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Introduction: Recently, we showed that various procedures for rigid Natural Orifice Transluminal Endoscopic Surgery (NOTES) can be successfully performed in piglets. However, the safety and effectiveness of endoscopic closure of the urinary bladder remains to be determined before introducing transurethral NOTES in children. Our study was designed to investigate the safety and impermeability of the urinary bladder after endoscopic closure in transurethrally assisted nephrouretectomy in piglets.Material and Methods: Five female piglets (mean weight 14.5 kg; range: 14-15) underwent right-sided transurethral nephroureterectomy using a hybrid technique with one 15 mm trocar placed umbilically and one 3 mm trocar placed transvesically. Hilar dissection was performed with a 5 mm Endoligasure vessel sealing device. After umbilical retrieval of the resected kidney, the urinary bladder was closed by an Endoloop via an umbilical "two in one system" with the assistance of a 2 mm transurethrally placed endoscopic clamp. Endpoints of the study were total operation time, duration of cystoscopy and transurethral trocar positioning, duration of nephrectomy, duration of bladder closure and determination of bladder impermeability. Intraoperatively, bladder filling was performed with normal saline (ml), while bursting pressure (mmHg) was measured by filling the harvested bladder with air.Results: All nephroureterectomies were successfully performed with negligible blood loss. Mean total operation time was 46 min (range: 35-69). Cystoscopy and transurethral trocar positioning took 14 min (range: 9-23), and nephrectomy took 28 min (range: 18-48). Mean duration of bladder closure was 4 min (range: 2-6). Mean volume of intraoperative bladder filling was 94 ml (range: 80-100), indicating adequate capacity after closure with Endoloops. Post-mortem bladder impermeability was confirmed by a mean air filling bursting pressure of 88 mmHg (range: 70-140) indicating sufficient bladder closure.Conclusion: A safe urinary bladder closure is mandatory for transurethral rigid NOTES procedures and can be adequately achieved with Endoloops. [ABSTRACT FROM AUTHOR]

Introduction:  Anorectal malformations (ARMs) are rare birth defects affecting the anorectum and oftentimes the genitourinary region. The management of ARM patients is complex and requires highly specialized surgical and medical care. The European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM applicable on a European level., Methods:  The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence, expert opinion, and the European context., Results:  Surgical and medical treatment of ARM, postoperative instructions, toilet training, and management of fecal and urinary incontinence were addressed. Seven new studies were identified. The panel adapted 23 recommendations, adopted 3, and developed 8 de novo. The overall level of newly found evidence was considered low., Conclusion:  Treatment of ARM patients requires a multidisciplinary team and expertise about anatomical and surgical aspects of the disease, as well as long-term follow-up. This guideline offers recommendations for surgical and medical treatment of ARM and associated complications, according to the best available evidence and applicable on a European level., Competing Interests: The authors would like to disclose that two of the authors of this adaptation report (I.D.B., C.S.) were also authors of the Dutch Quality Standard. However, it is important to note that neither I.D.B. nor C.S. has any conflict of interest to declare and they did not advocate for any particular viewpoints or positions in relation to the content of the Dutch Quality Standard. No conflicting interests were declared from the other authors., (Thieme. All rights reserved.)

Introduction:  Anorectal malformations (ARMs) are complex congenital anomalies of the anorectal region, oftentimes also affecting the genitourinary system. Although successful surgical correction can often be achieved in the neonatal period, many children will experience functional problems in the long term. The European Reference Network for rare and complex urogenital conditions (eUROGEN) assembled a panel of experts to address these challenges and develop comprehensive guidelines for the management of ARM., Methods:  The Dutch Quality Standard for ARM served as the foundation for the development of guidelines applicable on a European level. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from 7 European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence and/or expert consensus., Results:  Lifelong follow-up, integration, and transition of care were assessed. A total of eight new studies were identified. The panel adapted 18 recommendations, adopted 6, and developed 6 de novo. Overall, the level of evidence was considered low., Conclusion:  Successful lifelong follow-up and transition of care require a dedicated team of pediatric and adult specialist and an individually tailored patient-centered approach. This guideline summarizes the best available evidence on follow-up of ARM patients and provides guidance for the development of structured transition programs., Competing Interests: We would like to disclose that two of the authors of this adaptation report (IDB, CEJS) were also authors of the Dutch Quality Standard. However, it is important to note that neither IDB nor CEJS have any conflict of interest to declare and they did not advocate for any particular viewpoints or positions in relation to the content of the Dutch Quality Standard. No conflicting interests were declared from the other authors., (Thieme. All rights reserved.)

Introduction:  The aims of this survey were to assess the experiences of the transition from in-person to virtual meetings among European pediatric surgeons since the beginning of the coronavirus disease 2019 (COVID-19) pandemic and to identify preferences for future formats., Materials and Methods:  An online questionnaire was circulated among members of the European Reference Network for rare Inherited and Congenital Anomalies Network (ERNICA) in 2022. Two time periods were compared (3 years before the COVID-19 pandemic vs. the year 2021)., Results:  A total of 87 pediatric surgeons from 16 countries completed the survey. In addition, 27% of respondents were trainees/residents and 73% consultants/lead surgeons. Consultants participated in significantly more in-person congresses prior to the COVID-19 pandemic compared with trainees (5.2 vs. 1.9; p  < 0.001). A significant increase in attendance of virtual meeting was reported during 2021 compared with pre-COVID-19 (1.4 vs. 6.7; p  < 0.001). Consultants had experienced significantly less absenteeism thanks to virtual meetings compared with trainees (42/61 vs. 8/23; p  < 0.05). Most surgeons considered virtual meetings more economic (82%), practical (78%), and family-friendly (66%). However, a majority reported missing social events (78%). The communication among attendees or between attendees and speakers or scientific faculty was deemed worse. A minority (14%) experienced equalized representation of trainees and consultants at virtual meetings. Most respondents (58%) agreed that future meeting strategies should focus on offering virtual formats. Regarding future congresses, respondents prefer hybrid (62%) over in-person (33%) or virtual (6%) formats., Conclusion:  According to European pediatric surgeons, virtual learning formats hold multiple advantages and should be continued. Improved technology must meet the challenges, particularly to enhance communication, equal representation, and networking between attendees., Competing Interests: None declared., (Thieme. All rights reserved.)

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., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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.

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction:  Micro-computed tomography (micro-CT) is an established tool to study fetal development in rodents. This study aimed to use micro-CT imaging to visualize the development of the urinary tract in fetal rats., Materials and Methods:  Fetal rats from embryonic day (ED) 15, ED17, ED19, ED21, and N0 (newborn) ( n  = 6 per group; 3 males) were fixed and desiccated using the "critical point" technique. We utilized the micro-CT system (SkyScan) and analyzed the resulting scans with CTAn, DataViewer, and ImageJ to visualize the morphology and quantify the volumes of kidney, bladder, adrenal gland, as well as length of the ureter., Results:  High-resolution micro-CT showed continuous growth of both kidneys from ED15 to N0, with the highest increase between ED19 and ED21. The length of the ureter increased from ED15 to ED21 and remained stable until birth. The volume of the bladder steadily increased from ED15 to N0.In females, a statistically higher volume of the adrenal gland on ED21 was observed, whereas no sex-specific differences were seen for kidney, ureter, and bladder development., Conclusion:  Micro-CT depicts an excellent tool to study urinary tract development in the fetal and neonatal rat. It enables the metric quantification of longitudinal anatomic changes in high definition without previous destructive tissue preparation. The present study revealed sex-specific differences of the adrenal gland development and provides comprehensive data for the understanding of fetal urinary tract development, inspiring future research on congenital urological malformations., Competing Interests: None declared., (Thieme. All rights reserved.)

Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in various embryonic developmental processes, including angiogenesis, by controlling actin cytoskeleton assembly and cell contractility. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos, leading to ventral body wall defects (VBWDs). Impaired angiogenesis has been hypothesized to contribute to VBWDs. ROCK is essential in transmitting signals downstream of vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis induces gene expressions and alterations of the actin cytoskeleton upon binding to VEGF receptors (VEGFRs). The aim of this study was to investigate effects of Y-27632 on angiogenesis in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Y-27632-treated embryos showed reduced extra-embryonic blood vessel formation with impaired circulation of the yolk sac, confirmed by fractal analysis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated myosin light chain. Interestingly, RT-PCR demonstrated increased gene expression of VEGF and VEGFR-2 1 h post-treatment. Protein levels of VEGF were higher in Y-27632-treated embryos at 8 h following treatment, whereas no difference was seen in membranes. We hypothesize that administration of Y-27632 impairs vessel formation during angiogenesis, which may contribute to failure of VWB closure, causing VBWDs.

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.

Purpose: Anorectal malformations (ARM) are one of the most challenging congenital malformations in pediatric surgery. We aimed to assess the research activity on ARM over the last five decades., Methods: Data on original research publications were retrieved from the Web of Science Core Collection (1970-2020), and analyzed for countries, authors, scientific journals, and top-ten papers. Scientific quantity was assessed by the number of publications. Research quality was estimated from the number of citations, average citation rate per item (ACI), and h-index., Results: A total number of 1595 articles with 19,419 citations (ACI = 12.2; h-index = 54) were identified. The annual number of publications and citations significantly increased over time ( p < 0.0001). The USA ( n = 386; 24.2%), Japan ( n = 153; 9.6%), and China ( n = 137; 8.6%) were the most productive countries; and the USA ( n = 7850; ACI = 20.3; h-index = 44), Japan ( n = 1937; ACI = 12.6; h-index = 21), and the Netherlands ( n = 1318; ACI = 17.3; h-index = 22) were the top cited countries. Articles were preferentially published in JPS ( n = 391; 24.5%), PSI ( n = 181; 11.3%), and EJPS ( n = 56; 3.5%). Top-ten cited papers focused on classification ( n = 1), surgical technique ( n = 3), associated syndromes ( n = 2), postoperative outcome ( n = 3), and basic research ( n = 1)., Conclusion: This bibliometric study provides valuable insights into the global development of ARM research, and shows that clinical studies and international collaborations dominate in this field.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10 -8 ; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10-5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10 -10 ; OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10 -16 ; OR = 1.75; 95% CI, 1.64-1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes., Competing Interests: The co-author C.M.B. declares the following interests: Shire (grant recipient, Scientific Advisory Board member), Idorsia (consultant), Lundbeckfonden (grant recipient), Pearson (author, royalty recipient), and Equip Health Inc. (Clinical Advisory Board). All other co-authors declare no competing interests., (© 2022 The Authors.)

Laparoscopy has a major role in the treatment of anorectal malformations (ARM) since Georgeson et al. introduced the laparoscopic assisted anorectoplasty in 2000. The majority of ARM can be repaired through a posterior sagittal incision without the need to enter the abdomen. Some ARM types require an abdominal approach to detach the rectum from the urinary tract in males or the vagina in females. Those malformations benefit from laparoscopy. In this article, we aimed to highlight the technical aspects relevant to the current laparoscopic repair of ARM.

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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: None declared.

Background: Wound dehiscence (WD) of the anocutaneous anastomosis or perineal body after posterior sagittal anorectoplasty (PSARP) is common. We aimed to evaluate the efficacy of a perineal vacuum-assisted closure (VAC) for prevention of WD following repair of anorectal malformations (ARM) with rectoperineal and rectovestibular fistula., Methods: A retrospective dual-center case-control study of children undergoing PSARP without colostomy between 2011 and 2019 was performed. The VAC group received preoperative bowel preparation (PBP), postoperative application of a VAC, loperamide (only Location A), intravenous antibiotics (IA), and total parenteral nutrition (TPN). The non-VAC group underwent PBP, loperamide (Location A), IA, and TPN without VAC. Primary outcome was WD at the anocutaneous anastomosis or reconstructed perineal body within the first 14 days after surgery., Results: The study population included 18 patients (VAC group) and 20 children (non-VAG group) with rectoperineal and rectovestibular fistula. The incidence of WD in the VAC group was 0% compared to 25% in the non-VAC group (0/18 vs. 5/20, p = 0.04). No VAC related complications occurred., Conclusion: Postoperative application of a VAC embedded in a perioperative treatment protocol has the potential to prevent wound dehiscence of the neoanus and reconstructed perineal body following PSARP., Type of Study: Case-control study., Level of Evidence: Level III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction:  Functional constipation (FC) is a common gastrointestinal disorder affecting up to 30 % of children. Voluntary stool withholding (e.g., after painful defecation) with consecutive harder and larger stools can result in avoidance patterns. Perianal abscesses (PA) are associated with anal pain and painful stooling. We hypothesized that patients with PA have a higher incidence of subsequent FC compared with children without PA., Materials and Methods:  Between January 2010 and December 2016, we retrospectively analyzed all infants (< 365 days of life) presenting at our institution with PA or unilateral inguinal hernia repair (IH; control group). We screened the clinical charts of these patients for outpatient or inpatient visits due to FC according to ROME IV criteria between 01/2010 and 10/2019. Statistical analysis was done using chi-squared test., Results:  We included a total of 37 infants with PA and 118 with IH repair (controls). Mean age at presentation for PA was 3.7 ± 0.5 months compared with 4.2 ± 0.3 months at surgery for IH. In the PA group, 6/37 (16%) developed FC compared with 1/118 (1%) in the control group ( p -value < 0.01). Patients with PA presented with FC at a mean age of 22.3 ± 4.6 months. Twenty-three of thirty-seven (62%) of PA patients underwent surgery. The development of FC in the PA group was independent of conservative versus surgical treatment (14 vs. 17%, p >0.05)., Conclusion:  Our study suggests that PA is associated with an increased risk of FC during the further course. Prophylactic stool softening in patients with PA may be considered to prevent subsequent FC., Competing Interests: None declared., (Thieme. All rights reserved.)

The pyridine derivative Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in numerous developmental processes during embryogenesis, primarily by controlling actin-cytoskeleton assembly and cell contractility. Somite formation requires rearrangement of the cytoskeleton and assists in major morphological mechanisms, including ventral body wall formation. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos leading to ventral body wall defects (VBWD) at later stages of development. The aim of this study was to investigate the effect of Y-27632 on somite development in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Following administration, abnormality rates were assessed. In treatment groups, embryos showed a kinked longitudinal body axis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated cofilin-2. Histology, Lysotracker studies and RT-PCR demonstrated increased cell death in somites, the neural tube and the ectoderm. RT-PCR and Western blot of factors known to be involved during somitogenesis revealed reduced expression in the treatment group compared to controls. We hypothesize that administration of Y-27632 disrupts somite development causing axial kinking and embryo malformation, which may lead to VBWD., (Copyright © 2020. Published by Elsevier Inc.)

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., (© 2020 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

To investigate the use of abdominal CT scanning in the management of pediatric blunt abdominal trauma in pediatric and non-pediatric departments.In this observational cohort study, anonymized data were extracted from 2 large German statutory health insurances (∼5.9 million clients) in a 7-year period (2010-2016). All patients with inpatient International Classification of Diseases (ICD) codes S36.- and S37.- (injury of intra-abdominal organs; injury of urinary and pelvic organs) aged ≤18 years were included. Demographic and clinical data were analyzed by logistic regression analysis for associations with the use of abdominal CT.A total of 524 children with blunt abdominal trauma (mean age 11.0 ± 5.2 years; 62.6% males) were included; 164 patients (31.3%) received abdominal CT-imaging. There were no significant differences in traumatic non-intraabdominal comorbidity patterns (injuries of external causes; injuries to the head or thorax). There was substantial variability in the rate of abdominal CT imaging among different medical disciplines ranging from 11.6% to 44.5%. Patients admitted to pediatric departments (Pediatrics and Pediatric Surgery) underwent abdominal CT imaging significantly less frequently (19.7%; N = 55) compared to patients treated in non-pediatric departments (General/Trauma Surgery: 44.5%; N = 109) irrespective of concomitant injuries. The estimated OR for the use of abdominal CT by General/Trauma Surgery was 6.2-fold higher (OR: 6.15 [95-%-CI:3.07-13.21]; P < .001) compared to Pediatric Surgery. Other risk factors associated with the use of abdominal CT were traumatic extra-abdominal comorbidities, increasing age, male gender, and admission to a university hospital.Abdominal CT imaging was significantly less frequently used in pediatric departments. The substantial variability of the abdominal CT rate among different medical disciplines and centers indicates a potential for reduction of CT imaging by implementation of evidence-based guidelines. Furthermore, our study underlines the need for centralization of pediatric trauma care in Germany not only to improve patient outcome but to avoid radiation-induced cancer mortality.

Perianal abscess (PA) and fistula-in-ano (FIA) are common entities in infancy. Although several hypotheses have been suggested, the pathogenesis of PA/FIA remains elusive. The natural course of these diseases in infancy is self-limiting in the majority of cases whereas older children show similarities to PA/FIA in adults. It is important to rule out rare differential diagnoses of PA/FIA such as inflammatory bowel disease (IBD), surgical complications after colorectal surgery, and immunodeficiencies. Treatment remains empiric, comprises conservative, as well as surgical approaches, and is dependent on the age of the patient. This review summarizes anatomical aspects, current evidence on disease pathogenesis, clinical presentation, and management of pediatric patients with PA and FIA., Competing Interests: None declared., (Thieme. All rights reserved.)

Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a . This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC., (Copyright © 2020 Rieke, Zhang, Braun, Yilmaz, Japp, Lopes, Pleschka, Hilger, Schneider, Newman, Beaman, Nordenskjöld, Ebert, Promm, Rösch, Stein, Hirsch, Schäfer, Schmiedeke, Boemers, Lacher, Kluth, Gosemann, Anderberg, Barker, Holmdahl, Läckgren, Keene, Cervellione, Giorgio, Di Grazia, Feitz, Marcelis, Van Rooij, Bökenkamp, Beckers, Keegan, Sharma, Dakal, Wittler, Grote, Zwink, Jenetzky, Brusco, Thiele, Ludwig, Schweizer, Woolf, Odermatt and Reutter.)

Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development., Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal., Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants., Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF., Competing Interests: The authors have declared that no competing interests exist.

The surgical management of patients with congenital diaphragmatic hernia (CDH) is challenging and ever changing. It requires the highest expertise not only on the surgical level but also of neonatologists and anesthesiologists. In selected patients traditional open surgery is increasingly replaced by thoracoscopic CDH repair in many centers worldwide. Despite obvious and well-described advantages of the minimally invasive approach like a shorter ventilatory time, less pain, a shorter hospital length of stay, and a better cosmesis, important controversies remain. This review discusses hot topics of minimally invasive CDH repair, such as extracorporeal membrane oxygenation, hypercapnia/acidosis, patch repair, surgical training, and recurrence., Competing Interests: R.W. has a patent UOM 2019–042 “Use of circular RNAs as prenatal biomarkers in congenital diaphragmatic hernia” licensed to Richard Wagner and Richard Keijzer. All the other authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

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.

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.

To investigate the use of neuroimaging in children and adolescents with minor brain injury in pediatric and non-pediatric departments.In this observational cohort study data were extracted from a large German statutory health insurance (AOK Plus Dresden ∼3.1 million clients) in a 7-year period (2010-2016). All patients with International Classification of Diseases (ICD) code S06.0 (concussion; minor brain injury; commotio cerebri) aged ≤ 18 years were included. Demographic and clinical data were analyzed by logistic regression analysis for associations with the use of CT and MRI (independent variables: gender, age, length of stay, pediatric vs non-pediatric department, university vs non-university hospital).A total of 14,805 children with minor brain injuries (mean age 6.0 ± 5.6; 45.5% females) were included. Treatment was provided by different medical departments: Pediatrics (N = 8717; 59%), Pediatric Surgery (N = 3582, 24%), General Surgery (N = 2197, 15%), Orthopedic Trauma Surgery (N = 309, 2.1%). Patients admitted to pediatric departments (Pediatrics and Pediatric Surgery) underwent head CT-imaging significantly less frequently (3.8%) compared to patients treated in non-pediatric departments (18.5%; P < .001; General Surgery: 15.6%; Orthopedic Trauma Surgery: 39.2%). Logistic regression confirmed a significantly higher odds ratio (OR) for the use of cranial CT by the non-pediatric departments (OR: 3.2 [95-%-CI: 2.72-3.76]).CT was significantly less frequently used in pediatric departments. Educational efforts and quality improvement initiatives on physicians, especially in non-pediatric departments may be an effective approach to decreasing rates of CT after minor traumatic brain injuries.

Introduction:  Surgery for ureteropelvic junction obstruction (UPJO) is performed by both pediatric surgeons (PS) and urologists (URO). The aim of this study was to analyze treatment modalities for UPJO and results in relation to the surgical technique and the operating discipline in Germany., Materials and Methods:  Data of patients aged 0 to 18 years were extracted from a major public health insurance (covering ∼5.7 million clients) during 2009 to 2016 and were analyzed for sociodemographic variables, surgical technique, and treating discipline. Logistic regression analysis was performed for the risk of a complication within the first postoperative year., Results:  A total of 229 children (31.0% female) were included. Laparoscopic pyeloplasty (LP) was performed in 58 (25.3%) patients (8.6 ± 6.4 years), and open pyeloplasty (OP) was applied in 171 (74.7%; 4.6 ± 5.9 years). LP was the dominant technique in females ( p  < 0.02); males preferentially underwent OP ( p  < 0.02). Length of hospital stay was 4.3 days ( p  = 0.0005) shorter in LP compared with that in OP, especially in children ≤ 2 years (6.7 days, p  = 0.007). PS operated on 162 children (70.7%), and URO performed surgery on 67 patients (29.3%). The mean age of children operated by PS (3.5 ± 4.7 years) was significantly younger compared with that operated by URO (10.8 ± 6.5 years, p  < 0.0001). Complication rates were independent of surgical technique or treating specialty., Conclusion:  In Germany, UPJO was treated by LP in 25.3% of patients, which was associated with a shorter length of stay, especially in children ≤ 2 years. Complication rates were independent of the operating specialty and surgical technique. Therefore, LP should be further promoted for the treatment of UPJO in small children., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective:  Recurrent esophageal strictures (ESs) following esophageal atresia repair or caustic ingestion represent a common clinical problem. Recently, Mitomycin C was reported to improve the outcome of patients by reducing the number of endoscopic dilatations. However, other groups failed to exhibit a beneficial effect. We report on our experience with topic Mitomycin C application following endoscopic dilatation for recurrent ES., Methods:  Retrospective chart review of patients with ES treated at the Hannover Medical School (Location A) and the University of Leipzig (Location B) between 2009 and 2015. A Mitomycin C-soaked cotton swab was endoscopically placed at the area of stricture in all subjects. Successful treatment was defined as resolution of stricture after Mitomycin C therapy with not more than three dilatations thereafter. Our results were compared with published outcomes of alternative studies that involved 10 or more patients., Results:  A total of 11 children received Mitomycin C concurrently with endoscopic dilatations. Seven children (64%) had gross type C esophageal atresia, two patients (18%) gross type A esophageal atresia, and two children (18%) caustic injury.After a median follow-up of 34 months (range, 14-75 months) and a median number of 3 ± 2.5 dilatations with Mitomycin C application per patient (range, 1-9), 6 of 11 patients (55%) achieved a resolution of their strictures. Five patients (45%) did not respond to Mitomycin C therapy, of which two needed esophageal redo-surgery., Conclusion:  We failed to confirm the high success rates of Mitomycin C treatment for recurrent ESs. Given the fact that there is limited data to prove the beneficial effect of Mitomycin C treatment, pediatric surgeons should carefully consider whether the advantages of this therapy outweigh the necessity of life-long endoscopic follow-ups. Further randomized controlled studies are recommended., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Extensive vascular remodeling causing pulmonary hypertension (PH) represents a major cause of mortality in patients with congenital diaphragmatic hernia (CDH). The chemokine monocyte chemoattractant protein-1 (MCP-1) is a biomarker for the severity of PH and its activation is accompanied by pulmonary influx of monocytes and extensive vascular remodeling. MCP-1 activation can be reversed by application of rosiglitazone (thiazolidinedione). We performed this study to evaluate the role of MCP-1 for the pathogenesis of PH in experimental CDH. We hypothesized that vascular remodeling and MCP-1 activation is accompanied by pulmonary influx of fetal monocytes and can be attenuated by prenatal treatment with rosiglitazone., Methods: In a first set of experiments pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D21 and divided into CDH and control. Quantitative real-time polymerase chain reaction, Western blot (WB), and immunohistochemistry (IHC) were used to evaluate MCP-1 expression, activation, and localization. Quantification and localization of pulmonary monocytes/macrophages were carried out by IHC. In a second set of experiments nitrofen-exposed dams were randomly assigned to prenatal treatment with rosiglitazone or placebo on D18+D19. Fetal lungs were harvested on D21, divided into control, CDH+rosiglitazone, and CDH+placebo and evaluated by WB as well as IHC., Results: Increased thickness of pulmonary arteries of CDH fetuses was accompanied by increased systemic and perivascular MCP-1 protein expression and significantly higher amounts of pulmonary monocytes/macrophages compared to controls (p<0.01). These effects were reversed by prenatal treatment with rosiglitazone (p<0.01 vs. CDH+P; control)., Conclusion: Prenatal treatment with rosiglitazone has the potential to attenuate activation of pulmonary MCP-1, pulmonary monocyte influx, and vascular remodeling in experimental CDH. These results provide a basis for future research on prenatal immunomodulation as a novel treatment strategy to decrease secondary effects of PH in CDH., Competing Interests: The authors have declared that no competing interests exist.

Background: Minimally invasive surgery (MIS) has gained increasing importance in neonatal surgery but the effects on neonatal physiology remain unclear. We aimed to characterize the impact of capnoperitoneum on physiologic parameters in a small animal model for neonatal MIS., Material and Methods: Twenty-four 10-day-old Sprague Dawley rats underwent inhalative anesthesia (1% isoflurane in 100% O 2 250 mL/minutes) and were allowed to breathe spontaneously. CO 2 was insufflated into the abdominal cavity for 1 hour via a 24G cannula. Anesthetized litter mates without insufflation served as sham controls, those without any treatment as external controls. Continuous monitoring included O 2 -saturation, heart and respiration rate, pulse and breath distension. After euthanasia, blood gas analysis was performed., Results: All animals survived the experiment. Capnoperitoneum was best tolerated at a pressure of 2 mmHg and a flow of 0.5 L/minutes. A significant decrease in heart rate was observed within the first 30 minutes of insufflation comparing the CO 2 and sham group (P < .05). In both, the CO 2 and sham group, postmortem pH-levels were lower and pCO 2 levels were higher compared to external controls (P < .05). Additionally, levels of pCO 2 were higher but pH levels remained unchanged in the CO 2 compared to sham group (P < .05)., Conclusion: We established a small animal model for neonatal laparoscopy. A pressure of 2 mmHg and flow of 0.5 L/minutes induced physiologic alterations but was well tolerated by the animals. These settings can be used in future studies on the impact of the capnoperitoneum in neonatal MIS.

Introduction  We aimed to analyze for the first time the characteristics, treatment modalities, and outcomes in infants with congenital abdominal wall defects (CAWDs) in Germany and to compare the results with current literature reports. Patients and Methods  Data of a health insurance covering approximately 10% of the German population were analyzed. Patients who had undergone CAWD closure during a period of nearly 6 years were included. Surgical approach was categorized into primary versus secondary closure. Complications were defined as any reintervention within 1 year after initial treatment. Results  Patients with gastroschisis were treated in 24 centers, newborns with omphalocele in 34 centers. There was no mortality, and the type of surgical approach had no significant impact on the incidence of complications in both gastroschisis and omphalocele. Out of 39 patients with gastroschisis, 72% had undergone primary closure being associated with a shorter duration of ventilation ( p  = 0.003) and hospitalization ( p  < 0.001). Out of 54 patients with omphalocele, 54% had undergone secondary closure, whereas modality of management did not affect duration of ventilation and hospitalization. Although heterogeneous, data of the current literature were comparable to those of this study. Conclusion  Unbiased data demonstrate for the first time that the quality of the current surgical management of newborns with CAWD across Germany is excellent. There was no correlation of complications with the method of closure in gastroschisis and omphalocele., Competing Interests: Conflict of Interest: The presented material is original research. The content of this manuscript has not been previously published or submitted for publication elsewhere. The manuscript has been seen and approved by all authors. The authors have no potential conflicts of interest to disclose (financial, professional, or personal)., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease of preterm human newborns with yet unresolved etiology. An established neonatal murine model for NEC employs oral administration of lipopolysaccharides (LPS) combined with hypoxia/hypothermia. In adult mice, feeding dextran sodium sulfate (DSS) represents a well-established model for experimental inflammatory bowel disease. Here we investigated the effect of DSS administration on the neonatal murine intestine in comparison with the established NEC model., Methods: 3-day-old C57BL/6J mice were either fed formula containing DSS or LPS. LPS treated animals were additionally stressed by hypoxia/hypothermia twice daily. After 72 h, mice were euthanized, their intestinal tissue harvested and analyzed by histology, qRT-PCR and flow cytometry. For comparison, adult C57BL/6J mice were fed with DSS for 8 days and examined likewise. Untreated, age matched animals served as controls., Results: Adult mice treated with DSS exhibited colonic inflammation with significantly increased Cxcl2 mRNA expression. In contrast, tissue inflammation in neonatal mice treated with DSS or LPS plus hypoxia/hypothermia was present in colon and small intestine as well. Comparative analysis of neonatal mice revealed a significantly increased lesion size and intestinal Cxcl2 mRNA expression after DSS exposure. Whereas LPS administration mainly induced local neutrophil recruitment, DSS treated animals displayed increased monocytes/macrophages infiltration., Conclusions: Our study demonstrates the potential of DSS to induce NEC-like lesions accompanied by a significant humoral and cellular immune response in the small and large intestine of neonatal mice. The new model therefore represents a good alternative to LPS plus hypoxia/hypothermia administration requiring no additional physical stress.

The treatment of esophageal atresia is not centralized in Germany. Therefore, high numbers of departments are involved. Data on the results of esophageal atresia repair from Germany are lacking. The aim of this study was to evaluate the early postoperative results after repair of esophageal atresia based on unbiased data of a German health insurance. We aimed to determine whether characteristics of the departments had an impact on outcome and compared the results from this study with the literature data from centers with a high caseload. Data of a German health insurance covering ∼10% of the population were analyzed. All patients who had undergone esophageal atresia repair from January 2007 to August 2012 were included. Follow-up data of 1 year postoperatively were analyzed. The potential impact of various characteristics of the treating surgical institutions was assessed. Results were compared with the latest international literature. Seventy-five patients with esophageal atresia underwent reconstructive surgery in 37 departments. The incidences of anastomotic leak (3%) and recurrent tracheoesophageal fistula (7%) were comparable with the literature (both 2-8%). Anastomotic stricture required dilatation in 57% of patients (mean 5.1 ± 5.6 dilatations) comparing unfavorably to most, but not all international reports. During 1-year follow-up, 93% of the patients were readmitted at least once (mean 3.9 ± 3.1 admissions). The incidence of complications did not correlate with any of the characteristics of the treating institutions such as academic affiliation, the number of consultants, beds, and preterm infants treated per year (all P > 0.05). Based on unbiased data, postoperative results after repair of esophageal atresia in Germany are comparable with recently published reports from international single centers. A correlation between the complication rate and characteristics of the treating institutions was not identified., (© 2015 International Society for Diseases of the Esophagus.)

Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host-pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches., Competing Interests: The authors declare no conflict of interest.

Background: Meta-analyses indicate advantages of laparoscopic compared to open appendectomy. Nationwide analyses on results of laparoscopic appendectomy are scarce and studies from Germany are not available. This observational cohort study based on a nationwide insurance database was performed to analyze results of pediatric laparoscopic versus open appendectomy in general use., Methods: Data were extracted from the largest German statutory health insurance TK (∼9 million clients) in a 3-year period (2010-2012). All patients aged 4-17 years with International Classification of Procedures in Medicine (ICPM) code "appendectomy" were included. Logistic regression analysis for the risk of a surgical complication within 180 postoperative days was performed., Results: Appendectomy was performed in 8110 patients (52.6 % male; 47.4 % female) and conducted laparoscopically in 75.0 % of the patients (conversion rate = 1.2 %). Laparoscopic compared to open surgery was associated with a shorter length of hospital stay in both uncomplicated and complicated appendicitis. Patients with complicated appendicitis had lower readmission rates for surgical complications after laparoscopic appendectomy and logistic regression analysis confirmed a significantly lower risk of readmission for surgical complications after laparoscopic compared to open operation in adolescents. Pediatric surgeons operated 23.9 % and general surgeons 76.1 % of patients. Laparoscopy was less frequently used and the conversion rate was significantly higher in pediatric surgical departments., Conclusion: This first nationwide German cohort study confirms that laparoscopic appendectomy is associated with a less complicated postoperative course compared to open appendectomy, particularly in patients with complicated appendicitis. Pediatric surgeons used laparoscopy less frequently compared to general surgeons. Laparoscopic appendectomy should therefore be further promoted in pediatric surgical centers in Germany.

The focus of this review article is on child abuse and the radiographic pattern of X‑ray findings. The radiologist should be able to recognize typical injuries resulting from child abuse. In some cases the findings are highly specific for abuse and these include metaphyseal corner fractures of the long bones in children aged up to 24 months. In other cases the fractures are not specific but highly indicative of child abuse: rib fractures, for example can be associated with child abuse in more than 50 % of the cases; however, maltreatment is difficult to diagnose without taking the entire pattern of skeletal findings into consideration so that a radiological screening of the entire skeleton is often necessary. The concept of sentinel injuries might be helpful for deciding in which cases a complete skeletal screening should be performed. In the age group up to 24 months old a complete skeletal status (with some exceptions) is recommended if one of the three sentinel injuries of rib fractures, intracranial bleeding and abdominal trauma is present.

Aim: The high morbidity and mortality in newborn infants diagnosed with congenital diaphragmatic hernia (CDH) is widely recognized to be due to pulmonary hypoplasia and persistent pulmonary hypertension (PH). The underlying structural and molecular pathomechanisms causing PH are not fully understood. Recently, activin receptor-like kinase 1 (ALK-1), an endothelial cell (EC) receptor, has been implicated in the pathogenesis of PH. ALK-1 transmits signals via a Smad pathway stimulating EC proliferation and migration leading to structural lung remodeling consecutively resulting in PH. Increased pulmonary expression of ALK-1 has been reported in patients with severe PH as well as in experimental models of PH. We designed this study to investigate the hypothesis that pulmonary ALK-1 expression is increased in nitrofen-induced CDH., Methods: Pregnant rats were exposed to nitrofen or vehicle on D9. Fetuses were sacrificed on D21 and divided into nitrofen (n = 16) and control group (n = 16). Quantitative real-time polymerase chain reaction, Western blotting, and confocal-immunofluorescence microscopy were performed to determine pulmonary gene and protein expression as well as vascular localization of expressed ALK-1., Results: Pulmonary gene expression levels of ALK-1 were significantly upregulated in nitrofen-treated lung tissue compared with controls. Western blotting showed increased pulmonary protein expression for ALK-1 in the CDH group when compared with control lung tissue. Confocal microscopy demonstrated markedly increased medial and adventitial thickness of pulmonary arteries in the CDH group and revealed increased ALK-1 protein expression of the pulmonary vasculature of CDH pups compared with controls., Conclusion: Upregulated gene and increased protein expression of ALK-1 in the pulmonary vasculature of nitrofen-induced CDH suggest that increased expression of ALK-1 may play a crucial role in the molecular pathogenesis of vascular remodeling induced PH in experimental CDH., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Signal transducer and activator of transcription (STAT) protein family (STAT1-6) regulates diverse cellular processes. Recently, the isoform STAT3 has been implicated to play a central role in the pathogenesis of pulmonary hypertension (PH). In human PH activated STAT3 (pSTAT3) was shown to directly trigger expression of the provirus integration site for Moloney murine leukemia virus (Pim-1), which promotes proliferation and resistance to apoptosis in SMCs. We designed this study to investigate the hypothesis that pSTAT3 and Pim-1 pulmonary vascular expression is increased in nitrofen-induced CDH., Methods: Pregnant rats were exposed to nitrofen or vehicle on D9.5. Fetuses were sacrificed on D21 and divided into nitrofen (n=16) and control group (n=16). QRT-PCR, western blotting, and confocal-immunofluorescence were performed to determine pulmonary gene and protein expression levels of pSTAT3 and Pim-1., Results: Pulmonary Pim-1 gene expression was significantly increased in the CDH group compared to controls. Western blotting and confocal-microscopy confirmed increased pulmonary protein expression of Pim-1 and increased activation of pSTAT3 in CDH lungs compared to controls., Conclusion: Markedly increased gene and protein expression of Pim-1 and activated pSTAT3 in the pulmonary vasculature of nitrofen-induced CDH lungs suggest that pSTAT3 and Pim-1 are important mediators of PH in nitrofen-induced CDH., (Copyright © 2015. Published by Elsevier Inc.)