Background-Procalcitonin has been advocated as a marker of bacterial infection.Objective-To evaluate diagnostic markers of infection in critically ill children, comparing procalcitonin with C reactive protein and leucocyte count in a paediatric intensive care unit (PICU). Methods-Procalcitonin, C reactive protein, and leucocyte count were measured in 175 children, median age 16 months, on admission to the PICU. Patients were classified as: non-infected controls (43); viral infection (14); localised bacterial infection without shock (25); bacterial meningitis/encephalitis (10); or septic shock (77). Six children with "presumed septic shock" (without suYcient evidence of infection) were analysed separately. Optimum sensitivity, specificity, predictive values, and area under the receiver operating characteristic (ROC) curve were evaluated. Results-Admission procalcitonin was significantly higher in children with septic shock (median 94.6; range 3.3-759.8 ng/ ml), compared with localised bacterial infection (2.9; 0-24.3 ng/ml), viral infection (0.8; 0-4.4 ng/ml), and non-infected controls (0; 0-4.9 ng/ml). Children with bacterial meningitis had a median procalcitonin of 25.5 (7.2-118.4 ng/ml). Area under the ROC curve was 0.96 for procalcitonin, 0.83 for C reactive protein, and 0.51 for leucocyte count. Cut oV concentrations for optimum prediction of septic shock were: procalcitonin > 20 ng/ml and C reactive protein > 50 mg/litre. A procalcitonin concentration > 2 ng/ml identified all patients with bacterial meningitis or septic shock. Conclusion-In critically ill children the admission procalcitonin concentration is a better diagnostic marker of infection than C reactive protein or leucocyte count. A procalcitonin concentration of 2 ng/ml might be useful in diVerentiating severe bacterial disease in infants and children. (Arch Dis Child 1999;81:417-421)

Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.

Glomerular hyperfiltration is associated with puberty and increasing ACR levels and is predictive of MA independent of HbA1c. This suggests that factors other than poor glycemic control may be involved in the pathogenesis of early diabetic nephropathy and early intervention with medical therapy to reduce GFR may be beneficial even before onset of MA.

Background-Functional adrenal insuYciency has been documented in critically ill adults. Objective-To document the incidence of adrenal insuYciency in children with septic shock, and to evaluate its eVect on catecholamine requirements, duration of intensive care, and mortality. Setting-Sixteen-bed paediatric intensive care unit in a university hospital. Methods-Thirty three children with septic shock were enrolled. Adrenal function was assessed by the maximum cortisol response after synthetic adrenocorticotropin stimulation (short Synacthen test). InsuYciency was defined as a post-Synacthen cortisol increment < 200 nmol/l. Results-Overall mortality was 33%. The incidence of adrenal insuYciency was 52% and children with adrenal insuYciency were significantly older and tended to have higher paediatric risk of mortality scores. They also required higher dose vasopressors for haemodynamic stability. In the survivor group, those with adrenal insuYciency needed a longer period of inotropic support than those with normal function (median, 3 v 2 days), but there was no significant diVerence in duration of ventilation (median, 4 days for each group) or length of stay (median, 5 v 4 days). Mortality was not significantly greater in children with adrenal insuYciency than in those with adequate adrenal function (6 of 17 v 5 of 16, respectively). Conclusion-Adrenal insuYciency is common in children with septic shock. It is associated with an increased vasopressor requirement and duration of shock. (Arch Dis Child 1999;80:51-55)

The admission PCT, like TNF and IL-10, is related to the severity of organ failure and mortality in children with septic shock. A fall in PCT after 24 hrs of treatment may have favorable prognostic significance.

Previous studies suggest reduced hepatic endothelial nitric oxide synthase activity contributes to increased intrahepatic resistance. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, undergoes hepatic metabolism via dimethylargininedimethylamino-hydrolase, and is derived by the action of protein-arginine-methyltransferases. Our study assessed whether ADMA, and its stereo-isomer symmetric dimethylarginine (SDMA), are increased in alcoholic hepatitis patients, and determined any relationship with severity of portal hypertension (hepatic venous pressure gradient measurement) and outcome. Fifty-two patients with decompensated alcoholic cirrhosis were studied, 27 with acute alcoholic hepatitis and cirrhosis, in whom hepatic venous pressure gradient was higher (P ‫؍‬ 0.001) than cirrhosis alone, and correlated with ADMA measurement. Plasma ADMA and SDMA were significantly higher in alcoholic hepatitis patients and in nonsurvivors. Dimethylarginine-dimethylaminohydrolase protein expression was reduced and protein-arginine-methyltransferase-1 increased in alcoholic hepatitis livers. ADMA, SDMA and their combined sum, which we termed a dimethylarginine score, were better predictors of outcome compared with Pugh score, MELD and Maddrey's discriminant-function. Conclusion: Alcoholic hepatitis patients have higher portal pressures associated with increased ADMA, which may result from both decreased breakdown (decreased hepatic dimethylarginine-dimethylamino-hydrolase) and/or increased production. Elevated dimethylarginines may serve as important biological markers of deleterious outcome in alcoholic hepatitis. (HEPATOLOGY 2007;45:62-71.)A lcoholic hepatitis (AH) is a severe presentation of alcoholic liver disease associated with high mortality. 1 Patients present with acute hepatic decompensation on the background of cirrhosis, related to complications associated with portal hypertension. A potential link between changes in portal blood flow and poor outcome in severe AH has been suggested. 2 Furthermore, elevated portal pressures in patients with decompensated cirrhosis independently predicts survival 3 although the pathophysiological mechanisms behind these haemodynamic disturbances are incompletely defined.Factors modulating intrahepatic resistance, an important component in the severity of portal hypertension include liver ultrastructural changes secondary to cirrhosis, in addition to variable components such as myofibroblastic stellate cell activity and vaso-active mediators such as nitric oxide (NO). 4 Data from animal studies strongly support the notion that in portal hypertension, there is a deficiency of intrahepatic NO resulting from a reduction in the activity of endothelial NO synthase (eNOS). 5,6 Hepatic NO delivery in these models reduces the severity of portal hypertension through a reduction in intrahepatic resistance. 7 .

Six trained male cyclists and triathletes participated in a double blind study to determine the effects of phosphate loading on maximal and endurance exercise performance. Subjects ingested either 1 gm of tribasic sodium phosphate or a glucose placebo four times daily for 3 days prior to performing either an incremental maximal cycling test or a simulated 40-km time trial on a computerized race simulator. They continued the supplementation protocol for an additional day and then performed the remaining maximal or performance exercise test. Subjects observed a 17-day washout period between testing sessions and repeated the experiment with the alternate supplement regimen in identical fashion. Metabolic data were collected at 15-sec intervals while venous blood samples and 2D-echocardiographic data were collected during each stage of exercise during the maximal exercise test and at 8-km intervals during the 404cm time trial. Results indicate that phosphate loading attenuated anaerobic threshold, increased myocardial ejection fraction and fractional shortening, increased maximal oxidative capacity, and enhanced endurance performance in competitive cyclists and triathletes.

Summary Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two‐day Pan‐European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus‐based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes.