Feasibility of bedside portable MRI in neonates and children during ECLS.

Magnetic resonance imaging (MRI) is the preferred neuroimaging technique in pediatric patients. However, in neonates and instable pediatric patients accessibility to MRI is often not feasible due to instability of patients and equipment not being feasible for MRI. Low-field MRI has been shown to be a feasible neuroimaging tool in pediatric patients. We present the first four patients receiving bedside high-quality MRI during ECLS treatment. We show that it is safe and feasible to perform bedside MRI in this patient population. This opens the route to additional treatment decisions and may guide optimized treatment in these patients.

The fetal gastrointestinal tract is exposed to melatonin and superoxide dismutase rich amniotic fluid throughout prenatal development.

Amniotic fluid (AF) is the first fluid to enter the gastrointestinal tract. Preterm birth is leading to a sudden interruption of AF swallowing. Understanding the composition of amniotic fluid is crucial to implement strategies preventing intestinal injury in preterm infants. We hypothesized that the fetal gastrointestinal tract (GIT) is exposed to melatonin and antioxidant enzymes via amniotic fluid throughout prenatal development. Amniotic fluid samples from 76 pregnant women with a median (range) gestational age of 38.0 (14.3-40.1) weeks have been collected. Immediately after birth blood samples were collected from the umbilical vein (n = 53). Median (Interquartile range) melatonin concentration was 30.5 pg/ml (12.7-118.3) and superoxide dismutase 1 (SOD1) concentration was 84 ng/ml (59-123). Extracellular glutathione peroxidase concentration was either not detectable or exceptionally low. We found a positive correlation between melatonin concentration in amniotic fluid and gestational age (Spearman's correlation coefficient, r = 0.570, p<0.001), while SOD1 concentration in amniotic fluid was inversely correlated with gestational age (r = -0.246, p = 0.032). Compared to serum samples, melatonin concentration was statistically significantly higher in amniotic fluid (p<0.001). Our results indicate that the fetal gastrointestinal system is continuously exposed to melatonin and SOD1 via the amniotic fluid throughout prenatal development.

Association of serum periostin levels with clinical features in children with asthma.

BACKGROUND: The aim of this study was to investigate the association of serum periostin levels with clinical features in children with asthma. METHODS: Children with physician-diagnosed asthma who attended regularly to an outpatient pediatric allergy and asthma center were enrolled in the study along with control subjects. Asthma severity and control status of the patients were evaluated according to the recent GINA guidelines. RESULTS: A total of 158 children (125 with asthma and 33 age- and sex-matched control subjects) with a median age of 10.2 years (range 5.9-17.0) were enrolled. Asthma severity was mild in 41 (32.8%), moderate in 63 (50.4%), and severe in 21 (16.8%) children. Children with asthma had significantly higher periostin levels than controls (53.1 ± 13.1 vs 43.0 ± 11.2 ng/mL, P < .001). The mean serum periostin levels in children with severe asthma (63.8 ± 10.8) were significantly higher than in children with moderate asthma (53.3 ± 12.7) and mild asthma (47.4 ± 11.1) (P < .001). Results of multivariable logistic regression analysis demonstrated an association between serum periostin levels and asthma severity in children (OR, 1.10; 95% CI, 1.04-1.15, P < .001). When analyzed for the best cut-off value with the highest combined sensitivity and specificity, a cut-off value of 52 ng/mL for serum periostin level was obtained with sensitivity, specificity, PPV, and NPV of 100%, 50%, 29%, and 100%, respectively. CONCLUSION: Although serum periostin levels are higher in children with asthma, its diagnostic role in identifying children with severe asthma is limited.

Characteristics of feeding tube dependency with respect to food aversive behaviour and growth.

The use of feeding tubes in pediatric medical procedures and management has dramatically increased over the last three decades. With this increase, the prevalence of Feeding Tube Dependency (FTD) - a reliance on enteral feeding following medical recovery due to lack of oral intake of nutrition, despite being able to eat- has increased too. It has been suggested, that cases with FTD show avoidant feeding behaviours such as food refusal, gagging or swallowing resistance, but evidence for this hypothesis is scarce. In a German population of 146 cases requesting feeding tube dependency treatment between 2005 and 2008 the frequency of occurrence of avoidant behaviour in FTD cases has been evaluated and was correlated to growth. The study includes children under 50 months of age being tube fed for at least three months. Parents received the Anamnestic Questionnaire for Feeding Disorder and Tube Weaning (AFT), which evaluates nutritional supply, tube feeding, feeding disorder symptoms, medical diagnosis, growth and psychosocial variables. The study group was comprised of 101 children (50 male, 51 female), with a median age of 15 months (IQR: 10-26.5) and a median tube feeding duration of 13 months (IQR: 8-27). The most prevalent medical diagnoses were congenital malformations (n = 51) and prematurity (n = 27). Parents reported daily symptoms of food aversion through all age groups, like food refusal 2 (IQR: 1-3), gagging 1 (IQR: 0-3), vomiting 1 (0.1-2) and total symptoms 6 (5-11). Vomiting was negatively correlated with weight and length percentile and head circumference. Cases with FTD show frequent and persistent food avoidant behaviors, which may be explain the need for specific psychological treatment during transitioning from tube dependency to oral eating.

Effect of Remote Ischemic Preconditioning on Intestinal Ischemia-Reperfusion Injury in Adults Undergoing On-Pump CABG Surgery: A Randomized Controlled Pilot Trial.

OBJECTIVE: Cardiopulmonary bypass (CPB) surgery commonly threatens the heart and remote organs with ischemia-reperfusion injury. Transient episodes of ischemia to nonvital tissue, known as remote ischemic preconditioning (RIPC), is thought to help local and remote vital organs to withstand subsequent ischemic insults. DESIGN: Prospective, randomized, double-blinded control trial. SETTING: Tertiary referral academic teaching hospital. PARTICIPANTS: Thirty patients undergoing elective CPB surgery INTERVENTION: RIPC was achieved via three 5-minute cycles of upper limb ischemia using a blood pressure cuff or control (sham cuff). MEASUREMENTS AND MAIN RESULTS: Primary outcome was the occurrence of intestinal injury, as measured by an increase in intestinal fatty acid binding protein (I-FABP). Secondary outcomes included incidence of gastrointestinal complications and duration of intensive care unit (ICU) stay. RIPC did not affect serum IFABP levels at the end of surgery and on the first postoperative day (p = 0.697 and p = 0.461, respectively). For all patients, mean I-FABP levels significantly increased at the end of surgery and decreased to under baseline levels on the first postoperative day (from a mean [± standard deviation] baseline value of 764 ± 492 pg/mL to 2,002 ± 974 pg/mL and decreased to 568 ± 319 pg/mL, p < 0.001). All patients remained clinically absent of gastrointestinal complications until hospital discharge. Duration of ICU stay was not correlated with I-FABP levels at the end of surgery. Neither duration of CPB nor duration of aortic clamping significantly correlated with postoperative I-FABP levels. CONCLUSIONS: These findings suggest that RIPC does not affect intestinal injury in patients undergoing CPB surgery. In patients undergoing cardiac surgery, intestinal injury appears to be moderate and transient without any clinical relevant complication.

Perinatal risk factors for asthma in children with allergic rhinitis and grass pollen sensitization.

BACKGROUND: Results of epidemiologic studies have determined several risk factors for asthma in school-age children. OBJECTIVE: To examine whether parental and perinatal risk factors, along with infantile feeding patterns, were associated with asthma in children with grass pollen allergy and allergic rhinitis. METHODS: We retrospectively analyzed the data of our cohort, which consisted of children with allergic rhinitis. Only children with grass pollen sensitization were enrolled. A detailed questionnaire regarding demographic features and perinatal events was given to the parents. RESULTS: A total of 293 children (200 boys [68.3%]; with median age, 10.2 years [interquartile range {IQR}, 7.4-13.0 years]) were included. A total of 109 children (37.2%) had accompanying asthma. The median age of onset of rhinitis symptoms was earlier (5.3 years [IQR, 4.0-8.0 years] versus 7.0 years [IQR, 5.0-10.0 years]; p = 0.001), histories of prematurity (16.7 versus 6.5%; p = 0.006), preeclampsia (5.5 versus 0%; p = 0.001), neonatal intensive care unit admission (15.1 versus 6.0%; p = 0.01), phototherapy (17.9 versus 7.1%; p = 0.004), early formula feeding (58.7 versus 41.2%; p = 0.006), and parental asthma (25.0 versus 11.4%; p = 0.002) were more frequent in children with asthma. Multivariate logistic regression analysis revealed prematurity (odds ratio [OR] 2.78 [95% confidence interval [CI],1.24-6.24]; p = 0.013), history of formula feeding (OR 1.81 [95% CI, 1.09-3.01]; p = 0.022), and parental asthma (OR 2.37 [95% CI, 1.22-4.63]; p = 0.011) were associated with asthma in school-age children with grass pollen-induced allergic rhinitis. CONCLUSION: Close monitoring of patients with these risk factors may help with an earlier diagnosis of asthma and prompt initiation of therapeutic interventions in children with allergic rhinitis and who were sensitized to grass pollen.

More than fetal urine: enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation.

UNLABELLED: The purpose of our study was to investigate the importance of amniotic fluid (AF) for fetal growth during late gestation using esophageal atresia (EA) patients as a model. In this retrospective cohort study, we compared the z-scores adapted for birth weights (BW z-scores) for each of 517 European newborns with congenital pre-gastric intestinal atresia, i.e., EA, to a European reference population. To account for the influence of the intestinal atresia on fetal growth per se, we compared adapted birth weights for each of 504 European newborns with post colonic intestinal atresia (anorectal malformation (ARM) with atresia of the anus) to the same European reference population. Analysis of the complete cohort showed (i) a significantly higher rate of small for gestational age newborns among EA compared to ARM newborns (p < 0.001) and (ii) significantly lower BW z-scores among EA compared to ARM newborns (p < 0.001). BW z-scores of EA newborns were significantly lower in term compared to preterm newborns with an inverse correlation with gestational age (GA) (Spearman correlation coefficient, r = -0.185, p < 0.001). CONCLUSIONS: Enteral uptake of AF seems to play a pivotal role in fetal growth during late gestation. WHAT IS KNOWN: • Peak velocity of fetal weight gain occurs at 33 weeks of gestation and continues until birth. During this period, fetal growth is mainly characterized by cellular hypertrophy. • Amniotic fluid (AF) comprises large amounts of hormones and growth regulators. What is New: • A significantly higher rate of small for gestational age and lower birth weights and z-scores are observed among newborn infants with congenital pre-gastric intestinal atresia. • These findings suggest that enteral uptake of AF is a major predictor for fetal growth during late gestation.

Alpha-1-Antitrypsin Deficiency in Children-Unmet Needs Concerning the Liver Manifestation.

OBJECTIVES: This study aimed to analyse the clinical course of 45 children with severe alpha-1-antitrypsin deficiency (AATD) registered in our clinic to detect possible predictors of poor outcomes. METHODS: The clinical and biological data of 45 patients with homozygous or compound heterozygous AATD were analysed. The data were collected retrospectively going back to 2005 and prospectively from May 2020 until October 2021. It was based on questionnaires, laboratory values, sonography, and biopsy findings. Liver disease was classified into four grades depending on the grade of liver disease: mild or no liver disease, moderate disease, severe disease, and liver transplantation. RESULTS: Thirty-nine patients (86.7%) had a Pi*ZZ and five (11.1%) a Pi*SZ genotype. One patient showed a new, not-yet-described compound heterozygous genotype (Pi*Z + Asp95Asn). A total of 66.7% of the cohort showed mild or no liver disease, 20% moderate, and 13.3% severe. AATD was diagnosed in most cases because of liver abnormalities, such as the elevation of transaminases (42.2%). A total of 29.4% of the patients with neonatal icterus prolongatus developed severe liver disease, and 25.7% were born small for their gestational age (SGA). Diseases of the atopic type were reported in 47.4% of the cases. CONCLUSIONS: The presence of neonatal icterus prolongatus in the first weeks of life was significantly more likely in severe courses of liver disease (r = 0.371, p = 0.012). A tendency toward atopic comorbidity in AAT-deficient children needs to be further evaluated.

CNV analysis in monozygotic twin pairs discordant for urorectal malformations.

Early post-twinning mutational events can account for discordant phenotypes in monozygotic (MZ) twin pairs. Such mutational events may comprise genomic alterations of different sizes, ranging from single nucleotides to large copy-number variations (CNVs). Anorectal malformations (ARM) and the bladder exstrophy-epispadias complex (BEEC) represent the most severe end of the urorectal malformation spectrum. Recently, CNV studies in patients with sporadic ARM and the BEEC have identified de novo events that occur in specific chromosomal regions. We hypothesized that early arising, post-twinning CNVs might contribute to discordance in MZ twin pairs with ARM or the BEEC; knowledge of such CNVs might help to identify additional chromosomal regions involved in the development of these malformations. We investigated four discordant MZ twin pairs (three ARM and one BEEC) using molecular karyotyping arrays comprising 1,140,419 markers with a median marker spacing of 1.5 kb. Filtering the coding regions for possible disease-causing post-twinning de novo CNVs present only in the affected twin, but not in the unaffected twin or the parents, identified a total of 136 CNVs. These 136 CNVs were then filtered against publicly available databases and finally re-evaluated visually. No potentially causative CNV remained after applying these filter criteria. Our results suggest that post-twinning CNV events that affect coding regions of the genome did not contribute to the discordant phenotypes in MZ twin pairs that we investigated. Possible causes for the discordant phenotypes include changes in regulatory elements or smaller genetic changes within coding regions which may be detectable by whole-exome sequencing.

A pilot study of the pleth variability index as an indicator of volume-responsive hypotension in newborn infants during surgery.

PURPOSE: The aim of this pilot study was to evaluate the diagnostic value of pleth variability index (PVI) to predict fluid responsiveness in newborn infants during surgery. METHODS: PVI was continuously recorded in 29 mechanically ventilated newborn infants during surgery, and episodes of clinically indicated volume expansion (VE) (≥10 ml/kg in ≤15 min) administration were evaluated. The upper limit of the reference range for PVI in mechanically ventilated newborns was defined by the 95th percentile of all PVI values from hemodynamically stable infants. RESULTS: The upper limit of the reference range of PVI was 18 %. One hundred and three VEs were evaluated in 58 sufficient VE size (SVES) episodes and 16 insufficient initial VE size (IVES) episodes requiring repeated VE; all but one fulfilled criteria of volume-responsive hypotension (VRH). The median (interquartile range) PVI value during arterial hypotension in the 73 episodes with VRH was 23 % (20-25 %); postvolume PVI was 16 % (13-18 %). In 63 of 73 VRH episodes, during-hypotension PVI values were >18 % (86 % sensitivity for VRH). The median intermediate PVI, measured between VE in IVES episodes, was significantly higher than post-VE PVI in SVES episodes [18 % (16-21 % vs. 16 % (13-18 %]. CONCLUSION: This preliminary evaluation shows that PVI may indicate VRH in newborn infants during surgery.

Nine new twin pairs with esophageal atresia: a review of the literature and performance of a twin study of the disorder.

BACKGROUND: Isolated esophageal atresia (EA) is a rare congenital malformation whose etiology remains largely unknown. Nine twin pairs with EA were identified from our clinical service, prompting the performance of a systematic review of the literature and the first reported twin study of isolated EA. METHODS: A total of 330 twin pairs with EA were identified from the literature. The zygosity, concordance, and malformation (isolated vs. nonisolated) status of all 339 twin pairs were evaluated. A total of 72 twin pairs (4 of 9 / 68 of 330) fulfilled the criteria for inclusion in a classic twin study of isolated EA. RESULTS: The pairwise concordance rates were 50% (95% confidence interval [CI], 34-66%) for monozygous (MZ) twin pairs and 26% (95% CI, 15-42%) for dizygous (DZ) twin pairs (p = 0.033). The probandwise concordance rates were 67% (95% CI, 53-78%) for MZ twin pairs and 42% (95% CI, 29-56%) for DZ twin pairs (p = 0.011). The MZ/DZ ratios were 1.9 for pairwise analysis and 1.6 for probandwise analysis. The familial risk ratios for MZ and DZ twin pairs were 1700 and 900, respectively. CONCLUSION: The observation of higher concordance rates for MZ compared to DZ twin pairs indicates that genetic factors contribute to isolated EA.

Melatonin status in pediatric intensive care patients with sepsis.

OBJECTIVE: Considering the potential immunomodulatory role of melatonin and its direct antioxidant activity, disturbances of the melatonin secretion pattern in the septic conditions could be particularly unfavorable. The aim of this study was to evaluate the nocturnal melatonin concentration and total 24-hr excretion of 6-sulfatoxymelatoninsulfate, melatonin's major urinary metabolite, in children with sepsis in the pediatric intensive care unit. DESIGN: Prospective observational pilot study. SETTING: A pediatric intensive care unit. PATIENTS: Twenty septic and 20 nonseptic children admitted between February 2008 and January 2010. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Blood and urine samples were obtained from each patient on days 1, 2, 3, 5, and 10. There were no significant differences between the groups concerning age and gender. The median nocturnal melatonin concentrations were not significantly different between septic and nonseptic patients during the study period (p > .05). A subgroup analysis in septic patients showed that the nocturnal melatonin concentrations in nonsurvivors were significantly higher than in survivors, whereas total 6-sulfatoxymelatoninsulfate excretions in nonsurvivors were significantly lower than in survivors (p = .001 and p = .015, respectively). Furthermore, nocturnal melatonin concentrations of septic patients in septic shock state were statistically significantly higher than those of septic patients without septic shock state (p = .002). The 24-hr 6-sulfatoxymelatoninsulfate excretions in septic patients with liver dysfunction were found significantly lower than those in septic patients without liver dysfunction (p = .015). The presence of sedation and mechanical ventilation had no effect on the nocturnal melatonin concentrations in septic patients (p = .953 and p = .922, respectively). CONCLUSION: The present study shows that, in contradiction to results in adult patients, the nocturnal melatonin concentrations are not decreased in septic pediatric intensive care unit patients despite severe disease. Further investigations are needed to identify whether treatment with melatonin may have beneficial effects in pediatric intensive care unit patients with sepsis/septic shock.

A classic twin study of isolated gastroschisis.

The etiology of gastroschisis remains elusive. A classic twin study was used to assess the relative contribution of environmental and genetic factors in its development. Screening of 4872 twin pregnancies identified three unreported twin pairs comprising two monozygous and one dizygous discordant pair of twins. Review of the literature identified an additional 21 twin pairs. We observed lower pair- and proband-wise concordance rates for monozygotic compared to dizygotic twin pairs, pair- and proband-wise concordance ratios below 1.0. Our results suggest environmental to play a greater role than genetic factors in the development of gastroschisis.

DMBT1 amount in amniotic fluid depends on gestational age.

OBJECTIVE: Amniotic fluid is a mixture containing many different proteins as immunomodulatory peptides and growth factors. The glycoprotein Deleted in Malignant Brain Tumors 1 (DMBT1) is participated in innate immunity, angiogenesis and epithelial differentiation. We analyzed the DMBT1 concentration in amniotic fluid during gestation. METHODS: DMBT1 concentration was quantified by ELISA. Amniotic fluid samples were collected from preterm and term neonates. Effects of maternal or neonatal parameters were analyzed. To evaluate the source of DMBT1 we examined RNA of fetal tissue in relation to DMBT1 expression. RESULTS: The median DMBT1 concentration in amniotic fluid was 54.4 ng/ml. Amniotic fluid obtained <28 weeks of gestation revealed significantly lower DMBT1 concentrations compared to ≥28 weeks. We found a positive correlation between DMBT1 concentration and gestational age (p = .026). The fetal DMBT1 expression was pronounced in the gastrointestinal tract. CONCLUSIONS: The results showed that DMBT1 concentrations in amniotic fluid correlate with the gestational age during gestation and that the fetal gastrointestinal tract is a potential source of DMBT1. BRIEF RATIONALE: Amniotic fluid contains not only nutrients, but also many immunomodulatory peptides and growth factors. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. The aim of this research was to study the DMBT1 content and the factors affecting its concentration in amniotic fluid during gestation. In summary, the results obtained in this study showed that DMBT1 is a component of amniotic fluid and that DMBT1 concentrations in amniotic fluid correlate with gestational age. In addition to this, the fetal gastrointestinal tract is a potential source of DMBT1 detected in amniotic fluid.

Human Milk Oligosaccharides Are Present in Amniotic Fluid and Show Specific Patterns Dependent on Gestational Age.

(1) Background: Human milk oligosaccharides (HMOs) are already found in maternal circulation in early pregnancy, changing with gestational age. HMOs are also present in cord blood and amniotic fluid (AF). We aimed to assess HMO profiles in AF over the course of gestation. (2) Methods: AF was collected during diagnostic amniocentesis, fetal surgery, or C-section from 77 women with a gestational age of ranging from 14.3 to 40.9 weeks. Samples were analysed using high performance liquid chromatography with fluorescence detection. (3) Results: We found lactose and up to 16 HMO structures in all AF samples investigated, starting at 14 weeks of gestation. Overall, 3'-sialyllactose (3'SL) and 2'-fucosyllactose (2'FL) were the most abundant HMOs. Individual and total HMO concentrations were significantly positively correlated with gestational age. HMO composition also changed between early, mid- and late pregnancy, with relative concentrations of 3'SL significantly decreasing (44%, 25%, 24%) and 2'FL increasing (7%, 13%, 21%), respectively. (4) Conclusion: Our study shows that HMOs are already present in AF early in pregnancy. This demonstrates extensive contact of the fetus with a broad variety of HMOs, suggesting roles for HMOs in fetal tissue development during the time course of pregnancy.

Biodynamic lighting conditions preserve nocturnal melatonin production in pregnant women during hospitalization: A randomized prospective pilot study.

Background and purpose: Maternal circadian rhythms are important for maintaining maternal and fetal homeostasis. The maternal circadian system coordinates the internal clock of the fetus with environmental lighting conditions via the melatonin signal. The intensity and wavelength of daylight influence nocturnal melatonin production. This study aims to evaluate the effect of environmental lighting conditions on melatonin production in pregnant women with reduced mobility during hospitalization. Methods: We installed a human-centric lighting system with biodynamic effects (BDL, biodynamic lighting) in the patient rooms. The pregnant women in the patient rooms with standard indoor conditions served as a control group. The illuminance (lux) and dose of effective circadian irradiation (Hec) were recorded every 10 seconds by light dosimeters (Lucerne University, Switzerland) attached to the patients` clothing. Results: We analyzed the illuminance status of 47 pregnant women with a median (IQR) gestational age of 29.9 (25.4-32.3) weeks of gestation. The median illuminance in the control group was significantly lower (p<0.05) than in the BDL group in the morning and afternoon from day 1 to 5. BDL patients had a significantly higher effective circadian irradiation in the morning. The effective circadian irradiation showed a significant daily rhythm only in the BDL group. The BDL group had a significantly higher melatonin production on day 3 (p=0.006) and day 5 (p=0.012) than the control group median (IQR) nocturnal 6-Sulfatoxymelatonin excretion 15840 (10140-22160) ng/12h vs. 6141 (2080-11328) ng/12h on day 3 and 18780 (11320-23562) ng/12h vs. 6380 (3500-17600) ng/12h on day 5). Conclusion: We have demonstrated that dramatically altered lighting conditions of hospitalized pregnant women may be optimized by installing biodynamic lighting systems in the patient rooms resulting in the maintenance of nocturnal melatonin production in pregnant women.

Use of nocturnal melatonin concentration and urinary 6-sulfatoxymelatonin excretion to evaluate melatonin status in children with severe sepsis.

The aim of this study was to evaluate whether nocturnal melatonin concentration (NMC) and urinary 6-sulphatoxymelatonin (aMT6s) excretion can predict melatonin status in patients with severe sepsis in the pediatric intensive care unit (PICU). Blood samples for the determination of NMC were obtained from each patient at 3 a.m. Urine samples for the determination of aMT6s excretion were obtained from each patient at 12 h intervals. We obtained 89 blood and 178 urine samples from 23 septic patients, and 52 blood and 104 urine samples from 13 non-septic patients. The NMC of septic patients in a state of septic shock was significantly higher than that of septic patients not in septic shock (p = 0.017) and those of non-septic patients (p = 0.019). In contrast, there was no significant difference for nocturnal (NaMT6s) and total aMT6s (TaMT6s) excretion between septic patients with and without septic shock and non-septic patients (p > 0.05). The NMC was significantly higher in septic patients in shock with and without hepatic dysfunction (HD) than in non-septic patients (p = 0.004 and p = 0.024, respectively). NaMT6s and TaMT6s excretion was significantly lower in septic patients with HD than in septic patient without HD (p = 0.040 and p = 0.029, for NaMT6s and TaMT6s, respectively). Our results showed that an elevated NMC may not reflect an increased MT production in septic patients in septic shock. It seems that, to evaluate the melatonin status of septic PICU patients, it is necessary to collect both serum and urine samples.

COVID-19-Associated Cerebral White Matter Injury in a Newborn Infant With Afebrile Seizure.

Coronavirus disease 2019 (COVID-19) symptoms in newborn infants are incompletely described. We present the first case of neuroradiologic abnormality associated with COVID-19 in a newborn infant with afebrile seizure. This case underlines the possible neurologic involvement of severe acute respiratory syndrome coronavirus 2 in this age group.

TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19.

Among children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild. Here, we describe the case of a 3.5-year-old girl with an unusually severe presentation of coronavirus disease (COVID-19). The child had an autoinflammatory disorder of unknown etiology, which had been treated using prednisolone and methotrexate, and her parents were half cousins of Turkish descent. After 5 days of nonspecific viral infection symptoms, tonic-clonic seizures occurred followed by acute cardiac insufficiency, multi-organ insufficiency, and ultimate death. Trio exome sequencing identified a homozygous splice-variant in the gene TBK1, and a homozygous missense variant in the gene TNFRSF13B. Heterozygous deleterious variants in the TBK1 gene have been associated with severe COVID-19, and the variant in the TNFRSF13B gene has been associated with common variable immunodeficiency (CVID). We suggest that the identified variants, the autoinflammatory disorder and its treatment, or a combination of these factors probably predisposed to lethal COVID-19 in the present case.