Search

Background: Obesity and cardiovascular disease (CVD) often co-exist, but the pathophysiologic mechanisms that link the two are not fully understood. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the modification of lipids within atheromatous plaques. Recently, circulating Lp-PLA2 was found to be predictive of thromboembolic episodes in adults, independently of a variety of other potential risk factors, including markers of inflammation, renal function, and hemodynamic stress. However, the function of this lipase and its importance as a biomarker in childhood obesity is much less studied. The aim of the study was to study Lp-PLA2, a non-traditional risk factor of CVD, in obese children. Methods: Sixty-seven lean [39 boys and 28 girls, mean body mass index (BMI) z-score -0.2±0.8] and 66 obese (32 boys and 34 girls, mean BMI z-score 4.4±1.2) age-matched (p=0.251) children, aged 6-12 years, were studied. BMI z-score was calculated based on the Greek BMI growth curves, and children were categorized as obese according to the Cole criteria. All children underwent physical examination and a fasting morning blood sample was obtained for glucose, insulin, lipid profile, and Lp-PLA2 assessment. Plasma concentrations of Lp-PLA2 were determined by a commercially available Lp-PLA2 enzyme-linked immunosorbent assay kit (PLAC Test), while other measurements were performed using standard methods. Results: Plasma Lp-PLA2 levels were significantly higher in obese children (322.5±77.8 ng/mL) compared with normal-weight ones (278.0±64.4 ng/mL, p<0.001). Lp-PLA2 concentrations were significantly correlated with the BMI z-score (p=0.004). Receiver operating characteristic analysis on Lp-PLA2 values resulted in significant areas under the curve (AUC) for distinguishing between obese and normal-weight groups of children (AUC, 0.726; p<0.001). Conclusions: We found significantly higher Lp-PLA2 levels in obese children than lean controls. Interestingly, they all had levels >200 ng/mL, which are considered to correlate with atherosclerosis and a high thromboembolic risk in adults. The positive correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between obesity and increased cardiovascular risk, which can be elevated even at a very young age. Measurement of Lp-PLA2 in plasma could therefore represent a further biomarker for assessing increased CVD risk in obese children and adolescents. [ABSTRACT FROM AUTHOR]

Objective: &agr;-Klotho (&agr;-KL), a protein with antiaging properties, regulates phosphate, calcium, and bone metabolism, induces resistance to oxidative stress, and may participate in insulin signaling. The role of &agr;-KL in neonates, known to be prone to metabolic disturbances and oxidative stress, is not known. The aim of this study was to evaluate circulating soluble &agr;-KL concentrations in preterm and full-term neonates and unravel possible correlations with growth, metabolism, and indices of oxidative stress. Design: Prospective study. Methods: Plasma-soluble &agr;-KL levels were determined by specific ELISA in 50 healthy neonates (25 preterm, mean (S.D.) gestational age (GA) 33.7 (1.1) weeks, and 25 full-term infants) at days 14 and 28 of life. Associations of &agr;-KL with anthropometric, metabolic parameters, and indices of oxidative stress were examined. Results: &agr;-KL levels were significantly higher in full-term than in preterm infants at both days 14 (1099 (480) pg/ml vs 884 (239) pg/ml respectively; P<0.05) and 28 (1277 (444) pg/ml vs 983 (264) pg/ml respectively; P<0.01). In both preterm and full-term infants, &agr;-KL levels increased significantly from day 14 to 28 of life (P<0.001). Circulating &agr;-KL concentrations correlated with GA (&bgr;=0.32, PZ0.001), body weight (&bgr;=0.34, P=0.001), body length (&bgr;=0.33, PZ0.001), 1,25-dihydroxy-vitamin D level (&bgr;=0.24, P!0.05), and malondialdehyde level (&bgr;=0.20, P!0.05) but not with glucose, insulin, or homeostasis model assessment index of insulin resistance values. Conclusions: Soluble &agr;-KL levels rise as GA and postnatal age advance in neonates and may have an impact on vitamin D metabolism and oxidative stress. Whether &agr;-KL may have a role in the regulation of infants' growth should be further studied. [ABSTRACT FROM AUTHOR]

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and -resource intervention to reduce antibiotic use in Greek NICUs implementing a "low-hanging fruit" approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016–06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [−45.33, −12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a "low-hanging fruit" approach. In resource-limited settings, similar targeted stewardship interventions can be applied. [ABSTRACT FROM AUTHOR]

Background: Neonatal respiratory distress syndrome (NRDS) is strongly associated with premature birth, but it can also affect term neonates. Unlike the extent of research in preterm neonates, risk factors associated with incidence and severity of NRDS in term neonates are not well studied. In this study, we examined the association of maternal and neonatal risk factors with the incidence and severity of NRDS in term neonates admitted to Neonatal Intensive Care Unit (NICU) in Cyprus. Methods: In a prospective, case-control design we recruited term neonates with NRDS and non-NRDS admitted to the NICU of Archbishop Makarios III hospital, the only neonatal tertiary centre in Cyprus, between April 2017–October 2018. Clinical data were obtained from patients' files. We used univariate and multivariate logistic and linear regression models to analyse binary and continuous outcomes respectively. Results: During the 18-month study period, 134 term neonates admitted to NICU were recruited, 55 (41%) with NRDS diagnosis and 79 with non-NRDS as controls. In multivariate adjusted analysis, male gender (OR: 4.35, 95% CI: 1.03–18.39, p = 0.045) and elective caesarean section (OR: 11.92, 95% CI: 1.80–78.95, p = 0.01) were identified as independent predictors of NRDS. Among neonates with NRDS, early-onset infection tended to be associated with increased administration of surfactant (β:0.75, 95% CI: − 0.02-1.52, p = 0.055). Incidence of pulmonary hypertension or systemic hypotension were associated with longer duration of parenteral nutrition (pulmonary hypertension: 11Vs 5 days, p < 0.001, systemic hypotension: 7 Vs 4 days, p = 0.01) and higher rate of blood transfusion (pulmonary hypertension: 100% Vs 67%, p = 0.045, systemic hypotension: 85% Vs 55%, p = 0.013). Conclusions: This study highlights the role of elective caesarean section and male gender as independent risk factors for NRDS in term neonates. Certain therapeutic interventions are associated with complications during the course of disease. These findings can inform the development of evidence-based recommendations for improved perinatal care. [ABSTRACT FROM AUTHOR]

Background: Two-dimensional (2-D) shear wave elastography is a new sonographic elastography method for noninvasive measurement of liver stiffness.Objective: The aim of this study was to establish reference values of normal liver stiffness on 2-D shear wave elastography in children.Materials and Methods: Two-dimensional shear wave elastography values were measured in 202 children with no liver disease from the neonatal period to puberty, who were divided into 4 age groups: newborns and infants, preschoolers, elementary school children and adolescents. We investigated the effects of age, depth of elastography measurement, transducer, number of measurements per child, liver size and Doppler parameters of hepatic blood flow on liver elasticity values.Results: The mean normal liver elasticity value in the study population was: 4.29±0.59  kilopascals (kPa). In neonates and infants, mean liver elasticity value was 4.63 (± 0.6) kPa, in preschoolers and elementary school children, 4.05 (± 0.57) kPa and 4.15 (± 0.52) kPa, respectively, and in adolescents, 4.39 (± 0.55) kPa. Values in neonates and infants as well as adolescents were significantly higher than in preschoolers and elementary school children (Kruskal-Wallis, P<0.001; Mann-Whitney U tests, P<0.05). There was no significant association between liver elasticity values and size of the right lobe or Doppler parameters of hepatic blood flow. Different depths and the number of elastography measurements had no effect on liver elasticity values.Conclusion: Two-dimensional shear wave elastography is achievable in a wide range of age in children. We established the reference values of normal liver stiffness on 2-D shear wave elastography in children. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic modified the epidemiology and the transmission of respiratory syncytial virus (RSV). We collected data on RSV positivity and incidence from children hospitalized in the largest tertiary paediatric hospital in Greece before (2018-2020, period A), during (2020-2021, period B), and after (2021-2023, period C) the COVID-19 lockdown. A total of 9,508 children were tested for RSV. RSV positivity (%) was 17.6% (552/3,134) for period A, 2.1% (13/629) for period B, and 13.4% (772/5,745) for period C (p < 0.001). The mean age (±SD) of RSV-positive children among the three periods was A: 5.9(±9.3), B: 13.6 (±25.3), and C: 16.7 (±28.6) months (p < 0.001). The peak of RSV epidemiology was shifted from January-March (period A) to October-December (period C). RSV in-hospital incidence per 1,000 hospitalizations in paediatric departments was A:16.7, B:1.0, and C:28.1 (p < 0.001), and the incidence in the intensive care unit was A: 17.3, B: 0.6, and C: 26.6 (p < 0.001). A decrease in RSV incidence was observed during the COVID-19 lockdown period, whereas a significant increase was observed after the lockdown. A change in epidemiological patterns was identified after the end of the lockdown, with an earlier seasonal peak and an age shift of increased RSV incidence in older children.

Background: Elevated soluble urokinase plasminogen activator receptor (suPAR) has been associated with a poor prognosis in serious infections. The aim of this study was to evaluate the clinical value of suPAR in children with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C)., Methods: Serum suPAR was measured using the suPARnostic AUTO Flex enzyme-linked immunosorbent assay in hospitalized children with COVID-19, MIS-C, bacterial pneumonia, and healthy controls., Results: A total of 211 children with a mean (±SD) age of 6.9 ± 4.96 years were tested; with COVID-19: 59 (28%), MIS-C: 36 (17%), pneumonia: 78 (37%) and healthy controls: 38 (18%). In the acute phase, the levels of suPAR (mean ± SD) were: MIS-C: 8.11 ± 2.80 ng/mL, COVID-19: 4.91 ± 1.90 ng/mL, pneumonia: 4.25 ± 1.44 ng/mL and controls: 2.09 ± 0.47 ng/mL ( P < 0.001). Children with acute COVID-19 and a severe or moderate clinical presentation had higher values than those with mild symptoms: 5.79 ± 1.58 versus 5.40 ± 1.94 versus 3.19 ± 0.73 ng/mL, respectively ( P < 0.001). In the MIS-C group, children hospitalized in the intensive care unit and in need of mechanical ventilation had higher suPAR than those who were not admitted to an intensive care unit: 9.32 ± 3.06 versus 7.13 ± 2.19 ng/mL, respectively ( P = 0.023). In children with COVID-19 or MIS-C, a correlation was detected between suPAR values and length of hospitalization ( rs = 0.418, P < 0.001)., Conclusions: The findings suggest that suPAR may be a valuable biomarker of disease severity in children with COVID-19 or MIS-C. This could facilitate the identification of children in need of intensive anti-inflammatory treatment, as it has been shown in adults with severe COVID-19., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A 3-day-old male neonate was referred to our hospital for a cardiac echocardiogram.

Mannan antigen (MA) in neonates as a marker of invasive candidemia is not well studied, although 4% of all neonatal intensive care unit admissions are attributed to Candida spp. infections. The aim of this case-control study was to evaluate the performance of MA (Platelia™ Candida AgPluskit, Bio-Rad) in neonates who had rectal Candida colonization or in non-colonized controls. We cultured 340 rectal swabs of neonates and MA was negative in 24/25 C. albicans colonized (96% specificity) and in 30/30 non-colonized neonates (100% specificity). The results indicate a high specificity of the assay, which could be useful in neonates with possible candidemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Endothelial microparticles (EMPs) act as early biomarkers of endothelial activation and damage. No studies have investigated EMPs in preterm-born individuals., Methods: Sixty-three preterm-born children and 52 children born full-term (controls) were studied. Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were measured in preterm-born children compared to controls; possible associations with cardiovascular risk factors and endothelial function parameters were also assessed., Results: Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were significantly higher in preterm-born children compared to controls (p = 0.003, p < 0.001, and p < 0.001, respectively). Preterm birth was recognized as an independent predictor of each EMP subpopulation studied; moreover, the mean pressure and velocity of pulmonary artery were independently correlated with CD62E(+) (β = 0.20, p = 0.04) and CD144(+) EMPs (β = 0.22, p = 0.02), respectively, whereas age (β = 0.21, p = 0.03) and being born SGA (β = 0.26, p = 0.01) correlated independently with CD31(+)/CD42b(-) EMPs in the study population. Furthermore, diastolic blood pressure (β = 0.24, p = 0.04), being born SGA (β = 0.24, p = 0.04) and the hyperemic peak velocity of the brachial artery (β = -0.65, p = 0.02) were independently associated with CD31(+)/CD42b(-) EMPs in the preterm-born group., Conclusion: Circulating EMPs were higher in preterm-born children compared to children born full-term. Whether EMPs could act, in clinical practice, as a complementary tool for non-invasive evaluation of endothelium in preterm-born children, remains under investigation., Impact: Circulating endothelial microparticles (EMPs) are small membrane vesicles released from endothelial cells and they act as novel biomarkers of endothelial activation and damage. No studies have investigated circulating EMPs in preterm-born individuals. Circulating EMPs were significantly higher in prepubertal preterm-born children compared to children born at term. In the preterm-born group, the hyperemic peak velocity of the brachial artery was independently associated with CD31(+)/CD42b(-) EMPs. Whether assessment of circulating EMPs could act, in clinical practice, as a complementary tool for non-invasive evaluation of endothelium in preterm-born children, remains to be defined in future investigations., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Endothelial progenitor cells (EPCs) ensure vascular integrity and neovascularization. No studies have investigated EPCs in preterm-born children beyond infancy., Methods: One hundred and thirty-six prepubertal children were enrolled: 63 preterm and 73 born at term (controls). Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were measured in preterm-born children compared to controls. Body mass index (BMI), waist-to-hip ratio (WHR), neck circumference, systolic and diastolic blood pressure (SBP and DBP, respectively), fasting glucose, insulin, lipid profile, common carotid and abdominal aortic intima-media thickness (cIMT and aIMT, respectively), endothelium-dependent brachial artery flow-mediated dilation (FMD), and echocardiographic parameters were also assessed., Results: Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were significantly higher in preterm-born children compared to controls (p < 0.001 and p < 0.001, respectively). In total study population and in the preterm-born group, EPCs were significantly lower in children born to mothers with gestational diabetes compared to non-diabetic mothers. Prematurity was associated with higher WHR, neck circumference, SBP, DBP, cIMT, aIMT, mean pressure, and velocity of pulmonary artery; the peak velocity of the brachial artery was significantly lower in children born prematurely. In multiple regression analysis, preterm birth and maternal gestational diabetes were recognized as independent predictors of EPCs., Conclusions: Circulating EPCs were increased in prepubertal preterm-born children in comparison with peers born full-term. Maternal gestational diabetes was associated with a decrease in EPCs., Impact: Mounting evidence supports the adverse effect of prematurity on cardiovascular health. However, the underlying mechanisms that could lead to endothelial dysfunction in preterm-born individuals are not fully understood. Endothelial progenitor cells (EPCs) ensure vascular integrity, normal endothelial function and neovascularization. No studies have investigated the EPCs counts in peripheral blood beyond infancy in children born prematurely. Circulating EPCs were significantly higher in preterm-born prepubertal children compared to controls, thus indicating that prematurity is possibly associated with endothelial damage. In total study population and in the preterm-born group, maternal gestational diabetes was associated with decreased EPCs concentrations., (© 2020. International Pediatric Research Foundation, Inc.)

The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1 year, with possible CNS infection and CSF pleocytosis (> 15 cells/mm 3 ). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value < 0.001). In aseptic meningitis cases a virus was detected in 27/61(44.2%) and in 11/66(16.7%) controls (P value < 0.001). Median (IQR) length of stay in cases and controls with aseptic meningitis was 5(4-8) and 8(6-10) days, respectively (P value < 0. 001). The median (IQR) duration of antimicrobials in cases and controls was 4(2-5.7) and 7(5-10) days, respectively (P value < 0.001). The hospitalization cost was calculated in cases and controls 1042€ (932-1372) and 1522€ (1302-1742), respectively (P value < 0.001). The use of FA-ME was able to reduce significantly the use of antimicrobials, the hospitalization days, and the total cost comparing to the control group in children with suspected CNS infection.

The recent economic crisis has been linked with declines in population health. Evidence on the impact of the crisis on stillbirth rates is scarce. The aim of this study was to assess trends of stillbirth rates in Greece during the pre-crisis (2004-2008) and crisis period (2009-2015) and explore risk factors. Nationwide data (n = 1,276,816 births; 5023 stillbirths) were used to assess rates and trends through Poisson and joinpoint regressions. Multivariable Poisson regressions by nationality were fitted. The overall annual stillbirth rate was 3.9/1000 births with higher rates among non-Greeks (5.0/1000) than Greeks (3.7/1000). Non-significant decreasing trends were noted for Greeks (- 0.5%, 95% confidence interval [CI] - 1.4, 0.4%) versus non-significant increasing trends in non-Greeks (1.4%, 95% CI - 0.5, 3.3%). After adjusting for possible confounders, the relative stillbirth risk (RR) increased during the crisis versus the pre-crisis period (RR Greeks 1.61, 95% CI 1.50, 1.74; RR non-Greeks 1.92, 95% CI 1.64, 2.26). Multiplicity, birth order, birth size, maternal education, marital status, and parental age were risk factors.Conclusions: Bidirectional stillbirth trends were observed among Greeks and non-Greeks, whereas the RR increased by 2-fold during the crisis. Persisting disparities require tailored employment of preventive measures ensuring optimal quality of the child's and maternal health.What is Known:• Stillbirth rate is a key population health indicator reflecting economic development and health care services within a population.• The recent economic crisis has been linked with declines in population health.What is New:• Economic crisis, ethnic minorities, and several modifiable factors seem to be significant determinants of stillbirth risk.

Objective: To determine if preterm birth is associated with components of the metabolic syndrome in adult life., Study Design: A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18 years of age) born preterm (<37 weeks of gestation) compared with adults born at term (37-42 weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data., Results: Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P = .03), SBP (P < .0001), DBP (P < .0001), 24-hour SBP (P < .001), and 24-hour DBP (P < .001). Furthermore, preterm-born adults presented higher values of fasting glucose (P = .01), insulin (P = .002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P = .05), and total cholesterol levels (P = .05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied., Conclusions: Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life., (Copyright © 2019 Elsevier Inc. All rights reserved.)