Increased Musculoskeletal Deformities And Decreased Lung Volume In Patients After Ea/Tef Repair - A Real-Time Mri Study.

OBJECTIVE: This study aims to assess morphological and functional postoperative changes after open or minimally invasive (MIS) repair of esophageal atresia (EA) compared to healthy controls by thoracic real-time MRI. SUMMARY BACKGROUND DATA: Musculoskeletal deformities and pulmonary morbidity are common in children after EA repair. The real-time MRI is a novel technique that provides ultrafast, high-quality images during spontaneous breathing, without sedation even in young children. METHODS: Children aged 3-18 years were prospectively examined with a 3 Tesla MRI. Musculoskeletal deformities, static thoracic cross-sectional areas (CSA) at three different levels and lung volumes, as well as dynamic right-to-left ratio of CSA of hemithoraces and lung volumes during forced breathing were evaluated. RESULTS: 72 children (42 open, 8 MIS, 22 controls) were recruited. In the EA group, rib fusions and adhesions (78%, P<0.01) and scoliosis (15%, P=0.32) were found after thoracotomy, but not after MIS. Mean right-to-left ratio of CSA and lung volumes were lower after EA repair compared to controls (P <0.05), indicating impaired thoracic and lung development. The number of thoracotomies was a significant risk factor for smaller thoracic volumes (P<0.05). CONCLUSIONS: For the first time, morphological changes and thoracic motility after EA repair were visualized by dynamic real-time MRI. Children after EA repair show decreased right-sided thoracic and lung development compared to controls. Open repair leads to significantly more musculoskeletal deformities. This study emphasizes that musculoskeletal morbidity following a thoracotomy in infancy is high.

Experimental congenital diaphragmatic hernia features an alteration of DNA sensing targets cGAS and STING.

BACKGROUND: The pathogenesis of congenital diaphragmatic hernia (CDH) depends on multiple factors. Activation of the DNA-sensing cyclic-GMP-AMP-synthase (cGAS) and Stimulator-of-Interferon-Genes (STING) pathway by double-stranded DNA (dsDNA) links environmental stimuli and inflammation. We hypothesized that nitrofen exposure alters cGAS and STING in human bronchial epithelial cells and fetal rat lungs. METHODS: We used the Quant-IT™-PicoGreen™ assay to assess dsDNA concentration in BEAS-2B cells after 24 h of nitrofen-exposure and performed immunofluorescence of cGAS/STING. We used nitrofen to induce CDH and harvested control and CDH lungs at embryonic day E15, E18 and E21 for cGAS/STING immunofluorescence, RT-qPCR and RNA-Scope™ in-situ-hybridization (E18, E21). RESULTS: We found a higher concentration of dsDNA following nitrofen treatment. Nitrofen-exposure to BEAS-2B cells increased cGAS and STING protein abundance. cGAS abundance was higher in nitrofen lungs at E15, E18 and E21. RNA-Scope in-situ-hybridization showed higher cGAS and STING expression in E18 and E21 lungs. RT-qPCR revealed higher mRNA expression levels of STING in E21 nitrofen-induced lungs. CONCLUSION: Our data suggest that nitrofen-exposure increases dsDNA content which leads to stimulation of the cGAS/STING pathway in human BEAS-2B cells and the nitrofen rat model of CDH. Consequently, DNA sensing and the cGAS-STING-pathway potentially contribute to abnormal lung development in CDH. IMPACT STATEMENT: We found an alteration of DNA sensing targets cGAS and STING in human BEAS-2B cells and experimental congenital diaphragmatic hernia with higher protein abundance and mRNA expression in cells and lung sections of nitrofen-treated rat pups. This is the first study to investigate DNA sensing, a potential link between environmental stimuli and inflammation, in experimental CDH. Our study extends the knowledge on the pathogenesis of experimental CDH.

Complementary and alternative medicine (CAM) is frequently used by parents for the treatment of functional constipation in children.

OBJECTIVES: Complementary and alternative medicine (CAM) has gained increasing attention as a supportive treatment for chronic diseases such as epilepsy, migraine, autism, and cancer in children. This study aimed to determine the frequency, motivation, and outcomes of CAM in children with functional constipation. METHODS: From January 2018 till September 2019, parents of patients (0-18 years) who were treated for functional constipation (ROME IV-criteria) at our colorectal center were asked to complete a questionnaire on the utilization of CAM. Demographic data and clinical assessments were documented and analyzed for patients with and without CAM treatment. RESULTS: A total of 115 patients were included (mean age: 5.1 years; 49% males), of whom 29 (25%) used CAM as an alternative (4/29,14%) or in addition to conventional therapy (CT), including osteopathy (48%), homeopathy (45%), and natural/herbal remedies (17%). The main reason parents reported for the use of CAM was the urge to leave no treatment option unattempted (76%). Multivariate analysis also identified persistent constipation under CT (72%), adverse effects of CT (24%), and parental use of CAM themselves (83%) as independent variables associated with CAM use. Parents reported positive changes in stool frequency (38%) and fecal incontinence (21%) with CAM. The vast majority (93%) plan to use CAM in the future, and even non-CAM users showed high interest (60%). CONCLUSION: One in four children with functional constipation receives CAM. Significant improvement in stool frequency and continence is missing in the majority. However, parental interest in CAM remains high. Physicians should be aware of CAM when counseling families for functional constipation in children.

Overactivated Epithelial NF-κB Disrupts Lung Development in Congenital Diaphragmatic Hernia.

Abnormal lung development is the main cause of morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH), a common birth defect (1:2,500) of largely unknown pathobiology. Recent studies discovered that inflammatory processes, and specifically NF-κB-associated pathways, are enriched in human and experimental CDH. However, the molecular signaling of NF-κB in abnormal CDH lung development and its potential as a therapeutic target require further investigation. Using sections and hypoplastic lung explant cultures from the nitrofen rat model of CDH and human fetal CDH lungs, we demonstrate that NF-κB and its downstream transcriptional targets are hyperactive during abnormal lung formation in CDH. NF-κB activity was especially elevated in the airway epithelium of nitrofen and human CDH lungs at different developmental stages. Fetal rat lung explants had impaired pseudoglandular airway branching after exposure to nitrofen, together with increased phosphorylation and transcriptional activity of NF-κB. Dexamethasone, the broad and clinically applicable antiinflammatory NF-κB antagonist, rescued lung branching and normalized NF-κB signaling in hypoplastic lung explants. Moreover, specific NF-κB inhibition with curcumenol similarly rescued ex vivo lung hypoplasia and restored NF-κB signaling. Last, we showed that prenatal intraperitoneal dexamethasone administration to pregnant rat dams carrying fetuses with hypoplastic lungs significantly improves lung branching and normalizes NF-κB in vivo. Our results indicate that NF-κB is aberrantly activated in human and nitrofen CDH lungs. Antiinflammatory treatment with dexamethasone and/or specific NF-κB inhibition should be investigated further as a therapeutic avenue to target lung hypoplasia in CDH.

Proteomic Profiling of Hypoplastic Lungs Suggests an Underlying Inflammatory Response in the Pathogenesis of Abnormal Lung Development in Congenital Diaphragmatic Hernia.

The pathogenesis of lung hypoplasia in congenital diaphragmatic hernia (CDH), a common birth defect, is poorly understood. The diaphragmatic defect can be repaired surgically, but the abnormal lung development contributes to a high mortality in these patients. To understand the underlying pathobiology, we compared the proteomic profiles of fetal rat lungs at the alveolar stage (E21) that were either exposed to nitrofen in utero (CDH lungs, n=5) or exposed to vehicle only (non-CDH control lungs, n=5). Pathway analysis of proteomic datasets showed significant enrichment in inflammatory response proteins associated with cytokine signaling and Epstein Barr Virus in nitrofen CDH lungs. Among the 218 significantly altered proteins between CDH and non-CDH control lungs were Tenascin C, CREBBP, LYN, and STAT3. We showed that Tenascin C was decreased around the distal airway branches in nitrofen rat lungs and human CDH lungs, obtained from stillborn fetuses that did not receive pre- or postnatal treatment. In contrast, STAT3 was significantly increased in the airway epithelium of nitrofen lungs at E21. STAT3 inhibition after direct nitrofen exposure to fetal rat lung explants (E14.5) partially rescued the hypoplastic lung phenotype ex vivo by increasing peripheral lung budding. Moreover, we demonstrated that several STAT3-associated cytokines (IL-15, IL-9, andIL-2) are increased in fetal tracheal aspirates of CDH survivors compared with nonsurvivors after fetoscopic endoluminal tracheal occlusion. With our unbiased proteomics approach, we showed for the first time that downstream inflammatory processes are likely involved in the pathogenesis of abnormal lung development in CDH.

Pectus excavatum in motion: dynamic evaluation using real-time MRI.

OBJECTIVES: The breathing phase for the determination of thoracic indices in patients with pectus excavatum is not standardized. The aim of this study was to identify the best period for reliable assessments of morphologic indices by dynamic observations of the chest wall using real-time MRI. METHODS: In this prospective study, patients with pectus excavatum underwent morphologic evaluation by real-time MRI at 3 T between January 2020 and June 2021. The Haller index (HI), correction index (CI), modified asymmetry index (AI), and modified eccentricity index (EI) were determined during free, quiet, and forced breathing respectively. Breathing-related differences in the thoracic indices were analyzed with the Wilcoxon signed-rank test. Motion of the anterior chest wall was analyzed as well. RESULTS: A total of 56 patients (11 females and 45 males, median age 15.4 years, interquartile range 14.3-16.9) were included. In quiet expiration, the median HI in the cohort equaled 5.7 (4.5-7.2). The median absolute differences (Δ) in the thoracic indices between peak inspiration and peak expiration were ΔHI = 1.1 (0.7-1.6, p < .001), ΔCI = 4.8% (1.3-7.5%, p < .001), ΔAI = 3.0% (1.0-5.0%, p < .001), and ΔEI = 8.0% (3.0-14.0%, p < .05). The indices varied significantly during different inspiratory phases, but not during expiration (p > .05 each). Furthermore, the dynamic evaluation revealed three distinctive movement patterns of the funnel chest. CONCLUSIONS: Real-time MRI reveals patterns of chest wall motion and indicate that thoracic indices of pectus excavatum should be assessed in the end-expiratory phase of quiet expiration. KEY POINTS: • The thoracic indices in patients with pectus excavatum depend on the breathing phase. • Quiet expiration represents the best breathing phase for determining thoracic indices. • Real-time MRI can identify different chest wall motion patterns in pectus excavatum.

Real-time MRI: a new tool of radiologic imaging in small children.

Real-time MRI (rt-MRI) in children is a new imaging technique that combines the advantages of US - at frame rates of up to 50 images per second - with the quality and features of MRI. Although still subject of research, it has become a standard tool in the diagnostic portfolio of two pediatric radiology departments in Germany. Based on ultrashort acquisition times, any detrimental effects of macroscopic movements of the child and the physiological movements of the organs are negligible. Especially in pediatric brain imaging, rt-MRI has already proven its value. With suitable indications, rt-MRI can reduce anesthesia and sedation examinations in children below 6 years of age by 40% due to its very short examination time and its robustness to motion. There is a high level of acceptance among parents and referrers when diagnostic possibilities and limitations are communicated correctly. CONCLUSION: Completely new diagnostic possibilities arise in the imaging of the moving lung, the beating heart, joint movements, and speaking and swallowing, as demonstrated in this video-backed review. WHAT IS KNOWN: • MRI in moving children has been burdened with severe artifacts. • Gross motion usually has to be handled by sedation and periodic motion of the heart and lungs has to be compensated with time-consuming techniques until now. WHAT IS NEW: • Real-time MRI allows image acquisition with up to 50 frames per second similar to ultrasound frame rate. • Real-time MRI proofs to be very promising for imaging children, reducing examination time and sedation rate drastically.

Testicular descent revisited: a micro-computed tomography study in fetal rats.

PURPOSE: There is a long history of research dealing with the embryology of the testicular descent. However, important aspects like the role of the gubernaculum and the development of the processus vaginalis peritonei are not understood. Micro-computed tomography (µCT) is an established tool for anatomical studies in rodents. Our study applied µCT imaging to visualize the testicular descent in rats and focused on the role of the gubernacular bulb and the development of the processus vaginalis peritonei. METHODS: Rats from embryonic day 15 (ED15) to ED21 and newborns (N0) were fixed and dried using the "critical point" technique. We ran a SkyScan® µCT system and scans were analyzed for gender-specific differentiation of the genital ridge and used for 3D visualization of relevant anatomic structures. RESULTS: µCT imaging confirmed the intraperitoneal location of the testicles from ED15 to N0. The components of the inner genital moved closer together while the intestinal volume expanded. The gubernacular bulb seemed to be involved in the formation of the processus vaginalis peritonei. CONCLUSION: Here, we utilized µCT imaging to visualize the testicular descent in the rat. Imaging provides new morphologic aspects on the development of the processus vaginalis peritonei.

Characterization of the congenital diaphragmatic hernia model in C57BL/6J fetal mice: a step toward lineage tracing experiments.

PURPOSE: Lineage tracing is key to study the fate of individual cells and their progeny especially in developmental biology. To conduct these studies, we aimed to establish a reproducible model of CDH in the most commonly used genetic background strain that is C57BL/6J mice. METHODS: CDH was induced in C57BL/6J dams by maternal administration of nitrofen + bisdiamine at E8.5. Fetuses from olive oil-gavaged mothers served as controls. Lungs from CDH and control fetuses were compared for (1) growth via radial airspace count (RAC), mean linear intercept (MLI) and gene expression for Fgf10, Nrp1, and Ctnnb1; (2) maturation (Pdpn, Spc, Ager, Abca3, Eln, Acta2, Pdgfra) via gene and protein expression; (3) vascularization via gene and protein expression (CD31, Vegfa, Vegfr1/2, Epas1, Enos). STATISTICS: unpaired t-test or Mann-Whitney test. RESULTS: Nitrofen + bisdiamine administration resulted in 36% left-sided CDH (31% mortality). CDH fetuses had hypoplastic lungs and impaired growth (lower RAC, higher MLI, lower Fgf10, Nrp1, Ctnnb1), maturation (decreased Pdpn, Ager, Eln gene expression), and vascularization (decreased Cd31, Vegfr1/2; Epas1 and Enos). Lower protein expression was confirmed for PDPN, ELN and CD31. CONCLUSION: Modeling CDH in C57BL/6J mouse fetuses is effective in reproducing the classical CDH hallmarks. This model will be critical for lineage tracing experiments.

Tenascin C is dysregulated in hypoplastic lungs of miR-200b-/- mice.

PURPOSE: We previously demonstrated that absence of miR-200b results in abnormal lung development in congenital diaphragmatic hernia due to imbalance between epithelial and mesenchymal cells. Tenascin C is a highly conserved extracellular matrix protein involved in epithelial to mesenchymal transition, tissue regeneration and lung development. Considering the involvement of Tenascin C and miR-200b and their potential interaction, we aimed to study Tenascin C during lung development in the absence of miR-200b. METHODS: We collected lungs of miR-200b-/- mice (male, 8 weeks). We performed Western blot (WB) analysis (N = 6) and immunofluorescence (N = 5) for Tenascin C and alpha smooth muscle actin and RT-qPCR for Tenascin C gene expression (N = 4). RESULTS: Using WB analysis, we observed a decreased total protein abundance of Tenascin C in miR-200b-/- lungs (miR-200b+/+: 3.8 × 107 ± 1 × 107; miR-200b-/-: 1.9 × 107 ± 5 × 106; p = 0.002). Immunofluorescence confirmed decreased total Tenascin C in miR-200b-/- lungs. Tenascin C was significantly decreased in the mesenchyme but relatively increased in the airways of mutant lungs. Total lung RNA expression of Tenascin C was higher in miR-200b-/- lungs. CONCLUSION: We report dysregulation of Tenascin C in lungs of miR-200b-/- mice. This suggests that absence of miR-200b results in abnormal Tenascin C abundance contributing to the lung hypoplasia observed in miR-200b-/- mice.

Musculoskeletal deformities in children with congenital thoracic malformations: a population-based cohort study.

PURPOSE: It is unclear if musculoskeletal deformities observed in patients with congenital diaphragmatic hernia (CDH), congenital lung lesion (CLL) and esophageal atresia/tracheoesophageal fistula (EA/TEF) are associated with the anomaly or are a result of the surgery required to treat the anomaly. This study compared the prevalence of musculoskeletal deformities for: (1) children with congenital thoracic anomalies to controls; (2) CLL to EA/TEF both repaired via thoracotomy; and (3) CLL and EA/TEF to CDH repaired via laparotomy. METHODS: We performed a retrospective study of children with CLL, CDH or EA/TEF between 1990 and 2016. Date-of-birth-matched control groups were generated from a population-based dataset. International Classification of Disease codes were used to identify scoliosis and pectus anomalies. We determined Hazard ratios (HR) for cases versus controls. RESULTS: We included 167 cases (CDH n = 82; CLL n = 29; EA/TEF n = 56) and 1670 controls. EA/TEF had a greater risk of scoliosis (HR 5.52, 95%CI 1.49,13.73) and pectus deformities (HR 4.07, 95%CI 1.96,8.45). CDH showed more scoliosis (HR 5.03, 95%CI 1.99,12.74) but not pectus anomalies. Musculoskeletal deformities were not more common in CLL. CONCLUSION: Children born with CDH or EA/TEF, but not CLL, had more musculoskeletal deformities than controls. The inconsistent association between musculoskeletal deformities and the surgical approach suggested a congenital predisposition.

Bunk-Bed-Related Fractures in Children: Are We Aware of the Risks?

Background and Objectives: Falls from heights are a common mechanism of trauma in children. However, data on bunk-bed-related (BBR) fractures are scarce. We aimed to assess types of fractures and age groups most at risk for BBR fractures. Material and Methods: We analyzed medical records and imaging procedures of patients aged <18 years who sustained a bunk bed injury and were treated at our department between January 2014 and December 2021. Demographic data, including age groups, mechanisms, types and anatomical regions of fractures, were assessed. Results: A total of 162 patients (median age 5 years, range 0−15; 59.9% male) was included. Fractures were recorded in 80 (49.4%) and contusions and abrasions in 49 (30.2%) cases. BBR fractures were recorded in 44.8% of children below the age of 3, in 50.8% aged 3−5, in 58.5% aged 6−9 and in 28.6% ≥ 10 years. Forearm fractures were most common (n = 34, 42.5%), followed by fractures of the clavicle (n = 13, 16.3%), humerus (n = 10, 12.5%), foot (n = 8, 10.0%), hand (n = 5, 6.3%), lower leg (n = 5, 6.3%) and skull (n = 5, 6.3%). Surgery was required in 12 (15.0%) cases, including closed reduction (n = 7) and closed reduction with internal fixation (n = 5). Overall, 21 (26.3%) patients were hospitalized with a mean length of stay of 2 ± 1.6 days. Conclusions: Caregivers should be aware that bunk beds cause a significant amount of severe trauma in children and adolescents, especially in those younger than 10 years of age. Caregivers would benefit from receiving information about these risks and evidence-based strategies to prevent BBR fractures.

Appendiceal Carcinoids in Children-Prevalence, Treatment and Outcome in a Large Nationwide Pediatric Cohort.

Background and Objectives: Appendiceal carcinoids are rare neuroendocrine tumors and mainly found incidentally during histopathological examination following appendectomy. This observational cohort study was performed to determine the prevalence, treatment modalities and outcomes in children diagnosed with an appendiceal carcinoid tumor. Materials and Methods: Data from the largest German statutory health insurance "Techniker Krankenkasse" were analyzed within an 8-year period: January 2010 to December 2012 and January 2016 to December 2020. Patient characteristics, surgical technique, type of surgical department, diagnostic management, and postoperative morbidity were analyzed. Results: Out of 40.499 patients following appendectomy, appendiceal carcinoids were found in 44 children, resulting in a prevalence of 0.11%. Mean age at appendectomy was 14.7 (±2.6) years. Laparoscopic approach was performed in 40 (91%) cases. Right-sided hemicolectomy was performed in 8 (18%) patients. Additional diagnostic work-up (CT and MRI) was recorded in 5 (11%) children. Conclusions: This large nationwide pediatric study shows that 1 in 1000 patients was found to have a neuroendocrine tumor of the appendix (prevalence 0.11%), emphasizing its low prevalence in the pediatric age group. The majority of patients were treated with appendectomy only. However, treatment modalities are still variable. Longer follow-up analyses are needed to evaluate published guidelines and recommendations to aim for a limited surgical approach.

Open versus laparoscopic pyloromyotomy for pyloric stenosis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) is a disorder of young children (aged one year or less) and can be treated by laparoscopic (LP) or open (OP) longitudinal myotomy of the pylorus. Since the first description in 1990, LP is being performed more often worldwide. OBJECTIVES: To compare the efficacy and safety of open versus laparoscopic pyloromyotomy for IHPS. SEARCH METHODS: We conducted a literature search on 04 February 2021 to identify all randomised controlled trials (RCTs), without any language restrictions. We searched the following electronic databases: MEDLINE (1990 to February 2021), Embase (1990 to February 2021), and the Cochrane Central Register of Controlled Trials (CENTRAL). We also searched the Internet using the Google Search engine (www.google.com) and Google Scholar (scholar.google.com) to identify grey literature not indexed in databases. SELECTION CRITERIA: We included RCTs and quasi-randomised trials comparing LP with OP for hypertrophic pyloric stenosis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references and extracted data from trial reports. Where outcomes or study details were not reported, we requested missing data from the corresponding authors of the primary RCTs. We used a random-effects model to calculate risk ratios (RRs) for binary outcomes, and mean differences (MDs) for continuous outcomes. Two review authors independently assessed risks of bias. We used GRADE to assess the certainty of the evidence for all outcomes. MAIN RESULTS: The electronic database search resulted in a total of 434 records. After de-duplication, we screened 410 independent publications, and ultimately included seven RCTs (reported in 8 reports) in quantitative analysis. The seven included RCTs enrolled 720 participants (357 with open pyloromyotomy and 363 with laparoscopic pyloromyotomy). One study was a multi-country trial, three were carried out in the USA, and one study each was carried out in France, Japan, and Bangladesh. The evidence suggests that LP may result in a small increase in mucosal perforation compared with OP (RR 1.60, 95% CI 0.49 to 5.26; 7 studies, 720 participants; low-certainty evidence). LP may result in up to 5 extra instances of mucosal perforation per 1,000 participants; however, the confidence interval ranges from 4 fewer to 44 more per 1,000 participants. Four RCTs with 502 participants reported on incomplete pyloromyotomy. They indicate that LP may increase the risk of incomplete pyloromyotomy compared with OP, but the confidence interval crosses the line of no effect (RR 7.37, 95% CI 0.92 to 59.11; 4 studies, 502 participants; low-certainty evidence). In the LP groups, 6 cases of incomplete pyloromyotomy were reported in 247 participants while no cases of incomplete pyloromyotomy were reported in the OP groups (from 255 participants). All included studies (720 participants) reported on postoperative wound infections or abscess formations. The evidence is very uncertain about the effect of LP on postoperative wound infection or abscess formation compared with OP (RR 0.59, 95% CI 0.24 to 1.45; 7 studies, 720 participants; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on postoperative incisional hernia compared with OP (RR 1.01, 95% CI 0.11 to 9.53; 4 studies, 382 participants; very low-certainty evidence). Length of hospital stay was assessed by five RCTs, including 562 participants. The evidence is very uncertain about the effect of LP compared to OP (mean difference -3.01 hours, 95% CI -8.39 to 2.37 hours; very low-certainty evidence). Time to full feeds was assessed by six studies, including 622 participants. The evidence is very uncertain about the effect of LP on time to full feeds compared with OP (mean difference -5.86 hours, 95% CI -15.95 to 4.24 hours; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on operating time compared with OP (mean difference 0.53 minutes, 95% CI -3.53 to 4.59 minutes; 6 studies, 622 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Laparoscopic pyloromyotomy may result in a small increase in mucosal perforation when compared with open pyloromyotomy for IHPS. There may be an increased risk of incomplete pyloromyotomy following LP compared with OP, but the effect estimate is imprecise and includes the possibility of no difference. We do not know about the effect of LP compared with OP on the need for re-operation, postoperative wound infections or abscess formation, postoperative haematoma or seroma formation, incisional hernia occurrence, length of postoperative stay, time to full feeds, or operating time because the certainty of the evidence was very low for these outcomes. We downgraded the certainty of the evidence for most outcomes due to limitations in the study design (most outcomes were susceptible to detection bias) and imprecision. There is limited evidence available comparing LP with OP for IHPS. The included studies did not provide sufficient information to determine the effect of training, experience, or surgeon preferences on the outcomes assessed.

Epithelial cell-adhesion protein cadherin 26 is dysregulated in congenital diaphragmatic hernia and congenital pulmonary airway malformation.

BACKGROUND: Congenital diaphragmatic hernia (CDH) and congenital pulmonary airway malformation (CPAM) are two inborn pathologies of the lung of unknown origin. Alterations of gene expression in airway epithelial cells are involved in the pathobiology of both diseases. We previously found decreased expression of the epithelial cell adhesion protein cadherin 26 (CDH26) in hypoplastic mice lungs. Here, our objective was to describe the expression and localization of CDH26 in hypoplastic CDH lungs and hyperproliferative CPAM tissues. METHODS: After ethical approval, we used human lung tissues from CDH and CPAM cases and age-matched control samples from a previously established biobank. Furthermore, lungs from the nitrofen rat model of CDH were included in the study. We performed immunohistochemistry and western blot analysis with antibodies against CDH26 to examine protein localization and abundance. Statistical analysis was performed using Mann-Whitney U test with significance set at p < 0.05. RESULTS: We observed an overexpression of CDH26 within the epithelium of cystic CPAM lesions compared to normal airways within the same lung and compared to control lungs. Western blot demonstrated a downregulation of CDH26 in the nitrofen rat model of CDH compared to healthy controls. Immunohistochemistry could not show consistent differences between CDH and control in human and rat lungs. In the studied human lung samples, CDH26 was localized to the apical part of the airway epithelial cells. CONCLUSION: CDH26 is differentially expressed in human CPAM lung tissues and may be downregulated in nitrofen-induced hypoplastic rat lungs compared to control lungs. Disruption of CDH26 associated pathways in lung development may be involved in the pathogenesis of lung hypoplasia or cystic lung disease.

Smartphone-Related Accidents in Children and Adolescents: A Novel Mechanism of Injury.

OBJECTIVES: Smartphones have become an integral part of daily life, often grabbing full attention of its user. We hypothesized that smartphone-associated trauma in children and adolescents has increased in the last decade. The objective of this study was to analyze smartphone-related injuries in children at two German centers for pediatric emergency care. METHODS: Smartphone-related injuries were recorded between January 2008 and March 2018 at two centers of pediatric surgery in Germany. Data were assessed for patient demography, cause of accident, type of injury, treatment, and outcome. RESULTS: Ten children (8 girls, 2 boys; mean ± SD age, 10.6 ± 6.0 years; range, 10 weeks to 17 years) were included. Two patients were injured in 2008 to 2015, eight in 2016 to 2018, of which three required hospital admissions. Six accidents happened in public spaces, and four within domestic environments. Eight children (mean ± SD age, 13.3 ± 2.4 years; 7 girls) were injured while using their smartphone, therefore being distracted. Two children (mean ± SD age, 6.5 ± 6.4 months) were involuntarily hurt by the smartphone of their caregivers. The causes of accident and related injuries were highly variable and ranged from minor trauma (mild head injury [n = 3], abrasions [n = 2], bruises of fingers [n = 2]/hand [n = 1]/ankle [n = 2]) to major injuries requiring intensive care treatment (pelvic [n = 1] or vertebral body fractures [n = 1]). CONCLUSIONS: Smartphone-associated injuries mainly caused by distraction gain increasing importance in pediatric traumatology. The frequency is higher in females compared with their male counterparts. The prevention of these accidents should become part of educational programs for children and adolescents.

High resolution three-dimensional imaging and measurement of lung, heart, liver, and diaphragmatic development in the fetal rat based on micro-computed tomography (micro-CT).

Understanding of normal fetal organ development is crucial for the evaluation of the pathogenesis of congenital anomalies. Various techniques have been used to generate imaging of fetal rat organogenesis, such as histological dissection with 3-dimensional reconstruction and scanning electron microscopy. However, these techniques did not imply quantitative measurements of developing organs (volumes, surface areas of organs). Furthermore, a partial or total destruction of the embryos prior to analysis was inevitable. Recently, micro-computed tomography (micro-CT) has been established as a novel tool to investigate embryonic development in non-dissected embryos of rodents. In this study, we used the micro-CT technique to generate 4D datasets of rat embryos aged between embryonic day 15-22 and newborns. Lungs, hearts, diaphragms, and livers were digitally segmented in order to measure organ volumes and analyze organ development as well as generate high-resolution 3D images. These data provide objective values compiling a 4D atlas of pulmonary, cardiac, diaphragmatic, and hepatic development in the fetal rat.

[Current Treatment of Esophageal Atresia with Tracheoesophageal Fistula - Updated Guidelines of the German Society of Pediatric Surgery]. / Behandlung der Ösophagusatresie mit unterer tracheoösophagealer Fistel ­ Zusammenfassung der aktuellen S2K-Leitlinie der DGKCH.

Esophageal atresia (EA) is a congenital anomaly that entails an interrupted esophagus with or without tracheoesophageal fistula (TEF). Depending on the distance of the two esophageal pouches a "short-gap" is distinguished from a "long-gap" variant. Up to 50% of newborns have additional anomalies. EA is prenatally diagnosed in 32-63% of cases. Recently, the interdisciplinary care in these children underwent substantial changes. Therefore, we summarize the current guideline of the German society of pediatric surgery for the treatment of patients with EA and distal TEF (Gross Type C). Controversies regarding the perioperative management include surgical-technical aspects, such as the thoracoscopic approach to EA, as well as general anesthesia (preoperative tracheobronchoscopy, intraoperative hypercapnia and acidosis). Moreover, postoperative complications and their management like anastomotic stricture are outlined. Despite significant improvements in the treatment of EA, there is still a relevant amount of long-term morbidity after surgical correction. This includes dysmotility of the esophagus, gastroesophageal reflux disease, recurrent respiratory infections, tracheomalacia, failure to thrive, and orthopedic complications following thoracotomy in the neonatal age. Therefore, close follow-up is mandatory to attain optimal quality of life.

Accidental bladder injury during elective inguinal hernia repair: a preventable complication with high morbidity.

INTRODUCTION: Bladder injury (BI) represents a rare complication of inguinal hernia surgery. Protrusions of the urinary bladder through the deep inguinal ring ("bladder ears") have been reported with an incidence of 9% in infants younger than 6 months of age and may be misinterpreted as the hernia sac. This literature review was designed to determine incidence and outcomes of bladder injuries during pediatric inguinal hernia repair. METHODS: A literature review of the literature (1967-2017) was performed using the keywords "bladder ears", "inguinal hernia", "iatrogenic bladder injury" and "bladder hernia". Publications were reviewed for epidemiology, presentation and extent of injury, treatment and outcome. RESULTS: Thirteen articles reporting on 30 cases of BI during inguinal hernia repair from 1967 to 2017 were included (19 boys, 2 girls, 9 unknown). Median age at herniotomy was 10.5 months (1 month-6 years). Out of 30 children, 14 (47%) experienced mild complications. Sixteen patients (53%) had severe complications after initial surgery and needed revisional surgery. Complications were noticed up to 4 years after the initial surgery. In 9 (56%) of the 16 severe cases, major damage to the bladder wall and impairment of bladder capacity occurred. In seven patients (44%), secondary closure was successful. In ten patients (63%), the bladder was partially resected, and in one child (6%), the entire bladder was removed. CONCLUSIONS: The degree of accidental BI during inguinal hernia repair was severe in in the majority of reported cases in the literature. Surgeons should be aware of the high prevalence of "bladder ears" in infants to prevent injury to the urinary tract.

Prenatal maternal biomarkers for the early diagnosis of congenital malformations: A review.

Congenital anomalies cause ~7% of all neonatal deaths, many of which have no identified pathophysiological cause. Because accurate and robust laboratory tests are unavailable for most birth defects, physicians rely on imaging such as ultrasound and MRI. Biomarkers from human body fluids are considered a powerful diagnostic tool to assess human disease and health as it mirrors an individual's condition. Minimally invasive 'liquid biopsies' from blood samples are highly valuable for diagnosis, prognosis, risk assessment, and treatment of many conditions. Recent large-scale analysis ('omics') have enabled researchers to identify novel biomarkers in different areas. To accurately facilitate the early detection of congenital anomalies, the identification of biomarkers from maternal plasma should be promoted. This approach will uncover new opportunities in prenatal diagnosing and likely lead to a better understanding of the pathogenesis of congenital anomalies.