Use of the bioMérieux VIDAS troponin I ultra assay for the diagnosis of myocardial infarction and detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome

BACKGROUND: We demonstrate the performance of the bioMérieux VIDAS Troponin I Ultra assay for diagnostic accuracy for detection of myocardial infarction (MI) and risk stratification. METHOD: cTnI was measured in 545 patients from 2 clinical centers with symptoms suggestive of ACS at admission, with an additional specimen at 4-12 h (453 patients). The 99th percentile value (0.01 microg/l) was used to assess clinical accuracy for diagnosis of acute MI. Primary endpoint for risk stratification was first of cardiac event or death in 302 patients (one center) followed for 60 days. RESULTS: 157 (28.8%) patients ruled in for an MI during index hospitalization. Sensitivities and specificities were 88.1% (95% CI 81.9 to 92.4%) and 79.9% (CI 75.5 to 83.6%) for baseline and 100% (CI 96.5 to 100%) and 79.4% (CI 74.4 to 83.4%) for follow-up specimens. ROC curve areas increased from 0.912 (CI 0.879 to 0.944) at baseline to 0.994 (CI 0.988 to 0.999) at second sampling (n=453, p<0.01); with no differences between sites. Primary endpoint rate for the 223 patients (74%) with normal cTnI on presentation was lower than the 79 patients (26%) with cTnI>0.01 ug/l (5.9% vs. 42.3%, p<0.0001). The relative risk for the >0.01 ug/l group was 8.9 (CI 4.6 to 17). CONCLUSION: The VIDAS cTnI assay is a sensitive diagnostic method for the early detection of MI and predicts increased risk for adverse events in patients with symptoms suggestive of ACS.     

Virulence potential of Staphylococcus aureus strains isolated from diabetic foot ulcers: a new paradigm

OBJECTIVE—The purpose of this study was to assess the virulence potential of Staphylococcus aureus strains isolated from diabetic foot ulcers and to discriminate noninfected from infected ulcers.RESEARCH DESIGN AND METHODS—Diabetic patients hospitalized in a diabetic foot department with a foot ulcer were prospectively enrolled if they had been free of antibiotic treatment over the previous 6 months. At admission, ulcers were classified as infected or noninfected on the basis of clinical examination, according to the International Working Group on the Diabetic Foot system. Only patients carrying S. aureus as the sole pathogen were included. In individuals with a grade 1 ulcer, a second bacterial specimen was obtained 1 month later. Using virulence genotyping markers, clonality tools, and an in vivo Caenorhabditis elegans model, we correlated the virulence of 132 S. aureus strains with grade, time of collection, and ulcer outcome.RESULTS—Among virulence genes, the most relevant combination derived from the logistic regression was the association of cap8, sea, sei, lukE, and hlgv (area under the curve 0.958). These markers were useful to distinguish noninfected (grade 1) from infected (grades 2–4) ulcers and to predict wound status at the follow-up. With use of the nematode model, S. aureus strains isolated from grade 1 ulcers were found to be significantly less virulent than strains from ulcers at or above grade 2 (P < 0.001).CONCLUSIONS—This study highlights the coexistence of two S. aureus populations on diabetic foot ulcers. A combination of five genes that may help distinguish colonized grade 1 from infected grade ≥2 wounds, predict ulcer outcome, and contribute to more appropriate use of antibiotics was discovered.Foot ulcers are common in diabetic patients, with prevalence as high as 25% (1). These ulcers frequently become infected, and spread of infections to soft tissue and to bony structures is a major causal factor for lower-limb amputation (2). Early diagnosis and adequate treatment are essential. Because microorganisms are always present on skin wounds, diagnosis of infection must be based not on microbiological findings but on clinical criteria, as emphasized by the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot (IWGDF) and more recently by the French Society for Infectious Pathology (3–5). However, because of the confounding impact of neuropathy and ischemia on local and systemic inflammatory response, diagnosing foot infection at an early stage in diabetic individuals may be difficult.Recently, we demonstrated the value of using a miniaturized oligonucleotide array covering different genes of Staphylococcus aureus, by far the most common and virulent pathogen in diabetic foot infection (3), and we showed that the virulence gene profile of S. aureus enables us to distinguish grade 1 from grades 2–4 ulcers because the former generally displayed a very low level of virulence genes (6). One of the main limitations in that work was the limited panel of genes used. Here we analyzed the most prevalent virulence-associated genes and the in vivo virulence potential of the different S. aureus strains isolated from diabetic foot ulcers. The aim was to detect genetic markers to distinguish noninfected and infected ulcer and to predict outcome of grade 1 ulcers.     

Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis

Hereditary sensory and autonomic neuropathy type IV (HSAN IV) or congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal-recessive disorder affecting the neurotrophin signal transduction pathway. HSAN IV is characterized by absence of reaction to noxious stimuli, recurrent episodes of fever, anhidrosis, self mutilating behaviour and frequent mental retardation. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1) are associated with this disorder. We investigated NTRK1 mutations in five HSAN IV patients and one less typical patient with hypohidrosis, insensitivity to pain as well as motor- and sensory deficits in the peripheral nervous system. For the HSAN IV patients we identified a homozygous missense mutation (p.I572S), a homozygous deletion of 1985bp (g.7335164-7336545del), a homozygous insertion c.722_723insC in exon 7 and two compound heterozygous mutations (p.Q558X+p.L717R). The less typical patient as well as one HSAN IV patient revealed no NTRK1 mutation.     

Effects of anti-depressants on olfactory sensitivity in mice

RATIONALE AND OBJECTIVES: Some studies have underlined a decrease in olfactory sensitivity in patients suffering from depression. The present study aims to evaluate the effects of current anti-depressant drugs on the olfactory sensitivity in mice. METHODS MICE: (N degrees =22) were tested in a Y-maze with a choice between an odorant (butanol) or distilled water before and during 3 weeks of daily intra-peritoneal injection of either citalopram or clomipramine. Their performance was compared with those of a control group (N degrees =11) injected with a saline solution. RESULTS: The results showed a significant decrease in olfactory sensitivity with both anti-depressants during the three weeks of treatment. CONCLUSION: The antidepressant induced alteration in serotonin and/or noradrenaline transmission in the olfactory bulb may account for the altered olfactory sensitivity observed in this study.     

Monocyte deactivation in neutropenic acute respiratory distress syndrome patients treated with granulocyte colony-stimulating factor

Introduction

In severely neutropenic septic acute respiratory distress syndrome (ARDS) patients, macrophages and monocytes are the last potentially remaining innate immune cells. We have previously shown, however, a deactivation of the alveolar macrophage in neutropenic septic ARDS patients. In the present study, we tried to characterize in vitro monocyte baseline cytokine production and responsiveness to lipopolysaccharide exposure.

Methods

Twenty-two consecutive patients with cancer were prospectively enrolled into a prospective observational study in an intensive care unit. All patients developed septic ARDS and were divided into two groups: neutropenic patients (n = 12) and non-neutropenic patients (n = 10). All of the neutropenic patients received granulocyte colony-stimulating factor whereas no patient in the non-neutropenic group received granulocyte colony-stimulating factor. We compared monocytes from neutropenic patients with septic ARDS with monocytes from non-neutropenic patients and healthy control individuals (n = 10). Peripheral blood monocytes were cultured, and cytokine levels (TNFα, IL-1β, IL-6, IL-10, and IL-1 receptor antagonist) were assayed with and without lipopolysaccharide stimulation.

Results

TNFα, IL-6, IL-10 and IL-1 receptor antagonist levels in unstimulated monocytes were lower in neutropenic patients compared with non-neutropenic patients. Values obtained in the healthy individuals were low as expected, comparable with neutropenic patients. In lipopolysaccharide-stimulated monocytes, both inflammatory and anti-inflammatory cytokine production were significantly lower in neutropenic patients compared with non-neutropenic patients and control individuals.

Conclusion

Consistent with previous results concerning alveolar macrophage deactivation, we observed a systemic deactivation of monocytes in septic neutropenic ARDS. This deactivation participates in the overall immunodeficiency and could be linked to sepsis, chemotherapy and/or the use of granulocyte colony-stimulating factor.     

A positive fluid balance is associated with a worse outcome in patients with acute renal failure

Introduction  

Despite significant improvements in intensive care medicine, the prognosis of acute renal failure (ARF) remains poor, with mortality ranging from 40% to 65%. The aim of the present observational study was to analyze the influence of patient characteristics and fluid balance on the outcome of ARF in intensive care unit (ICU) patients.     

Adenomatous polyposis of the gallbladder and Gardner's syndrome. A rare association

We report one case of adenomatous polyposis of the gallbladder in a 57 year-old woman with Gardner's syndrome presenting with cholangitis. On gross examination the gallbladder contained two calculi and numerous flat or polypoid adenomas less than 1 cm in size. On microscopic examination, the adenomas showed low and high grade intraepithelial neoplasia. Only 10 cases of gallbladder adenomas have been reported in the literature in patients presenting with familial adenomatous polyposis (FAP). Cholecystectomy is usually performed for cholecystitis or cholangitis. These adenomatous gallbladder lesions are discovered late, often when the patient is older than 40. Pathogenesis of gallbladder adenomas is still unclear. It is difficult to assess the risk of malignancy: only 6 cases of gallbladder adenocarcinomas have been reported in patients with FAP.     

Surgical management of chronic pancreatitis

Surgical indications for chronic pancreatitis can be schematically separated into five main groups: pain, effects of fibrosis on adjacent organs, the consequences of main pancreatic duct rupture above an obstruction, and suspected cancer. Finally surgery is also indicated in patients who cannot undergo endoscopic procedures (no accessible papilla) or who have too recently undergone this procedure. Surgical procedures include derivation (pancreatic, cystic, biliary) or mixed procedures combining derivation/resection or pancreatic resection. Finally splanchnicectomy can be discussed. Whatever the indication, surgical treatment must meet several goals: the approach to surgery must be multidisciplinary, surgery must be associated with low morbidity and mortality, preserve as much endocrine function as possible, improve quality of life, and be evaluated in the long term, as well as prospectively if possible. We clarify some important points about the management of patients with chronic pancreatitis before discussing the various treatments in detail.