Sacral neuromodulation in children and adolescents with defecation disorders.

BACKGROUND: Even if understanding of neuronal enteropathies, such as Hirschsprung's disease and functional constipation, has been improved, specialized therapies are still missing. Sacral neuromodulation (SNM) has been established in the treatment of defecation disorders in adults. The aim of the study was to investigate effects of SNM in children and adolescents with refractory symptoms of chronic constipation. METHODS: A two-centered, prospective trial has been conducted between 2019 and 2022. SNM was applied continuously at individually set stimulation intensity. Evaluation of clinical outcomes was conducted at 3, 6, and 12 months after surgery based on the developed questionnaires and quality of life analysis (KINDLR). Primary outcome was assessed based on predefined variables of fecal incontinence and defecation frequency. KEY RESULTS: Fifteen patients enrolled in the study and underwent SNM (median age 8.0 years (range 4-17 years)): eight patients were diagnosed with Hirschsprung's disease (53%). Improvement of defecation frequency was seen in 8/15 participants (53%) and an improvement of fecal incontinence in 9/12 patients (75%). We observed stable outcome after 1 year of treatment. Surgical revision was necessary in one patient after electrode breakage. Urinary incontinence was observed as singular side effect of treatment in two patients (13%), which was manageable with the reduction of stimulation intensity. CONCLUSIONS: SNM shows promising clinical results in children and adolescents presenting with chronic constipation refractory to conservative therapy. Indications for patients with enteral neuropathies deserve further confirmation.

Sacral neuromodulation for constipation and fecal incontinence in children and adolescents - study protocol of a prospective, randomized trial on the application of invasive vs. non-invasive technique.

BACKGROUND: A therapeutic effect of sacral neuromodulation (SNM) on fecal incontinence (FI) and quality of life has been proven in adults. SNM is, however, rarely used in pediatric cases. The aim of the study is to investigate effects of SNM in pediatric constipation in a prospective parallel-group trial. METHODS: A monocentric, randomized, unblinded, parallel-group trial is conducted. SNM is conducted in the invasive variant and in an innovative, external approach with adhesive electrodes (enteral neuromodulation, ENM). We include patients with constipation according to the ROME IV criteria and refractory to conventional options. Patients with functional constipation and Hirschsprung's disease are able to participate. Participants are allocated in a 1:1 ratio to either SNM or ENM group. Clinical data and quality of life is evaluated in regular check-ups. Neuromodulation is applied continuously for 3 months (end point of the study) with follow-up-points at 6 and 12 months. Findings are analyzed statistically considering a 5% significance level (p ≤ 0.05). Outcome variables are defined as change in (1) episodes of abdominal pain, (2) episodes of FI, (3) defecation frequency, (4) stool consistency. Improvement of proprioception, influence on urinary incontinence, quality of life and safety of treatment are assessed as secondary outcome variables. We expect a relevant improvement in both study groups. DISCUSSION: This is the first trial, evaluating effects of neuromodulation for constipation in children and adolescents and comparing effects of the invasive and non-invasive application (SNM vs. ENM). TRIAL REGISTRATION: The study is registered with clinicaltrials.gov, Identifier NCT04713085 (date of registration 01/14/2021).

Differences in neonatal gastric tubes during insertion into a 3D model in relation to risk of potential perforation.

OBJECTIVES: Perforation of esophagus or stomach is a potential complication during and after insertion of a gastric tube in neonates. The aim of this study was to analyze different types of gastric tubes in a three-dimensional (3D) model of neonatal esophagus and stomach regarding potential perforations. METHODS: A 3D model of esophagus and stomach was created based on computed tomography data of a term neonate. Three types of gastric tubes were inserted into the 3D model, the localization was examined by radioscopy and the behavior, stiffness and manageability of each gastric tube was evaluated. RESULTS: Insertion of gastric tubes with higher stiffness was easier. The rates of correct localization differed significantly between the gastric tubes with the highest rate of correct localization in the softest tube (48.5%) and the lowest rate in the tube with the highest stiffness (21.2%). Additionally, the softest tube showed the lowest rate of localization of its tip at the stomach wall. CONCLUSIONS: The study illustrates differences between various types of gastric tubes regarding stiffness, behavior and resiliency. Softer gastric tubes may be beneficial. These differences may be relevant in neonatal care of very immature and very sick infants.

The Subdiaphragmatic Angle Of The Gastric Tube In Neonates - A Potential Predictor For Perforations?

BACKGROUND: Traumatic subdiaphramatic perforation of esophagus or stomach in neonates represents a rare clinical complication following the insertion of a gastric tube and is associated with high morbidity and mortality. The aim of the present study was to evaluate whether the angle of the gastric tube depicted on a plain radiograph may serve as a diagnostic tool to predict subdiaphragmatic traumatic (or iatrogenic) perforation. PATIENTS AND METHODS: Thoraco-abdominal radiographs of 128 preterm and term neonates without perforation and 15 neonates with perforation of the esophagogastric junction or the stomach were retrospectively analysed. RESULTS: The angle of the gastric tube increases with postnatal age (p=0.0380). In the control group, the angle of the gastric tube varied between 13° and 48° (median: 31°), whereas the values ranged from -31° to 42° (median: 11°) in neonates with subdiaphragmatic perforation. Perforation should thus be suspected in cases with an angle of<20° (sensitivity: 93.3%; specificity: 91.4%). Moreover, an unusual localization of the tip beyond the gastric bubble is highly indicative of perforation. DISCUSSION: The present study emphasizes the importance of verifying the correct course of an inserted gastric tube. CONCLUSIONS: In daily clinical practice, an angle of<20° should be followed by thorough physical examination, abdominal ultrasound and if applicable contrast medium examinations to exclude perforation.

A comparative observational study on intrasphincteric injections with Botulinum toxin vs. enteral neuromodulation in chronic refractory constipation.

PURPOSE: Botulinum toxin injections in the anal sphincter apparatus (Botox) and enteral neuromodulation (ENM) are options for treatment of refractory chronic constipation. We present a retrospective comparative observational study. PATIENTS AND METHODS: From 2014 to 2022, pediatric patients with chronic constipation were either treated with Botox or ENM with continuation of conservative treatment. Comparison was conducted regarding the primary outcome variables defecation frequency, stool consistency, and abdominal pain. Secondary outcomes were fecal incontinence, enuresis, change of medication and safety of treatment. RESULTS: 19 Botox patients (10 boys, 9 girls, 12 patients with Hirschsprung disease (HD), 7 patients with functional constipation (FC)) were compared to 24 ENM patients (18 boys, 6 girls, 12 HD patients, 7 FC patients). Groups differed significantly in age (5.0 years (Botulinum toxin) and 6.5 years (ENM), mean values, p-value 0.008). Improvement of constipation was seen in 68% (n = 13/19) of Botox and 88% (n = 21/24) of ENM patients (p = 0.153). Influence of etiology on therapeutic effects was not observed. Complications were minor. CONCLUSIONS: Botox and ENM can be considered as valuable and effective treatment options in refractory chronic constipation. Prospective, large-population studies should be designed to enable improved evidence.

A loss-of-function variant in canine GLRA1 associates with a neurological disorder resembling human hyperekplexia.

Hereditary hyperekplexia is a rare neuronal disorder characterized by an exaggerated startle response to sudden tactile or acoustic stimuli. In this study, we present a Miniature Australian Shepherd family showing clinical signs, which have genetic and phenotypic similarities with human hereditary hyperekplexia: episodes of muscle stiffness that could occasionally be triggered by acoustic stimuli. Whole genome sequence data analysis of two affected dogs revealed a 36-bp deletion spanning the exon-intron boundary in the glycine receptor alpha 1 (GLRA1) gene. Further validation in pedigree samples and an additional cohort of 127 Miniature Australian Shepherds, 45 Miniature American Shepherds and 74 Australian Shepherds demonstrated complete segregation of the variant with the disease, according to an autosomal recessive inheritance pattern. The protein encoded by GLRA1 is a subunit of the glycine receptor, which mediates postsynaptic inhibition in the brain stem and spinal cord. The canine GLRA1 deletion is located in the signal peptide and is predicted to cause exon skipping and subsequent premature stop codon resulting in a significant defect in glycine signaling. Variants in GLRA1 are known to cause hereditary hyperekplexia in humans; however, this is the first study to associate a variant in canine GLRA1 with the disorder, establishing a spontaneous large animal disease model for the human condition.

Treatment of pediatric fistula-in-ano-Sphincter-sparing non-cutting seton placement as the future treatment of choice?

Background: Therapeutic principles of fistula-in-ano (FIA) are lacking evidence-based consensus on treatment options. Non-cutting, sphincter-sparing options have not been published for infancy and childhood FIA. Patients and methods: We are presenting retrospective data on FIA treatment with non-cutting seton placement between 2011 and 2020. Data were collected based on medical records and complemented by patients' contact for follow-up analyses between November 2021 and October 2022. Data were analyzed regarding the outcome variables of recurrent FIA and recurrent perianal abscess. Furthermore, outcomes in different age groups were compared (<1/1.5-12 years of age). Results: Treatment duration with non-cutting seton was at a median of 4.6 months and was not associated with recurrent FIA (p = 0.8893). Overall recurrence rate of FIA within an observation time of 9 months postsurgically was at 7% (n = 3/42) and was only seen in infancy, whereas recurrent perianal abscess was mainly observable in children (n = 2, p = 0.2132). Comparison of age groups revealed no significant differences. Of the 42 included patients, 37 responded in the follow-up analysis, resulting in a response rate of 88% with a median follow-up time of 4.9 years. Fecal incontinence was postsurgically only seen in two patients, who were diagnosed prior to surgery and symptoms remained unchanged. Conclusions: Non-cutting seton placement might be a promising option in the treatment of FIA in infancy and childhood. Perioperative settings like duration of placed seton and antibiotic treatment have to be discussed in further prospective, enlarged population-based studies.

Relationship between early nutrition and deep gray matter and lateral ventricular volumes of preterm infants at term-equivalent age.

BACKGROUND: The survival of preterm infants has improved over the last decade, but impaired brain development leading to poor neurological outcomes is still a major comorbidity associated with prematurity. The aim of this study was to evaluate the effect of nutrition on neurodevelopment in preterm infants and identify markers for improved outcomes. METHODS: Totally 67 premature infants with a gestational age of 24-34 weeks and a birth weight of 450-2085 g were included. Clinical parameters and documented diet were collected from medical records. The nutritional analysis comprised the protein, fat, carbohydrate, and energy intake during different time spans. Brain development was assessed by determining deep gray matter (DGM; basal ganglia and thalamus) and lateral ventricular (LV) volumes as measured on cerebral magnetic resonance imaging scans obtained at term-equivalent age (TEA), and potential associations between nutrition and brain volumetrics were detected by regression analysis. RESULTS: We observed a negative correlation between mean daily protein intake in the third postnatal week and MRI-measured DGM volume at TEA (P = 0.007). In contrast, head circumference at a corrected age of 35 weeks gestation (P < 0.001) and mean daily fat intake in the fourth postnatal week (P = 0.004) were positively correlated with DGM volume. Moreover, mean daily carbohydrate intake in the first postnatal week (P = 0.010) and intraventricular hemorrhage (P = 0.003) were revealed as independent predictors of LV volume. CONCLUSION: The study emphasizes the importance of nutrition for brain development following preterm birth.

Noninvasive Sacral Neuromodulation in Children and Adolescents: A Case-Control Study of Patients With Chronic Refractory Constipation.

OBJECTIVES: In adult patients with chronic refractory constipation, invasive sacral neuromodulation (SNM) has been applied successfully. There is a need for less invasive solutions while providing comparable therapeutic effects in children and adolescents. We present a prospective, interventional case-control study on the application of noninvasive SNM. MATERIALS AND METHODS: Patients with chronic constipation refractory to conservative treatment were prospectively included in the study from 2018 to 2021 and randomized to either SNM (SNM group: single current stimulation for 24 h/d, frequency 15 Hz, pulse width 210 µs, intensity 1-10 mA) or conventional treatment (controls: full range of pharmacologic and nonpharmacologic options). Treatment was conducted for 12 weeks. Treatment effects were collected with specialized questionnaires and quality-of-life analysis (KINDLR). Outcome variables were defecation frequency, stool consistency, fecal incontinence (FI) episodes, and abdominal pain. RESULTS: Analysis was conducted in 28 patients with SNM and 31 controls (median age 7.0, range 3-16 years). Overall responsiveness to treatment was 86% of the SNM group and 39% of the control group (p < 0.001). All outcome variables were positively influenced by SNM treatment. Defecation frequency improved in 46% of patients with SNM and in 19% of controls (p = 0.026), as did stool consistency in 57% of patients with SNM and in 26% of controls (p = 0.014). Fecal incontinence was significantly reduced in 76% of patients with SNM (n = 16/21 vs 42% of controls [n = 11/26], p = 0.042). Quality of life improved significantly during SNM treatment (71.32 [baseline] vs 85.00 [after 12 weeks], p < 0.001) and confirmed a positive influence of SNM treatment compared with the control group (85.00 [SNM after 12 weeks] vs 79.29 [controls after 12 weeks], p = 0.047). CONCLUSIONS: Outcome of noninvasive SNM treatment in patients with chronic refractory constipation is better than conventional treatment.

Human papillomavirus vaccination of girls in the German model region Saarland: Insurance data-based analysis and identification of starting points for improving vaccination rates.

In Germany, the incidence of cervical cancer, a disease caused by human papillomaviruses (HPV), is higher than in neighboring European countries. HPV vaccination has been recommended for girls since 2007. However, it continues to be significantly less well received than other childhood vaccines, so its potential for cancer prevention is not fully realized. To find new starting points for improving vaccination rates, we analyzed pseudonymized routine billing data from statutory health insurers in the PRÄZIS study (prevention of cervical carcinoma and its precursors in women in Saarland) in the federal state Saarland serving as a model region. We show that lowering the HPV vaccination age to 9 years led to more completed HPV vaccinations already in 2015. Since then, HPV vaccination rates and the proportion of 9- to 11-year-old girls among HPV-vaccinated females have steadily increased. However, HPV vaccination rates among 15-year-old girls in Saarland remained well below 50% in 2019. Pediatricians vaccinated the most girls overall, with a particularly high proportion at the recommended vaccination age of 9-14 years, while gynecologists provided more HPV catch-up vaccinations among 15-17-year-old girls, and general practitioners compensated for HPV vaccination in Saarland communities with fewer pediatricians or gynecologists. We also provide evidence for a significant association between attendance at the children´s medical check-ups "U11" or "J1" and HPV vaccination. In particular, participation in HPV vaccination is high on the day of U11. However, obstacles are that U11 is currently not financed by all statutory health insurers and there is a lack of invitation procedures for both U11 and J1, resulting in significantly lower participation rates than for the earlier U8 or U9 screenings, which are conducted exclusively with invitations and reminders. Based on our data, we propose to restructure U11 and J1 screening in Germany, with mandatory funding for U11 and organized invitations for HPV vaccination at U11 or J1 for both boys and girls.

Prediction of High Bell Stages of Necrotizing Enterocolitis Using a Mathematic Formula for Risk Determination.

Necrotizing enterocolitis (NEC) continues to cause high morbidity and mortality. Identifying early predictors for severe NEC is essential to improve therapy and optimize timing for surgical intervention. We present a retrospective study of patients with NEC, treated between 2010 and 2020, trying to identify factors influencing the severity of NEC. Within the study period, 88 affected infants with NEC or NEC-like symptoms are analyzed. A multiple logistic regression analysis reveals the following three independent predictors for NEC in Bell stage III: red blood cell transfusion (p = 0.027 with odds ratio (OR) = 3.298), sonographic findings (p = 0.037; OR = 6.496 for patients with positive vs. patients without pathological findings) and cardiac anatomy (p = 0.015; OR = 1.922 for patients with patent ductus arteriosus (PDA) vs. patients with congenital heart disease (CHD); OR = 5.478/OR = 2.850 for patients with CHD/PDA vs. patients without cardiac disease). Results are summarized in a clinical score for daily application in clinical routine. The score is easy to apply and combines clinically established parameters, helping to determine the timing of surgical intervention.

Increased expression of OLFM4 and lysozyme during necrotizing enterocolitis in neonates: an observational research study.

BACKGROUND: In neonatal patients with necrotizing enterocolitis (NEC) the inflammatory response is mediated by a plurality of different proteins. The proteins olfactomedin 4 (OLFM4) and lysozyme (LYZ) are part of the intestinal mucosal defense and especially OLFM4 has rarely been evaluated in neonatal gastrointestinal diseases. The aim of this study was to analyze whether expression levels of both proteins of innate immunity, OLFM4 and lysozyme, were increased during NEC in neonates. METHODS: Intestinal tissues of patients with NEC were examined with immunohistochemical staining of formalin-fixed and paraffin-embedded sections of resected tissue using antibodies against OLFM4 and lysozyme. Staining-positive tissues were semi-quantitatively scored from 0 (no staining), 1 (weak staining), 2 (moderate staining) to 3 (highly intense staining) by two individual investigators. Intestinal tissue of infants with volvulus was used as a control as other intestinal tissue without major inflammation was not available. RESULTS: Both applied antibodies against OLFM4 showed different staining patterns with higher staining intensity of the antibody OLFM4 (D1E4M). OLFM4 (median score of the antibody OLFM4 (D1E4M): 3.0) and lysozyme (median score: 3.0) are highly expressed in intestinal and immune cells during NEC. Expression of OLFM4 and lysozyme in the control samples with volvulus was observable but significantly lower (median score of the antibody OLFM4 (D1E4M): 1.25; median score of the antibody against LYZ: 2.0; p = 0.033 and p = 0.037, respectively). CONCLUSIONS: Both proteins, OLFM4 and lysozyme, may play a role in the pathogenesis of NEC in neonatal patients, but the exact mechanisms of OLFM4 and lysozyme function and their role in immunological responses have not yet been resolved in detail. These observations add new insights as basis for further large-scale population research.

DMBT1 is upregulated in cystic fibrosis, affects ciliary motility, and is reduced by acetylcysteine.

BACKGROUND: Cystic fibrosis (CF) is the most common genetic disorder in the Caucasian population. Despite remarkable improvements in morbidity and mortality during the last decades, the disease still limits survival and reduces quality of life of affected patients. Moreover, CF still represents substantial economic burden for healthcare systems. Inflammation and infection already start in early life and play important roles in pulmonary impairment. The aim of this study is to analyze the potential role of DMBT1, a protein with functions in inflammation, angiogenesis, and epithelial differentiation, in CF. RESULTS: Immunohistochemically DMBT1 protein expression was upregulated in lung tissues of CF patients compared to healthy controls. Additionally, pulmonary expression of Dmbt1 was approximately 6-fold increased in an established transgenic mouse model of CF-like lung disease (ENaC tg) compared to wild-type mice as detected by qRT-PCR. Since acetylcysteine (ACC) has been shown to reduce inflammatory markers in the airways, its potential influence on DMBT1 expression was analyzed. A549 cells stably transfected with an expression plasmid encoding the largest (8kb) DMBT1 variant (DMBT1+ cells) or an empty vector control (DMBT1- cells) and incubated with ACC both showed significantly reduced DMBT1 concentrations in the culture medium (p = 0.0001). To further elucidate the function of DMBT1 in pulmonary airways, respiratory epithelial cells were examined by phase contrast microscopy. Addition of human recombinant DMBT1 resulted in altered cilia motility and irregular beat waves (p < 0.0001) suggesting a potential effect of DMBT1 on airway clearance. CONCLUSIONS: DMBT1 is part of inflammatory processes in CF and may be used as a potential biomarker for CF lung disease and a potential tool to monitor CF progression. Furthermore, DMBT1 has a negative effect on ciliary motility thereby possibly compromising airway clearance. Application of ACC, leading to reduced DMBT1 concentrations, could be a potential therapeutic option for CF patients.

DMBT1 expression and neutrophil-to-lymphocyte ratio during necrotizing enterocolitis are influenced by impaired perfusion due to cardiac anomalies.

BACKGROUND: Deleted in malignant brain tumors 1 (DMBT1) is involved in innate immunity and epithelial differentiation. It has been proven to play a role in various states of inflammation or hypoxia of fetal gastrointestinal and pulmonary diseases. Discrimination of pathogenesis in necrotizing enterocolitis (NEC) based on cardiac status improves the understanding of NEC in different patient subgroups. We aimed at examining DMBT1 expressions regarding their association with cardiac status leading to impaired intestinal perfusion, intraoperative bacteria proof, and a fulminant course of NEC. METHODS: Twenty-eight patients with NEC were treated surgically between 2010 and 2019 at our institution. DMBT1 expression was examined in intestinal sections using immunohistochemistry to detect DMBT1 protein. Associations of clinical parameters and DMBT1 expression were analyzed. RESULTS: We examined DMBT1 levels in 10 patients without cardiac defects and 18 patients with persisting ductus arteriosus (PDA) and congenital heart defects (CHD). Compared to patients without cardiac malformations, DMBT1 levels tended to score higher in patients with PDA/CHD (p = 0.2113) and were negatively correlated with C-reactive protein in these infants (p = 0.0172; r = - 0.5533). The number of DMBT1-expressing macrophages was elevated in the PDA/CHD-subgroup (p = 0.0399). Ratios of neutrophils and monocytes to lymphocytes were significantly higher in infants with PDA/CHD (p = 0.0319 and 0.0493). DMBT1 expression was significantly associated with positive bacterial culture of intraoperative swabs (p = 0.0252) and DMBT1 expression of the serosa was associated with a fulminant course of NEC (p = 0.0239). CONCLUSIONS: This study demonstrates that DMBT1 expression may be influenced by cardiac anomalies with an impaired intestinal perfusion in the neonatal intestine. NEC in PDA/CHD infants is associated with more DMBT1-positive macrophages and a significantly elevated neutrophil-to-lymphocyte ratio.

Latency duration of preterm premature rupture of membranes and neonatal outcome: a retrospective single-center experience.

In preterm premature rupture of membranes (PPROM), a decision between early delivery with prematurity complications and pregnancy prolongation bearing the risk of chorioamnionitis has to be made. To define disadvantages of delayed prolongation, latency duration of PPROM in expectantly managed pregnancies was investigated. We included those PPROMs > 48 h leading to preterm birth prior 37 weeks' gestation and retrospectively analyzed 84 preterm infants fulfilling these criteria. The association between latency duration/appearance of PPROM and respiratory outcome (primary outcomes) and neurological outcome (secondary outcomes) was investigated. The study showed that latency duration of PPROM is not associated with clinical or histological chorioamnionitis (p = 0.275; p = 0.332). As the numerous clinical parameters show multicollinearity between each other, we performed a multiple regression analysis to consider this fact. Respiratory distress syndrome is significantly associated with gestational age at PPROM (p < 0.001), and surfactant application is significantly associated with PPROM duration (p = 0.014). The other respiratory parameters including steroids and diuretics therapy, bronchopulmonary dysplasia, and the neurological parameters (intraventricular hemorrhage, Bayley II testing at a corrected age of 24 months) were not significantly associated with PPROM duration or gestational age at PPROM diagnosis.Conclusion: Latency duration of PPROM was not associated with adverse neonatal outcome in expectantly and carefully managed pregnancies, but respiratory distress syndrome was pronounced. The observed effect of pronounced respiratory distress syndrome can be treated with surfactant preparations and was not followed by increased rate of bronchopulmonary dysplasia. What is Known: • In case of preterm premature rupture of membranes, a decision between pregnancy prolongation with the risk of chorioamnionitis and early delivery with prematurity complications has to be made. • Chorioamnionitis is a dangerous situation for the pregnant woman and the fetus. • Impaired neurodevelopmental outcome is strongly correlated with pronounced prematurity due to the increased rate of serious complications. What is New: • Respiratory distress syndrome is significantly associated with gestational age at PPROM, and surfactant application is significantly associated with PPROM duration. • Latency duration of PPROM is not associated with adverse respiratory neonatal outcome (therapy with continuous positive airway pressure, therapy with diuretics and/or steroids, bronchopulmonary dysplasia) in expectantly and carefully managed pregnancies. • Intraventricular hemorrhage and Bayley II testing at a corrected age of 24 months are not associated with latency duration of PPROM when pregnancies are carefully observed.

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.

Cholelithiasis and cholecystitis in children and adolescents: Does this increasing diagnosis require a common guideline for pediatricians and pediatric surgeons?

BACKGROUND: In contrast to adults, for whom guidelines on the cholelithiasis treatment exist, there is no consistent treatment of pediatric patients with cholelithiasis throughout national and international departments, most probably due to the lack of evidence-based studies. METHODS: We evaluated the German management of pediatric cholelithiasis in a dual approach. Firstly, a retrospective, inter-divisional study was established, comparing diagnostics and therapy of patients of the pediatric surgery department with the management of patients aged < 25 years of the visceral surgery department in our institution over the past ten years. Secondarily, a nation-wide online survey was implemented through the German Society of Pediatric Surgery. RESULTS: Management of pediatric patients with cholelithiasis was primarily performed by pediatricians in the retrospective analysis (p < 0.001). Pediatric complicated cholelithiasis was not managed acutely in the majority of cases with a median time between diagnosis and surgery of 22 days (range 4 days-8 months vs. 3 days in visceral surgery subgroup (range 0 days-10 months), p = 0.003). However, the outcome remained comparable. The hospital's own results triggered a nation-wide survey with a response rate of 38%. Primary pediatric medical management of patients was confirmed by 36 respondents (71%). In case of acute cholecystitis, 22% of participants perform a cholecystectomy within 24 h after diagnosis. Open questions revealed that complicated cholelithiasis is managed individually. CONCLUSIONS: The management of pediatric cholelithiasis differs between various hospitals and between pediatricians and pediatric surgeons. Evidence-based large-scale population studies as well as a common guideline may represent very important tools for treating this increasing diagnosis.

Characterization of aEEG During Sleep and Wakefulness in Healthy Children.

INTRODUCTION: Interpretation of amplitude-integrated EEG (aEEG) is hindered by lacking knowledge on physiological background patterns in children. The aim of this study was to find out whether aEEG differs between wakefulness and sleep in children. METHODS: Forty continuous full-channel EEGs (cEEG) recorded during the afternoon and overnight in patients <18 years of age without pathologies or only solitary interictal epileptiform discharges were converted into aEEGs. Upper and lower amplitudes of the C3-C4, P3-P4, C3-P3, C4-P4, and Fp1-Fp2 channels were measured during wakefulness and sleep by two investigators and bandwidths (BW) calculated. Sleep states were assessed according to the American Academy of Sleep Medicine. Median and interquartile ranges (IQR) were calculated to compare the values of amplitudes and bandwidth between wakefulness and sleep. RESULTS: Median age was 9.9 years (IQR 6.1-14.7). All patients displayed continuous background patterns. Amplitudes and BW differed between wakefulness and sleep with median amplitude values of the C3-C4 channel 35 µV (IQR: 27-49) for the upper and 13 µV (10-19) for the lower amplitude. The BW was 29 µV (21-34). During sleep, episodes with high amplitudes [upper: 99 µV (71-125), lower: 35 µV (25-44), BW 63 µV (44-81)] corresponded to sleep states N2-N3. High amplitude-sections were interrupted by low amplitude-sections, which became the longer toward the morning [upper amplitude: 39 µV (30-51), lower: 16 µV (11-20), BW 23 µV (19-31)]. Low amplitude-sections were associated with sleep states REM, N1, and N2. With increasing age, amplitudes and bandwidths declined. CONCLUSION: aEEGs in non-critically ill children displayed a wide range of amplitudes and bandwidths. Amplitudes were low during wakefulness and light sleep and high during deep sleep. Interpretation of pediatric aEEG background patterns must take into account the state of wakefulness in in clinical practice and research.

Association of clinical factors with postoperative complications of esophageal atresia.

BACKGROUND: Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) remains one of the most common gastrointestinal neonatal malformations. Even though postoperative management is standardized, it differs between hospitals and disease-associated clinical factors that may play a role in outcome have not yet been assessed in detail. METHODS: In this monocentric retrospective study, data of 43 patients with EA between 2010 and 2018 were analyzed. Analysis includes assessment of the clinical background, surgical technique, postoperative management including application of continuous muscle relaxation (CMR), influence of coagulation parameters such as factor XIII and incidence of complications. RESULTS: 21 patients (49%) were preterm infants with birth weights between 490 and 2840 g (median 1893 g). Only 35% (n = 15) presented without any concomitant malformations. Within the entire study population, representing Vogt II, IIIb and IIIc, we observed an association between the development of a postoperative pneumothorax and anastomotic failure (AF) (p = 0.0013). Furthermore, pneumothorax was associated with anastomotic stenosis (AS) in Vogt IIIb patients (p = 0.0129). CMR (applied since March 2017 in 7 patients in an attempt to prevent anastomotic problems due to high complication rates) and coagulation factor XIII did not significantly correlate with postoperative outcome. CONCLUSION: Appearance of pneumothorax was correlated with postoperative complications. These children should be monitored carefully in closer scheduled gastroenterological follow-up esophago-gastro-duodenoscopies. CMR and factor XIII substitution did not reduce anastomotic leakage but should be tested within an enlarged study population.