Performance and safety of the PRICO closed-loop oxygen saturation targeting system in neonates: pragmatic multicentre cross-over study (TarOx Study).

OBJECTIVE: This study aims to evaluate the performance of the fabian-Predictive-Intelligent-Control-of-Oxygenation (PRICO) system for automated control of the fraction of inspired oxygen (FiO2). DESIGN: Multicentre randomised cross-over study. SETTING: Five neonatal intensive care units experienced with automated control of FiO2 and the fabian ventilator. PATIENTS: 39 infants: median gestational age of 27 weeks (IQR: 26-30), postnatal age 7 days (IQR: 2-17), weight 1120 g (IQR: 915-1588), FiO2 0.32 (IQR: 0.22-0.43) receiving both non-invasive (27) and invasive (12) respiratory support. INTERVENTION: Randomised sequential 24-hour periods of automated and manual FiO2 control. MAIN OUTCOME MEASURES: Proportion (%) of time in normoxaemia (90%-95% with FiO2>0.21 and 90%-100% when FiO2=0.21) was the primary endpoint. Secondary endpoints were severe hypoxaemia (<80%) and severe hyperoxaemia (>98% with FiO2>0.21) and prevalence of episodes ≥60 s at these two SpO2 extremes. RESULTS: During automated control, subjects spent more time in normoxaemia (74%±22% vs 51%±22%, p<0.001) with less time above and below (<90% (9%±8% vs 12%±11%, p<0.001) and >95% with FiO2>0.21 (16%±19% vs 35%±24%) p<0.001). They spent less time in severe hyperoxaemia (1% (0%-3.5%) vs 5% (1%-10%), p<0.001) but exposure to severe hypoxaemia was low in both arms and not different. The differences in prolonged episodes of SpO2 were consistent with the times at extremes. CONCLUSIONS: This study demonstrates the ability of the PRICO automated oxygen control algorithm to improve the maintenance of SpO2 in normoxaemia and to avoid hyperoxaemia without increasing hypoxaemia.

No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients.

A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.

Effect of Pre- and Perinatal Factors and Infant Nutrition on the Intestinal Microbiota.

The intestinal microbiota is an essential determinant of human health [...].

Association of the rs3039851 Insertion/Deletion in the Gene PPP3R1, Which Encodes the Regulatory Calcineurin Subunit B Type 1, with Left Ventricular Mass in Polish Full-Term Newborns.

BACKGROUND: The five base-pair (bp) insertion/deletion (rs3039851) polymorphism in the PPP3R1 gene, which encodes calcineurin subunit B type 1, has been found to be associated with left ventricular hypertrophy (LVH) in hypertensive patients and in athletes. The aim of this study is to analyze the possible association between PPP3R1:rs3039851 polymorphism and left ventricular mass (LVM) in full-term healthy newborns. METHODS: The study group consisted of 162 consecutive, full-term, healthy newborns. Two-dimensional M-mode echocardiography was used to assess LVM. The PPP3R1:rs3039851 polymorphism was identified by PCR-RFLP in genomic DNA extracted from cord blood leukocytes. RESULTS: No significant differences were found between newborns homozygous for the reference allele (5I/5I, n = 135) and newborns carrying at least one 5D allele (n = 27) for LVM standardized for body mass, body length or body surface area (LVM/BM, LVM/BL or LVM/BSA, respectively). However, the frequency of PPP3R1:rs3039851 genotypes with a 5D allele (5I/5D + 5D/5D) among newborns with the largest LVM/BM or LVM/BSA (upper tertile) was statistically significantly higher compared with the prevalence in individuals with the lowest values of both indices (lower tertile). CONCLUSIONS: Our results suggest that the PPP3R1:rs3039851 polymorphism may contribute to subtle variation in left ventricular mass at birth.

Analysis of Fecal Short-Chain Fatty Acids (SCFAs) in Healthy Children during the First Two Years of Life: An Observational Prospective Cohort Study.

Short-chain fatty acids (SCFAs) are important metabolites of the gut microbiota. The aim is to analyze the influence of perinatal factors, which can affect the gut microbiota, on the concentrations of fecal SCFAs over the first two years of life. Gas chromatography was used to analyze SCFA in a total of 456 fecal samples from 86 children. Total SCFA concentrations increased until 12 months and stabilized after that. Antibiotic treatment during pregnancy was associated with an increase in acetic acid, propionic acid and total SCFA in meconium and a decrease in the same SCFAs at 6 months. Butyric acid was increased after Caesarean delivery until 1 month. In formula-fed children, propionic acid (at 1 month) and butyric acid and total SCFA (at 12 months) were increased. Acetic and linear butyric acids and total SCFAs were also increased at 12 months in children born vaginally that were also formula-fed. Higher butyric acid was observed in children of mothers with normal pre-pregnancy weight and adequate weight gain during pregnancy. Butyric acid was also elevated in 6-month-old infants with a higher body weight (≥85th percentile). Acetic acid concentrations were significantly higher in 2-year-old females vs. males. We conclude that perinatal factors are linked to changes in fecal SCFAs and further long-term epidemiological studies are warranted.

Analysis of the Influence of Pre-Pregnancy BMI and Weight Gain during Pregnancy on the Weight of Healthy Children during the First 2 Years of Life: A Prospective Study.

BACKGROUND: Increased pre-pregnancy maternal BMI (pBMI) and gestational weight gain (GWG) have been found to increase infants' birthweight and result in the programming of child weight and impact its later weight gain. AIM: To assess the impact of pBMI and GWG on the weight of children from birth to 2 years of age and over the duration of breastfeeding. METHODS: Single Centre observational prospective longitudinal cohort study. Data were collected from medical records, and medical history. The analysis of multiple linear and mixed models was involved. FINDINGS: 20% of females were overweight, while 13% were obese before the pregnancy. An overall model, including gender and smoking, indicated a significant impact of pBMI category on a child's birth mass (p = 0.01). The GWG category affected a child's birth weight (p = 0.018, Effect size 0.41). pBMI did not affect the breastfeeding duration. CONCLUSION: pBMI and GWG correlate with birth weight and weight in neonatal period, however they become insignificant in later childhood. Weight assessment methods among children aged up to two years of age require standardization. Maternal weight before the pregnancy nor the weight gain during the pregnancy do not influence the length of breastfeeding. The biggest limitation was the small sample size and the failure to account for weight gain per trimester of pregnancy. Further research on a larger population should be continued.

Adverse Neonatal Outcome of Pregnancies Complicated by Preeclampsia.

Despite many available treatments, infants born to preeclamptic mothers continue to pose a serious clinical problem. The present study focuses on the evaluation of infants born to preeclamptic mothers for the occurrence of early-onset complications and attempts to link the clinical status of such infants to the angiogenesis markers in maternal blood (sFlt-1, PlGF). The study included 77 newborns and their mothers diagnosed with preeclampsia. The infants were assessed for their perinatal outcomes, with an emphasis on adverse neonatal outcomes such us infections, RDS, PDA, NEC, IVH, ROP, or BPD during the hospitalization period. The cutoff point was established using the ROC curve for the occurrence of any adverse neonatal outcome and it was 204 for the sFlt-1/PlGF and 32 birth week with AOC 0.644 and 0.91, respectively. The newborns born to mothers with high ratios had longer hospitalization times and, generally, were more frequently diagnosed with any of the aforementioned adverse neonatal outcomes. Also, the neonates born prior to or at 32 wkGA with higher sFlt-1/PlGF ratios were statistically significantly more common to be diagnosed with any of the adverse neonatal outcomes compared to those with lower ratio born prior to or at 32 wkGA. The sFlt-1/PlGF ratio can be a useful tool in predicting short-term adverse neonatal outcomes. Infants born after a full 33 weeks gestation developed almost no severe neonatal complications. Appropriate screening and preventive healthcare for preeclampsia can contribute significantly to reducing the incidence of neonatal complications.

Breastfeeding Affects Concentration of Faecal Short Chain Fatty Acids During the First Year of Life: Results of the Systematic Review and Meta-Analysis.

Short chain fatty acids (SCFAs) are important metabolites of the gut microbiota. It has been shown that the microbiota and its metabolic activity in children are highly influenced by the type of diet and age. Our aim was to analyse the concentration of fecal SCFAs over two years of life and to evaluate the influence of feeding method on the content of these compounds in feces. We searched PubMed/MEDLINE/Embase/Ebsco/Cinahl/Web of Science from the database inception to 02/23/2021 without language restriction for observational studies that included an analysis of the concentration of fecal SCFAs in healthy children up to 3 years of age. The primary outcome measures-mean concentrations-were calculated. We performed a random-effects meta-analysis of outcomes for which ≥2 studies provided data. A subgroup analysis was related to the type of feeding (breast milk vs. formula vs. mixed feeding) and the time of analysis (time after birth). The initial search yielded 536 hits. We reviewed 79 full-text articles and finally included 41 studies (n = 2,457 SCFA analyses) in the meta-analysis. We found that concentrations of propionate and butyrate differed significantly in breastfed infants with respect to time after birth. In infants artificially fed up to 1 month of age, the concentration of propionic acid, butyric acid, and all other SCFAs is higher, and acetic acid is lower. At 1-3 months of age, a higher concentration of only propionic acid was observed. At the age of 3-6 months, artificial feeding leads to a higher concentration of butyric acid and the sum of SCFAs. We concluded that the type of feeding influences the content of SCFAs in feces in the first months of life. However, there is a need for long-term evaluation of the impact of the observed differences on health later in life and for standardization of analytical methods and procedures for the study of SCFAs in young children. These data will be of great help to other researchers in analyzing the relationships between fecal SCFAs and various physiologic and pathologic conditions in early life and possibly their impact on health in adulthood.

Protocol for a multicenter, double-blind, randomized, placebo-controlled phase III trial of the inhaled ß2-adrenergic receptor agonist salbutamol for transient tachypnea of the newborn (the REFSAL trial).

Background: Transient tachypnea of the newborn (TTN), which results from inadequate absorption of fetal lung fluid, is the most common cause of neonatal respiratory distress. Stimulation of ß-adrenergic receptors enhances alveolar fluid absorption. Therefore, the ß2-adrenergic receptor agonist salbutamol has been proposed as a treatment for TTN. This study aims to evaluate the efficacy and safety of salbutamol as supportive pharmacotherapy together with non-invasive nasal continuous positive airway pressure (NIV/nCPAP) for the prevention of persistent pulmonary hypertension of the newborn (PPHN) in infants with TTN. Methods and analysis: This multicenter, double-blind, phase III trial will include infants with a gestational age between 32 and 42 weeks who are affected by respiratory disorders and treated in eight neonatal intensive care units in Poland. A total of 608 infants within 24 h after birth will be enrolled and randomly assigned (1:1) to receive nebulized salbutamol with NIV or placebo (nebulized 0.9% NaCl) with NIV. The primary outcome is the percentage of infants with TTN who develop PPHN. The secondary outcomes are the severity of respiratory distress (assessed with the modified TTN Silverman score), frequency of need for intubation, duration of NIV and hospitalization, acid-base balance (blood pH, partial pressure of O2 and CO2, and base excess), and blood serum ionogram for Na+, K+, and Ca2+. Discussion: The Respiratory Failure with Salbutamol (REFSAL) study will be the first clinical trial to evaluate the efficacy and safety of salbutamol in the prevention of persistent pulmonary hypertension in newborns with tachypnea, and will improve short term outcomes. If successful, the study will demonstrate the feasibility of early intervention with NIV/nCPAP together with nebulized salbutamol in the management of TTN. Ethics and dissemination: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland on November 16, 2020 (decision number KB/190/2020). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. Clinical Trial Registration: It is registered at ClinicalTrials.gov NCT05527704, EudraCT 2020-003913-36; Protocol version 5.0 from 04/01/2022.

The gut microbiota is associated with the small intestinal paracellular permeability and the development of the immune system in healthy children during the first two years of life.

BACKGROUND: The intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing an important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scarce. METHODS: We analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. RESULTS: Zonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after childbirth and began to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first 2 years of life and were correlated with zonulin and calprotectin levels. Faecal calprotectin correlated inversely with alpha diversity (Shannon index, r = - 0.30, FDR P (Q) = 0.039). It also correlated with seven taxa; i.a. negatively with Ruminococcaceae (r = - 0.34, Q = 0.046), and Clostridiales (r = - 0.34, Q = 0.048) and positively with Staphylococcus (r = 0.38, Q = 0.023) and Staphylococcaceae (r = 0.35, Q = 0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r = - 0.52, Q = 0.0004), Clostridiales (r = 0.48, Q = 0.001) and the Ruminococcus (torques group) (r = 0.40, Q = 0.026). When time intervals were considered only changes in abundance of the Ruminococcus (torques group) were associated with changes in calprotectin (ß = 2.94, SE = 0.8, Q = 0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (ß = - 4.54, SE = 1.08, Q = 0.028) and Clostridium acetobutylicum fermentation (ß = - 4.48, SE = 1.16, Q = 0.026). CONCLUSIONS: The small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first 2 years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required.

'Dr. Google, is caesarean section good for me?' - the global Internet searches associated with mode of birth methods: Retrospective analysis of Google trends data.

OBJECTIVE: We investigated Google queries in the years 2004-2019 as related to mode of birth methods in scope of global and local popularity, secular trends, and associations with real-world data. DESIGN: We retrieved data from Google Trends (GT) over time and regional interest in (n = 9) topics related to birth. We calculated the interest of all the topics in proportion to the Relative Search Volume (RSV) of 'Caesarean section'"(CS). We retrieved WHO data on the CS rate and the World Bank data on the fertility rate. We analysed secular trends. FINDINGS: Globally, the highest popularity was observed for these topics: 'Childbirth' (6.93 [times higher than CS]), 'Caesarean section' (1.00), and 'Preterm birth' (0.59). The regional RSV of 'Caesarean section' was associated with the real CS rate (r = 0.29; p = 0.016) and the interest in 'Childbirth' was associated with the regional fertility rate (r = 0.48; p < 0.001). Globally, the most dynamic rate of increase of interest was observed for 'Vaginal delivery' (+4.96 RSV/year) and 'Caesarean section' (+4.88 RSV/year), while a decrease was noted only for 'Home birth' (-3.04 RSV/year) and 'Water birth' (-1.84 RSV/year). CONCLUSIONS: The interest of Google users in most of the birth-related topics increased over time and is associated with real-world data. Using GT may provide insight into the interest of Google users regarding different birth-related matters. IMPLICATION FOR PRACTICE: Health professionals should be active in e-discourse to provide reliable information and recommend trustworthy websites to women and those who support them.

The Effect of Probiotics and Synbiotics on Risk Factors Associated with Cardiometabolic Diseases in Healthy People-A Systematic Review and Meta-Analysis with Meta-Regression of Randomized Controlled Trials.

We aimed to systematically review the effectiveness of probiotic/synbiotic formulations to counteract cardiometabolic risk (CMR) in healthy people not receiving adjunctive medication. The systematic search (PubMed/MEDLINE/Embase) until 1 August 2019 was performed for randomized controlled trials in >20 adult patients. Random-effect meta-analysis subgroup and meta-regression analysis of co-primary (haemoglobin A1c (HbA1C), glucose, insulin, body weight, waist circumference (WC), body mass index (BMI), cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and blood pressure) and secondary outcomes (uric acid, plasminogen activator inhibitor-1-PAI-1, fibrinogen, and any variable related to inflammation/endothelial dysfunction). We included 61 trials (5422 persons). The mean time of probiotic administration was 67.01 ± 38.72 days. Most of probiotic strains were of Lactobacillus and Bifidobacterium genera. The other strains were Streptococci, Enterococci, and Pediococci. The daily probiotic dose varied between 106 and 1010 colony-forming units (CFU)/gram. Probiotics/synbiotics counteracted CMR factors (endpoint data on BMI: standardized mean difference (SMD) = -0.156, p = 0.006 and difference in means (DM) = -0.45, p = 0.00 and on WC: SMD = -0.147, p = 0.05 and DM = -1.21, p = 0.02; change scores on WC: SMD = -0.166, p = 0.04 and DM = -1.35, p = 0.03) in healthy persons. Overweight/obese healthy people might additionally benefit from reducing total cholesterol concentration (change scores on WC in overweight/obese: SMD: -0.178, p = 0.049). Poor quality of probiotic-related trials make systematic reviews and meta-analyses difficult to conduct and draw definite conclusions. "Gold standard" methodology in probiotic studies awaits further development.

The Effect of Probiotics on Symptoms, Gut Microbiota and Inflammatory Markers in Infantile Colic: A Systematic Review, Meta-Analysis and Meta-Regression of Randomized Controlled Trials.

Immaturity in digestive-tract motor function and altered intestinal microbiome may play roles in pathogenesis of infantile colic. We assessed the impact of probiotic therapy on crying duration day, in newborns experiencing colic attacks. The PubMed, Embase, Cinnahl, Web of Science databases, and a clinical trials registry (ClinicalTrials.gov) were searched from inception until 12/02/2020. Random-effects meta-analyses were used to derive standardized mean differences/differences in means and risk ratios. We included 16 studies, which involved 1319 newborns aged up to 6 months. Lactobacillus reuteri strain DSM17938 was administered predominantly (n = 10). Probiotic intervention reduced the duration of crying (standardized mean difference = -2.012, 95% confidence interval: -2.763 to -1.261, z = -5.25, p < 0.0001). The probability of at least a 50% reduction in crying duration was at least 1.98 times higher in the intervention group than in controls (Z = 4.80, p < 0.0001). The effects of the intervention were not significantly affected by the risk of bias assessment, percentage of breastfed infants, and duration of the study. In 11 studies, data concerning gut microbiota composition and function and/or immunological markers were given. Probiotics significantly shortened the crying duration, but a causal relationship between the modulatory effect of probiotics on microbiota and the immune system has not been confirmed.

Replication study of four keloid-associated polymorphisms in patients of European descent - a single centre study.

Keloid is defined as a benign dermal fibro-proliferative growth that extends outside the original wound and invades adjacent dermal tissue. Its pathogenesis is complex and much evidence suggests the influence of genetic factors, including the rs873549, rs1511412, rs940187 and rs8032158 polymorphisms associated with keloid risk in Japanese patients. The aim of our study was to investigate possible associations between rs873549, rs1511412, rs940187 and rs8032158 variants and the risk of keloid in Polish patients of European descent. The genetic polymorphisms were identified by sequencing genomic DNA extracted from peripheral blood leukocytes from 86 keloid patients and from newborn cord blood leukocytes from 100 newborns as a control group. No significant differences (p > 0.05) in the distributions of rs873549, rs1511412, rs940187 and rs8032158 alleles were found between keloid patients and newborn controls (26.7% vs. 25.5%, 9.9% vs.7.0%, 19.8% vs. 12.5%, and 41.9% vs. 33.5%, respectively). Logistic regression with adjustment for gender revealed that only the CC homozygous genotype of rs8032158 polymorphism was significantly more frequent in keloid patients as compared with controls (19.8% vs. 11.0%, respectively). Our results suggest that in contrast to Asian populations only the rs8032158 polymorphism at locus 15q21.3 is associated with the susceptibility to keloid scarring in patients of European descent.

Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study.

Factors affecting the intestinal-barrier permeability of newborns, such as body mass index (BMI), nutrition and antibiotics, are assumed to affect intestinal-barrier permeability in the first two years of life. This study assessed 100 healthy, full-term newborns to 24 months old. Faecal zonulin/calprotectin concentrations were measured at 1, 6, 12, 24 months as gut-permeability markers. Zonulin concentrations increased between 1 and 12 months (medians: 114.41, 223.7 ng/mL; respectively), whereas calprotectin concentrations decreased between one and six months (medians: 149. 29, 109.28 µg/mL); both then stabilized (24 months: 256.9 ng/mL zonulin; 59.5 µg/mL calprotectin). In individual children, high levels at one month gave high levels at older ages (correlations: calprotectin: between 1 and 6 or 12 months: correlation coefficient (R) = 0.33, statistical significance (p) = 0.0095; R = 0.28, p = 0.032; zonulin: between 1 and 24 months: R = 0.32; p = 0.022, respectively). Parameters which gave marker increases: antibiotics during pregnancy (calprotectin; six months: by 80%, p = 0.038; 12 months: by 48%, p = 0.028); vaginal birth (calprotectin: 6 months: by 140%, p = 0.005); and > 5.7 pregnancy-BMI increase (zonulin: 12 months: by 74%, p = 0.049). Conclusions: "Closure of the intestines" is spread over time and begins between the sixth and twelfth month of life. Antibiotic therapy, BMI increase > 5.7 during pregnancy and vaginal birth are associated with increased intestinal permeability during the first two years of life. Stool zonulin and calprotectin concentrations were much higher compared with previous measurements at older ages; clinical interpretation and validation are needed (no health associations found).

Two Functional TP53 Genetic Variants and Predisposition to Keloid Scarring in Caucasians.

INTRODUCTION: Keloid is defined as a benign proliferative scar that grows beyond the confines of the original insult to the skin, invading into adjacent normal tissue. The pathogenesis of keloid is complex, and many evidences suggest the influence of genetic factors, among them the polymorphisms of the TP53 gene encoding tumor protein p53. OBJECTIVE: To investigate the association of rs1042522 (c.215G>C, p.Arg72Pro) and rs17878362 (16-bp insertion/duplication in intron 3) variants, two most frequently analyzed TP53 functional polymorphisms and the risk of keloid in Polish patients. MATERIALS AND METHODS: The rs1042522 and rs17878362 polymorphisms were identified by sequencing genomic DNA extracted from peripheral blood leukocytes of 86 keloid patients and from cordial blood leukocytes of 100 newborn infants consisting control group. RESULTS: The rs1042522 and rs17878362 TP53 genotype distributions both in keloid patients and in the control group conformed to the expected Hardy-Weinberg equilibrium. No significant differences in the distribution of rs1042522 and rs17878362 TP53 alleles or genotypes have been found between keloid patients and newborn controls. There is tight, but not complete, linkage disequilibrium between rs1042522 and rs17878362 TP53 polymorphisms (D' = 0.667, r = 0.448, and p=0). No significant differences in the distribution of rs1042522 and rs17878362 TP53 haplotypes or diplotypes have been found between keloid patients and newborn controls. CONCLUSIONS: Our results suggest the lack of association of rs1042522 and rs17878362 TP53 polymorphisms and their haplotypes or diplotypes with the susceptibility to keloid scarring in Polish patients.

The Influence of Maternal-Foetal Parameters on Concentrations of Zonulin and Calprotectin in the Blood and Stool of Healthy Newborns during the First Seven Days of Life. An Observational Prospective Cohort Study.

BACKGROUND: It can be hypothetically assumed that maternal and perinatal factors influence the intestinal barrier. METHODS: The study was conducted with 100 healthy, full-term newborns breastfed in the first week of life, with similar analyses for their mothers. Zonulin and calprotectin levels were used as intestinal permeability markers. RESULTS: The median (range) zonulin concentrations (ng/mL) were in mothers: serum, 21.39 (6.39⁻57.54); stool, 82.23 (42.52⁻225.74); and newborns: serum cord blood, 11.14 (5.82⁻52.34); meconium, 54.15 (1.36⁻700.65); and stool at age seven days, 114.41 (29.38⁻593.72). Calprotectin median (range) concentrations (µg/mL) in mothers were: stool, 74.79 (3.89⁻211.77); and newborns: meconium, 154.76 (6.93⁻8884.11); and stool at age seven days 139.12 (11.89⁻627.35). The use of antibiotics during pregnancy resulted in higher zonulin concentrations in umbilical-cord serum and calprotectin concentrations in newborn stool at seven days, while antibiotic therapy during labour resulted in higher zonulin concentrations in the stool of newborns at seven days. Zonulin concentrations in the stool of newborns (at seven days) who were born via caesarean section were higher compared to with vaginal birth. With further analyses, caesarean section was found to have a greater effect on zonulin concentrations than prophylactic administration of antibiotics in the perinatal period. Pregnancy mass gain >18 kg was associated with higher calprotectin concentrations in maternal stool. Body Mass Index (BMI) increase >5.7 during pregnancy was associated with decreased zonulin concentrations in maternal stool and increased calprotectin concentrations in stool of mothers and newborns at seven days. There was also a negative correlation between higher BMI increase in pregnancy and maternal zonulin stool concentrations and a positive correlation between BMI increase in pregnancy and maternal calprotectin stool concentrations. CONCLUSION: Maternal-foetal factors such as caesarean section, antibiotic therapy during pregnancy, as well as change in mother's BMI during pregnancy may increase intestinal permeability in newborns. Changes in body mass during pregnancy can also affect intestinal permeability in mothers. However, health consequences associated with increased intestinal permeability during the first days of life are unknown. Additionally, before the zonulin and calprotectin tests can be adopted as universal diagnostic applications to assess increased intestinal permeability, validation of these tests is necessary.

The Use of Noninvasive Ventilation with High Frequency in Newborns-A Single-Center Experience.

OBJECTIVE: The aim of the study is to evaluate the efficacy of noninvasive high-frequency ventilation (nHFV) in respiratory-deficient infants. STUDY DESIGN: Retrospective analysis of 32 cases of nHFV in 30 term (n = 4) and preterm (n = 26) newborns using a noninvasive ventilation (NIV) device. nHFV avoided intubation of children performed with NIV and reintubation after long-term mechanical ventilation (MV). Patients were divided into three groups: Group 1: NIV from birth (n = 18, mean birth weight [BW]: 1,987 g, gestational age [GA]: 33.1 weeks); Group 2: MV, also used temporarily, and NIV (n = 10, BW: 1,074 g, GA: 28.2 weeks); and Group 3: two cases with nHFV avoided reintubation after long-term MV (BW: 725 g, GA: 24.5 weeks). RESULTS: From 32 episodes of nHFV application, positive effect was achieved 26 times (81%) (24 of 30 children). All newborns had a significant increase in pH (7.23-7.27) and reduction in partial pressure of CO2 (66.7-58.9 mm Hg, over 1-2 hours). Failures in application of nHFV reported only in Group 1 (6/18, 33%) (failures primarily due to increasing demand for oxygen). There were two reports of pneumothorax in preterm infants with congenital pneumonia. No other nHFV-related complications were noted. CONCLUSION: nHFV is a promising NIV mode which can be also used with NIV devices.

Correlation of Retinopathy of Prematurity with Bronchopulmonary Dysplasia.

Retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) are diseases that occur only in preterm infants. The etiology of these disorders is multifactorial; however, it is believed that some of the factors in children presenting with BPD affect both the initiation and severity of ROP. The aim of the study was to evaluate the degree of clinical severity of ROP in infants with BPD compared to those without BPD. METHODOLOGY: Infants were divided into two groups: the BPD+ study group and BPD- control group. Parameters including the incidence of ROP and its severity were compared. RESULTS: In neonates with BPD, more severe forms of ROP occurred significantly more frequently than in infants without BPD. Newborns with BPD required significantly longer use of mechanical ventilation; moreover, the number of days in which the concentration of oxygen in the respiratory mixture exceeded 50% was greater in BPD+ children. Children with BPD also received more blood transfusions compared to children without BPD. CONCLUSIONS: Newborns in the BPD+ study group showed advanced stages of ROP more often than newborns in the BPD- control group. The etiology of ROP and BPD is multifactorial; however, our findings suggest oxygen plays a significant role in the development of these diseases.

From clinical uncertainties to precision medicine: the emerging role of the gut barrier and microbiome in small bowel functional diseases.

INTRODUCTION: Over the last decade, remarkable progress has been made in the understanding of disease pathophysiology. Many new theories expound on the importance of emerging factors such as microbiome influences, genomics/omics, stem cells, innate intestinal immunity or mucosal barrier complexities. This has introduced a further dimension of uncertainty into clinical decision-making, but equally, may shed some light on less well-understood and difficult to manage conditions. Areas covered: Comprehensive review of the literature on gut barrier and microbiome relevant to small bowel pathology. A PubMed/Medline search from 1990 to April 2017 was undertaken and papers from this range were included. Expert commentary: The scenario of clinical uncertainty is well-illustrated by functional gastrointestinal disorders (FGIDs). The movement towards achieving a better understanding of FGIDs is expressed in the Rome IV guidelines. Novel diagnostic and therapeutic protocols focused on the GB and SB microbiome can facilitate diagnosis, management and improve our understanding of the underlying pathological mechanisms in FGIDs.