Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: time for an eosinophil guided clinical trial?

Childhood wheezing is common particularly in children under the age of 6 years and in this age group is generally referred to as preschool wheezing. Particular diagnostic and treatment uncertainties exist in these young children due to the difficulty in obtaining objective evidence of reversible airways narrowing and inflammation. A diagnosis of asthma depends on the presence of relevant clinical signs and symptoms and the demonstration of reversible airways narrowing on lung function testing, which is difficult to perform in young children. Few treatments are available and inhaled corticosteroids are the recommended preventer treatment in most international asthma guidelines. There is, however, considerable controversy about its effectiveness in children with preschool wheeze and a corticosteroid responder phenotype has not been established. These diagnostic and treatment uncertainties in conjunction with the knowledge of corticosteroid side effects, in particular the reduction of growth velocity, have resulted in a variable approach to inhaled corticosteroid prescribing by medical practitioners and a reluctance in carers to regularly administer the treatment. Identifying children who are likely responders to corticosteroid therapy would be a major benefit in the management of this condition. Eosinophils have emerged as a promising biomarker of corticosteroid responsive airways disease, and evaluation of this biomarker in sputum has successfully been employed to direct management in adults with asthma. Obtaining sputum from young children is time consuming and difficult, and it is hard to justify more invasive procedures such as a bronchoscopy in young children routinely. Recently, in children, interest has shifted to assessing the value of less invasive biomarkers of likely corticosteroid response and the biomarker ‘blood eosinophils’ has emerged as an attractive candidate. The aim of this review was to summarize the evidence for blood eosinophils as a predictive biomarker for corticosteroid responsive disease with a particular focus on the difficult area of preschool wheeze.     

Exogenous neuropeptide Y promotes in vivo hippocampal neurogenesis

Adult neurogenesis mainly occurs in two brain regions, the subventricular zone and the dentate gyrus (DG) of the hippocampus. Neuropeptide Y (NPY) is widely expressed throughout the brain and is known to enhance in vitro hippocampal cell proliferation. Mice lacking either NPY or the Y1 receptor display lower levels of cell proliferation, thereby suggesting a role for NPY in basal in vivo neurogenesis. Here, we investigated whether exogenous NPY stimulates DG progenitors proliferation in vivo. We show that intracerebroventricular administration of NPY increases DG cell proliferation and promotes neuronal differentiation in C57BL/6 adult mice. In these mice, the proliferative effect of NPY is mediated by the Y1 and not the Y2 receptor, as a Y1 ([Leu³¹,Pro³⁴]), but not a Y2 (NPY_3–36), receptor agonist enhanced proliferation. In addition, no NPY‐induced DG cellular proliferation is observed following NPY injection when coadministered with a Y1 antagonist or in the Y1 receptor knockout mouse. These results are in line with data obtained in Y1^?/? mice, demonstrating that NPY regulates in vivo hippocampal neurogenesis. © 2010 Wiley‐Liss, Inc.     

Perception gustative des lipides alimentaires

The profound technical and economic changes of the 20^th Century had a deep effect on our way of life and, consequently, on our eating behaviour. For the first time in its history, much of the world's population no longer has to “run after calories”. An abundance of food has obvious consequences: it promotes our specific appetites. Lipids account for about 40% of the calories ingested in Western countries, whereas nutritional recommendations are 5 to 10% lower. This excessive lipid intake, associated with a qualitative imbalance (excess of saturated fatty acids and cholesterol, too high ω6/ω3 ratio) strongly favours the development of obesity and associated diseases (atherosclerosis, non insulin-dependent diabetes, hypertension, cancer). This attraction to fatty foods is not specific to humans. Rats and mice spontaneously prefer lipid-rich foods if provided with a free choice. Until recently, it was thought that oral lipid detection involved only somesthesic and olfactory cues. This restrictive view has been challenged by recent observations suggesting that sense of taste is also involved in spontaneous fat preference underlying that the “fatty” taste might constitute a sixth gustatory modality. This mini-review highlights recent findings in this new field of investigations in both rodents and humans.     

Cognition across the lifespan: Antiepileptic drugs,epilepsy, or both?

Cognitive problems in persons with epilepsy manifest over a lifetime; however, whether abnormal cognition in an individual with epilepsy is a result of comorbid brain substrate, the epilepsy itself or its underlying etiology, the antiepileptic agents used to control it, or a combination of these and other factors remains controversial. There is a continuing need for improved therapies to control seizures and reduce the incidence of adverse events, especially those involving the central nervous system that compromise attention, intelligence, language skills, verbal and nonverbal memory, executive function, and psychomotor speeds. Although cognitive decline typically occurs among patients with more severe epilepsy, physicians must judiciously select therapy with an eye toward not only controlling seizures but also ensuring that all patients retain as much function as possible throughout their lives.     

Measurement of Serum Anti-staphylococcal Antibodies Increases Positive Predictive Value of Preoperative Aspiration for Hip Prosthetic Joint Infection

BackgroundPreoperative synovial fluid culture is pivotal in the early diagnosis of prosthetic joint infection (PJI) but may yield false-positive and false-negative results. We evaluated the predictive value of synovial fluid culture results combined with the measurement of serum anti-staphylococcal antibodies (SASA).Questions/purposes(1) For hip and knee PJI, does combining positive SASA results with preoperative synovial culture results improve the positive predictive value (PPV) of preoperative synovial fluid culture alone? (2) Does combining preoperative synovial fluid culture results with a positive cell count and differential result increase the PPV of preoperative synovial fluid culture alone? (3) What proportion of isolated organisms exhibit concordance in antibiotic susceptibility: preoperative aspiration versus intraoperative isolates?MethodsA prospective study was conducted at two French reference centers that manage bone and joint infections and included 481 adult patients who had a revision or resection arthroplasty between June 25, 2012 and June 23, 2014. Exclusion criteria including no serum sample available for immunoassay, the lack of microbiological documentation, and the absence of preoperative aspiration reduced the patient number to 353. Seven patients with an undetermined SASA result were excluded from the analysis. We also excluded patients with PJI involving more than one Staphylococcus species (polystaphylococcal infection) and those in whom more than one Staphylococcus species was recovered from the preoperative synovial fluid culture (polystaphylococcal synovial fluid culture). In total, 340 patients were included in the analysis (no infection, 67% [226 of 340]; staphylococcal infection, 21% [71 of 340]; other infection, 13% [43 of 340]). The preoperative synovial fluid analysis included a cell count and differential and bacterial culture. SASAs were measured using a multiplex immunoassay. The diagnosis of PJI was determined using the Infectious Diseases Society of America (IDSA) criteria [14] and intraoperative tissue culture at the time of revision surgery was used as the gold standard (at least one positive intraoperative sample for a “virulent” organism (such as S. aureus) or two positive samples for a “non-virulent” (for example S. epidermidis).ResultsSASA increased the PPV compared with synovial fluid culture alone (92% [95% CI 82 to 97] versus 79% [95% CI 68 to 87]; p = 0.04); when stratified by site, an increase in PPV was seen in hip infections (100% [95% CI 89 to 100] versus 77% [95% CI 63 to 88]; p = 0.01) but not in knee infections (84% [95% CI 66 to 95] versus 80% [95% CI 64 to 91]; p = 0.75). A positive cell count and differential result increased the PPV of staphylococcal synovial fluid cultures compared with synovial fluid culture alone (86% [95% CI 70 to 95] versus 79% [95% CI 68 to 87]; p = 0.36); when stratified by site, no difference in hip and knee infections was observed (86% [95% CI 67 to 96] versus 77% [95% CI 63 to 88]; p = 0.42) and 86% [95% CI 70 to 95] versus 80% [95% CI 64 to 91]; p = 0.74).ConclusionSASA measurement improves the predictive value of synovial fluid cultures of the hip for all staphylococcal organisms, including coagulase-negative staphylococci, but the PPV of SASA plus synovial fluid culture it is not superior to the PPV of synovial fluid cell count/differential plus synovial culture for the knee.Level of EvidenceLevel III, diagnostic study.