Valérie Gissot

12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial

BACKGROUND The efficacy of corticosteroids in reducing the incidence of postextubation laryngeal oedema is controversial. We aimed to test our hypothesis that methylprednisolone started 12 h before a planned extubation could prevent postextubation laryngeal oedema. METHODS We did a placebo-controlled, double-blind multicentre trial in 761 adults in intensive-care units. Patients who were ventilated for more than 36 h and underwent a planned extubation received intravenous 20 mg methylprednisolone (n=380) or placebo (381) 12 h before extubation and every 4 h until tube removal. The primary endpoint was occurrence of laryngeal oedema within 24 h of extubation. Laryngeal oedema was clinically diagnosed and deemed serious if tracheal reintubation was needed. Analyses were done on a per protocol and intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00199576. FINDINGS 63 patients could not be assessed, mainly because of self-extubation (n=16) or cancelled extubation (44) between randomisation and planned extubation. 698 patients were analysed (343 in placebo group, 355 in methylprednisolone group). Methylprednisolone significantly reduced the incidence of postextubation laryngeal oedema (11 of 355, 3%vs 76 of 343, 22%, p<0.0001), the global incidence of reintubations (13 of 355, 4%vs 26 of 343, 8%, p=0.02), and the proportion of reintubations secondary to laryngeal oedema (one of 13, 8 %vs 14 of 26, 54%, p=0.005). One patient in each group died after extubation, and atelectasia occurred in one patient given methylprednisolone. INTERPRETATION Methylprednisolone started 12 h before a planned extubation substantially reduced the incidence of postextubation laryngeal oedema and reintubation. Such pretreatment should be considered in adult patients before a planned extubation that follows a tracheal intubation of more than 36 h.

Accuracy of Bedside Glucometry in Critically Ill Patients: Influence of Clinical Characteristics and Perfusion Index

OBJECTIVES To determine the accuracy of bedside glucose strip assay on capillary blood and on whole blood and to identify factors predictive of discrepancies with the laboratory method. PATIENTS AND METHODS We conducted a prospective 3-month (July 1-September 30, 2003) study in 85 consecutive patients who required blood glucose monitoring. Values obtained with a glucose test strip on capillary blood and on whole blood were compared with those obtained in the laboratory during serial blood sampling (up to 4 samples per patient). The test strip values were considered to disagree significantly with the laboratory values when the difference exceeded 20%. Clinical and biological parameters and the perfusion index, based on percutaneous oxygen saturation monitoring, were recorded when each sample was obtained. RESULTS Capillary glucose values conflicted with laboratory reference values in 15% of samples. A low perfusion index was predictive of conflicting values (P=.04). Seven percent of values obtained with glucose strip on whole-blood samples conflicted with laboratory reference values; factors associated with these discrepancies were mean arterial hypotension (P=.007) and generalized mottling (P=.04). CONCLUSION Bedside blood glucose values must be interpreted with care in critically ill patients. A low perfusion index, reflecting peripheral hypoperfusion, is associated with poor glucose strip performance. Bedside measurements in whole blood seem to be most reliable, except in patients with arterial hypotension and generalized mottling.

Refusal of Intensive Care Unit Admission Due to a Full Unit

RATIONALE Intensive care unit (ICU) beds are a scarce resource, and patients denied intensive care only because the unit is full may be at increased risk of death. OBJECTIVE To compare mortality after first ICU referral in admitted patients and in patients denied admission because the unit was full. METHODS Prospective observational multicenter cohort study of consecutive patients referred for ICU admission during two 45-day periods, conducted in 10 ICUs. MEASUREMENTS AND MAIN RESULTS Of 1,762 patients, 430 were excluded from the study, 116 with previously denied admission to another ICU and 270 because they were deemed too sick or too well to benefit from ICU admission. Of the remaining 1,332 patients, 1,139 were admitted, and 193 were denied admission because the unit was full (65 were never admitted, 39 were admitted after bumping of another patient, and 89 were admitted on subsequent referral). Crude Day 28 and Day 60 mortality rates in the nonadmitted and admitted groups were 30.1 versus 24.3% (P = 0.07) and 33.3 versus 27.2% (P = 0.06), respectively. Day 28 mortality adjusted on age, previous disease, Glasgow scale score less than or equal to 8, shock, creatinine level greater than or equal to 250 μmol/L, and prothrombin time greater than or equal to 30 seconds was nonsignificantly higher in patients refused ICU admission only because of a full unit compared with patients admitted immediately. Patients admitted after subsequent referral had higher mortality rates on Day 28 (P = 0.05) and Day 60 (P = 0.04) compared with directly admitted patients. CONCLUSIONS Delayed ICU admission due to a full unit at first referral is associated with increased mortality.

Sequence and Functional Analysis of the Envelope Glycoproteins of Hepatitis C Virus Variants Selectively Transmitted to a New Host

ABSTRACT Hepatitis C virus (HCV) remains a challenging public health problem worldwide. The identification of viral variants establishing de novo infections and definition of the phenotypic requirements for transmission would facilitate the design of preventive strategies. We explored the transmission of HCV variants in three cases of acute hepatitis following needlestick accidents. We used single-genome amplification of glycoprotein E1E2 gene sequences to map the genetic bottleneck upon transmission accurately. We found that infection was likely established by a single variant in two cases and six variants in the third case. Studies of donor samples showed that the transmitted variant E1E2 amino acid sequences were identical or closely related to those of variants from the donor virus populations. The transmitted variants harbored a common signature site at position 394, within hypervariable region 1 of E2, together with additional signature amino acids specific to each transmission pair. Surprisingly, these E1E2 variants conferred no greater capacity for entry than the E1E2 derived from nontransmitted variants in lentiviral pseudoparticle assays. Mutants escaping the antibodies of donor sera did not predominate among the transmitted variants either. The fitness parameters affecting the selective outgrowth of HCV variants after transmission in an immunocompetent host may thus be more complex than those suggested by mouse models. Human antibodies directed against HCV envelope effectively cross-neutralized the lentiviral particles bearing E1E2 derived from transmitted variants. These findings provide insight into the molecular mechanisms underlying HCV transmission and suggest that viral entry is a potential target for the prevention of HCV infection.

A pair analysis of the delayed graft function in kidney recipient: the critical role of the donor.

PURPOSE The aim of this study was to analyze the importance of donor factors and especially the potential role of hemodynamic management in regard to delayed graft function in paired kidney recipient patients after renal transplantation and to analyze the urine of organ donors by proton-nuclear magnetic resonance spectroscopy to identify urine markers potentially correlated with delayed graft function in recipient patients. METHODS A prospective multicenter epidemiologic study was conducted. A logistic regression model taking into account paired data was used. RESULTS Data from 72 donors and the 144 corresponding paired recipients were analyzed. Univariate analysis showed that age of donor, previous history of tobacco, ischemic cause of brain death, norepinephrine infusion, and recipient age were the risk factors for delayed graft function. After adjusting for correlated outcome data and controlling for other potential prognostic factors, 3 variables remained significantly associated with outcome: donor age (odds ratio [OR], 10.7), hemodynamic status (OR, 0.167), and hydroxyl-ethyl starch infusion (OR, 0.135). Proton-nuclear magnetic resonance analysis evidenced 3 metabolites of interest in donors (trimethylamine-N-oxide, citrate, and lactate). However, these peaks were not correlated the clinical parameters in donors. CONCLUSIONS Paired analysis of kidney transplantation emphasizes the important role of factor donor associated with delayed graft function in recipient. Thus, a particular attention should be paid to the hemodynamic management of donor.

Brain [18F]FDDNP binding and glucose metabolism in advanced elderly healthy subjects and Alzheimer's disease patients.

BACKGROUND Positron emission tomography (PET) imaging of brain amyloid (Aβ) and neurofibrillary tangle (NFT) load is a candidate biomarker of Alzheimers disease (AD). OBJECTIVES To compare brain Aβ and NFT load and glucose metabolism in advanced elderly (70 years and older) patients with AD and healthy controls (HCs) by PET with [18F]FDDNP and [18F]FDG. METHODS Seven AD patients (mean ± SD age 79.3 ± 3.6 y, Mini-Mental State Examination (MMSE) score 22.1 ± 2.5) and eight HCs (mean age ± SD, 75.7 ± 3.9 y; MMSE score 29.0 ± 1.2) underwent PET with [18F]FDDNP and [18F]FDG. RESULTS Global [18F]FDDNP uptake was significantly higher (p < 0.05) in AD patients (1.15 ± 0.04) than in HCs (1.10 ± 0.06), while global brain metabolism was lower in AD patients than in HCs (AD patients 0.96 ± 0.09; HCs 1.13 ± 0.11; p < 0.05). In HCs, brain glucose metabolism was correlated with age for both the global [18F]FDG SUVr and in the parietal and posterior cingulate regions, while no correlation was found between age and [18F]FDDNP uptake. In AD patients, global [18F]FDDNP uptake and uptake in the frontal and anterior cingulate regions of interest were correlated with MMSE score, while no correlation was observed with brain glucose metabolism. CONCLUSION Imaging Aβ load and NFT with [18F]FDDNP can distinguish AD patients from HCs in an advanced elderly population. It seems to be less sensitive than [18F]FDG to the brain changes observed with normal aging, but more sensitive to cognitive decline in advanced elderly AD patients.

Helicobacter pylori infection is not associated with an increased hemorrhagic risk in patients in the intensive care unit

IntroductionThe potential role of Helicobacter pylori in acute stress ulcer in patients in an intensive care unit (ICU) is controversial. The aim of this study was to determine the frequency of H. pylori infection in ICU patients by antigen detection on rectal swabs, and to analyze the potential relationship between the presence of H. pylori and the risk of digestive gastrointestinal bleeding.MethodsIn this prospective, multicenter, epidemiological study, the inclusion criteria were as follows: patients admitted to the 12 participating ICU for at least two days, who were free of hemorrhagic shock and did not receive more than four units of red blood cells during the day before or the first 48 hours after admission to the ICU. Rectal swabs were obtained within the first 24 hours of admission to the ICU and were tested for H. pylori antigens with the ImmunoCard STAT! HpSA kit. The following events were analyzed according to H. pylori status: gastrointestinal bleeding, unexplained decline in hematocrit, and the number of red cell transfusions.ResultsThe study involved 1,776 patients. Forty-nine patients (2.8%) had clinical evidence of upper digestive bleeding. Esophagogastroduodenoscopy was performed in 7.6% of patients. Five hundred patients (28.2%) required blood transfusion. H. pylori antigen was detected in 6.3% of patients (95% confidence interval 5.2 to 7.5). H. pylori antigen positivity was associated with female sex (p < 0.05) and with a higher Simplified Acute Physiology Score II (SAPS II; p < 0.05). H. pylori antigen status was not associated with the use of fiber-optic gastroscopy, the need for red cell transfusions, or the number of red cell units infused.ConclusionThis large study reported a small percentage of H. pylori infection detected with rectal swab sampling in ICU patients and showed that the patients infected with H. pylori had no additional risk of gastrointestinal bleeding. Thus H. pylori does not seem to have a major role in the pathogenesis of acute stress ulcer in ICU patients.

Brain Tissue Pulsatility is Increased in Midlife Depression: a Comparative Study Using Ultrasound Tissue Pulsatility Imaging

Cerebrovascular disease (CVD) is consistently associated with late-life depression but poorly documented in midlife depression. It can be hypothesized that the relatively low sensitivity of conventional neuroimaging techniques does not allow the detection of subtle CVD in midlife depression. We used tissue pulsatility imaging (TPI), a novel ultrasound (US) neuroimaging technique that has demonstrated good sensitivity to detect changes in the pulsatility of small brain volumes, to identify early and subtle changes in brain vascular function in midlife depression. We compared the maximum and mean brain tissue pulsatility (MaxBTP and MeanBTP), as identified by TPI, between three groups of middle-aged females matched for age: patients with depression (n=25), patients with remitted depression (n=24) and community controls (n=25). MRI arterial spin labeling, white matter hyperintensities (WMHs) and transcranial doppler (TCD) were used as control conventional markers for CVD. We found no difference in the MRI and TCD measures among the three groups. In contrast, depressive patients showed an increased BTP related to the mean global brain pulsatility (MeanBTP) and no change related to large vessels (MaxBTP) in comparison with the remitted and control groups. US neuroimaging is a highly accurate method to detect brain pulsatility changes related to cerebrovascular functioning, and TPI identified an increased BTP in midlife depressed patients, suggesting early and subtle vascular impairments in this population at risk for CVD such as stroke or WMHs. Because high pulsatility could represent prodromal cerebrovascular changes that damage the brain over time, this paper provides a potential target for blocking the progression of CVD.

Variations of hepcidin and iron‐status parameters during the menstrual cycle in healthy women

Hepcidin is the central regulator of systemic iron metabolism (Ganz, 2013). In clinical practice, measurements of serum hepcidin (SH) could help to determine the cause of anaemia, iron deficiency and iron overload, to predict iron absorption from food, to optimize the treatment of haemochromatosis and to manage erythropoietin therapy. Interpretation of SH measurement in practice will be dependent on understanding physiological variations of this hormone. Previous studies have suggested that SH varied according to a diurnal cycle (Ganz et al, 2008) and was modified by meals (Schaap et al, 2013). Gender should also be taken into account, as women tend to have lower hepcidin values than men. Moreover, in women, age should be also considered, because values of hepcidin are higher in postthan in pre-menopausal women. Nevertheless, iron status is the main determinant of SH concentration (Galesloot et al, 2011). Blood loss during menses, the main cause of iron deficiency in young women, varies between 20 and 80 ml during a period, representing a loss of 10–40 mg of iron in women with regular menstrual cycles (MC) (Higham et al, 1990). This is significant compared to the unregulated 1 mg eliminated daily through skin, intestinal and urinary cell desquamation, the only other physiological way to eliminate iron. To date, no study has examined whether menses induce significant variations in SH values. The present study (Clinical Trial.gov NCT01764412) was conducted in four French hospitals. Ninety healthy women, aged 18-45 years, with normal iron parameters, regular cycles and normal duration of menses (4 1 days) were included. Fifty-four used oral contraception. Transferrin saturation (TS), serum ferritin (SF), haemoglobin (Hb), serum iron (SI) and SH were measured at six visits distributed throughout the MC. All visits were planned on fasting subjects, between 8am and 9am. Day 0 was defined as the day after menses began. The following 3 visits were scheduled during menses and the following days. The last two visits took place respectively at the middle and at the end of the cycle. Serum hepcidin-25 was quantified using a CE-marked Enzyme Immunoassay (Bachem Inc., Torrance, CA, USA).

Sustained attention and prediction: distinct brain maturation trajectories during adolescence

Adolescence is a key period for frontal cortex maturation necessary for the development of cognitive ability. Sustained attention and prediction are cognitive functions critical for optimizing sensory processing, and essential to efficiently adapt behaviors in an ever-changing world. The aim of the current study was to investigate the brain developmental trajectories of attentive and predictive processing through adolescence. We recorded EEG in 36 participants from the age of 12–24 years (three age groups: 12–14, 14–17, 18–24 years) to target development during early and late adolescence, and early adulthood. We chose a visual target detection task which loaded upon sustained attention, and we manipulated target predictability. Continued maturation of sustained attention after age 12 was evidenced by improved performance (hits, false alarms (FAs) and sensitivity) in a detection task, associated with a frontal shift in the scalp topographies of the Contingent Negative Variation (CNV) and P3 responses, with increasing age. No effect of age was observed on predictive processing, with all ages showing similar benefits in reaction time, increases in P3 amplitude (indexing predictive value encoding and memorization), increases in CNV amplitude (corresponding to prediction implementation) and reduction in target-P3 latency (reflecting successful prediction building and use), with increased predictive content. This suggests that adolescents extracted and used predictive information to generate predictions as well as adults. The present results show that predictive and attentive processing follow distinct brain developmental trajectories: prediction abilities seem mature by the age of 12 and sustained attention continues to improve after 12-years of age and is associated with maturational changes in the frontal cortices.