Normal neonatal TREC and KREC levels in early onset juvenile idiopathic arthritis

Objective: Dysregulated central tolerance predisposes to autoimmune diseases. Reduced thymic output as well as compromised central B cell tolerance checkpoints have been proposed in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate neonatal levels of T-cell receptor excision circles (TRECs) and kappa-deleting element excision circles (KRECs), as markers of T- and B-cell output at birth, in patients with early onset JIA. Methods: TRECs and KRECs were quantitated by multiplex qPCR from dried blood spots (DBS), collected 2–5 days after birth, in 156 children with early onset JIA and in 312 matched controls. Results: When analysed from neonatal dried blood spots, the median TREC level was 78 (IQR 55–113) in JIA cases and 88 (IQR 57–117) copies/well in controls. The median KREC level was 51 (IQR 35–69) and 53 (IQR 35–74) copies/well, in JIA cases and controls, respectively. Stratification by sex and age at disease onset did not reveal any difference in the levels of TRECs and KRECs. Conclusion: T- and B-cell output at birth, as measured by TREC and KREC levels in neonatal dried blood spots, does not differ in children with early onset JIA compared to controls

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Fetal cardiac arrhythmia - haemodynamic consequence and clinical siqnificance

Peer Reviewe

A critical appraisal of the use of umbilical artery Doppler ultrasound in high-risk pregnancies: use of meta-analyses in evidence-based obstetrics

Objectives To reanalyze randomized controlled trials on the use of umbilical artery Doppler velocimetry in high-risk pregnancies and determine which high-risk pregnancies benefit from the use of Doppler velocimetry, Methods Searching Medline, the Cochrane Library and Embase we found 13 randomized controlled trials on the use of Doppler velocimetry in high-risk pregnancies. Of these, six included pregnancies with strictly defined suspected intrauterine growth restriction and/or hypertensive disease of pregnancy ('well-defined studies;); the rest included a great variety of high-risk pregnancies (general risk studies'). The studies were analyzed with particular regard 50 the heterogeneity and to outcome. Audits of the perinatal deaths reported in the randomized controlled trials were performed by a panel of 32 international experts. Results The 'well-defined studies ' had a more uniform study design as compared to the 'general risk studies' and they showed a significant reduction in antenatal admissions (odds ratio, 0.56; 95% confidence interval, 0.43 - 0. 72), inductions of labor (0. 78; 0.63 -0. 96), elective deliveries (inductions of labor and elective Cesarean sections) (0. 73; 0.61-0.88) and Cesarean sections (0. 78; 0, 65 - 0. 94). By perinatal audit it was found that more perinatal deaths in the 'well-defined studies' were potentially avoidable by use of Doppler velocimetry (P < 0.0005) and the rate of avoidable perinatal deaths was higher among controls (50%) than cases (20%) in this group. Conclusion The randomized controlled trials on umbilical artery Doppler velocimetry show major differences regarding study design and technical and clinical issues and, therefore, they should not be pooled in a simple meta-analysis. By stratification it was found that only in pregnancies with suspected intrauterine growth restriction and/or hypertensive disease of pregnancy will the use of umbilical artery Doppler velocimetry reduce the number of perinatal deaths and unnecessary obstetric interventions