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Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the "bio depression score"). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P

Background Pharmachild is a pharmacovigilance registry on children with JIA treated mainly with biologics±methotrexate (MTX). Little evidence exists in literature about the role of JIA or its immunosuppressive therapy in determining infections, especially caused by opportunistic pathogens. Objectives To provide an update on opportunistic infections (OI) revised by an independent Safety Adjudication Committee (SAC) (3 paediatric rheumatologists and 2 paediatric infectious disease specialists). Methods The participating centres were asked to report all infections encountered by their JIA patients. PRINTO and the medical monitor (MM) classified events based on MedDRA dictionary. Moderate/serious/severe/very severe infections were then revised blindly by the SAC, who was asked to answer 6 questions. The events with consensus of at least 3/5 experts on the first 3 questions (‘Is this an infection?’, ‘Is it common?’, ’Is it opportunistic?’) were retained for the analysis. With referral to the recommendations by Withrop et al.1, for the first time a list of OIs in children with JIA on immunosuppressive therapy was elaborated and approved by consensus, through three Delphi steps. Finally, we compared the OI list defined by the SAC to the list of OI approved by the specialists. Results A total of 772 safety events related to 634 patients were submitted to the SAC. 689 (89.2%) events received consensus among the experts on the 3 questions and, of these, 682 (99.0%) were considered as infections, corresponding to 153 different Preferred Terms (PT), according to MedDRA dictionary. Among the 682 infections, 603 (88.4%) were defined by the experts as common and 119 (17.4%) as opportunistic. For 92 (60%) of the 153 PT, the MM and SAC used the same PT, while the remaining 40% was adjudicated by a third examiner, who analysed again the case reports and assigned the PT which was the most appropriate taking into account the experts’ opinion. Among the final number of infections emerged that herpes viral, respiratory and EBV infections were the most frequent (Table). Analysing the infections by PT (n=149), the experts adjudicated: 22 as OI, 119 as not OI, 8 discordant. Comparing the experts’ adjudication with the approved list of OI by PT, there was full agreement for the 22 PT classified as OI, while 19/117 (16.2%) PT resulted in the list, but were not classified as OI by the experts. Conclusions Our analysis showed a significant number of OI in JIA patients on immunosuppressants and provided an approved document stating the most frequent OI in children with JIA. The most frequent opportunistic pathogens resulted herpes virus, excluding varicella, and mycobacteria, but the list of definite and probable OIs needs to be validated/revised with the analysis of future datasets. Reference [1] Winthrop, et al. Ann Rheum Dis2015;74:2107–16. Disclosure of Interest None declared

Introduction: Thiamine is an essential cofactor in carbohydrate metabolism, and deficiency can therefore cause various organ dysfunctions. Little is known about the prevalence and possible worsening of thiamine deficiency in critically ill patients. In this study, we investigated the prevalence of thiamine deficiency at admission to the intensive care unit (ICU) and hypothesized that intensive insulin therapy, aimed at regulating glucose levels, increases thiamine utilization and therefore might cause or worsen deficiency in patients with limited thiamine stores. Materials and Methods: An observational prospective cohort study was carried out in a medical–surgical ICU in a general teaching hospital in Apeldoorn, the Netherlands. All adults who were treated during that time with intensive insulin therapy were included. Deficiency was defined as a thiamine level Results: A total of 58 patients were available for analysis. Median thiamine level at admission was 111 nmol/L. Deficiency was present in 39.7% of patients and was significantly associated with the presence of gastrointestinal pathology and with recent surgery. Thiamine levels increased a median of 14 nmol/L in 48 hours. Only 3.4% of patients showed a predefined relevant decline in thiamine levels. Conclusion: Intensive insulin therapy does not appear to cause or worsen thiamine deficiency. However, based on the high prevalence of deficiency at admission, it might be warranted to supplement thiamine in all patients admitted to the ICU, especially when there is an underlying gastrointestinal disease or recent surgery.

Prothrombin Complex Concentrate (PCC) is indicated for the acute reversal of oral anticoagulation therapy. To compare the efficacy of a "standard" dosage of 20 ml PCC equivalent to about 500 IU factor IX (group A), and an "individualized" dosage based on a target-INR of 2.1 or 1.5, the initial-INR and the patient's body weight (group B), we performed an open, prospective, randomized, controlled trial. The in vivo response and in vivo recovery of factor II, VII, IX and X in these patients on oral anticoagulation was determined. Ninety three patients (group A: 47; group B: 46) with major bleedings or admitted for urgent (surgical) interventions were enrolled. PCC and Vitamin K (10 mg) were administered intravenously. We evaluated the effect of treatment by the decrease of INR and the clinical outcome. The number of patients reaching the target-INR 15 min after the dosage of PCC was significantly higher in the group treated with an "individualized" dosage, compared to the group treated with a standard dose, (89% versus 43%; p

Chronic renal failure (CRF) is associated, especially in young children, with delayed cognitive development of unknown origin. As cerebrospinal fluid (CSF) reflects the composition of the extracellular fluid of the brain, not only plasma but also CSF amino acids concentrations were determined in 8 infants (age 2-8 months) and 3 children (age 26, 32 and 56 months) with CRF (creatinine clearance 13 +/- 9 ml/min/ 1.73 m2). In three of these children investigations were repeated after six weeks of CAPD treatment. In the infants, a significant decrease was found in CSF of alpha-aminobutyric acid, valine, isoleucine, leucine, tyrosine, tryptophane, histidine and n-zeta-methyl-1-lysine, whereas there was a significant increase of 3-methylhistidine. In plasma serine, valine, leucine, tyrosine and histidine were significantly decreased, whereas there was a significant increase of aspartic acid, citrulline, and 3-methylhistidine. These abnormalities remained constant after the start of CAPD except for the normalization in CSF and plasma of 3-methylhistidine. These data indicate a generalized disturbance of amino acids in young children with CRF. An abnormal substrate is offered to the neurons and astroglia in children with CRF.

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Introduction: Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. Objective: To determine whether ventilator settings in critically ill patients without acute lung injury (ALI) at onset of mechanical ventilation affect the development of AKI. Design, Setting, and Patients: Secondary analysis of a randomized controlled trial (N = 150), comparing conventional tidal volume (V-T, 10 mL/kg) with low tidal volume (V-T, 6 mL/kg) mechanical ventilation in critically ill patients without ALI at randomization. During the first 5 days of mechanical ventilation, the RIFLE class was determined daily, whereas neutrophil gelatinase-associated lipocalin and cystatin C levels were measured in plasma collected on days 0, 2, and 4. Results: Eighty-six patients had no AKI at inclusion, and 18 patients (21%) subsequently developed AKI, but without significant difference between ventilation strategies. (Cumulative hazard, 0.26 vs 0.23; P - .88.) The courses of neutrophil gelatinase-associated lipocalin and cystatin C plasma levels did not differ significantly between randomization groups. Conclusion: In the present study in critically patients without ALI at onset of mechanical ventilation, lower tidal volume ventilation did not reduce the development or worsening of AKI compared with conventional tidal volume ventilation. (C) 2012 Elsevier Inc. All rights reserved