Pleural CD14+ monocytes/macrophages of healthy adolescents show a high expression of metallothionein family genes.

Nowadays laparoscopic interventions enable the collection of resident macrophage populations out of the human cavities. We employed this technique to isolate pleural monocytes/macrophages from healthy young adults who underwent a correction of pectus excavatum. High quality CD14+ monocytes/macrophages (plMo/Mφ) were used for RNA-sequencing (RNA-seq) in comparison with human monocyte-derived macrophages (MDM) natural (MDM-0) or IL-4-polarized (MDM-IL4). Transcriptome analysis revealed 7166 and 7076 differentially expressed genes (DEGs) in plMo/Mφ relative to natural MDM-0 and polarized MDM-IL4, respectively. The gene set enrichment analysis, which was used to compare RNA-seq data from plMo/Mφ with single-cell (scRNA-seq) data online from human bronchial lavage macrophages, showed that plMo/Mφs are characterized by a high expression of genes belonging to the metallothionein (MT) family, and that the expression of these genes is significantly higher in plMo/Mφ than in MDM-0 or MDM-IL4. Our results provide additional insights on high MTs-expressing macrophage subsets, which seem to be present not only in bronchial lavage of healthy adults or in pleural exudates of lung cancer patients but also in pleural fluid of healthy young adults. Macrophage subsets expressing high MTs may have specific roles in lung defense, repair, and homeostasis, and require further investigations.

Heterozygous variants in the DVL2 interaction region of DACT1 cause CAKUT and features of Townes-Brocks syndrome 2.

Most patients with congenital anomalies of the kidney and urinary tract (CAKUT) remain genetically unexplained. In search of novel genes associated with CAKUT in humans, we applied whole-exome sequencing in a patient with kidney, anorectal, spinal, and brain anomalies, and identified a rare heterozygous missense variant in the DACT1 (dishevelled binding antagonist of beta catenin 1) gene encoding a cytoplasmic WNT signaling mediator. Our patient's features overlapped Townes-Brocks syndrome 2 (TBS2) previously described in a family carrying a DACT1 nonsense variant as well as those of Dact1-deficient mice. Therefore, we assessed the role of DACT1 in CAKUT pathogenesis. Taken together, very rare (minor allele frequency ≤ 0.0005) non-silent DACT1 variants were detected in eight of 209 (3.8%) CAKUT families, significantly more frequently than in controls (1.7%). All seven different DACT1 missense variants, predominantly likely pathogenic and exclusively maternally inherited, were located in the interaction region with DVL2 (dishevelled segment polarity protein 2), and biochemical characterization revealed reduced binding of mutant DACT1 to DVL2. Patients carrying DACT1 variants presented with kidney agenesis, duplex or (multi)cystic (hypo)dysplastic kidneys with hydronephrosis and TBS2 features. During murine development, Dact1 was expressed in organs affected by anomalies in patients with DACT1 variants, including the kidney, anal canal, vertebrae, and brain. In a branching morphogenesis assay, tubule formation was impaired in CRISPR/Cas9-induced Dact1-/- murine inner medullary collecting duct cells. In summary, we provide evidence that heterozygous hypomorphic DACT1 variants cause CAKUT and other features of TBS2, including anomalies of the skeleton, brain, distal digestive and genital tract.

Implementation and validation of a novel instrument for the grading of unexpected events in paediatric surgery: Clavien-Madadi classification.

BACKGROUND: Inconsistent definitions of complications and unexpected events have limited accurate analysis of surgical outcomes. Perioperative outcome classifications currently used for adult patients have limitations when used for children. METHODS: A multidisciplinary group of experts modified the Clavien-Dindo classification to increase its utility and accuracy in paediatric surgery cohorts. Organizational and management errors were considered in the novel Clavien-Madadi classification, which focuses on procedural invasiveness rather than anaesthetic management. Unexpected events were prospectively documented in a paediatric surgery cohort. Results of the Clavien-Dindo and Clavien-Madadi classifications were compared and correlated with procedure complexity. RESULTS: Unexpected events were prospectively documented in a cohort of 17 502 children undergoing surgery between 2017 and 2021. The results of both classifications were highly correlated (ρ = 0.95), although the novel Clavien-Madadi classification identified 449 additional events (organizational and management errors) over the Clavien-Dindo classification, increasing the total number of events by 38 per cent (1605 versus 1158 events). The results of the novel system correlated significantly with the complexity of procedures in children (ρ = 0.756). Furthermore, grading of events > grade III according to the Clavien-Madadi classification showed a higher correlation with procedure complexity (ρ = 0.658) than the Clavien-Dindo classification (ρ = 0.198). CONCLUSION: The Clavien-Madadi classification is a tool for the detection of surgical and non-medical errors in paediatric surgery populations. Further validation in paediatric surgery populations is required before widespread use.

[Solid Pseudopapillary Neoplasm of the Pancreas in Children and Adolescents - Tailored Diagnostic and Operative Concepts in Four Patients]. / Solide pseudopapilläre Pankreasneoplasie bei Kindern und Jugendlichen.

BACKGROUND: Pancreatic tumors in children and adolescents are rare entities that can stay asymptomatic for long periods. They often become apparent as incidental findings or due to clinical symptoms, like abdominal pain. Solid pseudopapillary neoplasms of the pancreas (SPN) are rare representatives of this group, being low-grade malignant processes and requiring radical surgical treatment. We present four cases of SPN with different diagnostic and therapeutic approaches. METHODS: A retrospective analysis of four cases of SPN treated between 2015 and 2020 was performed. RESULTS: Four female patients (11-17 years) were found to have SPN during diagnostic procedures. Three of them were located in the pancreatic head. Histological confirmation was obtained with endosonographic-, CT-guided and open biopsy, respectively. R0 resection was achieved by a pylorus preserving, partial duodenopancreatectomy according to Traverso-Longmire. In one patient the tumor was located in the pancreatic tail with tumor adherence to the splenic vessels. A CT guided biopsy confirmed an SPN. A distal pancreatectomy and splenectomy was performed. Follow-up (6 months - 6 years) revealed no evidence of tumor recurrence, metastasis, or pancreoprive diabetes. CONCLUSION: For the treatment plan preoperative histological confirmation of SPN is necessary. Based on the tailored diagnostic and operative concepts, treatment at a center with a specialized pediatric surgery, pediatric oncology, pediatric gastroenterology, pediatric radiology and pathology is mandatory.

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.

Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

Newborn infants have a high disposition to develop systemic inflammatory response syndromes (SIRSs) upon inflammatory or infectious challenges. Moreover, there is a considerable trafficking of hematopoietic cells to tissues already under noninflammatory conditions. These age-specific characteristics suggest a hitherto unappreciated crucial role of the vascular endothelium during the neonatal period. Here, we demonstrate that healthy neonates showed already strong endothelial baseline activation, which was mediated by a constitutively increased production of TNF-α. In mice, pharmacological inhibition of TNF-α directly after birth prevented subsequent fatal SIRS but completely abrogated the recruitment of leukocytes to sites of infection. Importantly, in healthy neonates, blocking TNF-α at birth disrupted the physiologic leukocyte trafficking, which resulted in persistently altered leukocyte profiles at barrier sites. Collectively, these data suggest that constitutive TNF-α-mediated sterile endothelial activation in newborn infants contributes to the increased risk of developing SIRS but is needed to ensure the postnatal recruitment of leukocytes to organs and interfaces.-Bickes, M. S., Pirr, S., Heinemann, A. S., Fehlhaber, B., Halle, S., Völlger, L., Willers, M., Richter, M., Böhne, C., Albrecht, M., Langer, M., Pfeifer, S., Jonigk, D., Vieten, G., Ure, B., von Kaisenberg, C., Förster, R., von Köckritz-Blickwede, M., Hansen, G., Viemann, D. Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

Low gestational age is associated with less anastomotic complications after open primary repair of esophageal atresia with tracheoesophageal fistula.

BACKGROUND: The aim of this study was to evaluate anastomotic complications after primary one-staged esophageal atresia (EA) repair relating to the patients` gestational age (GA). METHODS: Retrospective data analyses of patients who underwent closure of tracheoesophageal fistula (TEF) and primary esophageal anastomosis from 01/2007 to 12/2018 in two pediatric surgical centers. Exclusion of EA other than Gross type C, long-gap EA, minimal invasive or staged approach. Postoperative complications during the first year of life were assessed. Associated malformations, the incidence of infant respiratory distress syndrome (IRDS) and intraventricular bleeding were analyzed. RESULTS: Inclusion of 75 patients who underwent primary EA repair. Low GA was associated with significantly lower incidence of anastomotic complications (p = 0.019, r = 0.596, 95% CI 0.10-0.85). Incidence of anastomotic leakage (0% vs. 5.5%; p = 0.0416), recurrent TEF (0% vs. 5.5%; p = 0.0416) und anastomotic stricture (0% vs. 14.5%; p = 0.0019) was significantly lower in patients < 34 gestational weeks. Incidence of IRDS (55% vs. 0%; p < 0.0001) and intraventricular bleeding (25% vs. 3.6%; p = 0.0299) was significantly higher in patients < 34 gestational weeks. CONCLUSIONS: Despite prematurity-related morbidity, low GA did not adversely affect surgical outcome after primary EA repair. Low GA was even associated with a better anastomotic outcome indicating feasibility and safety of primary esophageal reconstruction.

Health-related quality of life experiences in children and adolescents born with esophageal atresia: A Swedish-German focus group study.

BACKGROUND: Esophageal atresia (EA) is a rare malformation of the esophagus, which needs surgical treatment. Survival rates have reached 95%, but esophageal and respiratory morbidity during childhood is frequent. Child and parent perspectives and cultural and age-specific approaches are fundamental in understanding children's health-related quality of life (HRQoL) and when developing a pediatric HRQoL questionnaire. We aimed to increase the conceptual and cross-cultural understanding of condition-specific HRQoL experiences among EA children from Sweden and Germany and investigate content validity for an EA-specific HRQoL questionnaire. METHODS: Eighteen standardized focus groups (FGs) with 51 families of EA children aged 2-17 years in Sweden (n = 30 families) and Germany (n = 21 families) were used to explore HRQoL experiences, which were content analyzed into HRQoL domains. The Swedish HRQoL domains were analyzed first and used as framework to evaluate HRQoL content reported in the German FGs. HRQoL experiences were then categorized as physical, social, and emotional HRQoL burden or resource. RESULTS: One thousand nine hundred eight HRQoL statements were recorded. All nine EA-specific HRQoL domains identified in the Swedish FGs (eating, social relationships, general life issues, communication, body issues, bothersome symptoms, confidence, impact of medical treatment, and additional difficulties due to concomitant anomalies) were recognized in the FGs held in Germany, and no additional EA-specific HRQoL domain was found. The HRQoL dimensions referenced physical burden (n = 655, 34.5%), social burden (n = 497, 26.0%), social resources (n = 303, 15.9%), emotional burden (n = 210, 11.0%), physical resources (n = 158, 8.3%), and emotional resources (n = 85, 4.5%). CONCLUSION: This first international FG study to obtain the EA child and his or her parents' perspective on HRQoL suggests Swedish-German qualitative comparability of the HRQoL domains and content validity for a cross-cultural EA-specific HRQoL questionnaire. EA children make positive and negative HRQoL experiences, but prominently related to physical and social burden, which underlines appropriate follow-up care and future research.

Quality of Life in Patients With Progressive Familial Intrahepatic Cholestasis: No Difference Between Post-liver Transplantation and Post-partial External Biliary Diversion.

OBJECTIVES: In patients with progressive familial intrahepatic cholestasis (PFIC), partial external biliary diversion (PEBD), which is associated with a permanent stoma, is recommended as first-line therapy, whereas primary liver transplantation (LTx) is restricted to those with cirrhosis. Our aim was to quantify the health-related quality of life (HRQOL) in patients with PFIC and to evaluate whether there is a difference in their HRQOL depending on the surgical approach. METHODS: A prospective HRQOL study on a consecutive series of PFIC was conducted using Pediatric Quality of Life Inventory 4.0 child-self and parent-proxy reports. Patients with PFIC after PEBD who still lived with their native livers were compared to those after LTx. Both groups were compared to healthy children. RESULTS: A total of 32 patients (53% girls) patients with a mean age of 17.7 ±â€Š7.3 years were studied. Twenty-two had undergone LTx at a mean age of 7.8 ±â€Š3.8 years and 10 had undergone PEBD at a mean age of 4.1 ±â€Š3.9 years. At the time of HRQOL assessment, the mean age was 18.9 ±â€Š7.5 years in the LTx group and 15.3 ±â€Š6.5 years in the PEBD group. Child-self and parent-proxy reports showed no significant difference in HRQOL between patients with PFIC after LTx and those after PEBD except for marginal difference in physical functioning/health (P = 0.07). Except for a lower score in patient school functioning of patients after LTx (P = 0.01), HRQOL-results showed no difference from healthy children in any group. CONCLUSIONS: The HRQOL of patients with PFIC after PEBD was similar to those after LTx. The HRQOL in both groups was also similar to that of healthy children. Thus, our data support the current policy of PEBD as primary surgical treatment for patients with PFIC without cirrhosis.

The Esophageal-Atresia-Quality-of-life Questionnaires: Feasibility, Validity and Reliability in Sweden and Germany.

OBJECTIVES: Esophageal atresia (EA) is a rare malformation characterized of discontinuity of the esophagus, concurrent with or without a tracheoesophageal fistula (TEF). We report the feasibility validity and reliability of a condition-specific quality-of-life (QOL) tool for EA/TEF children, the age-adapted EA-QOL-questionnaires, when used in Sweden and Germany. METHODS: A total of 124 families of children with EA/TEF participated in the study; 53 parents completed the EA-QOL-questionnaire for children aged 2 to 7 years; 62 children/71 parents the EA-QOL-questionnaire for children 8 to 17 years. Feasibility was determined from the percentage of missing item responses. Based on clinical data and previously validated generic QOL-instruments (PedsQL 4.0, DISABKIDS-12), the final EA-QOL scores were evaluated against hypotheses of validity (known-groups/concurrent/convergent) and reliability (internal consistency/retest reliability of scores for 3 weeks). Significant level was P < 0.05. RESULTS: In the questionnaire for EA/TEF children aged 2 to 7 years, 16/18 items were completed with missing values <6% (range 0%-7.5%), and in the questionnaire for 8 to 17-year-olds, 24/24 child-reported items (range 0%-4.8%) and 21/24 parent-reported items (range 0%-7.0%). In both age-specific EA-QOL-questionnaires, desirable standards for known-groups and concurrent validity were fulfilled; digestive symptoms and feeding difficulties negatively impacted EA-QOL-Total-scores (P < 0.001), and as hypothesized, in 2 to 7-year-olds, respiratory symptoms decreased EA-QOL-Total-scores (P = 0.002). Correlations between the EA-QOL and generic QOL questionnaires supported convergent validity. Internal consistency reliability was satisfactory. The level of agreements of EA-QOL-scores between the field- and retest study were good to excellent. CONCLUSIONS: The overall psychometric performance of the EA-QOL-questionnaires for EA/TEF children is satisfactory and can enhance outcome evaluations in future research and clinical practice.

Biliary atresia and other cholestatic childhood diseases: Advances and future challenges.

Biliary Atresia and other cholestatic childhood diseases are rare conditions affecting the function and/or anatomy along the canalicular-bile duct continuum, characterised by onset of persistent cholestatic jaundice during the neonatal period. Biliary atresia (BA) is the most common among these, but still has an incidence of only 1 in 10-19,000 in Europe and North America. Other diseases such as the genetic conditions, Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC), are less common. Choledochal malformations are amenable to surgical correction and require a high index of suspicion. The low incidence of such diseases hinder patient-based studies that include large cohorts, while the limited numbers of animal models of disease that recapitulate the spectrum of disease phenotypes hinders both basic research and the development of new treatments. Despite their individual rarity, collectively BA and other cholestatic childhood diseases are the commonest indications for liver transplantation during childhood. Here, we review the recent advances in basic research and clinical progress in these diseases, as well as the research needs. For the various diseases, we formulate current key questions and controversies and identify top priorities to guide future research.

Distinct phenotypic features of neonatal murine macrophages.

Neonates rely on their innate immune system. Resident tissue macrophages are considered to be initiators and regulators of the innate immune response and thus, appear to be especially important to neonates. We hypothesized that the phenotype and function of neonatal tissue macrophages differ from their adult counterparts. Peritoneal macrophages from neonatal (<24 h) and adult (6 weeks old) C57BL/6J mice were isolated and analyzed by high-content chipcytometry. After stimulation for 6 h with LPS (0, 1, 10, 100 ng/mL), macrophage transcriptome was analyzed by microarray and cytokine release was measured using multiparametric bead assays. Antigen presenting capacity was compared by T-cell stimulation assays. We observed that neonatal murine peritoneal macrophages are characterized by selective lack of expression of F4/80, MHC class II, and costimulatory molecules (CD80, CD86). Furthermore, we found differences in the transcriptome between neonatal and adult macrophages, unstimulated and after LPS stimulation. Although neonatal macrophages showed a significantly increased secretion of proinflammatory cytokines upon LPS stimulation, their potential to induce T-cell proliferation was significantly reduced. In conclusion, we observed a distinct phenotype of the neonatal macrophage population. The specific functions of this macrophage population could help to understand the excessive inflammatory reactions observed in the very young.

The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice.

BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease in premature infants with high mortality and morbidity with uncertain pathogenesis. Recent research focused on the role of intraluminal bacteria and lipopolysaccharide (LPS). However, an additional role of viral agents in the pathogenesis of NEC has recently been postulated. We assessed the role of polyinosinic:polycytidylic acid (pIC) mimicking viral dsRNA in contributing to the development of NEC in neonatal mice. METHODS: Four-d-old C57BL/6J pups were stressed by asphyxia and hypothermia twice daily. Animals were either fed by formula only (FO), formula containing LPS or pIC. After 72 h, mice were euthanized, intestines harvested, and the severity of NEC was assessed. RESULTS: Breastfed mice showed no evidence of NEC. Very mild NEC-like lesions were observed in mice fed by FO. Supplementation of LPS or pIC to the formula led to increased intestinal tissue damage and inflammation compared with FO in a similar manner. CONCLUSION: Our study demonstrates the ability of viral factors to induce NEC in neonatal mice even in the absence of LPS. Furthermore, we present a new mouse model of pIC-induced NEC which may be used to obtain further mechanistic insights in the pathogenesis of this disease.

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

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

3-Dimensional (3D) laparoscopy improves operating time in small spaces without impact on hemodynamics and psychomental stress parameters of the surgeon.

BACKGROUND AND PURPOSE: Three-dimensional (3D) imaging, a recent technical innovation in laparoscopic surgery, has been postulated to enhance depth perception and facilitate operations. However, it has never been evaluated in conditions where the focus is close to the optical system. Thus, it is unclear whether 3D cameras can improve laparoscopic surgical performance in neonates and infants. We tested 3D versus two-dimensional (2D) vision during laparoscopic surgery in rabbits, mimicking the size of a neonatal patient. MATERIALS AND METHODS: Cadaver New Zealand white rabbits (mean weight 2,755 g) were operated by two surgeons experienced in 2D laparoscopic surgery and two surgical residents (with basic skills in 2D laparoscopy). All surgeons had never performed 3D laparoscopic surgery. Animals underwent six operations: Nissen fundoplication, small bowel anastomosis, and closure of a diaphragmatic defect using either 2D or 3D. Primary endpoint was cumulative operating time and operating time of each operation. Secondary endpoints included the hemodynamic response and psychomental stress level of the surgeons. Finally, subjective data on depth perception were assessed by questionnaires. RESULTS: Cumulative operating time of all three types of operations was significantly shorter with 3D laparoscopy in experts (3D: 23.01 ± 5.65 min vs 2D: 29.51 ± 7.51 min, p < 0.01) and residents (3D: 27.95 ± 3.69 min vs 2D: 33.95 ± 6.21 min, p < 0.05). This effect could be shown for each operation in the expert group and the Nissen fundoplication in the resident group. There were no differences in the hemodynamic response as well as the psychomental stress level between 2D and 3D imaging. 3D provided better depth perception. CONCLUSION: 3D laparoscopy in small spaces is associated with a significant shorter operating time. It induces no additional physical or psychomental stress in surgeons naive to 3D imaging. 3D may therefore facilitate minimal invasive surgery in neonates and infants.

Survey on the management of anorectal malformations (ARM) in European pediatric surgical centers of excellence.

PURPOSE: Various management strategies for anorectal malformations (ARM) have been proposed. The aim of this study was to assess the current management in centers of excellence in Europe. METHODS: An online survey on the pre- and post-operative concepts, surgical techniques, and the management of complications was sent to the representative experts of 28 selected European centers of pediatric surgery with special expertise in the treatment of ARM. RESULTS: The survey was completed by 25 experts from 14 countries. To assess the level of the rectal pouch in newborns 60% of participants perform a prone cross-table X-ray and 52% ultrasound. If an ostomy is required, 84% create divided Peña stomas. Primary repair in the newborn period is performed in females with rectoperineal (92%), rectovestibular (60%), and no fistula (32%), and in males with rectoperineal (92%), rectourinary (17%) and no fistula (38%). For 68 % of surgeons, the PSARP is the preferred surgical approach for "low" malformations. Laparoscopically assisted pull-throughs are routinely performed by 48% of experts for ARM with bladderneck and 28% for rectoprostatic fistula. 88% perform postoperative dilations. CONCLUSIONS: The management of ARM in Europe is very heterogeneous. High-quality clinical studies are needed to provide scientific evidence for the optimal treatment strategies.

A noise-reduction program in a pediatric operation theatre is associated with surgeon's benefits and a reduced rate of complications: a prospective controlled clinical trial.

OBJECTIVE: We assessed the impact of a noise-reduction program in a pediatric operating theatre. BACKGROUND: Adverse effects from noise pollution in theatres have been demonstrated. METHODS: In 156 operations spatially resolved, sound levels were measured before and after a noise-reduction program on the basis of education, rules, and technical devices (Sound Ear). Surgical complications were recorded. The surgeon's biometric (saliva cortisol, electrodermal activity) and behavioral stress responses (questionnaires) were measured and correlated with mission protocols and individual noise sensitivity. RESULTS: Median noise levels in the control group versus the interventional group were reduced by -3 ± 3 dB(A) (63 vs 59 dB(A), P < 0.001) with a grossly decreased number of peaks greater than 70 dB(A) (Δn = -61/hour, P < 0.01). The intervention significantly reduced non-operation-related noise. The incidence of postoperative complications was significantly lower in patients of the intervention group (n = 10/56 vs 20/58 control; P < 0.05). "Responders," surgeons with an above-average noise sensitivity (correlation r = -0.6 for the work subscale of the NoiseQ questionnaire, P < 0.05), experienced improved intrateam communication, a decrease in disturbing conversations and sudden noise peaks (P < 0.05). Biometrically, the intervention decreased both the surgeon's pre- to postoperative rise in cortisol by approximately 20% and the surgeon's electrodermal potentials of greater than 15 µS, indicating severe stress by 60% (P > 0.05). CONCLUSIONS: Spontaneous noise during pediatric operations attains the magnitude of a lawn mower and peaks resemble a passing truck. The sound intensity could be reduced by 50% by specific measures. This reduction was associated with a significantly lowered number of postoperative complications. The surgeon's benefits are idiosyncratic with "responders" experiencing marked improvements.

Benchmarks for Pediatric Surgical Registries: Recommendations for the Assessment and Grading of Complications.

Procedure-related registries in general surgical practice offer a platform for prospective trials, the pooling of data, and detailed outcome analysis. Recommendations by the Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) collaboration and Outcome4Medicine have further improved the uniform reporting of complications and adverse events.In the pediatric surgical network, disease-specific registries for rare and inherited congenital anomalies are gaining importance, fostering international collaborations on studies of low-incidence diseases. However, to date, reporting of complications in the pediatric surgical registries has been inconsistent. Therefore, the European Reference Network for Rare Inherited and Congenital Anomalies (ERNICA) recently endorsed the validation of the first severity grading system for children. The planned reform of the European Paediatric Surgical Audit (EPSA) registry, which includes the implementation of the Clavien-Madadi classification, represents a further effort to establish uniform outcome reporting.This article provides an overview of experiences with surgical registries and complication reporting, along with the potential application of this knowledge to future pediatric surgical practice.

Lost in transition? Loss of follow-up and quality of life in adults after resection of choledochal malformation in childhood.

Objectives: Choledochal malformation (CM) is a rare disease that can lead to malignancy and potential long-term sequelae despite surgical resection. There is no long-term follow-up data on patients after CM resection in Germany. We aimed to determine the long-term outcome of our patients with a duration of follow-up >10 years and focused on long-term sequelae and health-related quality of life (HRQOL). Methods: All patients who had undergone CM-resection in our department from 01/1978 to 06/2009 were contacted. Patients were interviewed about postoperative complications and their present medical attendance. HRQOL was determined using Pediatric Quality of Life Inventory 4.0 (PedsQL), version for adults. The PedsQL scales the HRQOL from 0 to 100, with higher scores indicating a better HRQOL. Scores were compared to those published for a healthy population. Results: Out of 56 patients who were contacted, 23 (41 %) participated. The median age at time of surgery was 3.1 years (6 days-16.1 years) and at time of the survey 24.3 years (11.1-53.8 years). Eighteen patients (78 %) had ceased their gastroenterologic follow-up at a median time of 4.3 years after surgery. Five (22 %) were still in gastroenterologic follow-up, two of these had an uneventful clinical course, and three (13 %) had ongoing complications attributed to the CM. One of these had undergone hemihepatectomy 34 years postoperatively due to bile duct stenosis, one had undergone removal of bile duct stones 14 years postoperatively, and one suffered from portal vein thrombosis with esophageal and jejunal varices. There was no mortality in our series. Median total HRQOL score was 89. There was no significant difference in the median total health, physical health, and psychosocial health scores of our patients in comparison to the healthy population. Conclusions: We confirmed that the majority of patients after CM resection are lost to follow-up. Those who answered our questionnaire showed a good HRQOL. Given the high rate of severe long-term complications and the life-long risk of malignancy, we recommend a transition program for all patients.

Validation of the Clavien-Madadi Classification for Unexpected Events in Pediatric Surgery: A Collaborative ERNICA Project.

BACKGROUND: The Clavien-Madadi classification is a novel instrument for the assessment and grading of unexpected events in pediatric surgery, based on the Clavien-Dindo classification. The system has been adjusted to better fit the pediatric population in a prospective single-center study. There is a need now to validate the Clavien-Madadi classification within an international expert network. METHODS: A pediatric surgical working group created 19 case scenarios with unexpected events in a multi-staged process. Those were circulated within the European Reference Network of Inherited and Congenital Anomalies (ERNICA) and surgeons were instructed to rate the scenarios according to the Clavien-Madadi vs. Clavien-Dindo classification. RESULTS: 59 surgeons from 12 European countries completed the questionnaire. Based on ratings of the case scenarios, the Clavien-Madadi classification showed significantly superior agreement rates of the respondents (85.9% vs 76.2%; p < 0.05) and was less frequently considered inaccurate for rating the pediatric population compared to Clavien-Dindo (2.1% vs 11.1%; p = 0.05). Fleiss' kappa analysis showed slightly higher strength of agreement using the Clavien-Madadi classification (0.74 vs 0.69). Additionally, intraclass correlation coefficient was slightly higher for the Clavien-Madadi compared to the Clavien-Dindo classification (ICCjust 0.93 vs 0.89; ICCunjust 0.93 vs 0.89). More pediatric surgeons preferred the Clavien-Madadi classification for the case scenarios (43.0% vs 11.8%; p = 0.002) and advantages of the Clavien-Madadi were confirmed by 81.4% of the surgeons. CONCLUSION: The Clavien-Madadi classification is an accurate and reliable instrument for the grading of unexpected events in pediatric surgery. We therefore recommend its application in clinical and academic pediatric surgical practice. LEVEL OF EVIDENCE: III.