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Bronchopulmonary dysplasia (BPD) is the most common lung disease of extreme prematurity, yet mechanisms that associate with or identify neonates with increased susceptibility for BPD are largely unknown. Combining artificial intelligence with gene expression data is a novel approach that may assist in better understanding mechanisms underpinning chronic lung disease and in stratifying patients at greater risk for BPD. The objective of this study is to develop an early peripheral blood transcriptomic signature that can predict preterm neonates at risk for developing BPD. Secondary analysis of whole blood microarray data from 97 very low birth weight neonates on day of life 5 was performed. BPD was defined as positive pressure ventilation or oxygen requirement at 28 days of age. Participants were randomly assigned to a training (70%) and testing cohort (30%). Four gene-centric machine learning models were built, and their discriminatory abilities were compared with gestational age or birth weight. This study adheres to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement. Neonates with BPD ( n = 62 subjects) exhibited a lower median gestational age (26.0 wk vs. 30.0 wk, P < 0.01) and birth weight (800 g vs. 1,280 g, P < 0.01) compared with non-BPD neonates. From an initial pool (33,252 genes/patient), 4,523 genes exhibited a false discovery rate (FDR)

Since the beginning of the pandemic, many reports have pointed to age as the most important risk factor for severe COVID-19 in adults, but this relationship is less clear in children. Between March 2020 and April 2022, 1405 pediatric COVID-19 patients were included in our prospective study, which aimed to analyze the disease’s characteristics in three age groups: infants, toddlers (1–5 years), and children (5–18 years). We observed male prevalence of the disease in infants and toddlers compared to female prevalence in children. Comorbidities appeared most often in children. In the first pandemic wave, the vast majority of pediatric patients were children, but later, the percentage of infant and toddler patients increased significantly. A total of 74% of hospitalized children were younger than five years. Upper respiratory tract symptoms were most common in infants and toddlers, and lower respiratory tract symptoms and gastroenterocolitis were more common in children. Neurological symptoms appeared similarly in all age groups. The activities of ALT, CK, and LDH were the most elevated in infants, along with D-dimers. The median length of hospitalization fluctuated between three and four days and was highest in infants. Severe courses were more common in adolescents.

Supplemental Digital Content is available in the text., Background: Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation, broad-spectrum, intravenous cephalosporin, which is currently approved for the treatment of adults with hospital-acquired or community-acquired pneumonia. Methods: Noncompartmental pharmacokinetics and safety were analyzed from 2 recently completed pediatric studies, a single-dose, phase 1 study in neonates and infants up to 3 months of age (7.5 mg/kg) and a phase 3 study in patients 3 months to 17 years of age with pneumonia (10–20 mg/kg with a maximum of 500 mg per dose every 8 hours for up to 14 days). Results: Total ceftobiprole plasma concentrations peaked at the end of infusion. Half life (median ranging from 1.9 to 2.9 hours) and overall exposure (median AUC ranging from 66.6 to 173 μg•h/mL) were similar to those in adults (mean ± SD, 3.3 ± 0.3 hours and 102 ± 11.9 μg•h/mL, respectively). Calculated free-ceftobiprole concentrations in the single-dose study remained above a minimum inhibitory concentration (MIC) of 4 mg/L (fT > MIC of 4 mg/L) for a mean of 5.29 hours after dosing. In the pneumonia study, mean fT > MIC of 4 mg/L was ≥5.28 hours in all dose groups. Ceftobiprole was well tolerated in both studies. Conclusions: Pharmacokinetic parameters of ceftobiprole characterized in the pediatric population were within the range of those observed in adults. In the pneumonia study, the lowest percentage of the dosing interval with fT > MIC of 4 mg/L was 50.8%, which suggests that pharmacokinetic-pharmacodynamic target attainment can be sufficient in pediatric patients. Ceftobiprole was well tolerated.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of extreme prematurity. Despite more than 50 years of research, current treatments are ineffective, and clinicians are largely unable to accurately predict which neonates the condition will develop in. A deeper understanding of the molecular mechanisms underlying the characteristic arrest in lung development are warranted. Integrating high-fidelity technology from precision medicine approaches may fill this gap and provide the tools necessary to identify biomarkers and targetable pathways. In this review, we describe insights garnered from current studies using omics for BPD prediction and stratification. We conclude by describing novel programs that will integrate multi-omics in efforts to better understand and treat the pathogenesis of BPD. [ Pediatr Ann . 2022;51(10):e396–e404.]

Purpose Preterm birth is associated with adverse pulmonary outcomes. We aimed to evaluate respiratory morbidities and lung function of very low birth weight (VLBW) Polish children followed up at the age of 7 years old, and to compare with electrical impedance segmentography (EIS) results recorded at 4 years of age. Materials and methods VLBW children were compared with term controls using impulse oscillometry and spirometry. Perinatal data and current respiratory morbidities were analyzed and pulmonary function test results were compared with previous EIS results. Results We included 40 VLBW children and 30 controls in the analysis. Elevated total airway resistance and forced expiratory volume in the first second below the lower limit of normal were more prevalent in VLBW children compared with term controls (15 vs 0%; 18 vs 0%). A positive bronchodilator response was more common in VLBW children (R5 Hz: 46 vs 13.3%; R5–20 ​Hz: 65 vs 36.7%). Children with bronchopulmonary dysplasia (BPD) had higher total airway resistance (R5 Hz/R5 Hz pred: 1.35 vs 0.95; p ​ Conclusion VLBW school-aged children with BPD presented with substantial respiratory morbidity and persistent reduction of lung function, affecting small and large airways and lung parenchyma. EIS may be an alternative tool for lung function assessment in children with BPD.

This is a single-center, prospective study that compared the clinical presentation and laboratory findings of hospitalized children during the first five waves of the COVID-19 pandemic. Data were collected, according to a standardized questionnaire, from 1407 children from 23 March 2020 to 30 April 2022. Significant differences in clinical courses were found among the five waves probably due to different SARS-CoV-2 variants. The median age was 95.8 months in the first wave versus 14.6–23 months in the others. The number of patients with upper respiratory infection was the highest in the fifth wave (74.4% versus 43.8–56.9% in the others) and for lower respiratory infection in the first wave (50.0% versus 16.4–32.5%). Gastroenterocolitis was more common in the fifth wave (24.4% versus 8.9–16.5%); neurological diagnoses appeared more frequently in the fourth wave (16.6% versus 0.6–9.9%), while anosmia and ageusia were higher in the fifth wave (13% versus 1.5–4%). Life-threatening courses were relatively rare. However, children with pneumonia, dehydration from high fever, gastrointestinal symptoms, loss of smell and taste, and neurological symptoms required hospitalization.

Some storage diseases, caused by a deficiency of a specific enzyme, which results in the systemic accumulation of non-metabolized substances, can be treated with enzyme replacement therapy (ERT), which can protect many organs, including the endocrine system.The aim of the study was to assess the function and morphology of the thyroid gland in children with storage diseases treated with ERT, and to review the literature.Eight patients were included in the study: 3 with Fabry disease (age: 17; 9.9; 10 years), 3 with Hunter's disease (12.3; 4.1; 9,3), and 2 with Pompe disease (6.8; 9,5). Thyroid function and morphology were assessed in each patient during ERT, and 4 of them were reassessed 27 months later.One patient with Fabry disease had been treated for hypothyroidism due to autoimmune thyroiditis diagnosed before the study. The remaining patients had normal thyroid tests and negative anti-thyroid antibodies at first and second evaluation; however, in all reassessed patients a decrease in TSH value was noted. Among the remaining patients with Fabry disease, one had normal and a second had heterogeneous echogenicity of the thyroid during first assessment. In the second patient, normalisation of echogenicity was observed at reassessment. Both patients with Pompe disease assessed once had slightly heterogeneous thyroid echogenicity. In 3 patients with Hunter's disease in the first ultrasound examination, no abnormalities were found. In re-evaluation, 2 of them showed heterogeneous thyroid echogenicity.We conclude that patients with storage diseases should undergo assessment of thyroid function and morphology before and during ERT.Niektóre z chorób spichrzeniowych, spowodowanych niedoborem określonych enzymów, prowadzących do nieprawidłowego metabolizowania substratów i wtórnego gromadzenia się ich w wielu tkankach, można leczyć za pomocą enzymatycznej terapii zastępczej (ETZ), która chroni przed dysfunkcją narządów, również endokrynnych.Celem pracy była ocena funkcji i morfologii gruczołu tarczowego u dzieci z chorobami spichrzeniowymi leczonych ETZ oraz przegląd piśmiennictwa.Badaniami objęto ośmiu pacjentów: trzech pacjentów z chorobą Fabry’ego (w wieku 17; 9,9; 10 lat), trzech z chorobą Huntera (12,3; 4,1; 9,9), dwóch z chorobą Pompego (6,8; 9,5). U każdego pacjenta oceniono czynność i morfologię tarczycy w trakcie ETZ, ponadto u czterech z nich dokonano reoceny po 27 miesiącach.Jeden pacjent z chorobą Fabry’ego był leczony z powodu niedoczynności tarczycy w przebiegu autoimmunizacyjnej choroby tarczycy zdiagnozowanej przed badaniem. U wszystkich pozostałych stwierdzono prawidłowe wyniki hormonów osi tarczycowej i ujemne przeciwciała przeciwtarczycowe, jakkolwiek u wszystkich ponownie ocenianych obserwowano obniżenie poziomu TSH. U kolejnego pacjenta z chorobą Fabry’ego w badaniu ultrasonograficznym stwierdzono niejednorodność miąższu gruczołu, z jego normalizacją po 27 miesiącach. U trzeciego z nich echogeniczność tarczycy była prawidłowa w pojedynczym badaniu USG. U obu pacjentów z chorobą Pompego uwidoczniono niejednorodną echogeniczność miąższu tarczycy ze współwystępowaniem pojedynczych torbieli koloidalnych. U trzech pacjentów z chorobą Huntera w pierwszym badaniu USG nie stwierdzano żadnych nieprawidłowości, po 27 miesiącach u dwóch z nich stwierdzono niejednorodną echogeniczność miąższu tarczycy.Pacjenci z rzadkimi chorobami spichrzeniowymi powinni mieć ocenianą funkcję i morfologię tarczycy zarówno przed, jak i w trakcie ETZ.

Background: Umbilical vessels present after birth allow a unique central access for both venous and arterial catheterization, yet the catheterization complications can be misdiagnosed as the complications of prematurity per se. Methods: A prospective observational study of 41 used polyurethane umbilical catheters, both venous and arterial was conducted in a tertiary neonatal intensive care unit. The study consisted of bedside ultrasound imaging and post-removal microbiological and microstructural analysis to assess the in vivo catheters’ changes and their clinical significance. Results: The study has shown that catheters’ surface thrombosis and bacterial colonization happen more often within umbilical venous than within arterial catheters (31% vs 8% in both cases) and are inversely proportional to the patient’s gestational age (thrombosis: Me: 28 weeks vs no thrombosis: 32 weeks; p = 0.05, bacterial colonization: 27 weeks vs no colonization: 30 weeks; p = 0.013), respectively. The clots formed near the catheter’s tip are correlated with catheter’s bacterial colonization. Chemical analysis with energy dispersive spectroscopy showed a higher calcium composition in used catheters (19.89% vs 0%, p = 0.016) and structure analysis in the scanning electron microscopy proved that within hours catheters become covered with an external coating of a constant thickness, not affected by the catheterization time. Conclusion: The following observations give a better insight to the complex in vivo interactions and call for a more intense bedside-monitoring of the indwelling devices.

Background Diagnosing acute kidney injury (AKI) in preterm newborns, who are particularly susceptible to renal damage, is a serious challenge as there is no definite consensus about the diagnostic criteria. Objectives The objective of this study was to measure the values for selected urinary biomarkers and estimated glomerular filtration rate (eGFR) among a population of preterm infants with uncomplicated clinical course as well as to determine whether these markers depend on birth weight (BW), gestational age (GA), postnatal age (PNA), or gender. Material and methods The prospective study was carried out in neonatal intensive care unit (NICU). The evaluation included 57 children that were divided into 3 categories according to BW: low birth weight (LBW) - 1501-2500 g (22 infants); very low birth weight (VLBW) - 1000-1500 g (25 infants); and extremely low birth weight (ELBW) - 750-999 g (10 infants). Urine samples were collected daily between the 4th and 28th day of life for measurements of creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and human kidney injury molecule 1 (hKIM1). Results The values of the 3 urine tubular biomarkers, serum creatinine and eGFR were taken in substantially healthy preterm infants with normal kidney function at 4 time intervals during the neonatal period. Their correlations were determined and a multivariable regression analysis was carried out with respect to BW, GA, PNA, and gender. Trends of the studied markers in terms of PNA and BW were also assessed with the Jonckheere-Terpstra test. Conclusions Glomerular and tubular function in preterm neonates during the 1st month of life is significantly influenced by BW, GA, PNA, and gender.

B a c k g r o u n d: The cause of the increased risk of hypertension in children born prematurely is still unclear. The aim of this study was to analyze the results of blood pressure monitoring and the levels of variety of kidney function markers at the 40-42 weeks postmenstrual age in children born prematurely and to compare them with the values obtained from full-term newborns. The analysis of the differences in the observed parameters could be used to assess the risk of developing hypertension in preterm infants in the following years of life. M e t h o d o l o g y: Prospective cohort study included 37 children born prematurely (35 weeks of gestation) and 20 full-term newborns. The 24-hour ambulatory blood pressure measurement, serum cystatin C and thrombomodulin levels, urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentration, renal ultrasound and bioelectrical impedance were performed. R e s u l t s: Analysis of the blood pressure monitoring reveled lower values of diastolic (DBP) and mean blood pressure (MAP) in the preterm group (DBP: 47.69 ± 4.79 vs. 53.96 ± 5.3 mmHg; p0.01; MAP 64 ± 6.7 vs. 68 ± 6 mmHg; p = 0.02), however the preterm children were significantly smaller at the time of evaluation. Moreover, the pulse pressure was significantly higher in the preterm group (44 ± 7.8 vs. 39.4 ± 5.7 mmHg; p = 0.017). In the preterm group serum cystatin C level was lower (1.397 ± 0.22 vs. 1.617 ± 0.22 mg/l; p0.01) and NGAL urine concentration was higher (57 ± 84 vs 15 ± 21 ng/ml; p = 0.04). There was substantial difference in body composition between groups - the total body water was lower in the preterm group (75.6 ± 13 vs. 82 ± 8%; p = 0.015). C o n c l u s i o n: At the predicted date of birth, preterm newborns show significant differences in blood pressure profile, body weight composition, and levels of cystatin C and NGAL compared to full-term babies.

Background In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. Methods Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(−) groups, according to the development of BPD. Results Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. Conclusions BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD.

Background: The aim of the study was to analyse body composition of preterm infants fed with either breast milk or formula compared to a control group of full-term newborns. Methods: Fifty-three newborns were enrolled: a group of 34 very low birth weight (VLBW) preterm newborns subdivided into a formula-fed (n = 23; group A) and breast milk-fed (n = 11; group B) group, and a control group of 19 full-term infants (group C). Their body composition was assessed by a bioelectrical impedance analysis (BIA) either at the estimated time of birth in the VLBW group or during the 1st week of life in the full-term group. Results: There was no difference in body weight or length between any of the three studied groups. However, we discovered that fat free mass (% FFM) was lower (83.5% vs. 85.5%; p

Nurses and midwives working in neonatal units play a key role in the assessment and treatment of pain. Due to their nature of work, which is based on continuous observation of the patient, they constitute a professional group that responds to changes in the child’s general condition. Thanks to this, the physicians get information about pain intensity or the need of pain treatment, which is relevant among patients who cannot report any symptoms of pain by themselves. The aim of the study was to describe nurses’ and midwives’ basic knowledge about pain and the practice regarding procedural pain assessment and management in Polish neonatal care units. The studies were carried out among 617 nurses and midwives working in neonatal units in Poland. We collected data by using a researcher-developed questionnaire. The significance level was set at p

Introduction: Preventing pain before and during medical procedures is a basic human right, regardless of age. Painful invasive procedures are frequently performed on infants admitted to neonatal units. Aim of the study: The aim of this study was to describe current neonatal pain management in Polish neonatal units according to the opinions of physicians. Material and methods: A survey of 100 Polish neonatal units was performed. Physicians were asked to complete a researcher-developed questionnaire. The survey comprised 40 questions. The frequency of use of selected pain medicines and pain treatment according to guidelines was assessed using Likert-scale questions.Results: Seventy-six units agreed to participate in the study. Data were available from 235 physicians. Most neonatal units did not have guidelines for the treatment of pain in newborns. There was no significant correlation between theoretical knowledge and pain treatment in accordance with the guidelines (r = -0.04, p = 0.6). Pain treatment before selected procedures seems to be insufficient. The study revealed the frequent use of paracetamol before painful procedures. Before central line insertion 42% of physicians from level III units very often or often administered paracetamol. About 40% of physicians used paracetamol before chest tube insertion. Phenobarbital intravenous/per os/per rectum was the most frequently used drug (76% of respondents from level III NICU). Almost 60% of physicians did not use written guidelines for pain management, but they followed their experience. Conclusions: Despite changes in the approach to pain management in neonates and the widespread availability of recommendations, pain treatment in Polish neonatal units is still insufficient. There is a need for the education of health professionals on neonatal pain management. This study suggests that Polish neonatal units need national guidelines for pain management.

Introduction:Umbilical catheterization provides a quick yet demanding central line that can lead to complications seen nowhere else. The aim of our study was to determine whether the repeated ultrasound scanning can influence the catheterization time, prevent some of the catheter-related complications, support the decision-making process and allow prolonged catheterization in patients without an alternative central access route.Methods:A prospective observational study was performed in a tertiary neonatal intensive care unit. A total of 129 patients and 194 umbilical catheters (119 venous and 75 arterial) were analyzed with a total of 954 scans. Ultrasound screening consisted of 1) assessing the catheter tip, location, movability, and surface and 2) analyzing the catheter trajectory. The outcome variables were defined as 1) catheter dislocation and 2) associated thrombosis.Results:Dislocation of catheter throughout the whole catheterization period was observed in 68% (81/119) of UVCs and 23% (17/75) of UACs. Thrombotic complications were observed in 34.5% (41/119) of UVCs and 12% (9/75) of UACs. 1/3 of UAC-associated thrombi were visible only after catheter removal. 51% (61/119) of UVC patients and 8% (6/75) of UAC patients made a clinical decision regarding the obtained catheter image.Conclusion:Bedside ultrasound imaging of catheters supports the decision-making process related to the catheterization duration, shortening the time if abnormalities are detected and allowing a safer prolonged UC stay when an alternative central line cannot be inserted.

Purpose To assess the association between glycaemic variability (GV) and type 1 retinopathy of prematurity (ROP) in infants with birth weights of less than 1251 grams. Method A case-control study of infants with birth weights of less than 1251g who developed type 1 ROP (n=20) was conducted. Controls had a less severe ROP or no eye disease and were individually matched for gestational age and birth weight (n=40). Odds ratios of ROP were calculated based on multiple factors including oxygen exposure, respiratory support, incidence of hyperglycaemia, and GV. For glucose measurements, a continuous glucose monitoring system was used. Results There were no significant differences in gender, antenatal steroid administration, severity of illness, and Apgar score. Univariate analyses suggest increased risk for the development of type 1 ROP based on incidence of intraventricular haemorrhage (IVH) grade 3 or 4 (p=0.048), duration of oxygen exposure (p=0.003), incidence of hyperglycaemia over 150 mg/dL (p=0.01), and GV according to significantly higher standard deviation (SD) (p=0.002), coefficient of variation (CV) (p=0.001), and mean amplitude of glucose excursion (MAGE) (p=0.008). Using a multiple regression model, increased risk of type 1 ROP was only found to be associated with duration of oxygen exposure and higher GV. Conclusion Our study demonstrates a relationship between GV and the development of severe ROP.

Background: The long-term impact of extreme prematurity on cardiac structure and function has not been fully evaluated. Aims: The aim of the study was to assess cardiac condition at 11 years of age in a local cohort of extremely low birth weight (ELBW) children born between 2002 and 2004 and to compare it to a previous study in the same group at 7 years of age. Methods: Sixty-four children with ELBW (median birth weight of 890 g) and 36 children born at full term underwent echocardiography and physical examination. Results: M-mode echocardiography parameters, expressed as z-scores for body surface area (mean [SD]), showed significant differences in left ventricular end-diastolic dimension (–1.01 [0.91] vs 0.35 [0.71]; P < 0.001), left ventricular end-systolic dimension (–0.29 [0.92] vs 0.57 [0.65]; P < 0.001), aorta dimension (0.63 [1.14] vs 1.63 [1.30]; P < 0.001), and left atrial dimension (–1.75 [0.97] vs –0.01 [0.86]; P < 0.001) between the study group and controls at 11 years of age. Fractional shortening (FS) and ejection fraction (EF) were higher in the ELBW children than in their full-term counterparts (33.6 [5.5] vs 30.8 [4.34]; P = 0.009 and 0.63 [0.07] vs 0.58 [0.06]; P = 0.005, respectively) at a mean age of 11 years. Conclusions: The ELBW children had smaller hearts than full-term controls at both 7 and 11 years of age. The FS and EF were elevated in the group of 11-year-old ELBW children. We observed comparable progress in cardiac growth (approximately 20%) in premature and full-term children over a 4-year study period.

The objective of the review is to present recent updates on anaphylaxis in paediatric population worldwide. The article summarizes the results of epidemiological studies, diagnostic methods and treatments. We present a new WAO definition of anaphylaxis (2019), which broader criteria excluding dermal symptoms should facilitate faster life-saving adrenaline use. Adrenaline remains the best treatment to manage severe symptoms and to prevent biphasic reactions. There is ongoing effort to increase adrenaline use, such as modified autoinjectors, individual training, and diversified dosing. There are five independent risk factors of lethal anaphylaxis in children, including history of asthma, almost immediate onset of symptoms, unwell appearance, tachycardia and hypotension. We also report improvements in diagnostics, like component-resolved diagnostics, and novel therapies stimulating immunotolerance. We signal the development of ICD-11 with updated coding of anaphylaxis, which corresponds better to clinical observations.

The aim of the study was to assess the usefulness of serum concentrations of YKL-40/ CHI3L1 (a 40-kilodalton glycoprotein also referred to as chitinase 3 like- 1 - CHI3L1) and PIIINP (N-terminal propeptide of type III procollagen), markers of fibrosis, in the monitoring of inflammatory processes and fibrosis in children with inflammatory bowel disease (IBD).In 60 patients (41 with Crohn's disease (CD), 19 with ulcerative colitis (UC)) concentrations of investigated parameters were measured at baseline (day 0), after 3 and after 6-8 weeks of pharmacological treatment.PIIINP concentrations were significantly higher in CD patients compared to UC (baseline results: median concentrations 1013.73 vs 78.30 ng/mL; P = 0.06 for the Kruskall-Wallis test; results at 6-8 weeks: 1076.48 vs 53.10 ng/mL, P = 0.01). Fibrosis was clearly present in patients with CD and its severity increased (reflected by both YKL-40/ CHI3L1 and PIIINP concentrations) in 6-8 weeks of follow up, regardless of the treatment used during that time. In patients with UC the levels of YKL-40/CHI3L1 and PIIINP were lower at baseline and further decreased after 6-8 weeks (median concentrations were respectively: 39.5 ng/mL vs 24.7 ng/mL and 78.3 ng/mL vs 53.1 ng/mL).Fibrosis was more severe in CD than in UC patients. The marker that more accurately reflected these differences was PIIINP.

Objective: To examine the gene expression regarding pulmonary vascular disease in experimental bronchopulmonary dysplasia in young mice. Premature delivery puts babies at risk of severe complications. Bronchopulmonary dysplasia (BPD) is a common complication of premature birth leading to lifelong affection of pulmonary function. BPD is recognized as a disease of arrested alveolar development. The disease process is not fully described and no complete cure or prevention is known. The focus of interest in the search for treatment and prevention of BPD has traditionally been at airspace level; however, the pulmonary vasculature is increasingly acknowledged in the pathology of BPD. The aim of the investigation was to study the gene expression in lungs with BPD with regards to pulmonary vascular disease (PVD). Methods: We employed a murine model of hyperoxia-induced BPD and gene expression microarray technique to determine the mRNA expression in lung tissue from young mice. We combined gene expression pathway analysis and analyzed the biological function of multiple single gene transcripts from lung homogenate to study the PVD relevant gene expression. Results: There were n = 117 significantly differentially regulated genes related to PVD through down-regulation of contractile elements, up- and down-regulation of factors involved in vascular tone and tissue-specific genes. Several genes also allowed for pinpointing gene expression differences to the pulmonary vasculature. The gene Nppa coding for a natriuretic peptide, a potent vasodilator, was significantly down-regulated and there was a significant up-regulation of Pde1a (phosphodiesterase 1A), Ptger3 (prostaglandin e receptor 3), and Ptgs1 (prostaglandin-endoperoxide synthase one). Conclusion: The pulmonary vasculature is affected by the arrest of secondary alveolarization as seen by differentially regulated genes involved in vascular tone and pulmonary vasculature suggesting BPD is not purely an airspace disease. Clues to prevention and treatment may lie in the pulmonary vascular system.

Background We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. Methods A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. Results There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. Conclusion There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.

Background Retinal gene expression pattern is severely altered after exposition to hyperoxia in mice with oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity. Gene ontology and signaling pathway analyses may add new insights into a better understanding of the pathogenesis of this disease. Methods Seven-day-old C57BL/6J mice (n = 60) were exposed to 75% oxygen for 5 days and then recovered in room air. The controls (n = 60) were kept in the normoxic conditions. Retinas were harvested immediately following hyperoxia, during the phase of maximal neovascularization, and at the time of neovascularization regression. The retinal RNA samples were evaluated for gene expression using mouse gene expression microarrays. DAVID annotation tools were used for gene ontology and pathway analyses. Results The most significantly enriched signaling pathways during the neovascularization phase of OIR were: focal adhesion; ECM-receptor interaction; PI3K-Akt; oxidative phosphorylation; and Alzheimer's, Parkinson's and Huntington's disease signaling pathways. Genes involved in apoptosis, cell proliferation, cell differentiation, and immune responses were associated with neovascularization regression. Conclusions Performed analyses revealed the possible involvement of various signaling pathways in OIR pathomechanism, mostly specific to the OIR phase. Dysregulation of genes involved in oxidative phosphorylation may have an impact on neovascularization development.

Introduction: High glycemic variability is commonly observed in intensive care patients, both in pediatrics and adults. The aim of the study was to evaluate the correlation between gestational age and glycemic variability in cohort of very low birth infants. Patients and methods: A prospective, single-center, open cohort study enrolled 74 very low birth weight infants with a mean birth weight of 1066 g. Continuous glucose monitoring system (Guardian Real-Time CGM®, Medtronic, Northridge, CA, USA) was used to measure glucose levels. Spearman’s rank correlation coefficients were calculated for glycemic variability indices and gestational age. Multiple linear regression analyses were used to assess the adjusted effect of multiple glycemic variability variables. Results: The correlations between all calculated glycemic variability indices and gestational age were negative. In multiple regression analysis, all glycemic variability indices negatively correlated with gestational age and positively correlated with mean interstitial fluid glucose concentration. Conclusions: Glycemic variability in very low birth weight infants correlates with gestational age and mean glucose concentrations.