extracts obtained from SCN of C3H/J mice at different times of the 24 hours day/night cycle. Further studies explored the circadian oscillations in these components and causality relationships in immortalized rat SCN2.2 cells. Diurnal rhythms in mNRXN1α and mNRXN2α transcription, SS#3/SS#4 exon-inclusion and PSD-95 gephyrin and neurexin-2α levels were found in the SCN in vivo. No such rhythms were found with mNRXN3α. SCN2.2 cells also exhibited autonomous circadian rhythms in rNRXN1/2 expression SS#3/SS#4 exon inclusion and PSD-95, gephyrin and neurexin-2α levels. rNRXN3α and rNRXN1/2β were not expressed. Causal relationships were demonstrated, by use of specific siRNAs, between rNRXN2α SS#3 exon included transcripts and gephyrin levels in the SCN2.2 cells. These results show for the first time dynamic, cell autonomous, diurnal rhythms in expression and splicing of NRXN1/2 and subsequent effects on the expression of neurexin-2α and postsynaptic scaffolding proteins in SCN across the 24-h cycle. NRXNs gene transcripts may have a role in coupling the circadian clock to diurnal rhythms in excitatory/inhibitory synaptic balance

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369