Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection

Funding: Statement of financial support: The study was financially supported by the VIRGO consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK 03012). The authors have indicated they have no personal financial relationships relevant to this article to disclose. Data Availability Statement: The data is accessible at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69606.Peer reviewedPublisher PD

Invasive pulmonary aspergillosis 10 years post bone marrow transplantation: a case report

Abstract Introduction Invasive pulmonary aspergillosis is a leading cause of mortality and morbidity in bone marrow transplant recipients. Establishing the diagnosis remains a challenge for clinicians working in acute care setting. However, prompt diagnosis and treatment can lead to favourable outcomes Case presentation We report a case of invasive aspergillosis occurring in a 39-year-old Caucasian female 10 years after an allogeneic haematopoietic bone marrow transplant, and 5 years after stopping all immunosuppression. Possible risk factors include bronchiolitis obliterans and exposure to building dust (for example, handling her husband's dusty overalls). There are no similar case reports in the literature at this time. Conclusion High clinical suspicion, especially in the setting of failure to respond to broad-spectrum antibiotics, should alert clinicians to the possibility of invasive pulmonary aspergillosis, which, in this case, responded to antifungal therapy.</p

Management of Invasive Fungal Disease in Neonates and Children.

Invasive fungal diseases (IFD) are an important cause of morbidity and mortality in premature neonates and immunocompromised pediatric patients. Their diagnostic and therapeutic management remains a challenge. A nationwide survey was conducted among 13 of the largest pediatric units in the United Kingdom, to obtain insight in the current management of IFD in neonates and children. All responding centers were tertiary teaching centers. The use of fungal diagnostic tools and imaging modalities varied among centers. Antifungal prophylaxis was prescribed in most centers for extreme-low birth weight (LBW) infants and high-risk hemato-oncologic patients, but with a huge variety in antifungals given. An empirical treatment was favored by most centers in case of febrile neutropenia. First line therapy for candidemia consists of either fluconazole or liposomal amphotericin B, with voriconazole being first-line therapy for invasive aspergillosis. Disseminated invasive aspergillosis was most often mentioned as a reason to prescribe combination antifungal therapy. In conclusion, this survey reinforces the fact that there are still important aspects in the management of pediatric IFD which should ideally be addressed in pediatric clinical trials. Attention needs to be given the knowledge gaps as observed in the results of our survey to optimize the management of IFD in children and neonates

Acute Cardiac Failure due to Intra-Atrial Mass Caused by Zygomycetes in an Immunocompromised Paediatric Patient

Cardiac zygomycosis can be a critical condition with sudden onset of severe congestive heart failure followed by severe hemodynamic deterioration. We report a fatal course of disseminated fungal infection with a massive intra-atrial thrombosis caused by a zygomycete, in a five year old boy treated for acute lymphoblastic leukaemia. In addition, we discuss the literature concerning infections caused by zygomycetes involving the heart. Prognosis is poor. A high index of suspicion and an aggressive diagnostic and therapeutic approach with the prompt start of preemptive antifungal therapy are key factors to improve outcome

A pitfall of whole exome sequencing:: variants in the 5 ' UTR Splice Site of BTK causing XLA

Transplantation and immunomodulatio

Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BACKGROUND: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged 44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). CONCLUSIONS: Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating

A new paediatric formulation of valaciclovir : development and bioequivalence assessment

Peer reviewedPostprin

Dissecting Disease-Suppressive Rhizosphere Microbiomes by Functional Amplicon Sequencing and 10x Metagenomics

Disease-suppressive soils protect plants against soilborne fungal pathogens that would otherwise cause root infections. Soil suppressiveness is, in most cases, mediated by the antagonistic activity of the microbial community associated with the plant roots. Considering the enormous taxonomic and functional diversity of the root-associated microbiome, identification of the microbial genera and mechanisms underlying this phenotype is challenging. One approach to unravel the underlying mechanisms is to identify metabolic pathways enriched in the disease-suppressive microbial community, in particular, pathways that harbor natural products with antifungal properties. An important class of these natural products includes peptides produced by nonribosomal peptide synthetases (NRPSs). Here, we applied functional amplicon sequencing of NRPS-associated adenylation domains (A domains) to a collection of eight soils that are suppressive or nonsuppressive (i.e., conducive) to Fusarium culmorum, a fungal root pathogen of wheat. To identify functional elements in the root-associated bacterial community, we developed an open-source pipeline, referred to as dom2BGC, for amplicon annotation and putative gene cluster reconstruction through analyzing A domain co-occurrence across samples. We applied this pipeline to rhizosphere communities from four disease-suppressive and four conducive soils and found significant similarities in NRPS repertoires between suppressive soils. Specifically, several siderophore biosynthetic gene clusters were consistently associated with suppressive soils, hinting at competition for iron as a potential mechanism of suppression. Finally, to validate dom2BGC and to allow more unbiased functional metagenomics, we performed 10× metagenomic sequencing of one suppressive soil, leading to the identification of multiple gene clusters potentially associated with the disease-suppressive phenotyp

Effect of transport length on in vivo oxidative status and breast meat characteristics in outdoor-reared chicken genotypes

The aim of the study was to evaluate the effect of transport length on in vivo oxidative status and breast meat characteristics in two chicken genotypes reared under free range conditions. A total of 200 male chicks, 100 from fast-growing (Ross 308) and 100 from medium-growing (Naked Neck) strain were used. Fifty-six of these, 28 for genotype, before slaughtering, were randomly allocated to 2 pre-slaughter conditions: absence (0 h) or 4 h of transport. The transport length significantly affected the in vivo oxidative status of broiler greatly reducing the α and δ-tocopherol, retinol and lutein + zeaxanthin content of plasma, and increased the oxidative stress (thiobarbituric acid reactive substances, TBARS) in both strains. Concerning meat quality, the pH (0, 2 and 24 h post-mortem) of breast muscles of chickens transported for 4 h, showed higher values, and respect to strains, Naked Neck had lower values. The pH values were negatively correlated with the lightness (2–24 h) and the shear force of meat. The transport length significantly affected the fatty acid profile of breast muscle, with a decrease in polyunsaturated fatty acids and an increase in TBARS value. Even the antioxidants content of breast was reduced by chicken transport (α-tocotrienol, α-, δ-tocopherol and lutein + zeaxanthin), especially in Naked Neck birds. In conclusion, the results indicate that transport for 4 h prior to slaughter, negatively affect the meat quality of poultry. Slow-growing chickens seem more sensible to stress transport due to the higher kinetic behaviour of these strains