Peroxisome proliferator-activated receptor-γ agonist pioglitazone reduces the development of necrotizing enterocolitis in a neonatal preterm rat model.

BACKGROUND: Factors affecting innate immunity and acting as inflammatory regulators, such as the nuclear peroxisome proliferator-activated receptors (PPAR) could be crucial in the pathogenesis of necrotizing enterocolitis (NEC). We hypothesized that the PPARγ agonist pioglitazone (PIO) might be effective in preventing the development of NEC and/or reducing its severity. METHODS: We studied preterm rats in which NEC was induced using the hypoxia-hypothermia model. The treatment group (TG; n = 30) received enteral PIO (10 mg/kg/d) for 72 h and the control group (CG; n = 30) did not. Animals were sacrificed 96 h after birth. NEC was diagnosed evaluating histological ileum changes, and mRNA levels of IL-4, IL-12, IL-6, IL-10, INF-γ, and TNF-α cytokines were measured. RESULTS: NEC occurrence was higher in the CG (18/30; 60%) than in the TG (5/30; 16.7%) and was more severe. Proinflammatory IL-12 and INF-γ mRNA levels were significantly lower in the TG than in the CG; conversely, the anti-inflammatory IL-4 mRNA level was significantly higher in the TG than in the CG. CONCLUSION: Our results demonstrate for the first time that PIO is effective in reducing the incidence and severity of NEC and in decreasing renal injuries in a preterm rat model.

Presepsin for the detection of late-onset sepsis in preterm newborns.

BACKGROUND: Late-onset sepsis (LOS) is among the leading causes of morbidity and mortality in preterm newborns, and currently available diagnostic tools are inadequate. The objective of this study was to evaluate the accuracy of presepsin (P-SEP) as novel biomarker of bacterial infection for the diagnosis of LOS in preterm newborns. METHODS: We prospectively studied newborns ≤32 weeks' gestational age with LOS (n = 19) and noninfected controls (n = 21) at 4 to 60 days' postnatal age. At enrollment, and 1, 3, and 5 days later, we ascertained the C-reactive protein, procalcitonin, and P-SEP in the LOS group, whereas P-SEP alone was ascertained in the control group. RESULTS: P-SEP at enrollment was higher in the LOS than the control group (median 1295 vs 562 ng/L, P = .00001) and remained higher throughout the study period. In the LOS group, P-SEP had a borderline reduction at day 1 versus values at enrollment (median 1011 vs 1295 ng/L, P = .05), whereas C-reactive protein and procalcitonin at day 1 did not differ from baseline values. The receiver operating characteristic curve of P-SEP at enrollment shows an area under the curve of 0.972. The best calculated cutoff value was 885 ng/L, with 94% sensitivity and 100% specificity. Negative likelihood ratio was 0.05, and positive likelihood ratio was infinity. CONCLUSIONS: We demonstrated for the first time in a cohort of preterm newborns that P-SEP is an accurate biomarker for the diagnosis of possible LOS and may also provide useful information for monitoring the response to therapeutic interventions.

Splanchnic Tissue Oxygenation for Predicting Feeding Tolerance in Preterm Infants.

BACKGROUND: Feeding intolerance is very frequent in preterm infants, and the development of an early effective biomarker for its prediction could be useful for carrying out a proper feeding strategy. Our aim was to evaluate if the measurement of splanchnic regional oxygenation (rSO2S) and splanchnic fractional oxygen extraction ratio (FOES) using near-infrared spectroscopy (NIRS) is correlated with the time needed to achieve full enteral feeding and if it can predict the development of feeding intolerance. MATERIALS AND METHODS: We measured rSO2S and FOES in preterm infants 25 ± 0 to 31 ± 6 weeks of gestational age at 24-72 hours of life during continuous enteral feeding. RESULTS: Linear regression analysis did not evidence any relationship between rSO2S and FOES and the time for achievement of full enteral feeding. Multivariate logistic regression analysis showed that birth weight <1000 g (relative risk [RR], 4.5; 95% confidence interval [CI], 1.23-16.45) and patent ductus arteriosus occurrence (RR, 9.3; 95% CI, 1.31-66.06) increased the risk of developing feeding intolerance in our population. CONCLUSION: Splanchnic oxygenation and oxygen extraction measured in the first days of life are not correlated with the time needed to achieve full enteral feeding in preterm infants receiving continuous enteral nutrition.

Circulating levels of the adipokines vaspin and omentin in patients with juvenile idiopathic arthritis, and relation to disease activity.

OBJECTIVES: Vaspin and omentin are two recently discovered adipokines that have been involved in chronic inflammatory processes. The aims of our study were to evaluate their serum levels in patients affected by juvenile idiopathic arthritis (JIA), in comparison to healthy controls, and to correlate circulating levels to parameters of disease activity. METHODS: Serum levels of omentin and vaspin were assayed by enzyme-linked immunosorbent assay in 40 patients with JIA classified according to the ILAR criteria and 26 healthy controls. RESULTS: Serum omentin levels were significantly higher in JIA patients versus healthy controls (p<0.0001) whereas serum vaspin levels did not significantly differ between the two groups. JIA children with active joints showed higher omentin serum levels than JIA children without active joints (p<0.001) and omentin serum levels significantly correlated with the presence of active joints (p<0.0001). Omentin serum levels were also significantly related with the number of active joints (p<0.002). Vaspin serum level did not show statistical significant differences between JIA children with active joints and those with no active joints. There was no correlation between plasma vaspin levels and the presence of active joints, or the number of active joints CONCLUSIONS: Our study is the first report on the new adipokines vaspin and omentin in patients with JIA, and it shows that omentin is significantly higher in JIA patients in comparison with healthy controls. In addition, we also report that omentin plasma levels are significantly correlated with the presence and the number of active joints.

Thyroid autoimmunity and type 1 diabetes in children and adolescents: screening data from Juvenile Diabetes Tuscany Regional Centre.

BACKGROUND AND AIMS: The incidence of autoimmune thyroiditis in patients with type 1 diabetes mellitus (T1DM) is higher than in healthy population. The aim of this study is to investigate epidemiology and natural history of thyroid autoimmunity (AIT), thyroiditis diagnosis and need for therapy in paediatric patients with T1DM and to find the most suitable timing of AIT screening. METHODS: T1DM patients (493 pts., 268 males and 225 females) treated in the Juvenile Diabetes Tuscany Regional Centre at Meyer's Children Hospital were enrolled to determine TSH, fT4, thyroid autoantibodies levels and to undergo thyroid ultrasound. Anamnestic data about T1DM onset, AIT onset, time frame between T1DM and AIT onsets and the relationship between AIT and celiac disease (CD) were studied. RESULTS: In the screened population 11.7% of patients presented with increased thyroid autoantibodies, and 63.6% of them showed positive thyroid ultrasound. AIT was significantly more frequent in females compared to males (p < 0.01). The mean age at AIT onset was 11.17 +/- 3.29 years (range 4.99-20, 30) and AIT onset before 12 yrs. of age was found in 54.5% of cases; 18.4% patients (all females) presented CD. The mean time between T1DM and AIT onset was 2.46 +/- 3.41 years (range 0-13, 41). The subgroup with increased thyroid autoantibodies was not statistically different from the whole population with regard to TDM1 duration and mean age at onset. CONCLUSIONS: AIT is frequently associated with T1DM (11.7%) regardless of age and duration of diabetes. We suggest a yearly screening for AIT after TDM1 onset, at every age.