Nosocomial bloodstream infection and clinical sepsis

Primary bloodstream infection (BSI) is a leading, preventable infectious complication in critically ill patients and has a negative impact on patients' outcome. Surveillance definitions for primary BSI distinguish those that are microbiologically documented from those that are not. The latter is known as clinical sepsis, but information on its epidemiologic importance is limited. We analyzed prospective on-site surveillance data of nosocomial infections in a medical intensive care unit. Of the 113 episodes of primary BSI, 33 (29%) were microbiologically documented. The overall BSI infection rate was 19.8 episodes per 1,000 central-line days (confidence interval [CI] 95%, 16.1 to 23.6); the rate fell to 5.8 (CI 3.8 to 7.8) when only microbiologically documented episodes were considered. Exposure to vascular devices was similar in patients with clinical sepsis and patients with microbiologically documented BSI. We conclude that laboratory-based surveillance alone will underestimate the incidence of primary BSI and thus jeopardize benchmarking.     

Blackberry anthocyanins are slightly bioavailable in rats

Anthocyanins are phenolic compounds widely distributed in fruits and vegetables. Several positive effects of anthocyanin feeding have been described. We evaluated the absorption and metabolism of anthocyanins (cyanidin 3-glucoside and malvidin 3-glucoside) in rats adapted for 8 d to a diet enriched with a lyophilized blackberry powder. Rats had free access to an anthocyanin-containing diet for 8 h/d. Food was consumed throughout this period, and no anthocyanin accumulated in plasma at any of the times of sampling. Anthocyanins were recovered in urine as the intact glycosidic forms, whereas neither aglycone nor conjugates were detected. Moreover, peonidin 3-glucoside was present in urine and could have resulted from hepatic methylation at the 3' hydroxyl moiety position of cyanidin 3-glucoside. Urinary recovery of cyanidin 3-glucoside in either intact or methylated forms was approximately 0.26% of the ingested amount, whereas that of malvidin 3-glucoside was 0.67%. This result suggested that structure of the aglycone moiety of anthocyanins could play an important role in their metabolism. Low amounts of glucosides as well as of cyanidin were recovered in cecal contents. This could result from adaptation of microflora to anthocyanin degradation. Overall, these data indicate that blackberry anthocyanins are excreted in urine as intact and methylated glucoside forms and that their bioavailability is very low compared with other flavonoids.     

Value of microimmunofluorescence for diagnosis and follow-up of Bartonella endocarditis

Bartonella endocarditis is a disease of emerging importance that causes serious complications and high rates of mortality. Due to the fastidious nature of Bartonella species and their high degrees of antibiotic susceptibility, cultures of clinical samples most often remain sterile and valvular biopsy specimens, the best specimens for PCR amplification, are seldom available. Therefore, serology appears to be the easiest diagnostic tool. In order to determine the best cutoff value for serology and its predictive values for the detection of Bartonella endocarditis, we studied 48 patients with culture- and/or PCR-confirmed Bartonella endocarditis. We also applied these serological criteria to 156 patients with blood culture-negative endocarditis. Furthermore, we compared the kinetics of the antibody responses to Bartonella spp. in order to estimate the value of serology for prediction of the occurrence of relapses. A titer of > or = 1:800 for immunoglobulin G antibodies to either Bartonella henselae or B. quintana has a positive predictive value of 0.810 for the detection of chronic Bartonella infections in the general population and a value of 0.955 for the detection of Bartonella infections among patients with endocarditis. When this cutoff was applied to 156 patients with blood culture-negative endocarditis, we were able to diagnose Bartonella infections in an additional 45 patients with definite endocarditis for whom a positive Bartonella serology was the only evidence of infection. On follow-up, the kinetics of the decrease in antibody titers were significantly delayed in two patients with relapses. In conclusion, we recommend the determination of antibodies to both B. quintana and B. henselae and the use of a cutoff value of 1:800 for the diagnosis of Bartonella endocarditis. We propose that this criterion, which may also help with the detection of late relapses, be included as a major criterion in the Duke criteria for the diagnosis of infective endocarditis.     

Aneruptive fever associated with antibodies to Rickettsia helvetica in Europe and Thailand

We report that eight patients from France, Italy, and Thailand had serological evidence of Rickettsia helvetica infection. The infection presented as a mild disease in the warm season and was associated with fever, headache, and myalgia but not with a cutaneous rash. R. helvetica should be suspected in patients with unexplained fever, especially following a bite from an Ixodes sp. tick.     

Mutations of the Imprinted CDKN1C Gene as a Cause of the Overgrowth Beckwith–Wiedemann Syndrome: Clinical Spectrum and Functional Characterization

Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder associating macroglossia, abdominal wall defects, visceromegaly, and a high risk of childhood tumor. Molecular anomalies are mostly epigenetic; however, mutations of CDKN1C are implicated in 8% of cases, including both sporadic and familial forms. We aimed to describe the phenotype of BWS patients with CDKN1C mutations and develop a functional test for CDKN1C mutations. For each propositus, we sequenced the three exons and intron–exon boundaries of CDKN1C in patients presenting a BWS phenotype, including abdominal wall defects, without 11p15 methylation defects. We developed a functional test based on flow cytometry. We identified 37 mutations in 38 pedigrees (50 patients and seven fetuses). Analysis of parental samples when available showed that all mutations tested but one was inherited from the mother. The four missense mutations led to a less severe phenotype (lower frequency of exomphalos) than the other 33 mutations. The following four tumors occurred: one neuroblastoma, one ganglioneuroblastoma, one melanoma, and one acute lymphoid leukemia. Cases of BWS caused by CDKN1C mutations are not rare. CDKN1C sequencing should be performed for BWS patients presenting with abdominal wall defects or cleft palate without 11p15 methylation defects or body asymmetry, or in familial cases of BWS.     

Hydrogen‐Bonding Effects for the C–ON Bond Homolysis and Reformation Reactions of Alkoxyamines

N‐(2‐methylpropyl)‐N‐(1‐diethylphosphono‐2,2‐dimethylpropyl)‐O‐(2‐carboxyprop‐2‐yl) hydroxylamine (BlocBuilder MA) is, among the commercially available alkoxyamines, one of the most efficient for nitroxide‐mediated polymerization (NMP). However, recent results have shown that it does not perform well for the NMP of isoprene. The occurrence of intramolecular hydrogen bonding (IHB) between the carboxylic function and the diethoxyphosphoryl group has been proposed as the reason for its low efficiency. In this article, the presence of this IHB is confirmed using IR, ³¹P NMR, ³¹P‐¹H HOESY, and DFT calculation results. The solvent effect on this IHB and consequently on k_d values is also investigated. However, combining kinetic analysis and rate measurements in various solvents, the influence of this IHB on the C? ON bond homolysis and reformation in alkoxyamine is shown to be very weak.

     

CD14 expression is increased on monocytes in patients with anti‐neutrophil cytoplasm antibody (ANCA)‐associated vasculitis and correlates with the expression of ANCA autoantigens

Monocyte subsets with differing functional properties have been defined by their expression of CD14 and CD16. We investigated these subsets in anti‐neutrophil cytoplasm antibody (ANCA)‐associated vasculitis (AAV) and determined their surface expression of ANCA autoantigens. Flow cytometry was performed on blood from 14 patients with active AAV, 46 patients with AAV in remission and 21 controls. The proportion of classical (CD14^highCD16^neg/low), intermediate (CD14^highCD16^high) and non‐classical (CD14^lowCD16^high) monocytes and surface expression levels of CD14 and CD16 were determined, as well as surface expression of proteinase 3 (PR3) and myeloperoxidase (MPO) on monocyte subsets. There was no change in the proportion of monocytes in each subset in patients with AAV compared with healthy controls. The expression of CD14 on monocytes from patients with active AAV was increased, compared with patients in remission and healthy controls (P < 0·01). Patients with PR3‐ANCA disease in remission also had increased monocyte expression of CD14 compared with controls (P < 0·01); however, levels in patients with MPO‐ANCA disease in remission were lower than active MPO‐ANCA patients, and not significantly different from controls. There was a correlation between CD14 and both PR3 and MPO expression on classical monocytes in AAV patients (r = 0·79, P < 0·0001 and r = 0·42, P < 0·005, respectively). In conclusion, there was an increase in monocyte CD14 expression in active AAV and PR3‐ANCA disease in remission. The correlation of CD14 expression with ANCA autoantigen expression in AAV may reflect cell activation, and warrants further investigation into the potential for increased CD14 expression to trigger disease induction or relapse.