Serum neutrophil gelatinase-associated lipocalin and cystatin C is associated with blood pressure in ex-preterm children and adolescents.

BACKGROUND: As preterm birth is a risk factor for hypertension (HTN), biomarkers for early prediction of HTN in childhood is an emerging need. The aims of the study were to evaluate serum biomarkers in ex-preterm children and examine for associations with office peripheral and central SBP (cSBP), ambulatory BP parameters and pulse wave velocity (PWV). METHODS: This case-control study included children and adolescents born prematurely (ex-preterms) and at full term (controls). All participants underwent office and ambulatory BP monitoring, assessment of cSBP, PWV and serum biomarkers at the same visit. Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-2, metalloproteinase-9 (MMP-2, MMP-9) and Cystatin C (CysC) were measured using ELISA. RESULTS: The study population included 52 ex-preterm individuals and 26 controls. Mean age was 10.7 ±â€Š3.6 years. NGAL, MMP-2, MMP-9, and CysC levels were similar between the ex-preterm and the control group. In the ex-preterm group, NGAL is associated with office SBP z score (ß = 1.007, 95% CI 1.001-0.014, P = 0.049), CysC with office DBP z score (ß = 1.003, 95% CI 1.001-0.005, P = 0.018) and cSBP z score (ß = 1.003, 95% CI 1.001-0.005, P = 0.006) independently of age, sex and BMI z score. Among ex-preterm children and adolescents 17% had ambulatory HTN and 31% had white-coat HTN. NGAL levels were higher in ex-preterm children with WCH compared with children with normal BP [57.9 (IQR 50.8) versus 34.6 (IQR 46.2)], P = 0.018]. CONCLUSION: WCH is common in ex-preterm children and adolescents and is associated with higher NGAL levels and CysC presents positive association with cSBP. The findings in this study provides preliminary evidence that NGAL and CysC may have a role in predicting the risk of developing hypertension later in life. Further studies are warranted.

Parents under siege: the psychological impact of COVID-19 outbreak on children's caregivers.

AIMS OF THE STUDY: It is well known that parenting stress is an important but often underestimated psychosocial variable. Data regarding the impact of the corona virus disease 2019 (COVID-19) outbreak on parental psychology are currently lacking. The aim of the present study was to assess parenting stress during the COVID-19 pandemic in Greece. METHODS: An Internet e-survey was conducted adhering to CHERRIES guidelines of the EQUATOR network and released from 16 March to 22 March 2020, using the Perceived Stress Scale (PSS) and Revised Impact of Event Scale (IES-R). A convenience sample of 1105 Greek parents of children with or without chronic or severe underlying disorders was enrolled, identified by a network of collaborating paediatricians across the country, and invited via personal emails. RESULTS: The participation rate was 91.6% and the completion rate was 100%. A total of 178 (16.1%) of the participants had children with underlying disorders (198 affected children in total). Parents of children with underlying disorders had significantly higher stress levels than those of healthy children (PSS 21.22 ± 5.06 vs 19.02 ± 6.85, p <0.001; IES-R 40.71 ± 11.58 v. 35.86 ± 12.69, p <0.001), particularly those caring for children with cardiovascular or respiratory disorders, or immunodeficiencies. The presence of children with underlying disorders was a strong predictor of PSS and IES-R scores, independently of parental sex, age, education and place of residence. CONCLUSIONS: The impact of COVID-19 outbreak on parental stress is substantial, and those caring for children with underlying disorders are more profoundly affected. Pending the global socioeconomic rebooting after the pandemic, the possible short- and long-term consequences of parental stress should not be ignored. As for other vulnerable groups, accurate health information and resources for psychological support should be provided to parents, especially those caring for children with underlying disorders.

Pediatric Pulmonary Function Testing in COVID-19 Pandemic and Beyond. A Position Statement From the Hellenic Pediatric Respiratory Society.

As the COVID-19 pandemic is still evolving, guidelines on pulmonary function testing that may dynamically adapt to sudden epidemiologic changes are required. This paper presents the recommendations of the Hellenic Pediatric Respiratory Society (HPRS) on pulmonary function testing in children and adolescents during the COVID-19 era. Following an extensive review of the relevant literature, we recommend that pulmonary function tests should be carried out after careful evaluation of the epidemiologic load, structured clinical screening of all candidates, and application of special protective measures to minimize the risk of viral cross infection. These principles have been integrated into a dynamic action plan that may readily adapt to the phase of the pandemic.

Subjective sleep-related breathing disorders and executive function in children with intermittent or mild persistent asthma.

OBJECTIVE: The impact on executive function performance of sleep-related disorders in asthmatic children has been scarcely studied in community settings. The aims of the present study were to assess the prevalence of sleep-related breathing disorders (SRBD) in children with intermittent or mild persistent asthma in primary care settings, and to examine the possible correlations with measures of executive function. METHODS: We performed a case-control study including 76 children with asthma (intermittent or mild persistent) and 85 healthy controls. The parents of both patients and controls completed the Paediatric Seep Questionnaire (PSQ) and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire. RESULTS: We did not find any statistically significant differences regarding the scales of PSQ. Additionally, there were no statistical differences between asthmatic children and controls regarding the scales of the BRIEF questionnaire. In both asthmatic children and controls the score of the scale of obstructive sleep-related breathing disorder was significantly correlated with the T scores of the two composite scales (BRI and MI) and the Global Executive Composite. CONCLUSION: In children with intermittent or mild persistent asthma under the care of private general paediatricians there were no statistically significant differences regarding subjective SBD compared to the healthy controls. Also there were no statistical differences between asthmatic children and controls regarding behavioural correlates of executive function during everyday life.

Uric Acid Associates With Executive Function in Children and Adolescents With Hypertension.

[Figure: see text].

Beware the inhaled steroids or corticophobia?

Inhaled corticosteroids have been the cornerstone of atopic, allergic asthma management for more than half a century. They have side effects (as does every medication), but they have transformed the control of asthma and saved many lives since their introduction. The current review revisits local and systemic side effects of inhaled corticosteroids and explores the prevalence and nature of parental fears (“corticophobia”) in different parts of the world. The empathetic physician treating asthma should bear in mind the impact of parental concerns on the management of this potentially life-threatening disease and try to dispel myths at every opportunity by emphasising the well-established benefits and excellent safety profile of inhaled corticosteroids.

Estimated Arterial Stiffness and Prediction of Vascular Aging: The Rising of a New Era.

Arterial stiffness has been associated with cardiovascular events and correlated with cardiovascular risk factors. In the new guidelines of the European Society of Hypertension, the evaluation of arterial stiffness, and specifically carotid-femoral pulse wave velocity (c-f PWV), was taken into account for the detailed screening of the hypertensive population. Despite the importance of arterial stiffness as a target organ damage, the measurement is time-consuming, not practical, needs expensive equipment and experienced staff. For all these reasons, c-f PWV is not recommended for the everyday clinical practice and its current use is restricted for research purposes. The importance of arterial properties in clinical practice and cardiovascular prevention is well known. Hence, the estimation of arterial stiffness and vascular health based on parameters that affect arterial stiffness, but without the use of a machine, is a new promising field. Furthermore, the relationship between age-related MRI abnormalities as well as ultrafast ultrasound with vascular effect gives a new promise for future vascular aging assessment.

Association of IL-10 gene promoter polymorphisms with food allergy susceptibility and serum IL-10 level in a pediatric Caucasian population.

BACKGROUND: Interleukin 10 has been shown to play a critical role in the regulation of the immune responses in allergic diseases. AIM: To investigate if genetic polymorphisms in the promoter region of the IL-10 gene are associated with food allergy (FA) susceptibility in Caucasian pediatric patients with concomitant allergic diseases and IL-10 levels. METHODS: The single nucleotide polymorphisms (SNPs) at -1082A > G (rs1800896), -819 T > C (rs1800871), and -592A > C (rs1800872) of 62 pediatric patients with IgE-mediated FA were analyzed and correlated with clinical parameters, serum IgE and IL-10 levels. The results were compared with those of 92 healthy controls without FA, personal and/or family history of atopy. RESULTS: Analysis and comparison of genotype distributions, allele frequencies, and haplotypes showed that none of the genotypes confers an increased risk of FA. The genotype -1082 AA in FA patients was associated with moderate to severe symptoms of FA, the development of atopic asthma, and higher levels of IL-10. In a linear regression study, we confirmed that the genotype -1082 AA acts as an independent factor for the higher levels of IL-10. A positive association was also observed between -819T/C and -592 A/C SNPs and later onset of FA. CONCLUSION: Polymorphisms in the promoter region of the IL-10 gene are not associated with FA susceptibility in our cohort. In FA patients, -1082 A/G SNPs seem to influence the production of IL-10, the severity of FA symptoms, and the development of atopic asthma in this population.

Interleukin 10: the critical role of a pleiotropic cytokine in food allergy

Despite advances in research, the pathophysiology of food allergy has not yet been fully elucidated. IL-10 has both a pro- and anti-inflammatory effect on the development of food allergy and in order to understand its different immune-modulatory effects the factors that influence the inflammatory microenvironment need to be taken into account. Specific single nucleotide polymorphisms of the IL-10 gene seem to confer an increased risk of developing food allergy, but to date there is a substantial lack of genome- wide association studies regarding the genetic and epigenetic underpinnings of the disease. Special interest has been drawn to the development of allergen-specific regulatory CD4+CD25+ T-cells secreting IL-10 in the immunotherapy of allergic diseases. In addition, a distinct population of human tolerogenic dendritic cells (DC), DC-10 seems to hold great potential and could potentially serve as a therapeutic tool to improve the management of food allergy

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Lung Function Variability in Children and Adolescents With and Without Asthma (LUV Study): Protocol for a Prospective, Nonrandomized, Clinical Trial.

BACKGROUND: Variability analysis of peak expiratory flow (PEF) and forced expiratory volume at 1 second (FEV1) has been used in research to predict exacerbations in adults with asthma. However, there is a paucity of data regarding PEF and FEV1 variability in healthy children and adolescents and those with asthma. OBJECTIVE: The objective of this study is the assessment of PEF and FEV1 variability in (1) healthy children and adolescents, to define the normal daily fluctuation of PEF and FEV1 and the parameters that may influence it, and (2) children and adolescents with asthma, to explore the differences from healthy subjects and reveal any specific variability changes prior to exacerbation. METHODS: The study will include 100 healthy children and adolescents aged 6-18 years (assessment of normal PEF and FEV1 variability) and 100 children and adolescents of the same age with diagnosed asthma (assessment of PEF and FEV1 variability in subjects with asthma). PEF and FEV1 measurements will be performed using an ultraportable spirometer (Spirobank Smart; MIR Medical International Research) capable of smartphone connection. Measurements will be performed twice a day between 7 AM and 9 AM and between 7 PM and 9 PM and will be dispatched via email to a central database for a period of 3 months. PEF and FEV1 variability will be assessed by detrended fluctuation and sample entropy analysis, aiming to define the normal pattern (healthy controls) and to detect and quantify any deviations among individuals with asthma. The anticipated duration of the study is 24 months. RESULTS: The study is funded by the "C. Caratheodory" Programme of the University of Patras, Greece (PN 47014/24.9.2018). It was approved by the Ethics Committee (decision 218/19-03-2019) and the Scientific Board (decision 329/02-04-2019) of the University Hospital of Patras, Greece. Patient recruitment started in January 2020, and as of June 2020, 100 healthy children have been enrolled (74 of them have completed the measurements). The anticipated duration of the study is 24 months. The first part of the study (assessment of lung function variability in healthy children and adolescents) will be completed in August 2020, and the results will be available for publication by October 2020. CONCLUSIONS: Healthy children and adolescents may present normal short- and long-term fluctuations in lung function; the pattern of this variability may be influenced by age, sex, and environmental conditions. Significant lung function variability may also be present in children and adolescents with asthma, but the patterns may differ from those observed in healthy children and adolescents. Such data would improve our understanding regarding the chronobiology of asthma and permit the development of integrated tools for assessing the level of control and risk of future exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04163146; https://clinicaltrials.gov/ct2/show/NCT04163146. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/20350.

Central SBP and executive function in children and adolescents with primary and secondary hypertension.

OBJECTIVES: The aims of the study were to assess executive function performance in children and adolescents with primary and secondary hypertension, and to investigate for associations with central SBP and ambulatory blood pressure. METHODS: Forty-six pediatric patients with secondary hypertension because of kidney diseases and 46 patients with primary hypertension underwent ambulatory blood pressure monitoring, pulse wave analysis, and assessment of executive function using Behavior Rating Inventory of Executive Function. Results for comparisons are presented as mean (SD). Analysis of covariance was performed to examine the effect of blood pressure parameters and hypertension cause. RESULTS: Patients with secondary hypertension had higher T scores in parent and self-reported Metacognition Indices compared with those with primary hypertension (51.2 ±â€Š8.9 vs. 47.6 ±â€Š7.5, P = 0.05 and 49.6 ±â€Š9.1 vs. 42.1 ±â€Š7.9, P = 0.001, respectively), but did not differ in Behavior Regulation Index T scores, as well as in mean arterial pressure z-score. Patients with secondary hypertension had higher central SBP z-scores (P = 0.05). Adjustment for central SBP attenuated differences in parent Metacognition Index between groups. Central SBP z-score associated with parent Metacognition (B = 0.95, 95% CI 0.02-1.87), Behavior Regulation (B = 1.14, 95% CI 0.07-2.21), and self-reported Metacognition Indices T scores (B = 1.48, 95% CI 0.39-2.56), independent of mean arterial pressure z-score, age, sex, socioeconomic status, hypertension cause, and antihypertensive treatment. CONCLUSION: Central SBP associates with executive function performance in youth with hypertension and could have complementary role to ambulatory blood pressure for identifying children at risk for adverse cognitive outcomes.

Impact of ambulatory SBP and overweight on executive function performance in children and adolescents.

BACKGROUND AND AIM: Neurocognitive impairment has recently emerged as a hypertensive target organ damage in children and adolescents. In the present study, we aimed to examine the effect of hypertension and overweight on executive function performance in youth. METHODS: The study population included 116 consecutive children and adolescents referred to our outpatient hypertension clinic who underwent ambulatory blood pressure monitoring (ABPM) and assessment of executive function by Behavior Rating Inventory of Executive Function (BRIEF). RESULTS: Children and adolescents with hypertension presented higher T scores in shift sub-scale of Behavior Regulation Index (BRI) compared with normotensives. Participants with hypertension in the ABPM also presented higher T scores in subscales of metacognition (metacognition index). Night-time SBP correlated with BRI (r = 0.21, P < 0.05) and metacognition index (r = 0.19, P < 0.05) composite scales. BMI z score also correlated with BRI (r = 0.28, P < 0.005) and metacognition index (r = 0.22, P < 0.05) scales. The associations of night-time SBP with monitor and plan/organize subscales of metacognition index remained significant after adjustment for BMI z score and socioeconomical status. However, the associations of BMI z score with monitor scale was found to be mediated by night-time SBP. In ROC curve analysis, only night-time SBP could predict impaired performance in monitor and plan/organize scales (AUC 0.68 and 0.70, respectively). CONCLUSION: Night-time SBP may predict a poor performance in domains of executive function in youth. Although overweight/obese status was negatively associated with executive performance, mediation analysis showed that not obesity per se, but BP exerted negative impact on executive performance.

Interleukin 10: the critical role of a pleiotropic cytokine in food allergy.

Despite advances in research, the pathophysiology of food allergy has not yet been fully elucidated. IL-10 has both a pro- and anti-inflammatory effect on the development of food allergy and in order to understand its different immune-modulatory effects the factors that influence the inflammatory microenvironment need to be taken into account. Specific single nucleotide polymorphisms of the IL-10 gene seem to confer an increased risk of developing food allergy, but to date there is a substantial lack of genome- wide association studies regarding the genetic and epigenetic underpinnings of the disease. Special interest has been drawn to the development of allergen-specific regulatory CD4+CD25+ T-cells secreting IL-10 in the immunotherapy of allergic diseases. In addition, a distinct population of human tolerogenic dendritic cells (DC), DC-10 seems to hold great potential and could potentially serve as a therapeutic tool to improve the management of food allergy.

Sleep disorders and executive function in children and adolescents with chronic kidney disease.

OBJECTIVE: The impact of sleep-related disorders in children and adolescents with chronic kidney disease on executive function performance has been scarcely studied. The aims of the present study were to assess the prevalence of sleep-related disorders in chronic kidney disease pediatric patients, and to examine possible correlations with measures of executive function. METHODS: We performed a case-control study including 51 children with chronic kidney disease stages 2-5, aged 5-18 years, and 51 healthy controls. The parents of both patients and controls completed the Pediatric Seep Questionnaire (PSQ), and the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire. RESULTS: Children with chronic kidney disease presented lower executive performance with higher scores in scales of executive function, and an increased risk of presenting a sleep-related disorder (odds ratio (OR) = 7.58, 95% confidence interval (CI) 2.36-24.31, p < 0.005) compared to controls. In the patient group, age of chronic kidney disease onset correlated with Behavior Regulation Index T-score (r = 0.32, p < 0.05). In multivariate analysis, differences between patients and controls for Metacognition Index T-scores did not persist after adjustment for sleep-related breathing disorder and insomnia scores, while differences in Behavior Regulation Index T-scores remained significant (54.15 vs 49.14, p < 0.02). Moreover, mediational analyses showed that sleep-related disorders mediated the effect of chronic kidney disease on metacognition, but not on behavioral regulation. CONCLUSION: Sleep-related disorders may in part explain the lower executive function performance during everyday life in chronic kidney disease pediatric patients. However, additional disease-related factors may influence executive function, especially in the domains of behavior regulation.

'They said it was bronchiolitis; is it going to turn into asthma doctor?'.

Acute bronchiolitis is a common paediatric disease of infancy. Its association with subsequent asthma development has puzzled clinicians and epidemiologists for decades. This article reviews the current state of knowledge regarding the role of acute bronchiolitis in the inception of asthma. There is little doubt that acute bronchiolitis is associated with an increased risk of recurrent wheezing throughout the primary school years although the direction of causality--i.e. whether bronchiolitis in infancy leads to asthma or it merely represents the first clinical presentation of predisposition to asthma--is uncertain. Existing evidence suggests that both host factors (e.g. prematurity, atopic predisposition) and acute viral infection characteristics (e.g. type of virus, severity) are operating in this relationship, perhaps with variable involvement in different individuals. Further clarification of these issues will help paediatricians provide evidence-based information regarding the long-term prognosis of this common disease to the families, and at the same time, it will facilitate prophylactic approaches and therapeutic strategies.

Wheezing defined.

Wheeze is both a symptom to parents (reported as noisy breathing) and a sign to clinical staff - with very differing perspectives between parents and clinicians on what constitutes "wheeze". The purpose of this article is to consider these differences of understanding from the perspective of different stakeholders so that nobody is "lost in translation". Misunderstandings may lead to epidemiologic and treatment faults. Every effort should be made to educate parents and improve their communications with clinicians.

Urinary tract infections caused by extended-spectrum betalactamase-producing bacteria in children: a matched casecontrol study.

Extended-spectrum beta-lactamase (ESBL)-producing pathogens are emerging as a cause of urinary tract infections (UTI) worldwide. In this matched-case control study, clinical characteristics and associated risk factors for ESBL UTI were evaluated. In a total of 463 positive urine cultures, 48 (10.4%) (from 39 patients, 23 boys) were phenotypically ESBL-producing bacteria. The most frequently isolated microorganism was , followed by Klebsiella spp. and Enterobacter cloacae. Children with ESBL UTI (n=39) were on prophylaxis more (21% vs. 6%, p=0.01), had higher rates of urinary tract anomalies (36% vs. 10%, p=0.0007), presented abnormal 99m Tcdimercaptosuccinic acid (DMSA) findings (i.e. scars) (23% vs. 4%, p=0.001), and had longer hospitalization (9.8 vs. 7.4 days, p=0.004) compared to those with non-ESBL UTI (n=117). The recognition of risk factors for UTI caused by ESBL bacteria in children may aid in the identification of high-risk cases and may enable proper management of these patients.

Life-threatening hyponatremia and acute renal failure due to iatrogenic neonatal bladder rupture.

Neonatal urinary ascites is a rare entity, usually associated with a spontaneous rupture of the bladder with an underlying pathology such as high pressure or wall disruption. Its presentation involves abdominal distension, metabolic derangement and respiratory compromise. We report the case of a male neonate with solitary functioning kidney presented with life-threatening persistent hyponatremia and acute renal failure due to iatrogenic bladder rupture after catheterization. The aim of our report is to raise awareness on the possibility of bladder perforation in neonates even in the absence of technical faults. We discuss the uncommon presentation of our case and highlight the need for early recognition and management of urinary ascites, addressing all subspecialties involved in diagnostic or therapeutic procedures of neonates with urinary abnormalities.