[Show abstract][Hide abstract] ABSTRACT: Objective:
To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers.
Multicenter, interventional study.
Two ICUs and one clinical research center.
Anemic critically ill patients treated with IV iron and healthy volunteers.
IV infusion of 100 mg of iron sucrose.
Measurements and main results:
Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7-9.2]) (men, 25 [66%]; aged 68 yr [48-77]; Simplified Acute Physiology Score II, 48.5 [39-59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29-50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation-8α-isoprostanes, protein oxidation-advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5-12.9] vs 4.6 pmol/L [3.5-5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes.
In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients.
Critical care medicine 11/2015; DOI:10.1097/CCM.0000000000001420 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infective endocarditis (IE) due to gram-negative bacilli (GNB) is rare. However, several studies described a change in the epidemiological profile of patients within the past few years.
We reviewed all cases diagnosed and followed in the infectious diseases ward of a French teaching hospital in Paris between 2009 and 2014, inclusive.
Among the 17 patients with definite GNB-IE (11 male, mean age 54 years), 12 (70%) were due to non-HACEK GNB and 5 (30%) to HACEK group GNB. A prosthetic valve was involved in 10 cases (8 in non-HACEK and 2 in HACEK group). Escherichia coli (4/12 patients) and Pseudomonas aeruginosa (3/12 patients) were the most common pathogens in the first group; all the pathogens in the second group were Haemophilus spp. One-third of the patients with non-HACEK GNB had nosocomial IE, whereas injection drug use-related infections were rare (2/12). All patients with HACEK infection had at least one complication (intracardiac abscess, stroke or other systemic embolization). All patients were treated by antibiotic combination therapy during a median time of 42 days (interquartile range (IQR) = 42-42) and 10 (59%) underwent cardiac surgery. One death at 9 months was observed in the non-HACEK group.
Regarding HACEK IE, this report supports the frequent association with vascular complications. Regarding non-HACEK GNB IE, this report supports the increasing proportion of nosocomial infections. We reported a high proportion of surgery in the therapeutic management of both HACEK and non-HACEK groups associated with no in-hospital mortality.
[Show abstract][Hide abstract] ABSTRACT: Clinical decision making relative to community acquired-pneumonia CAP diagnosis is difficult. Chest X-ray is key in establishing parenchymal lung involvement. However, radiological performance may lead to misdiagnosis, rendering questionable the utility of chest CT-scan in patients with clinically-suspected CAP.
To assess whether early multidetector chest CT-scan affects diagnosis and management of patients visiting the emergency department with suspected CAP.
319 prospectively enrolled patients with clinically suspected CAP patients underwent multidetector chest CT-scan within 4 hours. CAP diagnosis probability (definite, probable, possible or excluded), and therapeutic plans (antibiotic initiation/discontinuation, hospitalisation/discharge) were established by emergency physicians before and after CT scan results. The adjudication committee established the final CAP classification on day 28.
Chest X-ray revealed a parenchymal infiltrate in 188 patients. CAP was initially classified as definite in 143 patients (44.8%), probable or possible in 172 (53.8%), excluded in 4 (1.2%). CT-scan revealed a parenchymal infiltrate in 40 (33%) of the patients without infiltrate on chest X-ray and excluded CAP in 56 (29.8%) of the 188 with parenchymal infiltrate on X-ray. CT-scan modified classification in 187 (58.6% 95%CI 53.2-64.0); leading to 50.8% definite CAP and 28.8% excluded CAP; 80% of modifications were in accordance with adjudication committee classification. Due to CT-scan, antibiotics were initiated in 51 (16%) and discontinued in 29 (9%), and hospitalisation was decided in 22 and discharge in 23.
In CAP-suspected patients visiting the emergency unit, early CT-scan findings complementary to chest X-ray markedly affect both diagnosis and clinical management. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01574066.
American Journal of Respiratory and Critical Care Medicine 07/2015; DOI:10.1164/rccm.201501-0017OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To update the epidemiology of S. aureus bloodstream infection (SAB) in a high-income country and its link with infective endocarditis (IE).
All consecutive adult patients with incident SAB (n = 2008) were prospectively enrolled between 2009 and 2011 in 8 university hospitals in France.
SAB was nosocomial in 54%, non-nosocomial healthcare related in 18% and community-acquired in 26%. Methicillin resistance was present in 19% of isolates. SAB Incidence of nosocomial SAB was 0.159/1000 patients-days of hospitalization (95% confidence interval [CI] 0.111-0.219). A deep focus of infection was detected in 37%, the two most frequent were IE (11%) and pneumonia (8%). The higher rates of IE were observed in injecting drug users (IE: 38%) and patients with prosthetic (IE: 33%) or native valve disease (IE: 20%) but 40% of IE occurred in patients without heart disease nor injecting drug use. IE was more frequent in case of community-acquired (IE: 21%, adjusted odds-ratio (aOR) = 2.9, CI = 2.0-4.3) or non-nosocomial healthcare-related SAB (IE: 12%, aOR = 2.3, CI = 1.4-3.5). S. aureus meningitis (IE: 59%), persistent bacteremia at 48 hours (IE: 25%) and C-reactive protein > 190 mg/L (IE: 15%) were also independently associated with IE. Criteria for severe sepsis or septic shock were met in 30% of SAB without IE (overall in hospital mortality rate 24%) and in 51% of IE (overall in hospital mortality rate 35%).
SAB is still a severe disease, mostly related to healthcare in a high-income country. IE is the most frequent complication and occurs frequently in patients without known predisposing conditions.
PLoS ONE 05/2015; 10(5):e0127385. DOI:10.1371/journal.pone.0127385 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infective endocarditis (IE) is a rare and severe disease whose diagnosis is challenging. Extracardiac manifestations of the disease, occurring in 30 to 80% of patients, impact on the prognosis. Their detection help to support the diagnosis when this one is doubtful and may lead to alter the therapeutic plan. FDG PET/CT allows to detect secondary septic locations in IE with a high sensitivity. In addition, it offers the possibility to provide both cardiac and extracardiac locations in a single scan. Radiolabelled leukocytes SPECT is very specific of infection. Its diagnostic value has been evidenced in native and prosthetic valve endocarditis. The optimal diagnostic strategy, tailored to the patient, remains to be established.
[Show abstract][Hide abstract] ABSTRACT: In a context of controversy about influenza antiviral treatments, this study assessed primary health care physicians' prescription of neuraminidase inhibitors (NIs) in France during pandemic and seasonal influenza between 2009 and 2013.
This observational study, using data recorded in three national databases, estimated the rate of NIs' prescription among influenza like-illness (ILI) patients seen in GPs' and paediatricians' consultations, and determined factors associated with this prescription according to a multivariate analysis. NIs' delivery by pharmacists was also evaluated.
Rates of NIs' prescription were estimated to 61.1% among ILI patients with a severe influenza risk factor seen in GPs' consultation during the A(H1N1)pdm2009 pandemic versus an average rate of 25.9% during the three following seasonal influenza epidemics. Factors associated with NIs' prescription were a chronic disease in patients under 65 years (OR, 14.85; 95%CI, 13.00-16.97) and in those aged 65 and older (OR, 7.54; 5.86-9.70), an age ≥ 65 years in patients without chronic disease (OR, 1.35; 1.04-1.74), a pregnancy (OR, 10.63; 7.67-15.76), obesity (OR, 4.67; 3.50-6.22), and a consultation during the pandemic A(H1N1)pdm2009 (OR, 3.19; 2.93-3.48). The number of antiviral treatments delivered by pharmacists during the A(H1N1)pdm2009 pandemic was 835 per 100 000 inhabitants, and an average of 275 per 100 000 inhabitants during the three following seasonal influenza epidemics.
Although physicians seem to follow the recommended indications for NIs in primary health care practice, this study confirms the low rate of NIs prescription to ILI patients with a severe influenza risk factor, especially during seasonal epidemics.
[Show abstract][Hide abstract] ABSTRACT: A major deleterious side effect of glucocorticoids is skin atrophy. Glucocorticoids activate the glucocorticoid and the mineralocorticoid (MR) receptor, both present in epidermis. We hypothesized that glucocorticoid-induced epidermal atrophy may be related to inappropriate occupancy of MR by glucocorticoids. We evaluated whether epidermal atrophy induced by the topical glucocorticoid clobetasol could be limited by co-administration of MR antagonist. In cultured human skin explants, the epidermal atrophy induced by clobetasol was significantly limited by MR antagonism (canrenoate, eplerenone). Blockade of the epithelial sodium channel ENaC by phenamil was also efficient, identifying a role of MR-ENaC cascade in keratinocytes, acting through restoration of clobetasol-induced impairment of keratinocyte proliferation. In the SPIREPI randomized double-blind controlled trial, gels containing clobetasol, the MR antagonist spironolactone, both agents or placebo were applied on four zones of the forearms of 23 healthy volunteers for 28 days. Primary outcome was histological thickness of the epidermis with clobetasol alone or clobetasol+spironolactone. Spironolactone alone did not affect epidermis thickness but co-application of clobetasol and spironolactone limited significantly clobetasol-induced atrophy and was well tolerated. Altogether these findings identify MR as a factor regulating epidermal homeostasis and suggest that topical MR blockade could limit glucocorticoid-induced epidermal atrophy.Journal of Investigative Dermatology accepted article preview online, 10 February 2015. doi:10.1038/jid.2015.44.
[Show abstract][Hide abstract] ABSTRACT: Aortic valve stenosis (AS) is a progressive disease, but the impact of baseline AS haemodynamic or anatomic severity on AS progression remains unclear.
In 149 patients (104 mild AS, 36 moderate AS and 9 severe AS) enrolled in 2 ongoing prospective cohorts (COFRASA/GENERAC), we evaluated AS haemodynamic severity at baseline and yearly, thereafter, using echocardiography (mean pressure gradient (MPG)) and AS anatomic severity using CT (degree of aortic valve calcification (AVC)).
After a mean follow-up of 2.9±1.0 years, mean MGP increased from 22±11 to 30±16 mm Hg (+3±3 mm Hg/year), and mean AVC from 1108±891 to 1640±1251 AU (arbitrary units) (+188±176 AU/year). Progression of AS was strongly related to baseline haemodynamic severity (+2±3 mm Hg/year in mild AS, +4±3 mm Hg/year in moderate AS and +5±5 mm Hg/year in severe AS (p=0.01)), and baseline haemodynamic severity was an independent predictor of haemodynamic progression (p=0.0003). Annualised haemodynamic and anatomic progression rates were significantly correlated (r=0.55, p<0.0001), but AVC progression rate was also significantly associated with baseline haemodynamic severity (+141±133 AU/year in mild AS, +279±189 AU/year in moderate AS and +361±293 AU/year in severe AS, p<0.0001), and both baseline MPG and baseline AVC were independent determinants of AVC progression (p<0.0001).
AS progressed faster with increasing haemodynamic or anatomic severity. Our results suggest that a medical strategy aimed at preventing AVC progression may be useful in all subsets of patients with AS including those with severe AS and support the recommended closer follow-up of patients with AS as AS severity increases.
COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088).
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
[Show abstract][Hide abstract] ABSTRACT: This phase I, pilot clinical study was designed to evaluate the safety and the pharmacokinetic (PK) profiles of the CIME (Metabolic Identity Card) combination of ten drugs, with a view to its use as a phenotyping cocktail. Ten healthy Caucasian subjects were orally dosed with the CIME combination (caffeine-CYP1A2, repaglinide-CYP2C8, tolbutamide-CYP2C9, omeprazole-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A, acetaminophen-UGT1A1, 6&9 and 2B15, digoxin-P-gp, rosuvastatin-OATP1B1&3 and memantine-active renal transport). Blood was collected over 3 days and on day 7. CIME probes and relevant metabolites were assayed by LC-MS/MS and PK parameters were calculated. Main results were: (1) good safety with reversible mild or moderate adverse effects, (2) an analytical method able to quantify simultaneously the 10 probes and the major metabolites, (3) calculation of PK parameters for all probes in general agreed with published values, and (4) identification of the low CYP2D6 metabolizer. This pilot study showed that the CIME combination was well tolerated and that its pharmacokinetics could be accurately measured in healthy volunteers. This combination can now confidently be checked for sensitivity and specificity and for lack of interaction to be validated as a phenotyping cocktail.
European Journal of Drug Metabolism and Pharmacokinetics 12/2014; DOI:10.1007/s13318-014-0239-0 · 1.56 Impact Factor