Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: The READIAB study.

OBJECTIVE: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. METHODS: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. MAIN RESULTS: The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P=0.078): OR(peroneTcopy): 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P=0.026), but was no longer significant at 1 year (P=0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P<0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32-2.28; P<0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P=0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P=0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P=0.72) or 1 year (P=0.64). CONCLUSION: This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.

[Which samples to obtain in the emergency department for the microbiological diagnosis of community-acquired pneumonia in the immunocompetent patient?] / Quels prélèvements aux urgences pour le diagnostic microbiologique d'une infection pulmonaire communautaire grave du sujet immunocompétent ?

Current diagnostic methods allow microbial identification in 50% of patients admitted with severe community-acquired pneumonia (CAP). Guidelines derived from epidemiological data help physicians to start empirical antimicrobial therapy. Definitive microbial diagnosis is useful to guide further pathogen-directed therapy. Blood cultures, cultures of respiratory specimens and urine antigen tests are recommended to determine the causative bacterial pathogen. Positive blood cultures range from 15 to 25% of CAP patients according to severity. Whether sputum specimens represent or not lower respiratory secretions determines its accuracy in CAP microbial diagnosis. In intubated patients, endotracheal aspirates are often of interest. Detection of positive pneumococcal or legionella urinary antigen is often associated with CAP severity. The sensitivity of this test is not decreased in patients who have received antibiotics prior to sampling. Viral pneumonia account for 10 to 40% of severe CAP. Nasal swabs are recommended for influenza identification using polymerase chain reaction (PCR) in order to deliver oseltamivir treatment. In the emergency department, atypical pneumonia serology is less useful than respiratory specimens obtained using fiberoptic bronchoscopy. Serum PCR to diagnose bacterial CAP is not superior to the other usual methods.

Evidence for reciprocal connections between the dorsochiasmatic area and the hypothalamo neurohypophyseal system and some related extrahypothalamic structures.

In the preceding article, a dorsochiasmatic area (DCh) was described that projects to both paraventricular (PVN) and supraoptic (SON) nuclei. The main afferents of the DCh, revealed by local injections of retrograde tracers, are the hypothalamic PVN and SON, lateral septal nuclei (LSV and SHy), bed nuclei of the stria terminalis (BST), anteroventral third ventricle region, particularly the median preoptic nucleus (MnPO), the subfornical organ, medial preoptic areas, arcuate hypothalamic nucleus, ventromedial hypothalamic nuclei, paraventricular thalamic nucleus, and, more caudally, several structures of the posterior hypothalamus and mesencephalon. The relations between DCh and BST, LSV, SHy, or MnPO appeared reciprocal. In view of their reciprocal relationships with the hypothalamo-neurohypophyseal system and some of their related extrahypothalamic structures, the DCh might be involved in the regulation of the vasopressin (AVP) and/or oxytocin (OT) systems, or in reproductive behavior.

Evidence for connections between a discrete hypothalamic dorsochiasmatic area and the supraoptic and paraventricular nuclei.

In order to check the existence of direct or indirect connections between the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, four retrograde traces were iontophoretically injected into these nuclei. The small injection sites were restricted to parts of the SON and PVN, enabling the identification of afferent neurons localized in their immediate vicinity. The tracer injections into any of these hypothalamic nuclei resulted in conspicuous labeling of cells gathered dorsally to the optic chiasma and the optic tract. This neuronal population was tentatively called dorsochiasmatic area. Double retrograde tracers injections into the ipsilateral SON and PVN gave evidence for some neurons containing both tracers in this dorsochiasmatic area. Otherwise, labeled parvocellular neurons were occasionally found in one PVN, after injecting retrograde tracer into either the ipsilateral SON or the contralateral PVN. As few connections exist between the four magnocellular nuclei, the dorsochiasmatic area connected with both the ipsilateral SON and PVN could play an important role in regulating the oxytocin and/or vasopressin systems.